588 results on '"Piemonti L"'
Search Results
102. Human pancreatic islets produce and secrete MCP-1/CCL2: Relevance in human islet transplantation
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Piemonti, L, Leone, B, Nano, R, Saccani, A, Monti, P, Maffi, P, Bianchi, G, Sica, A, Peri, G, Melzi, R, Aldrighetti, L, Secchi, A, Di Carlo, V, Allavena, P, Bertuzzi, F, LEONE, BIAGIO EUGENIO, Bertuzzi, F., Piemonti, L, Leone, B, Nano, R, Saccani, A, Monti, P, Maffi, P, Bianchi, G, Sica, A, Peri, G, Melzi, R, Aldrighetti, L, Secchi, A, Di Carlo, V, Allavena, P, Bertuzzi, F, LEONE, BIAGIO EUGENIO, and Bertuzzi, F.
- Abstract
We investigated the capacity of human islets to produce monocyte chemoattractant protein-1 (MCP-1). Primary cultures of pancreatic islets expressed and secreted MCP-1, as determined by Northern blot, immunohistochemistry, in situ hybridization, and enzyme-linked immunosorbent assay. The produced MCP-1 was biologically active as it attracted monocytes in chemotaxis assay, and chemotactic activity was almost abrogated by a neutralizing anti-MCP-1 monoclonal antibody. Expression of MCP-1 was increased by primary inflammatory cytokines (interleukin-1beta, tumor necrosis factor-alpha) and lipopolysaccharide at both the mRNA and protein levels but not by glucose. However, MCP-1 did not modulate insulin secretion. MCP-1 secreted by pancreatic islets plays a relevant role in the clinical outcome of islet transplant in patients with type I diabetes. In fact, low MCP-1 secretion resulted as the most relevant factor for long-lasting insulin independence. This finding opens new approaches in the management of human islet transplantation. Finally, the finding that MCP-1 appears constitutively present in normal human islet beta-cells (immunohistochemistry and in situ hybridization), in the absence of an inflammatory infiltrate, suggests that this chemokine could have functions other than monocyte recruitment and opens a new link between the endocrine and immune systems
- Published
- 2002
103. Ghrelin-producing epsilon cells in the developing and adult human pancreas
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Andralojc, K. M., primary, Mercalli, A., additional, Nowak, K. W., additional, Albarello, L., additional, Calcagno, R., additional, Luzi, L., additional, Bonifacio, E., additional, Doglioni, C., additional, and Piemonti, L., additional
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- 2008
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104. Intrahepatic Islet Transplant in the Mouse: Functional and Morphological Characterization
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Melzi, R., primary, Sanvito, F., additional, Mercalli, A., additional, Andralojc, K., additional, Bonifacio, E., additional, and Piemonti, L., additional
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- 2008
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105. A preclinical evaluation of pemetrexed and irinotecan combination as second-line chemotherapy in pancreatic cancer
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Mercalli, A, primary, Sordi, V, additional, Formicola, R, additional, Dandrea, M, additional, Beghelli, S, additional, Scarpa, A, additional, Di Carlo, V, additional, Reni, M, additional, and Piemonti, L, additional
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- 2007
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106. Raltitrexed–eloxatin salvage chemotherapy in gemcitabine-resistant metastatic pancreatic cancer
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Reni, M, primary, Pasetto, L, additional, Aprile, G, additional, Cordio, S, additional, Bonetto, E, additional, Dell'oro, S, additional, Passoni, P, additional, Piemonti, L, additional, Fugazza, C, additional, Luppi, G, additional, Milandri, C, additional, Nicoletti, R, additional, Zerbi, A, additional, Balzano, G, additional, Di Carlo, V, additional, and Brandes, A A, additional
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- 2006
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107. Strategies for tumor immune escape
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Piemonti, L., primary, Zerbi, A., additional, and Carlo, V.D., additional
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- 2003
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108. Receptor expression and responsiveness of human dendritic cells to a defined set of CC and CXC chemokines.
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Sozzani, S, primary, Luini, W, additional, Borsatti, A, additional, Polentarutti, N, additional, Zhou, D, additional, Piemonti, L, additional, D'Amico, G, additional, Power, C A, additional, Wells, T N, additional, Gobbi, M, additional, Allavena, P, additional, and Mantovani, A, additional
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- 1997
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109. Glucagon improves insulin secretion from pig islets in vitro
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Bertuzzi, F, primary, Berra, C, additional, Socci, C, additional, Davalli, A M, additional, Calori, G, additional, Freschi, M, additional, Piemonti, L, additional, De Nittis, P, additional, Pozza, G, additional, and Pontiroli, A E, additional
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- 1995
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110. Migration of dendritic cells in response to formyl peptides, C5a, and a distinct set of chemokines.
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Sozzani, S, primary, Sallusto, F, additional, Luini, W, additional, Zhou, D, additional, Piemonti, L, additional, Allavena, P, additional, Van Damme, J, additional, Valitutti, S, additional, Lanzavecchia, A, additional, and Mantovani, A, additional
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- 1995
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111. Isolation and function of adult pig Islets
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Socci, C., primary, Bertuzzi, F., additional, Nittis, P., additional, Piemonti, L., additional, Taglietti, M.V., additional, Berra, C., additional, Birkeland, P., additional, Freschi, M., additional, Carlo, V. Di, additional, and Pozza, G., additional
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- 1995
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112. Prevalence, metabolic features, and prognosis of metabolically healthy obese Italian individuals: the Cremona Study.
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Calori G, Lattuada G, Piemonti L, Garancini MP, Ragogna F, Villa M, Mannino S, Crosignani P, Bosi E, Luzi L, Ruotolo G, Perseghin G, Calori, Giliola, Lattuada, Guido, Piemonti, Lorenzo, Garancini, Maria Paola, Ragogna, Francesca, Villa, Marco, Mannino, Salvatore, and Crosignani, Paolo
- Abstract
Objective: Some obese individuals have normal insulin sensitivity. It is controversial whether this phenotype is associated with increased all-cause mortality risk.Research Design and Methods: Fifteen-year all-cause mortality data were obtained through the Regional Health Registry for 2,011 of 2,074 Caucasian middle-aged individuals of the Cremona Study, a population study on the prevalence of diabetes in Italy. Individuals were divided in four categories according to BMI (nonobese: <30 kg/m²; obese: ≥30 kg/m²) and estimated insulin resistance (insulin sensitive: homeostasis model assessment of insulin resistance <2.5; insulin resistant ≥2.5).Results: Obese insulin-sensitive subjects represented 11% (95% CI 8.1-14.5) of the obese population. This phenotype had similar BMI but lower waist circumference, blood pressure, fasting glucose, triglycerides, and fibrinogen and higher HDL cholesterol than obese insulin-resistant subjects. In the 15-year follow-up, 495 deaths (cardiovascular disease [CVD]: n = 221; cancer: n = 180) occurred. All-cause mortality adjusted for age and sex was higher in the obese insulin-resistant subjects (hazard ratio 1.40 [95% CI 1.08-1.81], P = 0.01) but not in the obese insulin-sensitive subjects (0.99 [0.46-2.11], P = 0.97) when compared with nonobese insulin-sensitive subjects. Also, mortality for CVD and cancer was higher in the obese insulin-resistant subjects but not in the obese insulin-sensitive subjects when compared with nonobese insulin-sensitive subjects.Conclusions: In contrast to obese insulin-resistant subjects, metabolically healthy obese individuals are less common than previously thought and do not show increased all-cause, cancer, and CVD mortality risks in a 15-year follow-up study. [ABSTRACT FROM AUTHOR]- Published
- 2011
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113. Association between plasma monocyte chemoattractant protein-1 concentration and cardiovascular disease mortality in middle-aged diabetic and nondiabetic individuals.
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Piemonti L, Calori G, Lattuada G, Mercalli A, Ragogna F, Garancini MP, Ruotolo G, Luzi L, Perseghin G, Piemonti, Lorenzo, Calori, Giliola, Lattuada, Guido, Mercalli, Alessia, Ragogna, Francesca, Garancini, Maria Paola, Ruotolo, Giacomo, Luzi, Livio, and Perseghin, Gianluca
- Abstract
Objective: Monocyte chemoattractant protein-1 (MCP-1/CCL2) is a chemokine involved into the pathogenesis of atherosclerosis and has prognostic value in the acute and chronic phases in patients with acute coronary syndromes.Research Design and Methods: MCP-1/CCL2 concentration was measured in plasma fractions of 363 middle-aged overweight/obese individuals (aged 61 +/- 12 years, BMI 30.1 +/- 6.6 kg/m(2), 15% with type 2 diabetes, and 12% with impaired glucose tolerance) of a population survey carried out in 1990-1991 in Lombardy, Italy (Cremona Study), and cardiovascular disease (CVD) mortality was assessed in 2006 through Regional Health Registry files.Results: At baseline MCP-1/CCL2 was increased in individuals with type 2 diabetes (P < 0.05) and showed significant correlations with biochemical risk markers of atherosclerosis. After 15 years, among the 363 subjects, there were 82 deaths due to CVD. In univariate analysis age, sex, fasting glucose and insulin, fibrinogen, glucose tolerance status, smoking habit, and MCP-1/CCL2 were associated with CVD mortality. Age, sex, fasting serum glucose, MCP-1/CCL2, and smoking habit maintained an independent association with CVD mortality in multiple regression analysis. In a subgroup of 113 subjects in whom data for C-reactive protein (CRP) were available, its level was not predictive of CVD mortality.Conclusions: In middle-aged overweight/obese individuals MCP-1/CCL2 was independently associated with CVD mortality. Further studies will be necessary to establish its role as a surrogate biomarker and as a potential therapeutic target. [ABSTRACT FROM AUTHOR]- Published
- 2009
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114. Rapamycin monotherapy in patients with type 1 diabetes modifies CD4+CD25+FOXP3+ regulatory T-cells.
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Monti P, Scirpoli M, Maffi P, Piemonti L, Secchi A, Bonifacio E, Roncarolo MG, Battaglia M, Monti, Paolo, Scirpoli, Miriam, Maffi, Paola, Piemonti, Lorenzo, Secchi, Antonio, Bonifacio, Ezio, Roncarolo, Maria-Grazia, and Battaglia, Manuela
- Abstract
Objective: Rapamycin is an immunosuppressive drug currently used to prevent graft rejection in humans, which is considered permissive for tolerance induction. Rapamycin allows expansion of both murine and human naturally occurring CD4(+)CD25(+)FOXP3(+) T regulatory cells (nTregs), which are pivotal for the induction and maintenance of peripheral tolerance. Preclinical murine models have shown that rapamycin enhances nTreg proliferation and regulatory function also in vivo. Objective of this study was to assess whether rapamycin has in vivo effects on human nTregs.Research Design and Methods: nTreg numbers and function were examined in a unique set of patients with type 1 diabetes who underwent rapamycin monotherapy before islet transplantation.Results: We found that rapamycin monotherapy did not alter the frequency and functional features, namely proliferation and cytokine production, of circulating nTregs. However, nTregs isolated from type 1 diabetic patients under rapamycin treatment had an increased capability to suppress proliferation of CD4(+)CD25(-) effector T-cells compared with that before treatment.Conclusions: These findings demonstrate that rapamycin directly affects human nTreg function in vivo, which consists of refitting their suppressive activity, whereas it does not directly change effector T-cell function. [ABSTRACT FROM AUTHOR]- Published
- 2008
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115. Transplant estimated function: a simple index to evaluate beta-cell secretion after islet transplantation.
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Caumo A, Maffi P, Nano R, Bertuzzi F, Luzi L, Secchi A, Bonifacio E, and Piemonti L
- Abstract
OBJECTIVE: The beta-score is a highly regarded approach to the assessment of transplant functionality. Our aim was to develop an index of beta-cell function that hinges on the pillars of the beta-score (daily insulin requirement and A1C), has a straightforward physiological interpretation, and does not require the execution of an insulin stimulation test. RESEARCH DESIGN AND METHODS: The new index is denoted transplant estimated function (TEF) and is obtained from the daily insulin requirement and A1C. TEF estimates the amount of insulin secreted daily and can be normalized to the number of transplanted islets, thus permitting evaluation of the cost-effectiveness of the transplant. TEF was compared with the area under the curve of C-peptide [AUC(C-pep)] concentration over 24 h, as well as the acute insulin response to intravenous glucose (AIR(glu)) and to arginine (AIR(arg)). The association between TEF and beta-score was also investigated. RESULTS: The correlation of TEF with 24-h AUC(C-pep) was r = 0.73 (P < 0.005), whereas that for beta-score versus 24-h AUC(C-pep) was r = 0.33 (NS). The correlation of TEF with AIR(glu) was r = 0.59 (P < 0.001) and close to that for beta-score versus AIR(glu) (r = 0.65, P < 0.001). The correlation of TEF with AIR(arg) was r = 0.33 (P < 0.005) and was similar to that for beta-score versus AIR(arg) (r = 0.34, P < 0.005). TEF and beta-score were correlated well (r = 0.69, P < 0.0001) and showed similar time profiles. CONCLUSIONS: TEF estimates daily insulin secretion, it is simpler than the beta-score, and its performance against reference indexes of beta-cell secretion is in line with that exhibited by beta-score. TEF can be normalized to the number of transplanted islets and thereby provides a benchmarking tool to evaluate the cost-effectiveness of the transplant. [ABSTRACT FROM AUTHOR]
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- 2008
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116. Effects of cryopreservation on in vitro and in vivo long-term function of human islets
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Piemonti, L., Bertuzzi, F., Nano, R., Leone, B.E., Socci, C., Pozza, G., and Di Carlo, V.
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- 1999
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117. Glucocorticoids increase the endocytic activity of human dendritic cells
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Piemonti, L., Monti, P., Allavena, P., Leone, B.E., Caputo, A., and Carlo, V. Di
- Abstract
We have investigated the effect of glucocorticoids (GC) on antigen uptake molecule expression and on endocytic activity of human dendritic cells (DC). Human monocyte-derived DC were differentiated in vitro for 7 days with granulocyte macrophage colony stimulating factor and IL-4 in the presence or absence of dexamethasone 10-8 M (Dex). Dex-treated DC showed an enhancement of mannose receptor (MR)-mediated endocytosis (measured as uptake of FITC-dextran) and of fluid-phase endocytosis [measured as uptake of Lucifer yellow (LY)] The effect was dose dependent and correlated with the length of exposure to Dex. The expression of receptors involved in antigen capture was investigated by FACS analysis. Dex up-regulates MR, CD16 and CD32 expression on DC. After maturation with tumor necrosis factor-α or CD40 ligand in Dex-treated DC, despite a reduction induced by maturation the endocytic activity of FITC-dextran and LY, the expression of MR, CD16 and CD32 remained higher than in control DC. In view of the fact that antigen capture was increased in cells cultured with Dex, we evaluated the ability to present soluble antigen that needs to be taken up and processed. Cells differentiated in the presence of Dex showed much lower efficiency in presenting tetanus toxin to specific autologous T cell lines. In conclusion our data suggest a new mechanism by which GC may influence immune responses. In fact with the increase in endocytic activity, Dex favors the scavenging of antigen from the external milieu, decreasing antigen concentration and availability, and simultaneously inhibiting the capacity to stimulate T cells.
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- 1999
118. The CC Chemokine MCP-1/CCL2 in Pancreatic Cancer Progression: Regulation of Expression and Potential Mechanisms of Antimalignant Activity
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Monti, P., Leone, B. E., Federica Marchesi, Balzano, G., Zerbi, A., Scaltrini, F., Pasquali, C., Calori, G., Pessi, F., Sperti, C., Di Carlo, V., Allavena, P., Piemonti, L., Monti, P, Leone, B, Marchesi, F, Balzano, G, Zerbi, A, Scaltrini, F, Pasquali, C, Calori, G, Pessi, F, Sperti, C, Di Carlo, V, Allavena, P, Piemonti, L, Leone, Be, and Piemonti, Lorenzo
- Subjects
Pancreatic Neoplasms ,MCP-1-CCL2, pancreatic cancer ,Cell Line, Tumor ,Macrophages ,Disease Progression ,Humans ,Prognosis ,Cell Division ,Chemokine CCL2 ,Carcinoma, Pancreatic Ductal - Abstract
The aim of this study was to discover whether MCP-1/CCL2, a CC chemokine able to attract macrophages, is expressed in human pancreatic cancer and how it modulates cancer progression. All primary tumors were tested, and 6 of 14 pancreatic cancer cell lines were constitutively secreted CCL2. Analysis of the regulation demonstrated that the expression of CCL2 was significantly elevated and in a synergistic manner by IFN-gamma, tumor necrosis factor alpha, and interleukin 1beta. By immunohistochemistry and in situ hybridization, CCL2 production was confirmed in neoplastic ducts from surgical specimens. Serum levels of CCL2 in pancreatic cancer patients were significantly higher than in normal healthy subjects (P0.0001). Patients with high circulating levels of CCL2 had significantly higher survival rate than low CCL2 producers. Serum CCL2 levels positively correlated with tumor macrophage infiltration and inversely correlated with tumor proliferative activity (Ki67 expression). A direct effect of CCL2 on tumor cells is to be excluded, either because primary tumors as well as cell lines have no detectable CCL2 receptor (CCR2) and because addition of CCL2 on tumor cells in vitro did not modify cell cycle progression or apoptosis. In vitro, a model of tumor microenvironment showed a direct antiproliferative and proapoptotic activity of monocytes toward pancreatic cancer cell, which is mediated at least in part by interleukin 1beta. Moreover, other proinflammatory cytokines such as tumor necrosis factor alpha and IFN-gamma appeared able to induce apoptosis and to reduce the proliferative rate of pancreatic cancer. On the whole, the results presented in our investigation suggest that CCL2 could be a relevant negative regulator of pancreatic cancer progression.
119. ISL1 expression in human pancreas and in pancreatic endocrine tumors
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Albarello, L., Andralojc, K., Piemonti, L., alessandro zerbi, Di Carlo, V., Arrigoni, G., Doglioni, C., Albarello, L, Andralojc, K, Piemonti, Lorenzo, Zerbi, A, Di Carlo, V, Arrigoni, G, and Doglioni, C.
120. Role of Immunosuppressive Therapy on Humoral Autoimmune Response after Islet Allotransplantation: A Long Term Survey
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Maffi, P., Piemonti, L., Federico Mescia, Scavini, M., Melzi, R., Nano, R., Magistretti, P., Delmaschio, A., Venturini, M., Bosi, E., Secchi, A., Maffi, P, Piemonti, Lorenzo, Mescia, F, Scavini, M, Melzi, R, Nano, R, Magistretti, P, DEL MASCHIO, Alessandro, Venturini, M, Bosi, E, and Secchi, A.
121. Ultra-marathon 100 km in an islet-transplanted runner
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Roberto Codella, Adamo M, Maffi P, Piemonti L, Secchi A, and Luzi L
122. IL-10 prevents the generation of dendritic cells from CD14+ blood monocytes, promotes the differentiation to mature macrophages and stimulates endocytosis of FITC-dextran
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Paola Allavena, Piemonti, L., Longoni, D., Bernasconi, S., Stoppacciaro, A., Ruco, L., and Mantovani, A.
123. Allotransplantation of fresh and cryopreserved islets in patients with type I diabetes: Two-year experience
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Socci, C., Davalli, A. M., Maffi, P., Falqui, L., Secchi, A., Bertuzzi, F., Vignali, A., Magistretti, P., Zammarchi, O., Scaglia, L., Francesca Gavazzi, Piemonti, L., Nittis, P., Ferrari, P., Di Carlo, V., and Pozza, G.
124. Overexpression of the Sm-like proto-oncogene in primary and metastatic pancreatic endocrine tumors
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Gumbs, A. A., Bassi, C., Moore, P. S., Falconi, M., FRIGERIO ISABELLA, Baron, A., Piemonti, L., Modlin, I., Scarpa, A., Gumbs, Aa, Bassi, C, Moore, P, Falconi, Massimo, Frigerio, I, Baron, A, Piemonti, Lorenzo, Modlin, I, and Scarpa, A.
- Abstract
CONTEXT: The cancer associated Sm-like proto-oncogene mRNA has been found to be overexpressed in the majority of pancreatic adenocarcinomas and is necessary for the transformed phenotype in pancreatic cancer cell lines. However, expression levels have not been examined in other types of pancreatic neoplasms, such as pancreatic endocrine tumors. SETTING: Fifteen primary pancreatic endocrine tumors, including five insulinomas and 10 non-functioning tumors, along with seven hepatic metastatic pancreatic endocrine tumors. MAIN OUTCOME MEASURES: Quantitative expression levels of cancer associated Sm-like mRNA were measured by real-time PCR. Overexpression was defined as a two-fold or greater value when compared to the expression levels found in normal pancreatic islet cells obtained from healthy donors. RESULTS: In primary tumors, four of the 10 non-functioning pancreatic endocrine tumors were found to overexpress cancer associated Sm-like mRNA (40%). Three of the five (60%) insulinomas also overexpressed cancer associated Sm-like mRNA. In total, cancer associated Sm-like mRNA was overexpressed in seven of 15 primary tumors (47%) and in the majority (71%, 5 of 7) of the hepatic metastases. CONCLUSIONS: Our results indicate that the cancer associated Sm-like mRNA gene may also play a role in the tumorigenesis of pancreatic endocrine tumors.
125. Labeling of human pancreatic islets of Langerhans with Endorem (R) for non-invasive MRI imaging in vivo
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MARIA LUISA MALOSIO, Poletti, A., Esposito, A., Losio, C., Piemonti, L., Melzi, R., Nano, R., Cobelli, F., Maffi, P., Bonifacio, E., Secchi, A., Del Maschio, A., Malosio, Ml, Poletti, A, Esposito, Antonio, Losio, C, Piemonti, Lorenzo, Melzi, R, Nano, R, DE COBELLI, Francesco, Maffi, P, Bonifacio, E, Secchi, A, and DEL MASCHIO, Alessandro
126. 40 EASD Annual Meeting of the European Association for the Study of Diabetes : Munich, Germany, 5-9 September 2004
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Veitenhansl, M., Stegner, K., Hierl, F-X, Dieterle, C., Feldmeier, H., Gutt, B., Landgraf, R., Garrow, A. P., Vileikyte, L., Findlow, A., Waterman, C., Boulton, A. J. M., Shankhdhar, K., Shankhdhar, L., Shankhdhar, U., Petrova, N. L., Foster, A. V. M., Edmonds, M. E., Ferraresi, R., Caravaggi, C., Giglio, R., Cavaiani, P., Pogliaghi, I., Sommariva, E., Katz, I. A., Harlan, A., Miranda-Palma, B., Prieto-Sanchez, L., Armstrong, D. G., Bowker, J. H., Mizel, M. S., Cernea, S., Wohlgelernter, J., Kidron, M., Modi, P., Raz, I., Arbit, E., Nosek, L., Kapitza, C., Beckett, P., Gelfand, R., Goldberg, M., Heise, T., Testa, M. A., Turner, R. R., Hayes, J. F., Scranton, R. E., Simonson, D. C., Yang, Y-W, Hsu, Y-J, Naujok, O., Francini, F., Jorns, A., Tiedge, M., Lenzen, S., Abdel-Wahab, Y. H. A., Marenah, L., Orr, D. F., Shaw, C., Flatt, P. R., Chokkalingam, K., Mansell, P. I., Clausen, P., Ekbom, P., Damm, P., Feldt-Rasmussen, U., Nielsen, B., Mathiesen, E. R., Feldt-Rasmussen, B., Dewan, S., Da Silva, N., Ternan, P. Mc, Leong, K. S., Wilding, J. P. H., Asatiani, N., Kurashvili, R., Dundua, M., Shelestova, E., Pagava, K., Ramazashvili, M., Hod, M., Smirnov, S., Petersen, J. L. A., Justesen, T. I., Ringholm Nielsen, L., Muller, C., Hojlund, K., Wensaas, A., Kase, E. T., Aas, V., Rustan, A. C., Thoresen, G. H., Levin, K., Beck-Nielsen, H., Gaster, M., Im, S-S, Kang, S-Y, Kim, S-Y, Ahn, Y-H, Lihn, A. S., Schmoll, D., Werner, T., Kienitz, A., Meyer, M., Barthel, A., Ailett, F., Sutherland, C., Walther, R., Grempler, R., Sasson, S., Reich, R., Tenenbaum, T., Alpert, E., Anfossi, G., Russo, I., Traversa, M., Massucco, P., Mattiello, L., Doronzo, G., Trovati, M., Lally, S., Tan, C. Y., Owens, D., Tomkin, G. H., Porchay, I., Pean, F., Bellili, N., Betoulle, D., Balkau, B., Tichet, J., Marre, M., Fumeron, F., Group D.E.S.I.R., Chatellier, G., Alhenc-Gelas, F., Diabhycar, Study Group, Nichols, G. A., Brown, J. B., Hayes, R. P., Bowman, L., Drexel, H., Saely, C. H., Marte, T., Benzer, W., Langer, P., Hoefle, G., Moll, W., Aczel, S., Karagiannis, E., Lubben, G., Urquhart, R., Edwards, G., Bruce, S., Howlett, H. S. C., Cugnardey, N., Turner, K. C., Park, J-S, Fiedorek, F. T., Avogaro, A., Gallo, A., Pinton, P., Rizzuto, R., Murphy, E., Ceolotto, G., Caterson, I., Guy-Grand, B., Hill, J., Barone, M., Aiello, A., Allochis, G., Borzi, V., Cannata, F., Caronna, S., D Avanzo, A., Elli, R., Formoso, G., Paroli, A., Scardapane, R., Sorichetti, P., Tatti, P., Viviani, G., Santeusanio, F., Italian Repaglinide Study Group, Manzella, D., Grella, R., Abbatecola, A. M., Paolisso, G., Sondergaard, L. G., Monster, T. B. M., Johnsen, S. P., Olsen, M. L., Mclaughlin, J. K., Sorensen, H. T., Lervang, H. H., Rungby, J., Lyssenko, V., Fredriksson, J., Almgren, P., Anevski, D., Orho-Melander, M., Sjogren, M., Tuomi, T., Groop, L., Jaziri, R., Aubert, R., Tuomilehto, J., Hu, G., Jousilahti, P., Peltonen, M., Lindstrom, J., Laina, A., Alevizaki, M., Philippou, G., Souvatzoglou, A., Anastasiou, E., Alba, S., Metcalf, B. S., Voss, L. D., Jeffery, A. N., Wilkin, T. J., Gluimer, C., Colagiuri, S., Vistisen, D., Borch-Johnsen, K., Haynes, A., Bower, C., Bulsara, M. K., Jones, T. W., Davis, E. A., Mortensen, H. B., Hougaard, P., Holl, R., Swift, P., Pociot, F., Knip, M., Hansen, L., Szadkowska, A., Pietrzak, I., Zmyslowska, A., Wyka, K., Bodalski, J., Holl, R. W., Swift, R., Hougaard, R., Gerstl, E-M, Engelsberger, I., Rabl, W., Rosenbauer, J., Grobe, H., Hofer, S. E., Krause, U., DPV-Wiss-Study Group, Dabelea, D., Morgan, T., Pettitt, D. J., Dolan, L., Mayer-Davis, E. J., Pihoker, C., Hillier, T. A., Imperatore, G., Ruggiero, A., Hamman, R. E., Stylianou, A., Tentolouris, N., Perrea, D., Tselepis, A. D., Lourida, E., Kitsou, E., Katsilambros, N., Vedovato, M., Dodesini, A. R., Lepore, G., Tiengo, A., Trevisan, R., Penno, G., Miccoli, R., Pucci, L., Lucchesi, D., Bandinelli, S., Fotino, C., Triscornia, S., Baldassari, E., Del Prato, S., Reboldi, P., Santeusanio, E., Fuller, J., Langham, R. G., Gow, R. M., Zhang, Y., Kelly, D. J., Christensen, P. K., Parving, H-H, Gilbert, R. E., Chibalin, A. V., Zhong, Z., Kotova, O., Davidescu, A., Ehren, I., Ekberg, K., Wahren, J., Wassef, L., Buckley, A. J., Rooney, K. B., Briody, J., Thompson, M., Ozanne, S. E., Thompson, C. H., Chamson-Reig, A., Summers, K., Arany, E. J. R., Hill, D. J., Solerte, S. B., Gazzaruso, C., Locatelli, E., Precerutti, S., Schifino, N., Ferrari, E., Fioravanti, M., Phenekos, C. V., Ginis, A., Fragaki, I., Chalkiadaki, M., Tzioras, C., Powell, L. A., Mcguire, G. M., Jewhurst, V., Trimble, E. R., Rasmussen, B. 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L., Hopkins, D., Anand, V., Lim, E., Raval, U., Sharp, P., Corder, R., Lipkin, D., Lahiri, A., Bartnik, M., Ryden, L., Ferrari, R., Malmberg, K., Pyorala, K., Simoons, M. L., Standl, E., Soler-Soler, J., Ohrvik, J., Euro Heart Survey Investigators, Bruce, D. G., Starkstein, S. E., Schauer, U. J. W., Astrup, A. S., Pietraszek, L., Nielsen, F. S., Rossing, P., Ali, S., Smidt, U. M., Yokoyama, H., Pavkov, M. E., Knowler, W. C., Bennett, P. H., Nelson, R. G., Lopez-Alba, A., Morcillo, L., Caballero, A., Montoya, L., Jimenez, A., Maceira, B., Lewis, J. B., Ravid, M., Wajman, A., Tadgell, C., Remuzzi, G., Hunsicker, L. G., Wessman, M., Taskinen, M-R, FinnDiane Study Group, Pugliese, G., Amadio, L., Menini, S., Oddi, G., Ricci, C., Iacobini, C., Pricci, F., Sorcini, M., Pesce, C., Migliaccio, E., Giorgio, M., Pelicci, P., Di Mario, U., Lassila, M., Jandeleit-Dahm, K., Seah, K. K., Calkin, A. C., Allen, T. J., Cooper, M. E., Lopes Faria, J. M., Cavakcanti, T. C., Silva, K. C., Ferrari, A. 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M., Baranova, L. Y., Ikeda, Y., Suehiro, T., Osaki, F., Ota, K., Arii, K., Kumon, Y., Hashimoto, K., Doney, A. S. F., Fischer, B., Morris, A. D., Palmer, C. N. A., Ahn, Y-M, Lee, B-C, Kim, S-I, Byun, S-H, Ahn, S-Y, Doo, H-K, Pagnin, E., Calo, L. A., Fadini, G., Kubaszek, A., Chai, S., Chai, Q., Rasmussen, L., Ledet, T., Wogensen, L., Lengyel, C., Varro, A., Virag, L., Magyar, J., Biro, T., Jost, N., Skoumal, R., Nanasi, P., Toth, M., Horkay, F., Papp, J. G., Zacharopoulou, O., Athanaselis, S., Tsokos, N., Doupis, J., Psallas, M., Cokkinos, D., Pavlatos, S., Liatis, S., Akhobadze, T., Dzneladze, L., Samarguliani, I., Taskiran, M., Rasmussen, V., Rasmussen, B., Jensen, G. B., Fisher, A. A., Petrovsky, N., Davis, M. W., Srikusalanukul, W., Budge, M. M., Trifunovic-Zamaklar, D. D., Zivkovic, M., Jelic, V., Vukomanovic, G., Ristic, A. D., Seferovic, P. M., Costa, J. V., Duarte, S., Manley, S. E., Sailesh, S., Venkataraman, A., Haider, Y., Groza, I., Oprean, M., Ardelean, A., Morosanu, A., Darkow, T., Vanderplas, A., Mamas, M. A., Mcelduff, P., Burns, J., Edwards, R., Fitchet, A., Young, R. J., Gibson, J. M., New, J. P., Lichiardopol, R., Niculescu, N., Totora, A., Pencea, C., Tomescu, I., Cinteza, M., Manicardi, V., Coscelli, C., Navazio, A., Catellani, E., Michelini, M., Dall Asta, D., Guberti, A., Piazza, A., Gasparini, E., Pantaleoni, M., Guiducci, U., Manari, A., Sejil, S., Janand-Delenne, B., Avierinos, J-F, Habib, G., Labastie, N., Vague, P., Lassmann-Vague, V., Luzniak, P., Wojciechowska Luzniak, A., Zairis, M., Lyras, A., Patsourakos, N., Tsirimbis, V., Foussas, S., Lupon, J., Urrutia, A., Herreros, J., Gonzalez, B., Coll, R., Altimir, S., Prats, M., Valle, V., Abreu-Padi, C., Rabago, G., Ivanova, L. A., Brasacchio, D., Calkin, A., Jandeleit-Dahm, K. A., Harno, E., Keenan, A. K., Li, H. L., Yu, Y. R., Lu, Z. M., Zhang, X. E., Ke, L., Liu, H., Zhang, X. X., Jeong, I-K, Chae, M-K, Choi, M-H, Yoo, H-J, Kim, C. D., Yun, M. R., Na, M. A., Kang, Y. H., Kong, O. N., Son, S. M., Kim, I. J., Kim, Y. K., Tanaka, N., Hosoi, M., Matsuyama, Y., Fukumoto, M., Yamakita, T., Yoshioka, K., Ishii, T., Sato, T., Fujii, S., Aoki, T., Shibata, T., Mizutani, N., Suzuki, J-Y, Fowelin, J. H. R., Samuelsson, P., Brandrup-Wogsen, G., Okumura, K., Tokmakova, A. Y., Staroverova, D. N., Antcieferov, M. B., Shutichina, I. V., Kuntchevich, G. I., Vriesendorp, T. M., Morelis, Q. J., Legemate, D. A., Schaper, F., Mainas, E. I., Gkioulmpasanis, I., Panagiotou, I., Vassilikos, G., Skorda, L., Sidira, M., Christoforidou, M., Alaveras, A., Artikis, V., Evdemon, E., Lechleitner, M., Koch, T., Ebenbichler, C., Sturm, W., Moretti, L., Moruzzo, D., Boldrini, E., Pandolfo, C., Kameyama, M., Iwasa, R., Cho, M-H, Nam, J-Y, Kim, C-S, Kim, D-M, Ahn, C-W, Cha, B-S, Lim, S-K, Kim, K-R, Lee, H-C, Huh, K-B, Kaplar, M., Paragh, G., Erdei, A., Csongradi, E., Garai, I., Varga, J., Galuska, L., Udvardy, M., Higa, M., Kaneko, Y., Hiroi, N., Koziarska, D., Nowacki, P., Majkowska, L., Wojciechowska-Luzniak, A., Tushuizen, M. E., Nieuwland, R., Snoeck, D. P., Sturk, A., Diamant, M., Aguiar, L. G. K., Bahia, L., Villela, N., Laflor, C., Conde, C., Bottino, D., Dorigo, D., Bouskela, E., Pu, S., Yu, H. L., Luo, Z. T., Lam, K. S. L., Dan, Q., Xu, A., Shen, J., Cheng, K., Xu, J. Y. U., Thamer, C., Stefan, N., Haap, M., Heller, E., Tschritter, O., Prado, A., Ortiz, A., Ybarra, J., Gich, I., Pou, J. M., Ehren, M., Meyer, M. F., Roggenland, D., Reinsen, B., Klein, H. H., Rittig, K., Stock, J., Kocher, B., Balletshofer, B., Lee, J., Shon, H. S., Chung, D. S., Nakatani, Y., Matsuhisa, M., Kaneto, H., Hatazaki, M., Yoshiuchi, K., Katakami, N., Kawamori, D., Ohtoshi, K., Sakamoto, K., Matsuoka, T-A, Ozawa, K., Ogawa, S., Hori, M., Yamasaki, Y., Zitouni, K., Harry, D., Nourooz-Zadeh, J., Betteridge, J. D., Earle, K. A., Rasmussen, L. M., Olesen, P., Franco, L., Corvaja, C., Semplicini, A., Rosen, P., Lee, I-K, Kim, M-J, Park, K-G, Jung, E-D, Shin, D-W, Jo, S-R, Obuobie, K., Prakash, P. K., Hanna, F. W., Evans, M., Lazarus, J., Varadhan, L., Gurushankar, J., James, D., Sheikh, S., Gaede, P., Li, H., Zou, D., Lee, S. J., Choi, M. G., Kim, D. S., Kim, T. W., Vilarrasa, N., Perez-Maraver, M., Mena, E., Perez, D., Setti, G., Buckingham, R., Urbancic, V., Stefanovska, A., Bernjak, A., Azman-Juvan, K., Kocijancic, A., Glowania, A., Filters, T. S., Fosmark, D. S., Torjesen, P. A., Kilhovd, B., Berg, T. 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M., Krusinova, E., Wohl, P., Klementova, M., Lanska, V., Mcdougall, C., Thomas, S. J., Kelly, I., Abbas, Z. G., Lutale, J. K., Archibald, L. K., Karunajeewa, H., Stingemore, N., Stuccio, G., Mcgechie, D., Muller, L. M. A., Hak, E., Goudzwaard, W. L., Montorsi, F., Homering, M., Sprenger, K., Goldstein, I., Asnaghi, V., Ferrari, G., Rastaldi, M., Gabellini, D., Antonio, G., Maestroni, A., Ruggieri, D., Luzi, L., Piemonti, L., Zerbini, G., Anafaroglu, I., Tutuncu, N. B., Sultana, M., Siddiqua, N., Iwasaki, T., Nakajima, A., Yoneda, M., Mukasa, K., Tanaka, S., and Sekihara, H.
127. ISLET ALLOTRANSPLANTATION IN COMBINATION WITH LIVER REPLACEMENT FOR METASTATIC NEUROENDOCRINE PANCREATIC TUMOR.
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Socci, C., Mazzaferro, V., Regalia, E., Bertuzzi, F., Andreola, S., Colella, G., Magistretti, P., Gavazzi, F., Piemonti, L., De Nittis, P., R., Doci, F., Bozzetti, V., Di Carlo, G., Pozza, and L., Gennari
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- 1993
128. Cryopreserved human islets in vitro alteration of insulin and pro-insulin secretion.
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Socci, C, Piemonti, L, Bertuzzi, F, Nittis, P De, Monti, L, Taglietti, MV, Magistretti, P, Nano, R, Carlo, V Di, and Pozza, G
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- 1996
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129. Isolation of human islets replacing fetal calf serum with human albumin.
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Socci, C, Bertuzzi, F, Nittis, P De, Inverardi, L, Taglietti, MV, Nano, R, Piemonti, L, Magistretti, P, Carlo, V Di, and Pozza, G
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- 1996
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130. Islet transplantation in IDDM patients
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Maffi, P, Secchi, A, Socci, C, Taglietti, MV, Bertuzzi, F, Nittis, V De, Piemonti, L, Carlo, V Di, and Pozza, G
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- 1996
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131. Dysglycemia after COVID-19 pneumonia: a six-month cohort study
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Molinari, Chiara, Laurenzi, Andrea, Caretto, Amelia, Rovere-Querini, Patrizia, Ciceri, Fabio, Lampasona, Vito, Scavini, Marina, Piemonti, Lorenzo, Molinari, C., Laurenzi, A., Caretto, A., Rovere-Querini, P., Ciceri, F., Lampasona, V., Scavini, M., and Piemonti, L.
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Adult ,Blood Glucose ,Male ,medicine.medical_specialty ,Coronavirus disease 2019 (COVID-19) ,Endocrinology, Diabetes and Metabolism ,030209 endocrinology & metabolism ,030204 cardiovascular system & hematology ,Group A ,Group B ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Risk Factors ,Internal medicine ,Diabetes mellitus ,Internal Medicine ,medicine ,Humans ,SARS-CoV-2 ,business.industry ,Diabetes ,COVID-19 ,Pneumonia ,Fasting ,General Medicine ,Impaired fasting glucose ,medicine.disease ,Fasting blood glucose ,Cohort ,Original Article ,business ,Cohort study - Abstract
Aim: The aim of this study was to understand whether the dysglycemia associated with SARS-CoV-2 infection persists or reverts when the viral infection resolves. Methods: We analyzed fasting blood glucose (FBG) after hospital discharge in a cohort of 621 adult cases with suspected COVID-19 pneumonia. Results: At admission, 18.8% of the patients in our cohort had pre-existing diabetes, 9.3% fasting glucose in the diabetes range without a prior diagnosis (DFG), 26% impaired fasting glucose (IFG), 44.9% normal fasting glucose (NFG), while 2% had no FBG available. FBG categories were similarly distributed in the 71 patients without confirmed COVID-19 pneumonia. During follow-up (median time 6month) FBG was available for 321 out of the 453 (70.9%) surviving patients and showed a trend to a marginal increase [from 97 (87–116) to 100 (92–114) mg/dL; p = 0.071]. Transitions between FBG categories were analyzed in subjects without pre-existing diabetes (265 out of 321). We identified three groups: (i) patients who maintained or improved FBG during follow-up [Group A, n = 185; from 100 (86–109) to 94 (88–99) mg/dL; p < 0.001]; (ii) patients who moved from the NFG to IFG category [Group B, n = 66: from 89 (85–96) to 106 (102–113) mg/dl; p < 0.001]; (iii) patients who maintained or reached DFG during follow-up [Group C, n = 14: from 114 (94–138) to 134 (126–143) mg/dl; p = 0.035]. Male sex and ICU admission during the hospitalization were more prevalent in Group C compared to Group A or B. Conclusions: Six months after the SARS-CoV-2 infection DFG was evident in only few patients who experienced severe COVID-19 pneumonia.
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- 2021
132. COVID-19 and islet transplantation: Different twins
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Piemonti, Lorenzo, Landoni, Giovanni, Piemonti, L., and Landoni, G.
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Chemokine ,infection and infectious agents - viral ,infectious disease ,Transplantation, Heterologous ,Islets of Langerhans Transplantation ,Inflammation ,Comorbidity ,030230 surgery ,Proinflammatory cytokine ,03 medical and health sciences ,0302 clinical medicine ,editorial/personal viewpoint ,medicine ,Humans ,Immunology and Allergy ,Pharmacology (medical) ,Blood Coagulation ,Complement Activation ,Pandemics ,Personal Viewpoint ,clinical decision-making ,Transplantation ,geography ,geography.geographical_feature_category ,biology ,SARS-CoV-2 ,business.industry ,islet transplantation ,immune regulation ,COVID-19 ,Pancreatic Diseases ,Islet ,clinical trial design ,Complement system ,Clinical trial ,cytokines/cytokine receptors ,Infectious disease (medical specialty) ,Immunology ,biology.protein ,Cytokines ,medicine.symptom ,business ,Biomarkers - Abstract
For those who work in the field of islet transplantation, the microvascular coronavirus disease 2019 (COVID-19) lung vessels obstructive thrombo-inflammatory syndrome (recently referred to as MicroCLOTS) is familiar, as one cannot fail to recognize the presence of similarities with the instant blood mediated inflammatory reaction (IBMIR) occurring in the liver hours and days after islet infusion. Evidence in both MicroCLOTS and IBMIR suggests the involvement of the coagulation cascade and complement system activation and proinflammatory chemokines/cytokines release. Identification and targeting of pathway(s) playing a role as "master regulator(s)" in the post-islet transplant detrimental inflammatory events could be potentially useful to suggest innovative COVID-19 treatments and vice versa. Scientific organizations across the world are fighting the COVID-19 pandemic. Islet transplantation, and more generally the transplantation scientific community, could contribute by suggesting strategies for innovative approaches. At the same time, in the near future, clinical trials in COVID-19 patients will produce an enormous quantity of clinical and translational data on the control of inflammation and complement/microthrombosis activation. These data will represent a legacy to be transformed into innovation in the transplant field. It will be our contribution to change a dramatic event into advancement for the transplant field and ultimately for our patients.
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- 2020
133. Management of metabolic alterations in adult kidney transplant recipients: A joint position statement of the Italian Society of Nephrology (SIN), the Italian Society for Organ Transplantation (SITO) and the Italian Diabetes Society (SID)
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Umberto Maggiore, Enzo Capocasale, Giuseppe Ietto, Rossana Caldara, Gianni Cappelli, Piero Marchetti, Antonio Secchi, Quirino Lai, Caterina Conte, Paola Salis, Lorenzo Piemonti, Conte, C., Maggiore, U., Cappelli, G., Ietto, G., Lai, Q., Salis, P., Marchetti, P., Piemonti, L., Secchi, A., Capocasale, E., and Caldara, R.
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Blood Glucose ,Nephrology ,Dyslipidaemia ,Endocrinology, Diabetes and Metabolism ,Medicine (miscellaneous) ,030204 cardiovascular system & hematology ,Overweight ,Organ transplantation ,0302 clinical medicine ,Risk Factors ,Hypolipidemic Agents ,Evidence-Based Medicine ,Nutrition and Dietetics ,Drug Substitution ,Prognosis ,Lipids ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,Risk assessment ,Immunosuppressive Agents ,medicine.medical_specialty ,Consensus ,Clinical Decision-Making ,030209 endocrinology & metabolism ,Risk Assessment ,03 medical and health sciences ,Diabetes mellitus ,Internal medicine ,Diabetes Mellitus ,medicine ,Humans ,Hypoglycemic Agents ,Post-transplant diabetes mellitus ,Obesity ,Kidney transplant ,Intensive care medicine ,Dyslipidemias ,business.industry ,Patient Selection ,Evidence-based medicine ,Guideline ,medicine.disease ,Kidney Transplantation ,Energy Metabolism ,business ,Risk Reduction Behavior ,Biomarkers - Abstract
Chronic metabolic alterations such as post-transplant diabetes mellitus (PTDM), dyslipidaemias and overweight/obesity significantly impact on kidney transplant (KT) outcomes. This joint position statement is based on the evidence on the management of metabolic alterations in KT recipients (KTRs) published after the release of the 2009 KDIGO clinical practice guideline for the care of KTRs. Members of the Italian Society of Nephrology (SIN), the Italian Society for Organ Transplantation (SITO) and the Italian Diabetes Society (SID) selected to represent professionals involved in the management of KTRs undertook a systematic review of the published evidence for the management of PTDM, dyslipidaemias and obesity in this setting. The aim of this work is to provide an updated review of the evidence on the prevention, diagnosis and treatment of metabolic alterations in KTRs, in order to support physicians, patients and the Healthcare System in the decision-making process when choosing among the various available options.
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- 2020
134. The risk of COVID-19 death is much greater and age-dependent with type I IFN autoantibodies
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Manry, Jérémy, Bastard, Paul, Gervais, Adrian, Le Voyer, Tom, Rosain, Jérémie, Philippot, Quentin, Michailidis, Eleftherios, Hoffmann, Hans-Heinrich, Eto, Shohei, Garcia-Prat, Marina, Bizien, Lucy, Parra-Martínez, Alba, Yang, Rui, Haljasmägi, Liis, Migaud, Mélanie, Särekannu, Karita, Maslovskaja, Julia, de Prost, Nicolas, Tandjaoui-Lambiotte, Yacine, Luyt, Charles-Edouard, Amador-Borrero, Blanca, Gaudet, Alexandre, Poissy, Julien, Morel, Pascal, Richard, Pascale, Cognasse, Fabrice, Troya, Jesús, Trouillet-Assant, Sophie, Belot, Alexandre, Saker, Kahina, Garçon, Pierre, Rivière, Jacques, Lagier, Jean-Christophe, Gentile, Stéphanie, Rosen, Lindsey, Shaw, Elana, Morio, Tomohiro, Tanaka, Junko, Dalmau, David, Tharaux, Pierre-Louis, Sene, Damien, Stepanian, Alain, Mégarbane, Bruno, Triantafyllia, Vasiliki, Fekkar, Arnaud, Heath, James, Franco, José Luis, Anaya, Juan-Manuel, Solé-Violán, Jordi, Imberti, Luisa, Biondi, Andrea, Bonfanti, Paolo, Castagnoli, Riccardo, Delmonte, Ottavia, Zhang, Yu, Snow, Andrew, Holland, Steven, Biggs, Catherine, Moncada-Vélez, Marcela, Arias, Andrés Augusto, Lorenzo, Lazaro, Boucherit, Soraya, Anglicheau, Dany, Planas, Anna, Haerynck, Filomeen, Duvlis, Sotirija, Ozcelik, Tayfun, Keles, Sevgi, Bousfiha, Ahmed, El Bakkouri, Jalila, Ramirez-Santana, Carolina, Paul, Stéphane, Pan-Hammarström, Qiang, Hammarström, Lennart, Dupont, Annabelle, Kurolap, Alina, Metz, Christine, Aiuti, Alessandro, Casari, Giorgio, Lampasona, Vito, Ciceri, Fabio, Barreiros, Lucila, Dominguez-Garrido, Elena, Vidigal, Mateus, Zatz, Mayana, van de Beek, Diederik, Sahanic, Sabina, Tancevski, Ivan, Stepanovskyy, Yurii, Boyarchuk, Oksana, Nukui, Yoko, Tsumura, Miyuki, Vidaur, Loreto, Tangye, Stuart, Burrel, Sonia, Duffy, Darragh, Quintana-Murci, Lluis, Klocperk, Adam, Kann, Nelli, Shcherbina, Anna, Lau, Yu-Lung, Leung, Daniel, Coulongeat, Matthieu, Marlet, Julien, Koning, Rutger, Reyes, Luis Felipe, Chauvineau-Grenier, Angélique, Venet, Fabienne, Monneret, Guillaume, Nussenzweig, Michel, Arrestier, Romain, Boudhabhay, Idris, Baris-Feldman, Hagit, Hagin, David, Wauters, Joost, Meyts, Isabelle, Dyer, Adam, Kennelly, Sean, Bourke, Nollaig, Halwani, Rabih, Sharif-Askari, Fatemeh Saheb, Dorgham, Karim, Sallette, Jérôme, Sedkaoui, Souad Mehlal, Alkhater, Suzan, Rigo-Bonnin, Raúl, Morandeira, Francisco, Roussel, Lucie, Vinh, Donald, Erikstrup, Christian, Condino-Neto, Antonio, Prando, Carolina, Bondarenko, Anastasiia, Spaan, András, Gilardin, Laurent, Fellay, Jacques, Lyonnet, Stanislas, Bilguvar, Kaya, Lifton, Richard, Mane, Shrikant, Anderson, Mark, Boisson, Bertrand, Béziat, Vivien, Zhang, Shen-Ying, Andreakos, Evangelos, Hermine, Olivier, Pujol, Aurora, Peterson, Pärt, Mogensen, Trine, Rowen, Lee, Mond, James, Debette, Stéphanie, de Lamballerie, Xavier, Burdet, Charles, Bouadma, Lila, Zins, Marie, Soler-Palacin, Pere, Colobran, Roger, Gorochov, Guy, Solanich, Xavier, Susen, Sophie, Martinez-Picado, Javier, Raoult, Didier, Vasse, Marc, Gregersen, Peter, Piemonti, Lorenzo, Rodríguez-Gallego, Carlos, Notarangelo, Luigi, Su, Helen, Kisand, Kai, Okada, Satoshi, Puel, Anne, Jouanguy, Emmanuelle, Rice, Charles, Tiberghien, Pierre, Zhang, Qian, Casanova, Jean-Laurent, Abel, Laurent, Cobat, Aurélie, Zhang, Peng, Seeleuthner, Yoann, Talouarn, Estelle, Marchal, Astrid, Matuozzo, Daniela, de la Chapelle, Aliénor, Chen, Jie, Chrabieh, Maya, Liu, Dana, Nemirowskaya, Yelena, Cruz, Inés Marín, Materna, Marie, Pelet, Sophie, Thibault, Chloé, Liu, Zhiyong, Abad, Jorge, Accordino, Giulia, Achille, Cristian, Aguilera-Albesa, Sergio, Aguiló-Cucurull, Aina, Özkan, Esra Akyüz, Darazam, Ilad Alavi, Albisures, Jonathan Antonio Roblero, Aldave, Juan, Ramos, Miquel Alfonso, Khan, Taj Ali, Aliberti, Anna, Nadji, Seyed Alireza, Alkan, Gulsum, Allardet-Servent, Jerome, Allende, Luis, Alonso-Arias, Rebeca, Alshahrani, Mohammed, Alsina, Laia, Alyanakian, Marie-Alexandra, Borrero, Blanca Amador, Amoura, Zahir, Antolí, Arnau, Aubart, Mélodie, Auguet, Teresa, Avramenko, Iryna, Aytekin, Gökhan, Azot, Axelle, Bahram, Seiamak, Bajolle, Fanny, Baldanti, Fausto, Baldolli, Aurélie, Ballester, Maite, Feldman, Hagit Baris, Barrou, Benoit, Barzaghi, Federica, Basso, Sabrina, Bayhan, Gulsum Iclal, Bezrodnik, Liliana, Bilbao, Agurtzane, Blanchard-Rohner, Geraldine, Blanco, Ignacio, Blandinières, Adeline, Blázquez-Gamero, Daniel, Bleibtreu, Alexandre, Bloomfield, Marketa, Bolivar-Prados, Mireia, Borghesi, Alessandro, Borie, Raphael, Botdhlo-Nevers, Elisabeth, Bousquet, Aurore, Boutolleau, David, Bouvattier, Claire, Bravais, Juliette, Briones, M. Luisa, Brunner, Marie-Eve, Bruno, Raffaele, Bueno, Maria Rita P., Bukhari, Huda, Bustamante, Jacinta, Agra, Juan José Cáceres, Capra, Ruggero, Carapito, Raphael, Carrabba, Maria, Casasnovas, Carlos, Caseris, Marion, Cassaniti, Irene, Castelle, Martin, Castelli, Francesco, de Vera, Martín Castillo, Castro, Mateus, Catherinot, Emilie, Celik, Jale Bengi, Ceschi, Alessandro, Chalumeau, Martin, Charbit, Bruno, Cheng, Matthew, Clavé, Pere, Clotet, Bonaventura, Codina, Anna, Cohen, Yves, Comarmond, Cloé, Combes, Alain, Comoli, Patrizia, Corsico, Angelo, Coşkuner, Taner, Cvetkovski, Aleksandar, Cyrus, Cyril, Danion, François, Darley, David Ross, Das, Vincent, Dauby, Nicolas, Dauger, Stéphane, de Munter, Paul, de Pontual, Loic, Dehban, Amin, Delplancq, Geoffroy, Demoule, Alexandre, Desguerre, Isabelle, Di Sabatino, Antonio, Diehl, Jean-Luc, Dobbelaere, Stephanie, Domínguez-Garrido, Elena, Dubost, Clément, Ekwall, Olov, Bozdemir, Şefika Elmas, Elnagdy, Marwa, Emiroglu, Melike, Endo, Akifumi, Erdeniz, Emine Hafize, Aytekin, Selma Erol, Lasa, Maria Pilar Etxart, Euvrard, Romain, Fabio, Giovanna, Faivre, Laurence, Falck, Antonin, Fartoukh, Muriel, Faure, Morgane, Arquero, Miguel Fernandez, Ferrer, Ricard, Ferreres, Jose, Flores, Carlos, Francois, Bruno, Fumadó, Victoria, Fung, Kitty, Fusco, Francesca, Gagro, Alenka, Solis, Blanca Garcia, Gaussem, Pascale, Gayretli, Zeynep, Gil-Herrera, Juana, Gatineau, Audrey Giraud, Girona-Alarcón, Mònica, Godínez, Karen Alejandra Cifuentes, Goffard, Jean-Christophe, Gonzales, Nacho, Gonzalez-Granado, Luis, González-Montelongo, Rafaela, Guerder, Antoine, Gülhan, Belgin, Gumucio, Victor Daniel, Hanitsch, Leif Gunnar, Gunst, Jan, Gut, Marta, Hadjadj, Jérôme, Hancerli, Selda, Hariyan, Tetyana, Hatipoglu, Nevin, Heppekcan, Deniz, Hernandez-Brito, Elisa, Ho, Po-Ki, Holanda-Peña, María Soledad, Horcajada, Juan, Hraiech, Sami, Humbert, Linda, Hung, Ivan, Iglesias, Alejandro, Íñigo-Campos, Antonio, Jamme, Matthieu, Arranz, María Jesús, Jimeno, Marie-Thérèse, Jordan, Iolanda, Kanık-Yüksek, Saliha, Kara, Yalcin Burak, Karahan, Aydın, Karbuz, Adem, Yasar, Kadriye Kart, Kasapcopur, Ozgur, Kashimada, Kenichi, Demirkol, Yasemin Kendir, Kido, Yasutoshi, Kizil, Can, Kılıç, Ahmet Osman, Daganou, Maria, Koukaki, Evangelia, Koutsoukou, Antonia, Rapti, Vasiliki, Syrigos, Konstantinos, Król, Zbigniew, Ksouri, Hatem, Kuentz, Paul, Kwan, Arthur, Kwan, Yat Wah M., Kwok, Janette, Lam, David, Conti, Francesca, Pession, Andrea, Lampropoulou, Vicky, Lanternier, Fanny, Bourgeois, Fleur Le, Leo, Yee-Sin, Lopez, Rafael Leon, Levin, Michael, Levy, Michael, Lévy, Romain, Li, Zhi, Lilleri, Daniele, Lima, Edson Jose Adrian Bolanos, Linglart, Agnes, López-Collazo, Eduardo, Lorenzo-Salazar, José, Louapre, Céline, Lubetzki, Catherine, Lung, Kwok-Cheung, Lye, David, Magnone, Cinthia, Mansouri, Davood, Marchioni, Enrico, Marioli, Carola, Marjani, Majid, Marques, Laura, Pereira, Jesus Marquez, Martín-Nalda, Andrea, Pueyo, David Martínez, Marzana, Iciar, Mata-Martínez, Carmen, Mathian, Alexis, Matos, Larissa Rb, Matthews, Gail, Mayaux, Julien, Mclaughlin-Garcia, Raquel, Meersseman, Philippe, Mège, Jean-Louis, Mekontso-Dessap, Armand, Melki, Isabelle, Meloni, Federica, Meritet, Jean-François, Merlani, Paolo, Akcan, Özge Metin, Mezidi, Mehdi, Migeotte, Isabelle, Millereux, Maude, Million, Matthieu, Mirault, Tristan, Mircher, Clotilde, Mirsaeidi, Mehdi, Mizoguchi, Yoko, Modi, Bhavi, Mojoli, Francesco, Moncomble, Elsa, Melián, Abián Montesdeoca, Martinez, Antonio Morales, Morange, Pierre-Emmanuel, Mordacq, Clémence, Morelle, Guillaume, Mouly, Stéphane, Muñoz-Barrera, Adrián, Nafati, Cyril, Nagashima, Shintaro, Nakagama, Yu, Neven, Bénédicte, Neves, João Farela, Ng, Lisa, Ng, Yuk-Yung, Nielly, Hubert, Medina, Yeray Novoa, Cuadros, Esmeralda Nuñez, Ocejo-Vinyals, J. Gonzalo, Okamoto, Keisuke, Oualha, Mehdi, Ouedrani, Amani, Özçelik, Tayfun, Ozkaya-Parlakay, Aslinur, Pagani, Michele, Papadaki, Maria, Parizot, Christophe, Parola, Philippe, Pascreau, Tiffany, Paz-Artal, Estela, Pedraza-Sánchez, Sigifredo, Gálvez-Romero, José Luis, Pellecer, Nancy Carolina González, Pellegrini, Silvia, Diego, Rebeca Pérez De, Pérez-Fernández, Xosé Luis, Philippe, Aurélien, Picod, Adrien, de Chambrun, Marc Pineton, Piralla, Antonio, Planas-Serra, Laura, Ploin, Dominique, Poncelet, Géraldine, Poulakou, Garyphallia, Pouletty, Marie, Pourshahnazari, Persia, Qiu-Chen, Jia Li, Quentric, Paul, Rambaud, Thomas, Raoult, Violette, Rebillat, Anne-Sophie, Redin, Claire, Resmini, Léa, Ricart, Pilar, Richard, Jean-Christophe, Rivet, Nadia, Rocamora-Blanch, Gemma, Rodero, Mathieu, Rodrigo, Carlos, Rodriguez, Luis Antonio, Rodriguez-Gallego, Carlos, Rodriguez-Palmero, Agustí, Romero, Carolina Soledad, Rothenbuhler, Anya, Roux, Damien, Rovina, Nikoletta, Rozenberg, Flore, Ruch, Yvon, Ruiz, Montse, Prado, Maria Yolanda Ruiz Del, Ruiz-Rodriguez, Juan Carlos, Sabater-Riera, Joan, Saks, Kai, Salagianni, Maria, Sanchez, Oliver, Sánchez-Montalvá, Adrián, Sánchez-Ramón, Silvia, Schidlowski, Laire, Schluter, Agatha, Schmidt, Julien, Schmidt, Matthieu, Schuetz, Catharina, Schweitzer, Cyril, Scolari, Francesco, Sediva, Anna, Seijo, Luis, Seminario, Analia Gisela, Seng, Piseth, Senoglu, Sevtap, Seppänen, Mikko, Llovich, Alex Serra, Shahrooei, Mohammad, Siguret, Virginie, Siouti, Eleni, Smadja, David, Smith, Nikaia, Sobh, Ali, Soler, Catherine, Soler-Palacín, Pere, Sözeri, Betül, Stella, Giulia Maria, Stepanovskiy, Yuriy, Stoclin, Annabelle, Taccone, Fabio, Taupin, Jean-Luc, Tavernier, Simon, Terrier, Benjamin, Thiery, Guillaume, Thorball, Christian, Thorn, Karolina, Thumerelle, Caroline, Tipu, Imran, Tolstrup, Martin, Tomasoni, Gabriele, Toubiana, Julie, Alvarez, Josep Trenado, Tsang, Owen, Tserel, Liina, Tso, Eugene, Tucci, Alessandra, Öz, Şadiye Kübra Tüter, Ursini, Matilde Valeria, Utsumi, Takanori, Uzunhan, Yurdagul, Vabres, Pierre, Valencia-Ramos, Juan, van den Rym, Ana Maria, Vandernoot, Isabelle, Velez-Santamaria, Valentina, Veliz, Silvia Patricia Zuniga, Viel, Sébastien, Villain, Cédric, Vilaire-Meunier, Marie, Villar-García, Judit, Vincent, Audrey, Vogt, Guillaume, Voiriot, Guillaume, Volokha, Alla, Vuotto, Fanny, Wauters, Els, Wu, Alan, Wu, Tak-Chiu, Yahşi, Aysun, Yesilbas, Osman, Yildiz, Mehmet, Young, Barnaby, Yükselmiş, Ufuk, Ghirardello, Stefano, Zuccaro, Valentina, Andrés, Ana De, van Praet, Jens, Lambrecht, Bart, van Braeckel, Eva, Bosteels, Cédric, Hoste, Levi, Hoste, Eric, Bauters, Fré, Clercq, Jozefien De, Heijmans, Cathérine, Slabbynck, Hans, Naesens, Leslie, Florkin, Benoit, Boulanger, Cécile, Vanderlinden, Dimitri, Foti, Giuseppe, Bellani, Giacomo, Citerio, Giuseppe, Contro, Ernesto, Pesci, Alberto, Valsecchi, Maria Grazia, Cazzaniga, Marina, Danielson, Jeffrey, Dobbs, Kerry, Kashyap, Anuj, Ding, Li, Dalgard, Clifton, Sottini, Alessandra, Quaresima, Virginia, Quiros-Roldan, Eugenia, Rossi, Camillo, Bettini, Laura Rachele, D’angio, Mariella, Beretta, Ilaria, Montagna, Daniela, Licari, Amelia, Marseglia, Gian Luigi, Batten, Isabella, Reddy, Conor, Mcelheron, Matt, Noonan, Claire, Connolly, Emma, Fallon, Aoife, Storgaard, Merete, Jørgensen, Sofie, Pedersen, Ole Birger, Sørensen, Erik, Mikkelsen, Susan, Dinh, Khoa Manh, Larsen, Margit Anita Hørup, Paulsen, Isabella Worlewenut, von Stemann, Jakob Hjorth, Hansen, Morten Bagge, Ostrowski, Sisse Rye, Townsend, Liam, Ni Cheallaigh, Cliona, Bergin, Colm, Martin-Loeches, Ignacio, Dunne, Jean, Conlon, Niall, O’farrelly, Cliona, Allavena, Clotilde, Andrejak, Claire, Angoulvant, François, Azoulay, Cecile, Bachelet, Delphine, Bartoli, Marie, Basmaci, Romain, Behillill, Sylvie, Beluze, Marine, Benech, Nicolas, Benkerrou, Dehbia, Bhavsar, Krishna, Bitker, Laurent, Bouscambert-Duchamp, Maude, Paz, Pauline Caraux, Cervantes-Gonzalez, Minerva, Chair, Anissa, Chirouze, Catherine, Coelho, Alexandra, Cordel, Hugues, Couffignal, Camille, Couffin-Cadiergues, Sandrine, D’ortenzio, Eric, de Montmollin, Etienne, Debard, Alexa, Debray, Marie-Pierre, Deplanque, Dominique, Descamps, Diane, Desvallée, Mathilde, Diallo, Alpha, Diouf, Alphonsine, Dorival, Céline, Dubos, François, Duval, Xavier, Eloy, Philippine, Enouf, Vincent, Epaulard, Olivier, Esperou, Hélène, Esposito-Farase, Marina, Etienne, Manuel, Garot, Denis, Gault, Nathalie, Gaymard, Alexandre, Ghosn, Jade, Gigante, Tristan, Gilg, Morgane, Goehringer, François, Guedj, Jérémie, Hoctin, Alexandre, Hoffmann, Isabelle, Houas, Ikram, Hulot, Jean-Sébastien, Jaafoura, Salma, Kafif, Ouifiya, Kaguelidou, Florentia, Kali, Sabrina, Kerroumi, Younes, Khalil, Antoine, Khan, Coralie, Kimmoun, Antoine, Laine, Fabrice, Laouénan, Cédric, Laribi, Samira, Le, Minh, Le Bris, Cyril, Le Gac, Sylvie, Le Hingrat, Quentin, Le Mestre, Soizic, Le Nagard, Hervé, Lemaignen, Adrien, Lemee, Véronique, Lescure, François-Xavier, Letrou, Sophie, Levy, Yves, Lina, Bruno, Lingas, Guillaume, Lucet, Jean Christophe, Machado, Moïse, Malvy, Denis, Mambert, Marina, Manuel, Aldric, Mentré, France, Meziane, Amina, Mouquet, Hugo, Mullaert, Jimmy, Neant, Nadège, Nguyen, Duc, Noret, Marion, Papadopoulos, Aurélie, Paul, Christelle, Peiffer-Smadja, Nathan, Peigne, Vincent, Petrov-Sanchez, Ventzislava, Peytavin, Gilles, Pham, Huong, Picone, Olivier, Piquard, Valentine, Puéchal, Oriane, Rosa-Calatrava, Manuel, Rossignol, Bénédicte, Rossignol, Patrick, Roy, Carine, Schneider, Marion, Su, Richa, Tardivon, Coralie, Tellier, Marie-Capucine, Téoulé, François, Terrier, Olivier, Timsit, Jean-François, Tual, Christelle, Tubiana, Sarah, van der Werf, Sylvie, Vanel, Noémie, Veislinger, Aurélie, Visseaux, Benoit, Wiedemann, Aurélie, Yazdanpanah, Yazdan, Annereau, Jean-Philippe, Briseño-Roa, Luis, Gribouval, Olivier, Jaïs, Jean-Philippe, Pelet, Anna, Alcover, Andres, Aschard, Hugues, Bousso, Philippe, Brodin, Petter, Bruhns, Pierre, Cerf-Bensussan, Nadine, Cumano, Ana, D’enfert, Christophe, Deriano, Ludovic, Dillies, Marie-Agnès, Di Santo, James, Dromer, Françoise, Eberl, Gérard, Enninga, Jost, Gomperts-Boneca, Ivo, Hasan, Milena, Hedestam, Gunilla Karlsson, Hercberg, Serge, Ingersoll, Molly, Lantz, Olivier, Kenny, Rose Anne, Ménager, Mickaël, Michel, Frédérique, Patin, Etienne, Pellegrini, Sandra, Rausell, Antonio, Rieux-Laucat, Frédéric, Rogge, Lars, Fontes, Magnus, Sakuntabhai, Anavaj, Schwartz, Olivier, Schwikowski, Benno, Shorte, Spencer, Tangy, Frédéric, Toubert, Antoine, Touvier, Mathilde, Ungeheuer, Marie-Noëlle, Zimmer, Christophe, Albert, Matthew, Alavoine, Loubna, Behillil, Sylvie, Charpentier, Charlotte, Dechanet, Aline, Ecobichon, Jean-Luc, Frezouls, Wahiba, Houhou, Nadhira, Lehacaut, Jonathan, Lucet, Jean-Christophe, Manchon, Pauline, Nouroudine, Mariama, Quintin, Caroline, Thy, Michael, Vignali, Valérie, Chahine, Abir, Waucquier, Nawal, Migaud, Maria-Claire, Djossou, Félix, Mergeay-Fabre, Mayka, Lucarelli, Aude, Demar, Magalie, Bruneau, Léa, Gérardin, Patrick, Maillot, Adrien, Payet, Christine, Laviolle, Bruno, Paris, Christophe, Desille-Dugast, Mireille, Fouchard, Julie, Pistone, Thierry, Perreau, Pauline, Gissot, Valérie, Le Goas, Carole, Montagne, Samatha, Richard, Lucie, Bouiller, Kévin, Desmarets, Maxime, Meunier, Alexandre, Bourgeon, Marilou, Lefèvre, Benjamin, Jeulin, Hélène, Legrand, Karine, Lomazzi, Sandra, Tardy, Bernard, Gagneux-Brunon, Amandine, Bertholon, Frédérique, Botelho-Nevers, Elisabeth, Kouakam, Christelle, Leturque, Nicolas, Roufai, Layidé, Amat, Karine, Espérou, Hélène, Hendou, Samia, van Agtmael, Michiel, Algera, Anne Geke, Appelman, Brent, van Baarle, Frank, Bax, Diane, Beudel, Martijn, Bogaard, Harm Jan, Bomers, Marije, Bonta, Peter, Bos, Lieuwe, Botta, Michela, de Brabander, Justin, de Bree, Godelieve, de Bruin, Sanne, Buis, David, Bugiani, Marianna, Bulle, Esther, Chouchane, Osoul, Cloherty, Alex, Dijkstra, Mirjam, Dongelmans, Dave, Dujardin, Romein, Elbers, Paul, Fleuren, Lucas, Geerlings, Suzanne, Geijtenbeek, Theo, Girbes, Armand, Goorhuis, Bram, Grobusch, Martin, Hafkamp, Florianne, Hagens, Laura, Hamann, Jorg, Harris, Vanessa, Hemke, Robert, Hermans, Sabine, Heunks, Leo, Hollmann, Markus, Horn, Janneke, Hovius, Joppe, de Jong, Menno, Lim, Endry, van Mourik, Niels, Nellen, Jeaninne, Nossent, Esther, Paulus, Frederique, Peters, Edgar, Pina-Fuentes, Dan, van der Poll, Tom, Preckel, Bennedikt, Prins, Jan, Raasveld, Jorinde, Reijnders, Tom, de Rotte, Maurits, Schinkel, Michiel, Schultz, Marcus, Schrauwen, Femke, Schuurman, Alex, Schuurmans, Jaap, Sigaloff, Kim, Slim, Marleen, Smeele, Patrick, Smit, Marry, Stijnis, Cornelis, Stilma, Willemke, Teunissen, Charlotte, Thoral, Patrick, Tsonas, Anissa, Tuinman, Pieter, van der Valk, Marc, Veelo, Denise, Volleman, Carolien, de Vries, Heder, Vught, Lonneke, van Vugt, Michèle, Wouters, Dorien, Zwinderman, A., Brouwer, Matthijs, Wiersinga, W. Joost, Vlaar, Alexander, Al-Muhsen, Saleh, Al-Mulla, Fahd, Arias, Andrés, Bogunovic, Dusan, Bolze, Alexandre, Bryceson, Yenan, Bustamante, Carlos, Butte, Manish, Chakravorty, Samya, Christodoulou, John, Constantinescu, Stefan, Cooper, Megan, Desai, Murkesh, Drolet, Beth, El Baghdadi, Jamila, Espinosa-Padilla, Sara, Froidure, Antoine, Henrickson, Sarah, Hsieh, Elena, Husebye, Eystein, Imai, Kohsuke, Itan, Yuval, Jarvis, Erich, Karamitros, Timokratis, Ku, Cheng-Lung, Ling, Yun, Lucas, Carrie, Maniatis, Tom, Maródi, László, Milner, Joshua, Mironska, Kristina, Novelli, Antonio, Novelli, Giuseppe, de Diego, Rebeca Perez, Perez-Tur, Jordi, Arkin, Lisa, Asano, Takaki, Oriol, Roger Colobran, Renia, Laurent, Resnick, Igor, Sancho-Shimizu, Vanessa, Seppänen, Mikko R.J., Shahrooei, Mohammed, Slaby, Ondrej, Tayoun, Ahmad Abou, Ramaswamy, Sathishkumar, Turvey, Stuart, Uddin, K., Uddin, Mohammed, von Bernuth, Horst, Zawadzki, Pawel, Grimbacher, Bodo, Pape, Jean, Perlin, David, Pesole, Graziano, García, Paula Andrea Gaviria, López, Gustavo Andrés Salguero, Rojas-Villaraga, Adriana, Vélez, Verónica Posada, Landinez, Lina Marcela Acevedo, Correales, Luisa Paola Duarte, Gómez, Oscar, Guaqueta, Jeser Santiago Grass, Pérez, Cristian Alejandro Ricaurte, Carrillo, Jorge, Vergara, José Alejandro Daza, Landinez, Sandra, Mantilla, Rubén, Yepes, Jairo David Torres, Ricaurte, Oscar Andrés Briceño, Pérez-Díaz, Carlos, Mateus, Yady Nataly, Navarro, Laura Mancera, Rodríguez, Yhojan, Acosta-Ampudia, Yeny, Monsalve, Diana, Rojas, Manuel, Nadif, Rachel, Goldberg, Marcel, Ozguler, Anna, Henny, Joseph, Lemonnier, Sylvie, Coeuret-Pellicer, Mireille, Got, Stéphane Le, Tzourio, Christophe, Dufouil, Carole, Soumaré, Aïcha, Lachaize, Morgane, Fievet, Nathalie, Flaig, Amandine, Martin, Fernando, Bonneaudeau, Brigitte, Cannet, Dorothée, Gallian, Pierre, Jeanne, Michel, Perroquin, Magali, Hamzeh-Cognasse, Hind, Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Rockefeller University [New York], Hiroshima University, Vall d’Hebron Research Institute (VHIR), University of Tartu, CHU Henri Mondor, Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de cardiologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Lariboisière-Fernand-Widal [APHP], Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Etablissement Français du Sang [La Plaine Saint-Denis] (EFS), Etablissement français du sang - Auvergne-Rhône-Alpes (EFS), Hospital Universitario Infanta Leonor [Madrid], Hospices Civils de Lyon (HCL), Grand Hôpital de l'Est Francilien (GHEF), Vall d'Hebron University Hospital [Barcelona], Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Assistance Publique - Hôpitaux de Marseille (APHM), National Institutes of Health [Bethesda] (NIH), Tokyo Medical and Dental University [Japan] (TMDU), Universitat de Barcelona (UB), Institut National de la Santé et de la Recherche Médicale (INSERM), Biomedical Research Foundation of the Academy of Athens (BRFAA), Institute for Systems Biology [Seattle] (ISB), Universidad de Antioquia = University of Antioquia [Medellín, Colombia], Universidad del Rosario [Bogota], Hospital Universitario de Gran Canaria Dr Negrin, Azienda Socio Sanitaria Territoriale Spedali Civili di Brescia [Brescia], Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), Uniformed Services University of the Health Sciences (USUHS), University of British Columbia (UBC), CHU Necker - Enfants Malades [AP-HP], Spanish National Research Council (CSIC), Ghent University Hospital, Goce Delchev University (UGD), Invitae Corporation, Bilkent University [Ankara], Necmettin Erbakan University [Konya, Turquie], Centre Hospitalier Universitaire Hassan II (CHU HII), CHU Ibn Rochd [Casablanca], Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Karolinska Institute, Réseau International des Instituts Pasteur (RIIP), Tel Aviv Sourasky Medical Center [Te Aviv], The Feinstein Institute for Medical Research, IRCCS San Raffaele Scientific Institute [Milan, Italie], IRCCS Ospedale San Raffaele [Milan, Italy], Universidade de São Paulo = University of São Paulo (USP), Fundacion Rioja Salud, Amsterdam Neuroscience [Pays-Bas], Vrije Universiteit Amsterdam [Amsterdam] (VU)-University of Amsterdam [Amsterdam] (UvA)-VU University Medical Center [Amsterdam], Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), Shupyk National Medical Academy of Postgraduate Education [Kiev] (SNMAPE), I.Horbachevsky Ternopil State Medical University, Ternopil, Ukraine, Hospital Donostia, Garvan Institute of medical research, Sorbonne Université (SU), Immunologie Translationnelle - Translational Immunology lab, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Institut Pasteur [Paris] (IP), Charles University [Prague] (CU), University Hospital Motol [Prague], Dmitriy Rogachev National Center for Pediatric Hematology, Oncology and Immunology [Moscow, Russia], The University of Hong Kong (HKU), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Morphogénèse et antigénicité du VIH et du virus des Hépatites (MAVIVH - U1259 Inserm - CHRU Tours ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of La Sabana = Universitad de la Sabana, Hôpital Robert Ballanger [Aulnay-sous-Bois], Sackler Faculty of Medicine, Tel Aviv University (TAU), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), University Hospitals Leuven [Leuven], Tallaght Hospital, Trinity College Dublin, University of Sharjah (UoS), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire CERBA [Saint Ouen l'Aumône], King Fahad University, Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), McGill University = Université McGill [Montréal, Canada], Aarhus University [Aarhus], Instituto de Pesquisa Pelé Pequeno Principe, Hôpital Jean Verdier [AP-HP], Ecole Polytechnique Fédérale de Lausanne (EPFL), Yale University [New Haven], University of California [San Francisco] (UC San Francisco), University of California (UC), Academy of Athens, Institució Catalana de Recerca i Estudis Avançats (ICREA), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Aix Marseille Université (AMU), Centre d'investigation Clinique [CHU Bichat] - Épidémiologie clinique (CIC 1425), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC Hôpital Bichat, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-UFR de Médecine, Université Paris-Saclay, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), European Genomic Institute for Diabetes - FR 3508 (EGID), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), IrsiCaixa (Institut de Recerca de la Sida), Hôpital Foch [Suresnes], Etablissement Français du Sang, EFS, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Howard Hughes Medical Institute, Rockefeller University, St. Giles Foundation, National Institutes of Health (US), George Mason University, Yale University, National Human Genome Research Institute (US), Fisher Center for Alzheimer's Research Foundation, Meyer Foundation, JPB Foundation, Agence Nationale de la Recherche (France), Fondation pour la Recherche Médicale, Agence Nationale de Recherches sur le SIDA et les Hépatites Virales (France), Scientific Committee on Oceanic Research, Ministre de l'Enseignement Supérieur, de la Recherche et de l'Innovation (France), Institut National de la Santé et de la Recherche Médicale (France), Université de Paris, Fondation Bettencourt Schueller, Centro de Investigación Biomédica en Red Enfermedades Raras (España), European Commission, G. Harold & Leila Y. Mathers Foundation, Hospital Universitario Infanta Leonor, National Institute of Allergy and Infectious Diseases (US), National Institute of Dental and Craniofacial Research (US), Estonian Research Council, Al Jalila Foundation, American University of Sharjah, National Health and Medical Research Council (Australia), University of New South Wales (Australia), Regione Lombardia, Instituto de Salud Carlos III, Japan Agency for Medical Research and Development, Sorbonne Université, Université de Bordeaux, National Cancer Institute (US), Research Foundation - Flanders, Hellenic Foundation for Research and Innovation, Sao Paulo Research Foundation, The Meath Foundation, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), INSERM UMRS-1144, Université Paris Cité, Réanimation Médicale et Toxicologique, Hôpital Lariboisière, Génétique Evolutive Humaine - Human Evolutionary Genetics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, The Rockefeller University, the St. Giles Foundation, the NIH (Grants R01AI088364 and R01AI163029), the National Center for Advancing Translational Sciences, NIH Clinical and Translational Science Awards program (Grant UL1 TR001866), a Fast Grant from Emergent Ventures, Mercatus Center at George Mason University, the Yale Center for Mendelian Genomics and the Genome Sequencing Program Coordinating Center funded by the National Human Genome Research Institute (Grants UM1HG006504 and U24HG008956), the Yale High Performance Computing Center (Grant S10OD018521), the Fisher Center for Alzheimer’s Research Foundation, the Meyer Foundation, the JPB Foundation, the French National Research Agency (ANR) under the 'Investments for the Future' program (Grant ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (Grant ANR-10-LABX-62-IBEID), the French Foundation for Medical Research (FRM) (Grant EQU201903007798), the French Agency for Research on AIDS and Viral hepatitis (ANRS) Nord-Sud (Grant ANRS-COV05), the ANR GENVIR (Grant ANR-20-CE93-003), AABIFNCOV (Grant ANR-20-CO11-0001), CNSVIRGEN (Grant ANR-19-CE15-0009-01), and GenMIS-C (Grant ANR-21-COVR-0039) projects, the Square Foundation, Grandir–Fonds de solidarité pour l’Enfance, the Fondation du Souffle, the SCOR Corporate Foundation for Science, The French Ministry of Higher Education, Research, and Innovation (Grant MESRI-COVID-19), Institut National de la Santé et de la Recherche Médicale (INSERM), REACTing-INSERM, and the University Paris Cité. P. Bastard was supported by the FRM (Award EA20170638020). P. Bastard., J.R., and T.L.V. were supported by the MD-PhD program of the Imagine Institute (with the support of Fondation Bettencourt Schueller). Work at the Neurometabolic Disease lab received funding from Centre for Biomedical Research on Rare Diseases (CIBERER) (Grant ACCI20-767) and the European Union's Horizon 2020 research and innovation program under grant agreement 824110 (EASI Genomics). Work in the Laboratory of Virology and Infectious Disease was supported by the NIH (Grants P01AI138398-S1, 2U19AI111825, and R01AI091707-10S1), a George Mason University Fast Grant, and the G. Harold and Leila Y. Mathers Charitable Foundation. The Infanta Leonor University Hospital supported the research of the Department of Internal Medicine and Allergology. The French COVID Cohort study group was sponsored by INSERM and supported by the REACTing consortium and by a grant from the French Ministry of Health (Grant PHRC 20-0424). The Cov-Contact Cohort was supported by the REACTing consortium, the French Ministry of Health, and the European Commission (Grant RECOVER WP 6). This work was also partly supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases and the National Institute of Dental and Craniofacial Research, NIH (Grants ZIA AI001270 to L.D.N. and 1ZIAAI001265 to H.C.S.). This program is supported by the Agence Nationale de la Recherche (Grant ANR-10-LABX-69-01). K.K.’s group was supported by the Estonian Research Council, through Grants PRG117 and PRG377. R.H. was supported by an Al Jalila Foundation Seed Grant (Grant AJF202019), Dubai, United Arab Emirates, and a COVID-19 research grant (Grant CoV19-0307) from the University of Sharjah, United Arab Emirates. S.G.T. is supported by Investigator and Program Grants awarded by the National Health and Medical Research Council of Australia and a University of New South Wales COVID Rapid Response Initiative Grant. L.I. reports funding from Regione Lombardia, Italy (project 'Risposta immune in pazienti con COVID-19 e co-morbidità'). This research was partially supported by the Instituto de Salud Carlos III (Grant COV20/0968). J.R.H. reports funding from Biomedical Advanced Research and Development Authority (Grant HHSO10201600031C). S.O. reports funding from Research Program on Emerging and Re-emerging Infectious Diseases from Japan Agency for Medical Research and Development (Grant JP20fk0108531). G.G. was supported by the ANR Flash COVID-19 program and SARS-CoV-2 Program of the Faculty of Medicine from Sorbonne University iCOVID programs. The 3C Study was conducted under a partnership agreement between INSERM, Victor Segalen Bordeaux 2 University, and Sanofi-Aventis. The Fondation pour la Recherche Médicale funded the preparation and initiation of the study. The 3C Study was also supported by the Caisse Nationale d’Assurance Maladie des Travailleurs Salariés, Direction générale de la Santé, Mutuelle Générale de l’Education Nationale, Institut de la Longévité, Conseils Régionaux of Aquitaine and Bourgogne, Fondation de France, and Ministry of Research–INSERM Program 'Cohortes et collections de données biologiques.' S. Debette was supported by the University of Bordeaux Initiative of Excellence. P.K.G. reports funding from the National Cancer Institute, NIH, under Contract 75N91019D00024, Task Order 75N91021F00001. J.W. is supported by a Research Foundation - Flanders (FWO) Fundamental Clinical Mandate (Grant 1833317N). Sample processing at IrsiCaixa was possible thanks to the crowdfunding initiative YoMeCorono. Work at Vall d’Hebron was also partly supported by research funding from Instituto de Salud Carlos III Grant PI17/00660 cofinanced by the European Regional Development Fund (ERDF/FEDER). C.R.-G. and colleagues from the Canarian Health System Sequencing Hub were supported by the Instituto de Salud Carlos III (Grants COV20_01333 and COV20_01334), the Spanish Ministry for Science and Innovation (RTC-2017-6471-1, AEI/FEDER, European Union), Fundación DISA (Grants OA18/017 and OA20/024), and Cabildo Insular de Tenerife (Grants CGIEU0000219140 and 'Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19'). T.H.M. was supported by grants from the Novo Nordisk Foundation (Grants NNF20OC0064890 and NNF21OC0067157). C.M.B. is supported by a Michael Smith Foundation for Health Research Health Professional-Investigator Award. P.Q.H. and L. Hammarström were funded by the European Union’s Horizon 2020 research and innovation program (Antibody Therapy Against Coronavirus consortium, Grant 101003650). Work at Y.-L.L.’s laboratory in the University of Hong Kong (HKU) was supported by the Society for the Relief of Disabled Children. MBBS/PhD study of D.L. in HKU was supported by the Croucher Foundation. J.L.F. was supported in part by the Evaluation-Orientation de la Coopération Scientifique (ECOS) Nord - Coopération Scientifique France-Colombie (ECOS-Nord/Columbian Administrative department of Science, Technology and Innovation [COLCIENCIAS]/Colombian Ministry of National Education [MEN]/Colombian Institute of Educational Credit and Technical Studies Abroad [ICETEX, Grant 806-2018] and Colciencias Contract 713-2016 [Code 111574455633]). A. Klocperk was, in part, supported by Grants NU20-05-00282 and NV18-05-00162 issued by the Czech Health Research Council and Ministry of Health, Czech Republic. L.P. was funded by Program Project COVID-19 OSR-UniSR and Ministero della Salute (Grant COVID-2020-12371617). I.M. is a Senior Clinical Investigator at the Research Foundation–Flanders and is supported by the CSL Behring Chair of Primary Immunodeficiencies (PID), by the Katholieke Universiteit Leuven C1 Grant C16/18/007, by a Flanders Institute for Biotechnology-Grand Challenges - PID grant, by the FWO Grants G0C8517N, G0B5120N, and G0E8420N, and by the Jeffrey Modell Foundation. I.M. has received funding under the European Union’s Horizon 2020 research and innovation program (Grant Agreement 948959). E.A. received funding from the Hellenic Foundation for Research and Innovation (Grant INTERFLU 1574). M. Vidigal received funding from the São Paulo Research Foundation (Grant 2020/09702-1) and JBS SA (Grant 69004). The NH-COVAIR study group consortium was supported by a grant from the Meath Foundation., HGID Lab, COVID Clinicians, COVID-STORM Clinicians, NIAID Immune Response to COVID Group, NH-COVAIR Study Group, Danish CHGE, Danish Blood Donor Study, St. James's Hospital, SARS CoV2 Interest Group, French COVID Cohort Study Group, Imagine COVID-Group, Milieu Intérieur Consortium, CoV-Contact Cohort, Amsterdam UMC Covid-19 Biobank Investigators, COVID Human Genetic Effort, CP-COVID-19 Group, CONSTANCES cohort, 3C-Dijon Study, Cerba Health-Care, Etablissement Français du Sang Study group, ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-20-COVI-0003,GENCOVID,Identification des défauts monogéniques de l'immunité responsables des formes sévères de COVID-19 chez les patients précédemment en bonne santé(2020), ANR-20-CE93-0003,GENVIR,Analyse multi-omique de l'immunité anti-virale: de l'identification des circuits biologiques pertinents à la découverte de défauts monogéniques héréditaires de l'immunité chez les patients avec infections virales sévères(2020), ANR-19-CE15-0009,CNSVIRGEN,Déficits immunitaires innés dans les infections sévères du tronc cérébral(2019), ANR-20-CO11-0001,AABIFNCOV,Bases génétiques et immunologiques des auto-anticorps contre les interférons de type I prédisposant aux formes sévères de COVID-19.(2020), ANR-21-COVR-0039,GenMIS-C,Recherche des Déficits immunitaires innées monogéniques prédisposant au syndrome inflammatoire multisystémique chez l'enfant.(2021), European Project: 948959,ERC-2020-STG,MORE2ADA2(2021), Manry, J, Bastard, P, Gervais, A, Le Voyer, T, Rosain, J, Philippot, Q, Michailidis, E, Hoffmann, H, Eto, S, Garcia-Prat, M, Bizien, L, Parra-Martínez, A, Yang, R, Haljasmägi, L, Migaud, M, Särekannu, K, Maslovskaja, J, de Prost, N, Tandjaoui-Lambiotte, Y, Luyt, C, Amador-Borrero, B, Gaudet, A, Poissy, J, Morel, P, Richard, P, Cognasse, F, Troya, J, Trouillet-Assant, S, Belot, A, Saker, K, Garçon, P, Rivière, J, Lagier, J, Gentile, S, Rosen, L, Shaw, E, Morio, T, Tanaka, J, Dalmau, D, Tharaux, P, Sene, D, Stepanian, A, Mégarbane, B, Triantafyllia, V, Fekkar, A, Heath, J, Franco, J, Anaya, J, Solé-Violán, J, Imberti, L, Biondi, A, Bonfanti, P, Castagnoli, R, Delmonte, O, Zhang, Y, Snow, A, Holland, S, Biggs, C, Moncada-Vélez, M, Arias, A, Lorenzo, L, Boucherit, S, Anglicheau, D, Planas, A, Haerynck, F, Duvlis, S, Ozcelik, T, Keles, S, Bousfiha, A, El Bakkouri, J, Ramirez-Santana, C, Paul, S, Pan-Hammarström, Q, Hammarström, L, Dupont, A, Kurolap, A, Metz, C, Aiuti, A, Casari, G, Lampasona, V, Ciceri, F, Barreiros, L, Dominguez-Garrido, E, Vidigal, M, Zatz, M, van de Beek, D, Sahanic, S, Tancevski, I, Stepanovskyy, Y, Boyarchuk, O, Nukui, Y, Tsumura, M, Vidaur, L, Tangye, S, Burrel, S, Duffy, D, Quintana-Murci, L, Klocperk, A, Kann, N, Shcherbina, A, Lau, Y, Leung, D, Coulongeat, M, Marlet, J, Koning, R, Reyes, L, Chauvineau-Grenier, A, Venet, F, Monneret, G, Nussenzweig, M, Arrestier, R, Boudhabhay, I, Baris-Feldman, H, Hagin, D, Wauters, J, Meyts, I, Dyer, A, Kennelly, S, Bourke, N, Halwani, R, Sharif-Askari, F, Dorgham, K, Sallette, J, Sedkaoui, S, Alkhater, S, Rigo-Bonnin, R, Morandeira, F, Roussel, L, Vinh, D, Erikstrup, C, Condino-Neto, A, Prando, C, Bondarenko, A, Spaan, A, Gilardin, L, Fellay, J, Lyonnet, S, Bilguvar, K, Lifton, R, Mane, S, Anderson, M, Boisson, B, Béziat, V, Zhang, S, Andreakos, E, Hermine, O, Pujol, A, Peterson, P, Mogensen, T, Rowen, L, Mond, J, Debette, S, de Lamballerie, X, Burdet, C, Bouadma, L, Zins, M, Soler-Palacin, P, Colobran, R, Gorochov, G, Solanich, X, Susen, S, Martinez-Picado, J, Raoult, D, Vasse, M, Gregersen, P, Piemonti, L, Rodríguez-Gallego, C, Notarangelo, L, Su, H, Kisand, K, Okada, S, Puel, A, Jouanguy, E, Rice, C, Tiberghien, P, Zhang, Q, Casanova, J, Abel, L, Cobat, A, Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Imagine Institute, Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Unité des Virus Emergents (UVE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cohortes épidémiologiques en population (CONSTANCES), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université Paris Cité (UPCité), UFR Médecine [Santé] - Université Paris Cité (UFR Médecine UPCité), Université Paris Cité (UPCité), Neurology, AII - Infectious diseases, ANS - Neuroinfection & -inflammation, Graduate School, Université Paris Cité - UFR Médecine [Santé] (UPCité UFR Médecine), Gunst, Jan, Acibadem University Dspace, Manry, Jérémy, Bastard, Paul, Gervais, Adrian, Le Voyer, Tom, Rosain, Jérémie, Philippot, Quentin, Michailidis, Eleftherio, Hoffmann, Hans-Heinrich, Eto, Shohei, Garcia-Prat, Marina, Bizien, Lucy, Parra-Martínez, Alba, Yang, Rui, Haljasmägi, Lii, Migaud, Mélanie, Särekannu, Karita, Maslovskaja, Julia, de Prost, Nicola, Tandjaoui-Lambiotte, Yacine, Luyt, Charles-Edouard, Amador-Borrero, Blanca, Gaudet, Alexandre, Poissy, Julien, Morel, Pascal, Richard, Pascale, Cognasse, Fabrice, Troya, Jesú, Trouillet-Assant, Sophie, Belot, Alexandre, Saker, Kahina, Garçon, Pierre, Rivière, Jacques G, Lagier, Jean-Christophe, Gentile, Stéphanie, Rosen, Lindsey B, Shaw, Elana, Morio, Tomohiro, Tanaka, Junko, Dalmau, David, Tharaux, Pierre-Loui, Sene, Damien, Stepanian, Alain, Mégarbane, Bruno, Triantafyllia, Vasiliki, Fekkar, Arnaud, Heath, James R, Franco, José Lui, Anaya, Juan-Manuel, Solé-Violán, Jordi, Imberti, Luisa, Biondi, Andrea, Bonfanti, Paolo, Castagnoli, Riccardo, Delmonte, Ottavia M, Zhang, Yu, Snow, Andrew L, Holland, Steven M, Biggs, Catherine M, Moncada-Vélez, Marcela, Arias, Andrés Augusto, Lorenzo, Lazaro, Boucherit, Soraya, Anglicheau, Dany, Planas, Anna M, Haerynck, Filomeen, Duvlis, Sotirija, Ozcelik, Tayfun, Keles, Sevgi, Bousfiha, Ahmed A, El Bakkouri, Jalila, Ramirez-Santana, Carolina, Paul, Stéphane, Pan-Hammarström, Qiang, Hammarström, Lennart, Dupont, Annabelle, Kurolap, Alina, Metz, Christine N, Aiuti, Alessandro, Casari, Giorgio, Lampasona, Vito, Ciceri, Fabio, Barreiros, Lucila A, Dominguez-Garrido, Elena, Vidigal, Mateu, Zatz, Mayana, van de Beek, Diederik, Sahanic, Sabina, Tancevski, Ivan, Stepanovskyy, Yurii, Boyarchuk, Oksana, Nukui, Yoko, Tsumura, Miyuki, Vidaur, Loreto, Tangye, Stuart G, Burrel, Sonia, Duffy, Darragh, Quintana-Murci, Llui, Klocperk, Adam, Kann, Nelli Y, Shcherbina, Anna, Lau, Yu-Lung, Leung, Daniel, Coulongeat, Matthieu, Marlet, Julien, Koning, Rutger, Reyes, Luis Felipe, Chauvineau-Grenier, Angélique, Venet, Fabienne, Monneret, Guillaume, Nussenzweig, Michel C, Arrestier, Romain, Boudhabhay, Idri, Baris-Feldman, Hagit, Hagin, David, Wauters, Joost, Meyts, Isabelle, Dyer, Adam H, Kennelly, Sean P, Bourke, Nollaig M, Halwani, Rabih, Sharif-Askari, Fatemeh Saheb, Dorgham, Karim, Sallette, Jérôme, Sedkaoui, Souad Mehlal, Alkhater, Suzan, Rigo-Bonnin, Raúl, Morandeira, Francisco, Roussel, Lucie, Vinh, Donald C, Erikstrup, Christian, Condino-Neto, Antonio, Prando, Carolina, Bondarenko, Anastasiia, Spaan, András N, Gilardin, Laurent, Fellay, Jacque, Lyonnet, Stanisla, Bilguvar, Kaya, Lifton, Richard P, Mane, Shrikant, Anderson, Mark S, Boisson, Bertrand, Béziat, Vivien, Zhang, Shen-Ying, Andreakos, Evangelo, Hermine, Olivier, Pujol, Aurora, Peterson, Pärt, Mogensen, Trine H, Rowen, Lee, Mond, Jame, Debette, Stéphanie, de Lamballerie, Xavier, Burdet, Charle, Bouadma, Lila, Zins, Marie, Soler-Palacin, Pere, Colobran, Roger, Gorochov, Guy, Solanich, Xavier, Susen, Sophie, Martinez-Picado, Javier, Raoult, Didier, Vasse, Marc, Gregersen, Peter K, Piemonti, Lorenzo, Rodríguez-Gallego, Carlo, Notarangelo, Luigi D, Su, Helen C, Kisand, Kai, Okada, Satoshi, Puel, Anne, Jouanguy, Emmanuelle, Rice, Charles M, Tiberghien, Pierre, Zhang, Qian, Casanova, Jean-Laurent, Abel, Laurent, Cobat, Aurélie, Vougny, Marie-Christine, and Amsterdam Neuroscience - Neuroinfection & -inflammation
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Adult ,Male ,Risk ,infection fatality rate ,[SDV.IMM] Life Sciences [q-bio]/Immunology ,autoantibodies ,chronic mucocutaneous candidiasis ,CHRONIC MUCOCUTANEOUS CANDIDIASIS ,Autoimmunity ,IMMUNITY ,[SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract ,Article ,DISEASE ,Basic medicine ,[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,INFECTION ,Medicine and Health Sciences ,Humans ,IMUNOLOGIA ,Aged ,Autoantibodies ,Aged, 80 and over ,disease ,[SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases ,Multidisciplinary ,SARS-CoV-2 ,type I IFNs ,Age Factors ,COVID-19 ,Type I IFNs ,Middle Aged ,autoantibodie ,immunity ,Antibodies, Neutralizing ,infection ,Infection fatality rate ,Relative risk ,relative risk ,[SDV.TOX]Life Sciences [q-bio]/Toxicology ,Interferon Type I ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,Female ,type I IFN - Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection fatality rate (IFR) doubles with every 5 y of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-β are found in ∼20% of deceased patients across age groups, and in ∼1% of individuals aged 4% of those >70 y old in the general population. With a sample of 1,261 unvaccinated deceased patients and 34,159 individuals of the general population sampled before the pandemic, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to noncarriers. The RRD associated with any combination of autoantibodies was higher in subjects under 70 y old. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRDs were 17.0 (95% CI: 11.7 to 24.7) and 5.8 (4.5 to 7.4) for individuals, The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute; The Rockefeller University; the St. Giles Foundation; the NIH (Grants R01AI088364 and R01AI163029); the National Center for Advancing Translational Sciences; NIH Clinical and Translational Science Awards program (Grant UL1 TR001866); a Fast Grant from Emergent Ventures; Mercatus Center at George Mason University; the Yale Center for Mendelian Genomics and the Genome Sequencing Program Coordinating Center funded by the National Human Genome Research Institute (Grants UM1HG006504 and U24HG008956); the Yale High Performance Computing Center (Grant S10OD018521); the Fisher Center for Alzheimer’s Research Foundation; the Meyer Foundation; the JPB Foundation; the French National Research Agency (ANR) under the “Investments for the Future” program (Grant ANR-10-IAHU-01); the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (Grant ANR-10-LABX-62-IBEID); the French Foundation for Medical Research (FRM) (Grant EQU201903007798); the French Agency for Research on AIDS and Viral hepatitis (ANRS) Nord-Sud (Grant ANRS-COV05); the ANR GENVIR (Grant ANR-20-CE93-003), AABIFNCOV (Grant ANR-20-CO11-0001), CNSVIRGEN (Grant ANR-19-CE15-0009-01), and GenMIS-C (Grant ANR-21-COVR-0039) projects; the Square Foundation; Grandir–Fonds de solidarité pour l’Enfance; the Fondation du Souffle; the SCOR Corporate Foundation for Science; The French Ministry of Higher Education, Research, and Innovation (Grant MESRI-COVID-19); Institut National de la Santé et de la Recherche Médicale (INSERM), REACTing-INSERM; and the University Paris Cité. P. Bastard was supported by the FRM (Award EA20170638020). P. Bastard., J.R., and T.L.V. were supported by the MD-PhD program of the Imagine Institute (with the support of Fondation Bettencourt Schueller). Work at the Neurometabolic Disease lab received funding from Centre for Biomedical Research on Rare Diseases (CIBERER) (Grant ACCI20-767) and the European Union's Horizon 2020 research and innovation program under grant agreement 824110 (EASI Genomics). Work in the Laboratory of Virology and Infectious Disease was supported by the NIH (Grants P01AI138398-S1, 2U19AI111825, and R01AI091707-10S1), a George Mason University Fast Grant, and the G. Harold and Leila Y. Mathers Charitable Foundation. The Infanta Leonor University Hospital supported the research of the Department of Internal Medicine and Allergology. The French COVID Cohort study group was sponsored by INSERM and supported by the REACTing consortium and by a grant from the French Ministry of Health (Grant PHRC 20-0424). The Cov-Contact Cohort was supported by the REACTing consortium, the French Ministry of Health, and the European Commission (Grant RECOVER WP 6). This work was also partly supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases and the National Institute of Dental and Craniofacial Research, NIH (Grants ZIA AI001270 to L.D.N. and 1ZIAAI001265 to H.C.S.). This program is supported by the Agence Nationale de la Recherche (Grant ANR-10-LABX-69-01). K.K.’s group was supported by the Estonian Research Council, through Grants PRG117 and PRG377. R.H. was supported by an Al Jalila Foundation Seed Grant (Grant AJF202019), Dubai, United Arab Emirates, and a COVID-19 research grant (Grant CoV19-0307) from the University of Sharjah, United Arab Emirates. S.G.T. is supported by Investigator and Program Grants awarded by the National Health and Medical Research Council of Australia and a University of New South Wales COVID Rapid Response Initiative Grant. L.I. reports funding from Regione Lombardia, Italy (project “Risposta immune in pazienti con COVID-19 e co-morbidità”). This research was partially supported by the Instituto de Salud Carlos III (Grant COV20/0968). J.R.H. reports funding from Biomedical Advanced Research and Development Authority (Grant HHSO10201600031C). S.O. reports funding from Research Program on Emerging and Re-emerging Infectious Diseases from Japan Agency for Medical Research and Development (Grant JP20fk0108531). G.G. was supported by the ANR Flash COVID-19 program and SARS-CoV-2 Program of the Faculty of Medicine from Sorbonne University iCOVID programs. The 3C Study was conducted under a partnership agreement between INSERM, Victor Segalen Bordeaux 2 University, and Sanofi-Aventis. The Fondation pour la Recherche Médicale funded the preparation and initiation of the study. The 3C Study was also supported by the Caisse Nationale d’Assurance Maladie des Travailleurs Salariés, Direction générale de la Santé, Mutuelle Générale de l’Education Nationale, Institut de la Longévité, Conseils Régionaux of Aquitaine and Bourgogne, Fondation de France, and Ministry of Research–INSERM Program “Cohortes et collections de données biologiques.” S. Debette was supported by the University of Bordeaux Initiative of Excellence. P.K.G. reports funding from the National Cancer Institute, NIH, under Contract 75N91019D00024, Task Order 75N91021F00001. J.W. is supported by a Research Foundation - Flanders (FWO) Fundamental Clinical Mandate (Grant 1833317N). Sample processing at IrsiCaixa was possible thanks to the crowdfunding initiative YoMeCorono. Work at Vall d’Hebron was also partly supported by research funding from Instituto de Salud Carlos III Grant PI17/00660 cofinanced by the European Regional Development Fund (ERDF/FEDER). C.R.-G. and colleagues from the Canarian Health System Sequencing Hub were supported by the Instituto de Salud Carlos III (Grants COV20_01333 and COV20_01334), the Spanish Ministry for Science and Innovation (RTC-2017-6471-1; AEI/FEDER, European Union), Fundación DISA (Grants OA18/017 and OA20/024), and Cabildo Insular de Tenerife (Grants CGIEU0000219140 and “Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19”). T.H.M. was supported by grants from the Novo Nordisk Foundation (Grants NNF20OC0064890 and NNF21OC0067157). C.M.B. is supported by a Michael Smith Foundation for Health Research Health Professional-Investigator Award. P.Q.H. and L. Hammarström were funded by the European Union’s Horizon 2020 research and innovation program (Antibody Therapy Against Coronavirus consortium, Grant 101003650). Work at Y.-L.L.’s laboratory in the University of Hong Kong (HKU) was supported by the Society for the Relief of Disabled Children. MBBS/PhD study of D.L. in HKU was supported by the Croucher Foundation. J.L.F. was supported in part by the Evaluation-Orientation de la Coopération Scientifique (ECOS) Nord - Coopération Scientifique France-Colombie (ECOS-Nord/Columbian Administrative department of Science, Technology and Innovation [COLCIENCIAS]/Colombian Ministry of National Education [MEN]/Colombian Institute of Educational Credit and Technical Studies Abroad [ICETEX, Grant 806-2018] and Colciencias Contract 713-2016 [Code 111574455633]). A. Klocperk was, in part, supported by Grants NU20-05-00282 and NV18-05-00162 issued by the Czech Health Research Council and Ministry of Health, Czech Republic. L.P. was funded by Program Project COVID-19 OSR-UniSR and Ministero della Salute (Grant COVID-2020-12371617). I.M. is a Senior Clinical Investigator at the Research Foundation–Flanders and is supported by the CSL Behring Chair of Primary Immunodeficiencies (PID); by the Katholieke Universiteit Leuven C1 Grant C16/18/007; by a Flanders Institute for Biotechnology-Grand Challenges - PID grant; by the FWO Grants G0C8517N, G0B5120N, and G0E8420N; and by the Jeffrey Modell Foundation. I.M. has received funding under the European Union’s Horizon 2020 research and innovation program (Grant Agreement 948959). E.A. received funding from the Hellenic Foundation for Research and Innovation (Grant INTERFLU 1574). M. Vidigal received funding from the São Paulo Research Foundation (Grant 2020/09702-1) and JBS SA (Grant 69004). The NH-COVAIR study group consortium was supported by a grant from the Meath Foundation.
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- 2022
135. COVID-19 in Solid Organ Transplant Recipient: Exploring Cumulative Incidence, Seroprevalence and Risk Factors for Disease Severity
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Rossana Caldara, Paola Maffi, Sabrina Costa, Elena Bazzigaluppi, Cristina Brigatti, Vito Lampasona, Paola Magistretti, Fabio Manenti, Ilaria Marzinotto, Silvia Pellegrini, Marina Scavini, Antonio Secchi, Lorenzo Piemonti, Caldara, R., Maffi, P., Costa, S., Bazzigaluppi, E., Brigatti, C., Lampasona, V., Magistretti, P., Manenti, F., Marzinotto, I., Pellegrini, S., Scavini, M., Secchi, A., and Piemonti, L.
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seroprevalence ,General Immunology and Microbiology ,COVID-19 ,pancreas transplantation ,islet transplantation ,SARS-CoV-2 ,QH301-705.5 ,Seroprevalence ,Pancreas transplantation ,Article ,General Biochemistry, Genetics and Molecular Biology ,Islet transplantation ,Biology (General) ,General Agricultural and Biological Sciences - Abstract
Simple Summary It is still uncertain whether recipients of solid organ transplant (SOT) are at increased risk of SARS-CoV-2 infection and/or poor outcomes due to COVID-19 in comparison to the general population. In this study, we report the cumulative incidence and outcomes of SARS-CoV-2 infection in a cohort of 291 SOT recipients. The COVID-19 cumulative incidence in SOT recipients resulted slightly higher compared to that of age-matched population during the study period. Moreover, the SARS-CoV-2 antibody frequency was around 2.6-fold higher than the incidence of cases who tested positive for SARS-CoV-2 RT-PCR, suggesting that the number of SOT recipients infected with SARS-CoV-2 is likely higher than described. In symptomatic recipients, kidney transplant was associated with a higher risk of developing moderate/critical disease, while common risk factors, including age and comorbidities, resulted less relevant for COVID-19 severity. Due to the high estimated crude mortality, symptomatic SOT recipients should be considered at high risk in case of SARS-CoV-2 infection. Abstract Background: Solid organ transplant (SOT) recipients may be at increased risk for severe disease and mortality from COVID-19 because of immunosuppression and prolonged end-stage organ disease. As a transplant center serving a diverse patient population, we report the cumulative incidence and outcomes of SARS-CoV-2 infection in our cohort of SOT recipients. Methods: We prospectively included in this observational study SOT recipients with a functioning kidney (n = 201), pancreas ± kidney (n = 66) or islet transplant (n = 24), attending outpatient regular follow-up at the San Raffaele Hospital from February 2020 to April 2021. Antibodies to SARS-CoV-2 were tested in all patients by a luciferase immunoprecipitation system assay. Results: Of the 291 SOT recipients, 30 (10.3%) tested positive for SARS-CoV-2 during the study period and prevalence was not different among different transplants. The SARS-CoV-2 antibody frequency was around 2.6-fold higher than the incidence of cases who tested positive for SARS-CoV-2 RT-PCR. As for the WHO COVID-19 severity classification, 19 (63.3%) SOT recipients were mild, nine (30%) were moderate, and two were critical and died yielding a crude mortality rate in our patient population of 6.7%. Kidney transplant (OR 12.9 (1.1–150) p = 0.041) was associated with an increased risk for moderate/critical disease, while statin therapy (OR 0.116 (0.015–0.926) p = 0.042) and pancreas/islet transplant (OR 0.077 (0.007–0.906) p = 0.041) were protective. Conclusions: The incidence of SARS-CoV-2 infection in SOT recipients may be higher than previously described. Due to the relative high crude mortality, symptomatic SOT recipients must be considered at high risk in case of SARS-CoV-2 infection.
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- 2021
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136. Case Report: Off-Label Liraglutide Use in Children With Wolfram Syndrome Type 1: Extensive Characterization of Four Patients
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Giulio Frontino, Tara Raouf, Daniele Canarutto, Eva Tirelli, Raffaella Di Tonno, Andrea Rigamonti, Maria Lucia Cascavilla, Cristina Baldoli, Roberta Scotti, Letizia Leocani, Su-Chun Huang, Franco Meschi, Graziano Barera, Vania Broccoli, Greta Rossi, Silvia Torchio, Raniero Chimienti, Riccardo Bonfanti, Lorenzo Piemonti, Frontino, G., Raouf, T., Canarutto, D., Tirelli, E., Di Tonno, R., Rigamonti, A., Cascavilla, M. L., Baldoli, C., Scotti, R., Leocani, L., Huang, S. -C., Meschi, F., Barera, G., Broccoli, V., Rossi, G., Torchio, S., Chimienti, R., Bonfanti, R., and Piemonti, L.
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Wolfram syndrome 1 (WFS1) ,liraglutide ,Wolfram syndrome ,monogenic diabetes ,Pediatrics, Perinatology and Child Health ,neurodegeneration ,Case Report ,GLP1 receptor agonists ,Pediatrics ,RJ1-570 - Abstract
Aims: Wolfram syndrome type 1 is a rare recessive monogenic form of insulin-dependent diabetes mellitus with progressive neurodegeneration, poor prognosis, and no cure. Based on preclinical evidence we hypothesized that liraglutide, a glucagon-like peptide-1 receptor agonist, may be repurposed for the off-label treatment of Wolfram Syndrome type 1. We initiated an off-label treatment to investigate the safety, tolerability, and efficacy of liraglutide in pediatric patients with Wolfram Syndrome type 1.Methods: Pediatric patients with genetically confirmed Wolfram Syndrome type 1 were offered off-label treatment approved by The Regional Network Coordination Center for Rare Diseases, Pharmacological Research IRCCS Mario Negri, and the internal ethics committee. Four patients were enrolled; none refused nor were excluded or lost during follow-up. Liraglutide was administered as a daily subcutaneous injection. Starting dose was 0.3 mg/day. The dose was progressively increased as tolerated, up to the maximum dose of 1.8 mg/day. The primary outcome was evaluating the safety, tolerability, and efficacy of liraglutide in Wolfram Syndrome type 1 patients. Secondary endpoints were stabilization or improvement of C-peptide secretion as assessed by the mixed meal tolerance test. Exploratory endpoints were stabilization of neurological and neuro-ophthalmological degeneration, assessed by optical coherence tomography, electroretinogram, visual evoked potentials, and magnetic resonance imaging.Results: Four patients aged between 10 and 14 years at baseline were treated with liraglutide for 8–27 months. Liraglutide was well-tolerated: all patients reached and maintained the maximum dose, and none withdrew from the study. Only minor transient gastrointestinal symptoms were reported. No alterations in pancreatic enzymes, calcitonin, or thyroid hormones were observed. At the latest follow-up, the C-peptide area under the curve ranged from 81 to 171% of baseline. Time in range improved in two patients. Neuro-ophthalmological and neurophysiological disease parameters remained stable at the latest follow-up.Conclusions: We report preliminary data on the safety, tolerability, and efficacy of liraglutide in four pediatric patients with Wolfram Syndrome type 1. The apparent benefits both in terms of residual C-peptide secretion and neuro-ophthalmological disease progression warrant further studies on the repurposing of glucagon-like peptide-1 receptor agonists as disease-modifying agents for Wolfram Syndrome type 1.
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- 2021
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137. Interventional Radiological Management and Prevention of Complications after Pancreatic Surgery: Drainage, Embolization and Islet Auto-Transplantation
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Cristina Mosconi, Maria Adriana Cocozza, Filippo Piacentino, Federico Fontana, Alberta Cappelli, Francesco Modestino, Andrea Coppola, Diego Palumbo, Paolo Marra, Paola Maffi, Lorenzo Piemonti, Antonio Secchi, Claudio Ricci, Riccardo Casadei, Gianpaolo Balzano, Massimo Falconi, Giulio Carcano, Antonio Basile, Anna Maria Ierardi, Gianpaolo Carrafiello, Francesco De Cobelli, Rita Golfieri, Massimo Venturini, Mosconi C., Cocozza M.A., Piacentino F., Fontana F., Cappelli A., Modestino F., Coppola A., Palumbo D., Marra P., Maffi P., Piemonti L., Secchi A., Ricci C., Casadei R., Balzano G., Falconi M., Carcano G., Basile A., Ierardi A.M., Carrafiello G., De Cobelli F., Golfieri R., and Venturini M.
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interventional radiology (IR) ,islet of Langerhans transplantation ,embolization ,General Medicine ,hemorrhage ,pancreatectomy ,drainage - Abstract
Pancreatic surgery still remains burdened by high levels of morbidity and mortality with a relevant incidence of complications, even in high volume centers. This review highlights the interventional radiological management of complications after pancreatic surgery. The current literature regarding the percutaneous drainage of fluid collections due to pancreatic fistulas, percutaneous transhepatic biliary drainage due to biliary leaks and transcatheter embolization (or stent–graft) due to arterial bleeding is analyzed. Moreover, also, percutaneous intra-portal islet auto-transplantation for the prevention of pancreatogenic diabetes in case of extended pancreatic resection is also examined. Moreover, a topic not usually treated in other similar reviewsas percutaneous intra-portal islet auto-transplantation for the prevention of pancreatogenic diabetes in case of extended pancreatic resection is also one of our areas of focus. In islet auto-transplantation, the patient is simultaneously donor and recipient. Differently from islet allo-transplantation, it does not require immunosuppression, has no risk of rejection and is usually efficient with a small number of transplanted islets.
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- 2022
138. Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths
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Bastard, Paul, Gervais, Adrian, Le Voyer, Tom, Rosain, Jérémie, Philippot, Quentin, Manry, Jérémy, Michailidis, Eleftherios, Hoffmann, Hans-Heinrich, Eto, Shohei, Garcia-Prat, Marina, Bizien, Lucy, Parra-Martínez, Alba, Yang, Rui, Haljasmägi, Liis, Migaud, Mélanie, Särekannu, Karita, Maslovskaja, Julia, de Prost, Nicolas, Tandjaoui-Lambiotte, Yacine, Luyt, Charles-Edouard, Amador-Borrero, Blanca, Gaudet, Alexandre, Poissy, Julien, Morel, Pascal, Richard, Pascale, Cognasse, Fabrice, Troya, Jesus, Trouillet-Assant, Sophie, Belot, Alexandre, Saker, Kahina, Garçon, Pierre, Rivière, Jacques G., Lagier, Jean-Christophe, Gentile, Stéphanie, Rosen, Lindsey B., Shaw, Elana, Morio, Tomohiro, Tanaka, Junko, Dalmau, David, Tharaux, Pierre-Louis, Sene, Damien, Stepanian, Alain, Megarbane, Bruno, Triantafyllia, Vasiliki, Fekkar, Arnaud, Heath, James R., Franco, José Luis, Anaya, Juan-Manuel, Solé-Violán, Jordi, Imberti, Luisa, Biondi, Andrea, Bonfanti, Paolo, Castagnoli, Riccardo, Delmonte, Ottavia M., Zhang, Yu, Snow, Andrew L., Holland, Steven M., Biggs, Catherine M., Moncada-Vélez, Marcela, Arias, Andrés Augusto, Lorenzo, Lazaro, Boucherit, Soraya, Coulibaly, Boubacar, Anglicheau, Dany, Planas, Anna M., Haerynck, Filomeen, Duvlis, Sotirija, Nussbaum, Robert L., Ozcelik, Tayfun, Keles, Sevgi, Bousfiha, Ahmed A., El Bakkouri, Jalila, Ramirez-Santana, Carolina, Paul, Stéphane, Pan-Hammarström, Qiang, Hammarström, Lennart, Dupont, Annabelle, Kurolap, Alina, Metz, Christine N., Aiuti, Alessandro, Casari, Giorgio, Lampasona, Vito, Ciceri, Fabio, Barreiros, Lucila A., Dominguez-Garrido, Elena, Vidigal, Mateus, Zatz, Mayana, van de Beek, Diederik, Sahanic, Sabina, Tancevski, Ivan, Stepanovskyy, Yurii, Boyarchuk, Oksana, Nukui, Yoko, Tsumura, Miyuki, Vidaur, Loreto, Tangye, Stuart G., Burrel, Sonia, Duffy, Darragh, Quintana-Murci, Lluis, Klocperk, Adam, Kann, Nelli Y., Shcherbina, Anna, Lau, Yu-Lung, Leung, Daniel, Coulongeat, Matthieu, Marlet, Julien, Koning, Rutger, Reyes, Luis Felipe, Chauvineau-Grenier, Angélique, Venet, Fabienne, Monneret, Guillaume, Nussenzweig, Michel C., Arrestier, Romain, Boudhabhay, Idris, Baris-Feldman, Hagit, Hagin, David, Wauters, Joost, Meyts, Isabelle, Dyer, Adam H., Kennelly, Sean P., Bourke, Nollaig M., Halwani, Rabih, Sharif-Askari, Narjes Saheb, Dorgham, Karim, Sallette, Jérome, Mehlal Sedkaoui, Souad, AlKhater, Suzan, Rigo-Bonnin, Raúl, Morandeira, Francisco, Roussel, Lucie, Vinh, Donald C., Ostrowski, Sisse Rye, Condino-Neto, Antonio, Prando, Carolina, Bondarenko, Anastasiia, Spaan, András N., Gilardin, Laurent, Fellay, Jacques, Lyonnet, Stanislas, Bilguvar, Kaya, Lifton, Richard P., Mane, Shrikant, Anderson, Mark S., Boisson, Bertrand, Béziat, Vivien, Zhang, Shen-Ying, Andreakos, Evangelos, Hermine, Olivier, Pujol, Aurora, Peterson, Pärt, Mogensen, Trine H., Rowen, Lee, Mond, James, Debette, Stéphanie, de Lamballerie, Xavier, Duval, Xavier, Mentré, France, Zins, Marie, Soler-Palacin, Pere, Colobran, Roger, Gorochov, Guy, Solanich, Xavier, Susen, Sophie, Martinez-Picado, Javier, Raoult, Didier, Vasse, Marc, Gregersen, Peter K., Piemonti, Lorenzo, Rodríguez-Gallego, Carlos, Notarangelo, Luigi D., Su, Helen C., Kisand, Kai, Okada, Satoshi, Puel, Anne, Jouanguy, Emmanuelle, Rice, Charles M., Tiberghien, Pierre, Zhang, Qian, Cobat, Aurélie, Abel, Laurent, Casanova, Jean-Laurent, Bigio, Benedetta, de la Chapelle, Aliénor, Chen, Jie, Chrabieh, Maya, Liu, Dana, Nemirowskaya, Yelena, Cruz, Inés Marín, Materna, Marie, Pelet, Sophie, Seeleuthner, Yoann, Thibault, Chloé, Liu, Zhiyong, Abad, Jorge, Accordino, Giulia, Achille, Cristian, Aguilera-Albesa, Sergio, Aguiló-Cucurull, Aina, Özkan, Esra Akyüz, Darazam, Ilad Alavi, Roblero Albisures, Jonathan Antonio, Aldave, Juan C, Ramos, Miquel Alfonso, Khan, Taj Ali, Aliberti, Anna, Nadji, Seyed Alireza, Alkan, Gulsum, Alkhater, Suzan A., Allardet-Servent, Jerome, Allende, Luis M, Alonso-Arias, Rebeca, Alshahrani, Mohammed S, Alsina, Laia, Alyanakian, Marie-Alexandra, Borrero, Blanca Amador, Amoura, Zahir, Antolí, Arnau, Aubart, Mélodie, Auguet, Teresa, Avramenko, Iryna, Aytekin, Gökhan, Azot, Axelle, Bahram, Seiamak, Bajolle, Fanny, Baldanti, Fausto, Baldolli, Aurélie, Ballester, Maite, Feldman, Hagit Baris, Barrou, Benoit, Barzagh, Federica, Basso, Sabrina, Bayhan, Gulsum Iclal, Bezrodnik, Liliana, Bilbao, Agurtzane, Blanchard-Rohner, Geraldine, Blanco, Ignacio, Blandinières, Adeline, Blázquez-Gamero, Daniel, Bleibtreu, Alexandre, Bloomfield, Marketa, Bolivar-Prados, Mireia, Borghesi, Alessandro, Borie, Raphael, Botdhlo-Nevers, Elisabeth, Bousfiha, Ahmed A, Bousquet, Aurore, Boutolleau, David, Bouvattier, Claire, Bravais, Juliette, Briones, M. Luisa, Brunner, Marie-Eve, Bruno, Raffaele, Bueno, Maria Rita P, Bukhari, Huda, Bustamante, Jacinta, Cáceres Agra, Juan José, Capra, Ruggero, Carapito, Raphael, Carrabba, Maria, Casasnovas, Carlos, Caseris, Marion, Cassaniti, Irene, Castelle, Martin, Castelli, Francesco, de Vera, Martín Castillo, Castro, Mateus V, Catherinot, Emilie, Celik, Jale Bengi, Ceschi, Alessandro, Chalumeau, Martin, Charbit, Bruno, Cheng, Matthew P., Clavé, Père, Clotet, Bonaventura, Codina, Anna, Cohen, Yves, Comarmond, Cloé, Combes, Alain, Comoli, Patrizia, Corsico, Angelo G, Coşkuner, Taner, Cvetkovski, Aleksandar, Cyrus, Cyril, Danion, François, Darley, David Ross, Das, Vincent, Dauby, Nicolas, Dauger, Stéphane, De Munter, Paul, de Pontual, Loic, Dehban, Amin, Delplancq, Geoffroy, Demoule, Alexandre, Desguerre, Isabelle, Di Sabatino, Antonio, Diehl, Jean-Luc, Dobbelaere, Stephanie, Domínguez-Garrido, Elena, Dubost, Clément, Ekwall, Olov, Bozdemir, Şefika Elmas, Elnagdy, Marwa H, Emiroglu, Melike, Endo, Akifumi, Erdeniz, Emine Hafize, Aytekin, Selma Erol, Lasa, Maria Pilar Etxart, Euvrard, Romain, Fabio, Giovanna, Faivre, Laurence, Falck, Antonin, Fartoukh, Muriel, Faure, Morgane, Arquero, Miguel Fernandez, Ferrer, Ricard, Ferreres, Jose, Flores, Carlos, Francois, Bruno, Fumadó, Victoria, Fung, Kitty S C, Fusco, Francesca, Gagro, Alenka, Solis, Blanca Garcia, Gaussem, Pascale, Gayretli, Zeynep, Gil-Herrera, Juana, Gatineau, Audrey Giraud, Girona-Alarcón, Mònica, Cifuentes Godínez, Karen Alejandra, Goffard, Jean-Christophe, Gonzales, Nacho, Gonzalez-Granado, Luis I, González-Montelongo, Rafaela, Guerder, Antoine, Gülhan, Belgin, Gumucio, Victor Daniel, Hanitsch, Leif Gunnar, Gunst, Jan, Gut, Marta, Hadjadj, Jérôme, Hancerli, Selda, Hariyan, Tetyana, Hatipoglu, Nevin, Heppekcan, Deniz, Hernandez-Brito, Elisa, Ho, Po-ki, Holanda-Peña, María Soledad, Horcajada, Juan P, Hraiech, Sami, Humbert, Linda, Hung, Ivan F N, Iglesias, Alejandro D., Íñigo-Campos, Antonio, Jamme, Matthieu, Arranz, María Jesús, Jimeno, Marie-Thérèse, Jordan, Iolanda, Yüksek, Saliha Kanık, Kara, Yalcin Burak, Karahan, Aydın, Karbuz, Adem, Yasar, Kadriye Kart, Kasapcopur, Ozgur, Kashimada, Kenichi, Demirkol, Yasemin Kendir, Kido, Yasutoshi, Kizil, Can, Kılıç, Ahmet Osman, Koutsoukou, Antonia, Król, Zbigniew J., Ksouri, Hatem, Kuentz, Paul, Kwan, Arthur M C, Kwan, Yat Wah M, Kwok, Janette S Y, Lam, David S Y, Lampropoulou, Vicky, Lanternier, Fanny, Le Bourgeois, Fleur, Leo, Yee-Sin, Lopez, Rafael Leon, Levin, Michael, Levy, Michael, Lévy, Romain, Li, Zhi, Lilleri, Daniele, Lima, Edson Jose Adrian Bolanos, Linglart, Agnes, López-Collazo, Eduardo, Lorenzo-Salazar, José M., Louapre, Céline, Lubetzki, Catherine, Lung, Kwok-Cheung, Lye, David C, Magnone, Cinthia, Mansouri, Davood, Marchioni, Enrico, Marioli, Carola, Marjani, Majid, Marques, Laura, Pereira, Jesus Marquez, Martín-Nalda, Andrea, Pueyo, David Martínez, Marzana, Iciar, Mata-Martínez, Carmen, Mathian, Alexis, Matos, Larissa RB, Matthews, Gail V, Mayaux, Julien, McLaughlin-Garcia, Raquel, Meersseman, Philippe, Mège, Jean-Louis, Mekontso-Dessap, Armand, Melki, Isabelle, Meloni, Federica, Meritet, Jean-François, Merlani, Paolo, Akcan, Özge Metin, Mezidi, Mehdi, Migeotte, Isabelle, Millereux, Maude, Million, Matthieu, Mirault, Tristan, Mircher, Clotilde, Mirsaeidi, Mehdi, Mizoguchi, Yoko, Modi, Bhavi P, Mojoli, Francesco, Moncomble, Elsa, Melián, Abián Montesdeoca, Martinez, Antonio Morales, Morange, Pierre-Emmanuel, Mordacq, Clémence, Morelle, Guillaume, Mouly, Stéphane J, Muñoz-Barrera, Adrián, Nafati, Cyril, Nagashima, Shintaro, Nakagama, Yu, Neven, Bénédicte, Neves, João Farela, Ng, Lisa FP, Ng, Yuk-Yung, Nielly, Hubert, Medina, Yeray Novoa, Cuadros, Esmeralda Nuñez, Ocejo-Vinyals, J. 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Montse, Ruiz del Prado, Maria Yolanda, Ruiz-Rodriguez, Juan Carlos, Sabater-Riera, Joan, Saks, Kai, Salagianni, Maria, Sanchez, Oliver, Sánchez-Montalvá, Adrián, Sánchez-Ramón, Silvia, Schidlowski, Laire, Schluter, Agatha, Schmidt, Julien, Schmidt, Matthieu, Schuetz, Catharina, Schweitzer, Cyril E, Scolari, Francesco, Sediva, Anna, Seijo, Luis, Seminario, Analia Gisela, Seng, Piseth, Senoglu, Sevtap, Seppänen, Mikko, Llovich, Alex Serra, Shahrooei, Mohammad, Siguret, Virginie, Siouti, Eleni, Smadja, David M, Smith, Nikaia, Sobh, Ali, Soler, Catherine, Soler-Palacín, Pere, Sözeri, Betül, Stella, Giulia Maria, Stepanovskiy, Yuriy, Stoclin, Annabelle, Taccone, Fabio, Taupin, Jean-Luc, Tavernier, Simon J, Tello, Loreto Vidaur, Terrier, Benjamin, Thiery, Guillaume, Thorball, Christian, THORN, Karolina, Thumerelle, Caroline, Tipu, Imran, Tolstrup, Martin, Tomasoni, Gabriele, Toubiana, Julie, Alvarez, Josep Trenado, Troya, Jesús, Tsang, Owen T Y, Tserel, Liina, Tso, Eugene Y K, Tucci, Alessandra, Tüter Öz, Şadiye Kübra, Ursini, Matilde Valeria, Utsumi, Takanori, Uzunhan, Yurdagul, Vabres, Pierre, Valencia-Ramos, Juan, Van Den Rym, Ana Maria, Vandernoot, Isabelle, Velez-Santamaria, Valentina, Zuniga Veliz, Silvia Patricia, Vidigal, Mateus C, Viel, Sébastien, Vilain, Cédric, Vilaire-Meunier, Marie E, Villar-García, Judit, Vincent, Audrey, Vogt, Guillaume, Voiriot, Guillaume, Volokha, Alla, Vuotto, Fanny, Wauters, Els, Wu, Alan K L, Wu, Tak-Chiu, Yahşi, Aysun, Yesilbas, Osman, Yildiz, Mehmet, Young, Barnaby E, Yükselmiş, Ufuk, Zecca, Marco, Zuccaro, Valentina, Jens, Van Praet, Lambrecht, Bart N., Eva, Van Braeckel, Cédric, Bosteels, Levi, Hoste, Eric, Hoste, Bauters, Fré, De Clercq, Jozefien, Cathérine, Heijmans, Hans, Slabbynck, Leslie, Naesens, Florkin, Benoit, Boulanger, Cécile, Vanderlinden, Dimitri, Foti, Giuseppe, Bellani, Giacomo, Citerio, Giuseppe, Contro, Ernesto, Pesci, Alberto, Valsecchi, Maria Grazia, Cazzaniga, Marina, Danielson, Jeffrey J., Dobbs, Kerry, 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Dijkstra, Mirjam, Dongelmans, Dave A., Dujardin, Romein W.G., Elbers, Paul, Fleuren, Lucas, Geijtenbeek, Suzanne Geerlings Theo, Girbes, Armand, Goorhuis, Bram, Grobusch, Martin P., Hafkamp, Florianne, Hagens, Laura, Hamann, Jorg, Harris, Vanessa, Hemke, Robert, Hermans, Sabine M., Heunks, Leo, Hollmann, Markus, Horn, Janneke, Hovius, Joppe W., de Jong, Menno D., Lim, Endry H.T., van Mourik, Niels, Nellen, Jeaninne, Nossent, Esther J., Paulus, Frederique, Peters, Edgar, Pina-Fuentes, Dan A.I., van der Poll, Tom, Preckel, Bennedikt, Prins, Jan M., Raasveld, Jorinde, Reijnders, Tom, de Rotte, Maurits C.F.J., Schinkel, Michiel, Schultz, Marcus J., Schrauwen, Femke A.P., Schuurmans, Alex, Schuurmans, Jaap, Sigaloff, Kim, Slim, Marleen A., Smeele, Patrick, Smit, Marry, Stijnis, Cornelis S., Stilma, Willemke, Teunissen, Charlotte, Thoral, Patrick, Tsonas, Anissa M, Tuinman, Pieter R., van der Valk, Marc, Veelo, Denise, Volleman, Carolien, de Vries, Heder, Vught, Lonneke A., van Vugt, Michèle, Wouters, Dorien, Zwinderman, A. H (Koos, Brouwer, Matthijs C., Wiersinga, W. Joost, Vlaar, Alexander P.J., Al-Muhsen, Saleh, Al-Mulla, Fahd, Arias, Andrés A., Bogunovic, Dusan, Bolze, Alexandre, Bryceson, Yenan, Bustamante, Carlos D., Butte, Manish J., Chakravorty, Samya, Christodoulou, John, Constantinescu, Stefan N., Cooper, Megan A., Desai, Murkesh, Drolet, Beth A., El Baghdadi, Jamila, Espinosa-Padilla, Sara, Froidure, Antoine, Henrickson, Sarah E., Hsieh, Elena W.Y., Husebye, Eystein S., Imai, Kohsuke, Itan, Yuval, Jarvis, Erich D., Karamitros, Timokratis, Ku, Cheng-Lung, Ling, Yun, Lucas, Carrie L., Maniatis, Tom, Maródi, László, Milner, Joshua D., Mironska, Kristina, Ng, Lisa F.P., Novelli, Antonio, Novelli, Giuseppe, de Diego, Rebeca Perez, Renia, Laurent, Resnick, Igor, Sancho-Shimizu, Vanessa, Seppänen, Mikko R.J., Shahrooei, Mohammed, Slaby, Ondrej, Abou Tayoun, Ahmad, Ramaswamy, Sathishkumar, Turvey, Stuart E, Uddin, K M Furkan, Uddin, Mohammed J., von Bernuth, Horst, Zawadzki, Pawel, Nadif, Rachel, Goldberg, Marcel, Ozguler, Anna, Henny, Joseph, Lemonnier, Sylvie, Coeuret-Pellicer, Mireille, Le Got, Stéphane, Tzourio, Christophe, Dufouil, Carole, Soumaré, Aïcha, Lachaize, Morgane, Fievet, Nathalie, Flaig, Amandine, Martin, Fernando, Bonneaudeau, Brigitte, Cannet, Dorothée, Gallian, Pierre, Jeanne, Michel, Perroquin, Magali, Hamzeh-Cognasse, Hind, Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Groupe de recherche clinique CARMAS (Cardiovascular and Respiratory Manifestations of Acute lung injury and Sepsis) (CARMAS), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-CHU Henri Mondor [Créteil], Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Hôpital Lariboisière-Fernand-Widal [APHP], Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Hôpital Roger Salengro [Lille], Etablissement Français du Sang [La Plaine Saint-Denis] (EFS), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Santé Ingénierie Biologie Saint-Etienne (SAINBIOSE), Centre Ingénierie et Santé (CIS-ENSMSE), École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Etablissement français du sang - Auvergne-Rhône-Alpes (EFS), Hospices Civils de Lyon (HCL), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Grand Hôpital de l'Est Francilien (GHEF), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Assistance Publique - Hôpitaux de Marseille (APHM), Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Recherche clinique appliquée à l'hématologie ((EA_3518)), Université Paris Diderot - Paris 7 (UPD7), Service de Réanimation Médicale et Toxicologique [Hôpital Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre d'Investigation Clinique - Epidémiologie Clinique Saint-Etienne (CIC-EC), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011 (RNMCD), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Immunologie Translationnelle - Translational Immunology lab, Institut Pasteur [Paris] (IP), Génétique Evolutive Humaine - Human Evolutionary Genetics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Collège de France - Chaire Génomique humaine et évolution, Collège de France (CdF (institution)), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Morphogénèse et antigénicité du VIH et du virus des Hépatites (MAVIVH - U1259 Inserm - CHRU Tours ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Robert Ballanger [Aulnay-sous-Bois], Hôpital Edouard Herriot [CHU - HCL], Physiopathologie de l'immunodépression associée aux réponses inflammatoires systémiques / Pathophysiology of Injury-induced Immunosuppression (PI3), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Hôpital Jean Verdier [AP-HP], Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité des Virus Emergents (UVE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'investigation Clinique [CHU Bichat] - Épidémiologie clinique (CIC 1425), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Cohortes épidémiologiques en population (CONSTANCES), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université Paris Cité (UPCité), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Modeling & analysis for medical imaging and Diagnosis (MYRIAD), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 (AGIR ), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, CHU Amiens-Picardie, French COVID cohort study group, Howard Hughes Medical Institute, Rockefeller University, European Commission, Jeffrey Modell Foundation, Université de Bordeaux, Meath Foundation, National Human Genome Research Institute, Agence Nationale de la Recherche, Fondation pour la Recherche Médicale, Fondation du Souffle, Instituto de Salud Carlos III, Institut National de la Santé et de la Recherche Médicale, St. Giles Foundation, Ministère des Solidarités et de la Santé, Sorbonne Université, Mutuelle Générale de l'Education Nationale, Conseil Régional Aquitaine, Conseil régional de Bourgogne-Franche-Comté, Meyer Foundation, Fondation de France, National Cancer Institute, European Regional Development Fund, Fundación DISA, Ministero della Salute, ANR-20-COVI-0003,GENCOVID,Identification des défauts monogéniques de l'immunité responsables des formes sévères de COVID-19 chez les patients précédemment en bonne santé(2020), ANR-20-CE93-0003,GENVIR,Analyse multi-omique de l'immunité anti-virale: de l'identification des circuits biologiques pertinents à la découverte de défauts monogéniques héréditaires de l'immunité chez les patients avec infections virales sévères(2020), ANR-20-CO11-0001,AABIFNCOV,Bases génétiques et immunologiques des auto-anticorps contre les interférons de type I prédisposant aux formes sévères de COVID-19.(2020), European Project: IdEx Bordeaux (ANR-10-IDEX- 003-02), Bastard, Paul, Gervais, Adrian, Le Voyer, Tom, Rosain, Jérémie, Philippot, Quentin, Manry, Jérémy, Michailidis, Eleftherio, Hoffmann, Hans-Heinrich, Eto, Shohei, Garcia-Prat, Marina, Bizien, Lucy, Parra-Martínez, Alba, Yang, Rui, Haljasmägi, Lii, Migaud, Mélanie, Särekannu, Karita, Maslovskaja, Julia, de Prost, Nicola, Tandjaoui-Lambiotte, Yacine, Luyt, Charles-Edouard, Amador-Borrero, Blanca, Gaudet, Alexandre, Poissy, Julien, Morel, Pascal, Richard, Pascale, Cognasse, Fabrice, Troya, Jesu, Trouillet-Assant, Sophie, Belot, Alexandre, Saker, Kahina, Garçon, Pierre, Rivière, Jacques G, Lagier, Jean-Christophe, Gentile, Stéphanie, Rosen, Lindsey B, Shaw, Elana, Morio, Tomohiro, Tanaka, Junko, Dalmau, David, Tharaux, Pierre-Loui, Sene, Damien, Stepanian, Alain, Megarbane, Bruno, Triantafyllia, Vasiliki, Fekkar, Arnaud, Heath, James R, Franco, José Lui, Anaya, Juan-Manuel, Solé-Violán, Jordi, Imberti, Luisa, Biondi, Andrea, Bonfanti, Paolo, Castagnoli, Riccardo, Delmonte, Ottavia M, Zhang, Yu, Snow, Andrew L, Holland, Steven M, Biggs, Catherine, Moncada-Vélez, Marcela, Arias, Andrés Augusto, Lorenzo, Lazaro, Boucherit, Soraya, Coulibaly, Boubacar, Anglicheau, Dany, Planas, Anna M, Haerynck, Filomeen, Duvlis, Sotirija, Nussbaum, Robert L, Ozcelik, Tayfun, Keles, Sevgi, Bousfiha, Ahmed A, El Bakkouri, Jalila, Ramirez-Santana, Carolina, Paul, Stéphane, Pan-Hammarström, Qiang, Hammarström, Lennart, Dupont, Annabelle, Kurolap, Alina, Metz, Christine N, Aiuti, Alessandro, Casari, Giorgio, Lampasona, Vito, Ciceri, Fabio, Barreiros, Lucila A, Dominguez-Garrido, Elena, Vidigal, Mateu, Zatz, Mayana, van de Beek, Diederik, Sahanic, Sabina, Tancevski, Ivan, Stepanovskyy, Yurii, Boyarchuk, Oksana, Nukui, Yoko, Tsumura, Miyuki, Vidaur, Loreto, Tangye, Stuart G, Burrel, Sonia, Duffy, Darragh, Quintana-Murci, Llui, Klocperk, Adam, Kann, Nelli Y, Shcherbina, Anna, Lau, Yu-Lung, Leung, Daniel, Coulongeat, Matthieu, Marlet, Julien, Koning, Rutger, Reyes, Luis Felipe, Chauvineau-Grenier, Angélique, Venet, Fabienne, Monneret, Guillaume, Nussenzweig, Michel C, Arrestier, Romain, Boudhabhay, Idri, Baris-Feldman, Hagit, Hagin, David, Wauters, Joost, Meyts, Isabelle, Dyer, Adam H, Kennelly, Sean P, Bourke, Nollaig M, Halwani, Rabih, Sharif-Askari, Narjes Saheb, Dorgham, Karim, Sallette, Jérome, Sedkaoui, Souad Mehlal, Alkhater, Suzan, Rigo-Bonnin, Raúl, Morandeira, Francisco, Roussel, Lucie, Vinh, Donald C, Ostrowski, Sisse Rye, Condino-Neto, Antonio, Prando, Carolina, Bonradenko, Anastasiia, Spaan, András N, Gilardin, Laurent, Fellay, Jacque, Lyonnet, Stanisla, Bilguvar, Kaya, Lifton, Richard P, Mane, Shrikant, Anderson, Mark S, Boisson, Bertrand, Béziat, Vivien, Zhang, Shen-Ying, Vandreakos, Evangelo, Hermine, Olivier, Pujol, Aurora, Peterson, Pärt, Mogensen, Trine H, Rowen, Lee, Mond, Jame, Debette, Stéphanie, de Lamballerie, Xavier, Duval, Xavier, Mentré, France, Zins, Marie, Soler-Palacin, Pere, Colobran, Roger, Gorochov, Guy, Solanich, Xavier, Susen, Sophie, Martinez-Picado, Javier, Raoult, Didier, Vasse, Marc, Gregersen, Peter K, Piemonti, Lorenzo, Rodríguez-Gallego, Carlo, Notarangelo, Luigi D, Su, Helen C, Kisand, Kai, Okada, Satoshi, Puel, Anne, Jouanguy, Emmanuelle, Rice, Charles M, Tiberghien, Pierre, Zhang, Qian, Cobat, Aurélie, Abel, Laurent, Casanova, Jean-Laurent, St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller University [New York], CHU Necker - Enfants Malades [AP-HP], Human genetics of infectious diseases : Mendelian predisposition (Equipe Inserm U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hiroshima University, Vall d’Hebron Research Institute (VHIR), University of Tartu, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Henri Mondor [Créteil], Service de Réanimation Médicale [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Mycologie moléculaire - Molecular Mycology, Members of the The Milieu Intérieur Consortium: Laurent Abel1 , Andres Alcover2 , Hugues Aschard2 , Philippe Bousso2 , Nollaig Bourke3 , Petter Brodin4 , Pierre Bruhns2 , Nadine Cerf-Bensussan5 , Ana Cumano2 , Christophe D’Enfert2 , Ludovic Deriano2 , Marie-Agnès Dillies2 , James Di Santo2 , Françoise Dromer2 , Gérard Eberl2 , Jost Enninga2 , Jacques Fellay6 , Ivo Gomperts-Boneca2 , Milena Hasan2 , Gunilla Karlsson Hedestam4 , Serge Hercberg7 , Molly A. Ingersoll2 , Olivier Lantz8 , Rose Anne Kenny3 , Mickaël Ménager5 , Frédérique Michel2 , Hugo Mouquet2 , Cliona O’Farrelly3 , Etienne Patin2 , Sandra Pellegrini2 , Antonio Rausell5 , Frédéric Rieux-Laucat5 , Lars Rogge2 , Magnus Fontes9 , Anavaj Sakuntabhai2 , Olivier Schwartz2 , Benno Schwikowski2 , Spencer Shorte2 , Frédéric Tangy2 , Antoine Toubert10 , Mathilde Touvier12 , Marie-Noëlle Ungeheuer2 , Christophe Zimmer2 , Matthew L. Albert11 , Darragh Duffy2 , Lluis Quintana-Murc, ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), European Project: 824110,H2020-INFRAIA-2018-1,EASI-Genomics(2019), European Project: 948959,ERC-2020-STG,MORE2ADA2(2021), National Institutes of Health (US), National Center for Advancing Translational Sciences (US), George Mason University, National Human Genome Research Institute (US), Agence Nationale de la Recherche (France), Institut National de la Santé et de la Recherche Médicale (France), Université de Paris, Ministère des Solidarités et de la Santé (France), National Health and Medical Research Council (Australia), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Cabildo de Tenerife, Fondation Bettencourt Schueller, Estonian Research Council, Michailidis, Eleftherios, García-Prat, Marina, Paul, Stephanie, Metz, Christine N., Barreiros, Lucila, Domínguez-Garrido, Elena, Vidigal, Mateus, Beek, Diederik van der, Stepanovskyy, Yuriy, Tangye, Stuart G., Quintana-Murci, Lluis, Kan, Nelli, Nussenzweig, Michel C., Baris, Hagit N., Dyer, Adam, Bourke, Nollaig, Vinh, Donald C., Spaan, András N., Fellay, Jacques, Mane, Shrikant M., Anderson, MarK S., Andreakos, Evangelos, Haljasmägi, Liis, Mogensen, Trine, Lamballerie, Xavier de, Soler-Palacín, Pere, Martínez-Picado, Javier, Gregersen, Peter K., Rodríguez-Gallego, Carlos, Notarangelo, Luigi D., Su, Helen C., Prost, Nicolas de, Amador-Borrero, Blanco, Troya, Jesús, Rivière, Jacques G., Gentile, Stephanie, Rosen, Lindsey B., Tharaux, Pierre-Louis, Stépanian, Alain, Mégarbane, Bruno, Heath, James R., Franco, José Luis, Anaya, Juan Manuel, Snow, Andrew L., Holland, Steven M., Biggs, Catherine M., Moncada-Velez, Marcela, Planas, Anna M., Nussbaum, Robert, Bousfiha, Ahmed Aziz, Ramírez-Santana, Carolina, Intensive care medicine, Internal medicine, AII - Infectious diseases, Pulmonary medicine, ACS - Pulmonary hypertension & thrombosis, Pathology, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, Amsterdam Neuroscience - Complex Trait Genetics, ACS - Diabetes & metabolism, Amsterdam Cardiovascular Sciences, Radiology and nuclear medicine, AMS - Rehabilitation & Development, VU University medical center, Laboratory Medicine, Amsterdam Neuroscience - Neurodegeneration, Amsterdam Neuroscience - Neuroinfection & -inflammation, Anesthesiology, APH - Quality of Care, ACS - Heart failure & arrhythmias, Özçelik, Tayfun, Children's Hospital, HUS Children and Adolescents, Clinicum, Department of Medicine, Infektiosairauksien yksikkö, HUS Inflammation Center, Admin, Oskar, Identification des défauts monogéniques de l'immunité responsables des formes sévères de COVID-19 chez les patients précédemment en bonne santé - - GENCOVID2020 - ANR-20-COVI-0003 - COVID-19 - VALID, Analyse multi-omique de l'immunité anti-virale: de l'identification des circuits biologiques pertinents à la découverte de défauts monogéniques héréditaires de l'immunité chez les patients avec infections virales sévères - - GENVIR2020 - ANR-20-CE93-0003 - AAPG2020 - VALID, Bases génétiques et immunologiques des auto-anticorps contre les interférons de type I prédisposant aux formes sévères de COVID-19. - - AABIFNCOV2020 - ANR-20-CO11-0001 - COVID-19 - VALID, Program Initiative d’Excellence - IdEx Bordeaux (ANR-10-IDEX- 003-02) - INCOMING, CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Henri Mondor, Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), INSERM U1059, SAINBIOSE - Santé, Ingénierie, Biologie, Saint-Etienne (SAINBIOSE-ENSMSE), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Parasitologie - Mycologie [CHU Pitié-Salpétrière], CIC Saint Etienne, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Nord (Saint Etienne), Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires (RNMCD - U1011), Physiopathologie de l'immunodépression associée aux réponses inflammatoires systémiques - EA 7426 (PI3), École pratique des hautes études (EPHE), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Neurology, ANS - Neuroinfection & -inflammation, Graduate School, Infectious diseases, Center of Experimental and Molecular Medicine, APH - Aging & Later Life, APH - Global Health, AII - Amsterdam institute for Infection and Immunity, APH - Health Behaviors & Chronic Diseases, Global Health, APH - Methodology, APH - Digital Health, APH - Personalized Medicine, ACS - Microcirculation, Bastard, P, Gervais, A, Le Voyer, T, Rosain, J, Philippot, Q, Manry, J, Michailidis, E, Hoffmann, H, Eto, S, Garcia-Prat, M, Bizien, L, Parra-Martínez, A, Yang, R, Haljasmägi, L, Migaud, M, Särekannu, K, Maslovskaja, J, de Prost, N, Tandjaoui-Lambiotte, Y, Luyt, C, Amador-Borrero, B, Gaudet, A, Poissy, J, Morel, P, Richard, P, Cognasse, F, Troya, J, Trouillet-Assant, S, Belot, A, Saker, K, Garçon, P, Rivière, J, Lagier, J, Gentile, S, Rosen, L, Shaw, E, Morio, T, Tanaka, J, Dalmau, D, Tharaux, P, Sene, D, Stepanian, A, Megarbane, B, Triantafyllia, V, Fekkar, A, Heath, J, Franco, J, Anaya, J, Solé-Violán, J, Imberti, L, Biondi, A, Bonfanti, P, Castagnoli, R, Delmonte, O, Zhang, Y, Snow, A, Holland, S, Biggs, C, Moncada-Vélez, M, Arias, A, Lorenzo, L, Boucherit, S, Coulibaly, B, Anglicheau, D, Planas, A, Haerynck, F, Duvlis, S, Nussbaum, R, Ozcelik, T, Keles, S, Bousfiha, A, El Bakkouri, J, Ramirez-Santana, C, Paul, S, Pan-Hammarström, Q, Hammarström, L, Dupont, A, Kurolap, A, Metz, C, Aiuti, A, Casari, G, Lampasona, V, Ciceri, F, Barreiros, L, Dominguez-Garrido, E, Vidigal, M, Zatz, M, van de Beek, D, Sahanic, S, Tancevski, I, Stepanovskyy, Y, Boyarchuk, O, Nukui, Y, Tsumura, M, Vidaur, L, Tangye, S, Burrel, S, Duffy, D, Quintana-Murci, L, Klocperk, A, Kann, N, Shcherbina, A, Lau, Y, Leung, D, Coulongeat, M, Marlet, J, Koning, R, Reyes, L, Chauvineau-Grenier, A, Venet, F, Monneret, G, Nussenzweig, M, Arrestier, R, Boudhabhay, I, Baris-Feldman, H, Hagin, D, Wauters, J, Meyts, I, Dyer, A, Kennelly, S, Bourke, N, Halwani, R, Sharif-Askari, N, Dorgham, K, Sallette, J, Sedkaoui, S, Alkhater, S, Rigo-Bonnin, R, Morandeira, F, Roussel, L, Vinh, D, Ostrowski, S, Condino-Neto, A, Prando, C, Bonradenko, A, Spaan, A, Gilardin, L, Fellay, J, Lyonnet, S, Bilguvar, K, Lifton, R, Mane, S, Anderson, M, Boisson, B, Béziat, V, Zhang, S, Vandreakos, E, Hermine, O, Pujol, A, Peterson, P, Mogensen, T, Rowen, L, Mond, J, Debette, S, de Lamballerie, X, Duval, X, Mentré, F, Zins, M, Soler-Palacin, P, Colobran, R, Gorochov, G, Solanich, X, Susen, S, Martinez-Picado, J, Raoult, D, Vasse, M, Gregersen, P, Piemonti, L, Rodríguez-Gallego, C, Notarangelo, L, Su, H, Kisand, K, Okada, S, Puel, A, Jouanguy, E, Rice, C, Tiberghien, P, Zhang, Q, Cobat, A, Abel, L, Casanova, J, Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Laboratory of Human Genetics of Infectious Diseases (Necker Branch - INSERM U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), HGID Lab, COVID Clinicians, COVID-STORM Clinicians, NIAID Immune Response to COVID Group, NH-COVAIR Study Group, Danish CHGE, Danish Blood Donor Study, St. James's Hospital, SARS CoV2 Interest group, French COVID Cohort Study Group, Imagine COVID-Group, Milieu Intérieur Consortium, CoV-Contact Cohort, Amsterdam UMC Covid-19, Biobank Investigators, COVID Human Genetic Effort, CONSTANCES cohort, 3C-Dijon Study, Cerba Health-Care, Etablissement du Sang study group, Bigio, B., Boucherit, S., de la Chapelle, A., Chen, J., Chrabieh, M., Coulibaly, B., Liu, D., Nemirowskaya, Y., Cruz, I.M., Materna, M., Pelet, S., Seeleuthner, Y., Thibault, C., Liu, Z., Abad, J., Accordino, G., Achille, C., Aguilera-Albesa, S., Aguiló-Cucurull, A., Aiuti, A., Özkan, E.A., Darazam, I.A., Roblero Albisures, J.A., Aldave, J.C., Ramos, M.A., Khan, T.A., Aliberti, A., Nadji, S.A., Alkan, G., Alkhater, S.A., Allardet-Servent, J., Allende, L.M., Alonso-Arias, R., Alshahrani, M.S., Alsina, L., Alyanakian, M.A., Borrero, B.A., Amoura, Z., Antolí, A., Arrestier, R., Aubart, M., Auguet, T., Avramenko, I., Aytekin, G., Azot, A., Bahram, S., Bajolle, F., Baldanti, F., Baldolli, A., Ballester, M., Feldman, H.B., Barrou, B., Barzagh, F., Basso, S., Bayhan, G.I., Belot, A., Bezrodnik, L., Bilbao, A., Blanchard-Rohner, G., Blanco, I., Blandinières, A., Blázquez-Gamero, D., Bleibtreu, A., Bloomfield, M., Bolivar-Prados, M., Bondarenko, A., Borghesi, A., Borie, R., Botdhlo-Nevers, E., Bousfiha, A.A., Bousquet, A., Boutolleau, D., Bouvattier, C., Boyarchuk, O., Bravais, J., Briones, M.L., Brunner, M.E., Bruno, R., Bueno, MRP, Bukhari, H., Bustamante, J., Cáceres Agra, J.J., Capra, R., Carapito, R., Carrabba, M., Casari, G., Casasnovas, C., Caseris, M., Cassaniti, I., Castelle, M., Castelli, F., de Vera, M.C., Castro, M.V., Catherinot, E., Celik, J.B., Ceschi, A., Chalumeau, M., Charbit, B., Cheng, M.P., Clavé, P., Clotet, B., Codina, A., Cohen, Y., Colobran, R., Comarmond, C., Combes, A., Comoli, P., Corsico, A.G., Coşkuner, T., Cvetkovski, A., Cyrus, C., Dalmau, D., Danion, F., Darley, D.R., Das, V., Dauby, N., Dauger, S., De Munter, P., de Pontual, L., Dehban, A., Delplancq, G., Demoule, A., Desguerre, I., Di Sabatino, A., Diehl, J.L., Dobbelaere, S., Domínguez-Garrido, E., Dubost, C., Ekwall, O., Bozdemir, Ş.E., Elnagdy, M.H., Emiroglu, M., Endo, A., Erdeniz, E.H., Aytekin, S.E., Lasa, MPE, Euvrard, R., Fabio, G., Faivre, L., Falck, A., Fartoukh, M., Faure, M., Arquero, M.F., Ferrer, R., Ferreres, J., Flores, C., Francois, B., Fumadó, V., Fung, KSC, Fusco, F., Gagro, A., Solis, B.G., Gaussem, P., Gayretli, Z., Gil-Herrera, J., Gilardin, L., Gatineau, A.G., Girona-Alarcón, M., Cifuentes Godínez, K.A., Goffard, J.C., Gonzales, N., Gonzalez-Granado, L.I., González-Montelongo, R., Guerder, A., Gülhan, B., Gumucio, V.D., Hanitsch, L.G., Gunst, J., Gut, M., Hadjadj, J., Haerynck, F., Halwani, R., Hammarström, L., Hancerli, S., Hariyan, T., Hatipoglu, N., Heppekcan, D., Hernandez-Brito, E., Ho, P.K., Holanda-Peña, M.S., Horcajada, J.P., Hraiech, S., Humbert, L., Hung, IFN, Iglesias, A.D., Íñigo-Campos, A., Jamme, M., Arranz, M.J., Jimeno, M.T., Jordan, I., Yüksek, S.K., Kara, Y.B., Karahan, A., Karbuz, A., Yasar, K.K., Kasapcopur, O., Kashimada, K., Keles, S., Demirkol, Y.K., Kido, Y., Kizil, C., Kılıç, A.O., Klocperk, A., Koutsoukou, A., Król, Z.J., Ksouri, H., Kuentz, P., Kwan, AMC, Kwan, YWM, Kwok, JSY, Lagier, J.C., Lam, DSY, Lampropoulou, V., Lanternier, F., Lau, Y.L., Le Bourgeois, F., Leo, Y.S., Lopez, R.L., Leung, D., Levin, M., Levy, M., Lévy, R., Li, Z., Lilleri, D., Lima, EJAB, Linglart, A., López-Collazo, E., Lorenzo-Salazar, J.M., Louapre, C., Lubetzki, C., Lung, K.C., Luyt, C.E., Lye, D.C., Magnone, C., Mansouri, D., Marchioni, E., Marioli, C., Marjani, M., Marques, L., Pereira, J.M., Martín-Nalda, A., Pueyo, D.M., Martinez-Picado, J., Marzana, I., Mata-Martínez, C., Mathian, A., Matos, L.R., Matthews, G.V., Mayaux, J., McLaughlin-Garcia, R., Meersseman, P., Mège, J.L., Mekontso-Dessap, A., Melki, I., Meloni, F., Meritet, J.F., Merlani, P., Akcan, Ö.M., Meyts, I., Mezidi, M., Migeotte, I., Millereux, M., Million, M., Mirault, T., Mircher, C., Mirsaeidi, M., Mizoguchi, Y., Modi, B.P., Mojoli, F., Moncomble, E., Melián, A.M., Martinez, A.M., Morandeira, F., Morange, P.E., Mordacq, C., Morelle, G., Mouly, S.J., Muñoz-Barrera, A., Nafati, C., Nagashima, S., Nakagama, Y., Neven, B., Neves, J.F., Ng, L.F., Ng, Y.Y., Nielly, H., Medina, Y.N., Cuadros, E.N., Ocejo-Vinyals, J.G., Okamoto, K., Oualha, M., Ouedrani, A., Özçelik, T., Ozkaya-Parlakay, A., Pagani, M., Pan-Hammarström, Q., Papadaki, M., Parizot, C., Parola, P., Pascreau, T., Paul, S., Paz-Artal, E., Pedraza, S., González Pellecer, N.C., Pellegrini, S., de Diego, R.P., Pérez-Fernández, X.L., Philippe, A., Philippot, Q., Picod, A., de Chambrun, M.P., Piralla, A., Planas-Serra, L., Ploin, D., Poissy, J., Poncelet, G., Poulakou, G., Pouletty, M.S., Pourshahnazari, P., Qiu-Chen, J.L., Quentric, P., Rambaud, T., Raoult, D., Raoult, V., Rebillat, A.S., Redin, C., Resmini, L., Ricart, P., Richard, J.C., Rigo-Bonnin, R., Rivet, N., Rivière, J.G., Rocamora-Blanch, G., Rodero, M.P., Rodrigo, C., Rodriguez, L.A., Rodriguez-Gallego, C., Rodriguez-Palmero, A., Romero, C.S., Rothenbuhler, A., Roux, D., Rovina, N., Rozenberg, F., Ruch, Y., Ruiz, M., Ruiz Del Prado, M.Y., Ruiz-Rodriguez, J.C., Sabater-Riera, J., Saks, K., Salagianni, M., Sanchez, O., Sánchez-Montalvá, A., Sánchez-Ramón, S., Schidlowski, L., Schluter, A., Schmidt, J., Schmidt, M., Schuetz, C., Schweitzer, C.E., Scolari, F., Sediva, A., Seijo, L., Seminario, A.G., Sene, D., Seng, P., Senoglu, S., Seppänen, M., Llovich, A.S., Shahrooei, M., Shcherbina, A., Siguret, V., Siouti, E., Smadja, D.M., Smith, N., Sobh, A., Solanich, X., Solé-Violán, J., Soler, C., Soler-Palacín, P., Sözeri, B., Stella, G.M., Stepanovskiy, Y., Stoclin, A., Taccone, F., Tandjaoui-Lambiotte, Y., Taupin, J.L., Tavernier, S.J., Tello, L.V., Terrier, B., Thiery, G., Thorball, C., Thorn, K., Thumerelle, C., Tipu, I., Tolstrup, M., Tomasoni, G., Toubiana, J., Alvarez, J.T., Triantafyllia, V., Trouillet-Assant, S., Troya, J., Tsang, OTY, Tserel, L., Tso, EYK, Tucci, A., Tüter Öz, Ş.K., Ursini, M.V., Utsumi, T., Uzunhan, Y., Vabres, P., Valencia-Ramos, J., Van Den Rym, A.M., Vandernoot, I., Velez-Santamaria, V., Zuniga Veliz, S.P., Vidigal, M.C., Viel, S., Vilain, C., Vilaire-Meunier, M.E., Villar-García, J., Vincent, A., Vogt, G., Voiriot, G., Volokha, A., Vuotto, F., Wauters, E., Wauters, J., Wu, AKL, Wu, T.C., Yahşi, A., Yesilbas, O., Yildiz, M., Young, B.E., Yükselmiş, U., Zatz, M., Zecca, M., Zuccaro, V., Jens, V.P., Lambrecht, B.N., Eva, V.B., Cédric, B., Levi, H., Eric, H., Bauters, F., De Clercq, J., Cathérine, H., Hans, S., Leslie, N., Florkin, B., Boulanger, C., Vanderlinden, D., Foti, G., Bellani, G., Citerio, G., Contro, E., Pesci, A., Valsecchi, M.G., Cazzaniga, M., Danielson, J.J., Dobbs, K., Kashyap, A., Ding, L., Dalgard, C.L., Sottini, A., Quaresima, V., Quiros-Roldan, E., Rossi, C., Bettini, L.R., D'Angio', M., Beretta, I., Montagna, D., Licari, A., Marseglia, G.L., Batten, I., Reddy, C., McElheron, M., Noonan, C., Connolly, E., Fallon, A., Storgaard, M., Jørgensen, S., Erikstrup, C., Pedersen, O.B., Sørensen, E., Mikkelsen, S., Dinh, K.M., Larsen, MAH, Paulsen, I.W., Von Stemann, J.H., Hansen, M.B., Ostrowski, S.R., Townsend, L., Cheallaigh, C.N., Bergin, C., Martin-Loeches, I., Dunne, J., Conlon, N., Bourke, N., O'Farrelly, C., Abel, L., Allavena, C., Andrejak, C., Angoulvant, F., Azoulay, C., Bachelet, D., Bartoli, M., Basmaci, R., Behilill, S., Beluze, M., Benech, N., Benkerrou, D., Bhavsar, K., Bitker, L., Bouadma, L., Bouscambert-Duchamp, M., Paz, P.C., Cervantes-Gonzalez, M., Chair, A., Chirouze, C., Coelho, A., Cordel, H., Couffignal, C., Couffin-Cadiergues, S., d'Ortenzio, E., De Montmollin, E., Debard, A., Debray, M.P., Deplanque, D., Descamps, D., Desvallée, M., Diallo, A., Diouf, A., Dorival, C., Dubos, F., Duval, X., Eloy, P., Enouf, V., Epaulard, O., Esperou, H., Esposito-Farese, M., Etienne, M., Garot, D., Gault, N., Gaymard, A., Ghosn, J., Gigante, T., Gilg, M., Goehringer, F., Guedj, J., Hoctin, A., Hoffmann, I., Houas, I., Hulot, J.S., Jaafoura, S., Kafif, O., Kaguelidou, F., Kali, S., Kerroumi, Y., Khalil, A., Khan, C., Kimmoun, A., Laine, F., Laouénan, C., Laribi, S., Le, M., Le Bris, C., Le Gac, S., Le Hingrat, Q., Le Mestre, S., Le Nagard, H., Lemaignen, A., Lemee, V., Lescure, F.X., Letrou, S., Levy, Y., Lina, B., Lingas, G., Lucet, J.C., Machado, M., Malvy, D., Mambert, M., Manuel, A., Mentré, F., Meziane, A., Mouquet, H., Mullaert, J., Neant, N., Nguyen, D., Noret, M., Papadopoulos, A., Paul, C., Peiffer-Smadja, N., Peigne, V., Petrov-Sanchez, V., Peytavin, G., Pham, H., Picone, O., Piquard, V., Puéchal, O., Rosa-Calatrava, M., Rossignol, B., Rossignol, P., Roy, C., Schneider, M., Su, R., Tardivon, C., Tellier, M.C., Téoulé, F., Terrier, O., Timsit, J.F., Tual, C., Tubiana, S., Van Der Werf, S., Vanel, N., Veislinger, A., Visseaux, B., Wiedemann, A., Yazdanpanah, Y., Annereau, J.P., Briseño-Roa, L., Gribouval, O., Pelet, A., Alcover, A., Aschard, H., Bousso, P., Brodin, P., Bruhns, P., Cerf-Bensussan, N., Cumano, A., D'Enfert, C., Deriano, L., Dillies, M.A., Di Santo, J., Dromer, F., Eberl, G., Enninga, J., Fellay, J., Gomperts-Boneca, I., Hasan, M., Hedestam, G.K., Hercberg, S., Ingersoll, M.A., Lantz, O., Kenny, R.A., Ménager, M., Michel, F., Patin, E., Rausell, A., Rieux-Laucat, F., Rogge, L., Fontes, M., Sakuntabhai, A., Schwartz, O., Schwikowski, B., Shorte, S., Tangy, F., Toubert, A., Touvier, M., Ungeheuer, M.N., Zimmer, C., Albert, M.L., Duffy, D., Quintana-Murci, L., Alavoine, L., Behillil, S., Burdet, C., Charpentier, C., Dechanet, A., Ecobichon, J.L., Frezouls, W., Houhou, N., Lehacaut, J., Manchon, P., Nouroudine, M., Quintin, C., Thy, M., van der Werf, S., Vignali, V., Chahine, A., Waucquier, N., Migaud, M.C., Djossou, F., Mergeay-Fabre, M., Lucarelli, A., Demar, M., Bruneau, L., Gérardin, P., Maillot, A., Payet, C., Laviolle, B., Paris, C., 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Hans-Heinrich [0000-0003-0554-0244], Eto, Shohei [0000-0002-2885-7490], García-Prat, Marina [0000-0001-5387-1908], Bizien, Lucy [0000-0001-9163-9122], Parra-Martínez, Alba [0000-0002-9564-8912], Dorgham, Karim [0000-0001-9539-3203], Alkhater, Suzan [0000-0001-7315-6581], Rigo-Bonnin, Raúl [0000-0001-5511-074X], Roussel, Lucie [0000-0001-5355-702X], Vinh, Donald C. [0000-0003-1347-7767], Ostrowski, Sisse Rye [0000-0001-5288-3851], Condino-Neto, Antonio [0000-0002-1069-3117], Prando, Carolina [0000-0002-9570-9770], Spaan, András N. [0000-0001-5981-7259], Gilardin, Laurent [0000-0001-9212-0859], Yang, Rui [0000-0003-4427-2158], Fellay, Jacques [0000-0002-8240-939X], Bilguvar, Kaya [0000-0002-7313-7652], Mane, Shrikant M. [0000-0002-3267-5139], Anderson, MarK S. [0000-0002-3093-4758], Boisson, Bertrand [0000-0001-5240-3555], Béziat, Vivien [0000-0002-4020-824X], Andreakos, Evangelos [0000-0001-5536-1661], Hermine, Olivier [0000-0003-2574-3874], Pujol, Aurora [0000-0002-9606-0600], Peterson, Pärt [0000-0001-6755-791X], Haljasmägi, Liis [0000-0001-7162-9808], Mogensen, Trine [0000-0002-1853-9704], Lamballerie, Xavier de [0000-0001-7895-2720], Zins, Marie [0000-0002-4540-4282], Soler-Palacín, Pere [0000-0002-0346-5570], Colobran, Roger [0000-0002-5964-536X], Gorochov, Guy [0000-0003-2097-9677], Solanich, Xavier [0000-0002-2572-2187], Susen, Sophie [0000-0001-5953-163X], Martínez-Picado, Javier [0000-0002-4916-2129], Gregersen, Peter K. [0000-0003-1613-1518], Migaud, Mélanie [0000-0003-3062-1214], Piemonti, Lorenzo [0000-0002-2172-2198], Rodríguez-Gallego, Carlos [0000-0002-4344-8644], Notarangelo, Luigi D. [0000-0002-8335-0262], Su, Helen C. [0000-0002-5582-9110], Kisand, Kai [0000-0002-5426-4648], Okada, Satoshi [0000-0002-4622-5657], Puel, Anne [0000-0003-2603-0323], Jouanguy, Emmanuelle [0000-0002-7358-9157], Tiberghien, Pierre [0000-0002-9310-8322], Zhang, Qian [0000-0002-9040-3289], Särekannu, Karita [0000-0002-5984-668X], Cobat, Aurélie [0000-0001-7209-6257], Abel, Laurent [0000-0001-7016-6493], Casanova, Jean-Laurent [0000-0002-7782-4169], Prost, Nicolas de [0000-0002-4833-4320], Tandjaoui-Lambiotte, Yacine [0000-0003-1123-4788], Luyt, Charles-Edouard [0000-0001-7424-2705], Amador-Borrero, Blanco [0000-0001-6170-8721], Poissy, Julien [0000-0001-6017-5353], Richard, Pascale [0000-0003-1864-3824], Cognasse, Fabrice [0000-0001-8041-928X], Troya, Jesús [0000-0001-7323-114X], Trouillet-Assant, Sophie [0000-0001-6439-4705], Belot, Alexandre [0000-0003-4902-5332], Saker, Kahina [0000-0001-8825-5400], Rivière, Jacques G. [0000-0003-1055-2063], Gentile, Stephanie [0000-0003-3858-9503], Rosen, Lindsey B. [0000-0001-5894-3878], Shaw, Elana [0000-0001-9265-8026], Dalmau, David [0000-0003-1936-478X], Tharaux, Pierre-Louis [0000-0002-6062-5905], Stépanian, Alain [0000-0002-2942-0901], Mégarbane, Bruno [0000-0002-2522-2764], Triantafyllia, Vasiliki [0000-0001-5832-4014], Fekkar, Arnaud [0000-0001-9954-075X], Heath, James R. [0000-0001-5356-4385], Franco, José Luis [0000-0001-5664-6415], Anaya, Juan Manuel [0000-0002-6444-1249], Imberti, Luisa[0000-0002-2075-8391], Bonfanti, Paolo [0000-0001-7289-8823], Castagnoli, Riccardo [0000-0003-0029-9383], Snow, Andrew L. [0000-0002-8728-6691], Holland, Steven M. [0000-0003-3207-5464], Biggs, Catherine M. [0000-0002-4363-2660], Moncada-Velez, Marcela [0000-0002-3073-5345], Arias, Andrés Augusto [0000-0002-9478-8403], Lorenzo, Lazaro [0000-0001-6648-8684], Boucherit, Soraya [0000-0002-8819-7594], Anglicheau, Dany [0000-0001-5793-6174], Planas, Anna M. [0000-0002-6147-1880], Haerynck, Filomeen [0000-0001-9161-7361], Duvlis, Sotirija [0000-0001-8587-7386], Nussbaum, Robert [0000-0003-3445-8880], Bousfiha, Ahmed Aziz [0000-0002-5011-9873], El Bakkouri, Jalila [0000-0003-2303-3369], Ramírez-Santana, Carolina [0000-0003-2137-4899], Paul, Stephanie [0000-0002-8830-4273], Pan-Hammarström, Qiang [0000-0003-1990-8804], Hammarström, Lennart [0000-0002-8635-9609], Dupont, Annabelle [0000-0002-1554-9931], Kurolap, Alina [0000-0002-7005-3621], Metz, Christine N. [0000-0002-1013-1691], Aiuti, Alessandro [0000-0002-5398-1717], Casari, Giorgio [0000-0002-0115-8980], Lampasona, Vito [0000-0001-5162-8445], Ciceri, Fabio [0000-0003-0873-0123], Barreiros, Lucila [0000-0002-9818-2345], Domínguez-Garrido, Elena [0000-0002-2066-0511], Vidigal, Mateus [0000-0002-8895-652X], Zatz, Mayana [0000-0003-3970-8025], Beek, Diederik van der [0000-0002-4571-044X], Stepanovskyy, Yuriy [0000-0001-6339-5490], Boyarchuk, Oksana [0000-0002-1234-0040], Nukui, Yoko [0000-0002-6123-5212], Vidaur, Loreto [0000-0002-6720-4900], Tangye, Stuart G. [0000-0002-5360-5180], Burrel, Sonia [0000-0002-7783-2601], Duffy, Darragh [0000-0002-8875-2308], Quintana-Murci, Lluis [0000-0003-2429-6320], Klocperk, Adam [0000-0002-1526-4557], Kan, Nelli [0000-0003-3564-6496], Shcherbina, Anna [0000-0002-3113-4939], Lau, Yu-Lung [0000-0002-4780-0289], Leung, Daniel [0000-0002-9360-6233], Coulongeat, Matthieu [0000-0003-1986-3546], Marlet, Julien [0000-0002-8645-8703], Koning, Rutger [0000-0003-3128-5072], Reyes, Luis Felipe [0000-0003-1172-6539], Venet, Fabienne [0000-0003-0462-4235], Monneret, Guillaume [0000-0002-9961-5739], Nussenzweig, Michel C. [0000-0003-0592-8564], Baris, Hagit N. [0000-0003-4065-7560], Hagin, David [0000-0003-2702-1031], Wauters, Joost [0000-0002-5983-3897], Meyts, Isabelle [0000-0003-1214-0302], Dyer, Adam [0000-0003-1356-510X], Bourke, Nollaig [0000-0003-4313-6859], Halwani, Rabih [0000-0002-6516-7771], and Sharif-Askari, Narjes Saheb [0000-0003-0482-6777]
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Interferon Type I/immunology ,AUTOIMMUNITY ,[SDV]Life Sciences [q-bio] ,Interferó ,Gastroenterology ,COVID-19 (Malaltia) ,Immunoglobulin G ,Basic medicine ,0302 clinical medicine ,Medicine and Health Sciences ,80 and over ,Immunologia ,Young adult ,Child ,Neutralizing ,MYASTHENIA-GRAVIS PATIENTS ,ComputingMilieux_MISCELLANEOUS ,Aged, 80 and over ,0303 health sciences ,education.field_of_study ,biology ,General Medicine ,Middle Aged ,3. Good health ,COVID-19/immunology ,Settore MED/03 ,030220 oncology & carcinogenesis ,Child, Preschool ,Interferon Type I ,Antibody ,medicine.symptom ,INTERFERON ,Adult ,medicine.medical_specialty ,Adolescent ,Critical Illness ,Immunology ,Population ,Aged ,Antibodies, Neutralizing ,Autoantibodies ,COVID-19 ,Case-Control Studies ,Humans ,Infant ,Infant, Newborn ,Interferon-alpha ,Young Adult ,Alpha interferon ,Immunoglobulins ,IMMUNITY ,Asymptomatic ,PATIENT ,03 medical and health sciences ,Internal medicine ,medicine ,Preschool ,education ,Antibodies, Neutralizing/blood ,HOMENS ,030304 developmental biology ,ANTINUCLEAR ,business.industry ,Autoantibody ,Case-control study ,Antibodies, Neutralizing/immunology ,Autoantibodies/blood ,Autoantibodies/immunology ,COVID-19/mortality ,Immunoglobulin G/blood ,Immunoglobulin G/immunology ,Interferon-alpha/immunology ,Newborn ,DISTINCT FUNCTIONS ,ALPHA ,[SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie ,3121 General medicine, internal medicine and other clinical medicine ,ANTIBODIES ,biology.protein ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,business ,Immunoglobulines - Abstract
Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/ml; in plasma diluted 1:10) of IFN-α and/or IFN-ω are found in about 10% of patients with critical COVID-19 (coronavirus disease 2019) pneumonia but not in individuals with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-α and/or IFN-ω (100 pg/ml; in 1:10 dilutions of plasma) in 13.6% of 3595 patients with critical COVID-19, including 21% of 374 patients >80 years, and 6.5% of 522 patients with severe COVID-19. These antibodies are also detected in 18% of the 1124 deceased patients (aged 20 days to 99 years; mean: 70 years). Moreover, another 1.3% of patients with critical COVID-19 and 0.9% of the deceased patients have auto-Abs neutralizing high concentrations of IFN-β. We also show, in a sample of 34,159 uninfected individuals from the general population, that auto-Abs neutralizing high concentrations of IFN-α and/or IFN-ω are present in 0.18% of individuals between 18 and 69 years, 1.1% between 70 and 79 years, and 3.4% >80 years. Moreover, the proportion of individuals carrying auto-Abs neutralizing lower concentrations is greater in a subsample of 10,778 uninfected individuals: 1% of individuals 80 years. By contrast, auto-Abs neutralizing IFN-β do not become more frequent with age. Auto-Abs neutralizing type I IFNs predate SARS-CoV-2 infection and sharply increase in prevalence after the age of 70 years. They account for about 20% of both critical COVID-19 cases in the over 80s and total fatal COVID-19 cases., The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH) (R01AI088364), the National Center for Advancing Translational Sciences (NCATS), NIH Clinical and Translational Science Awards (CTSA) program (UL1 TR001866), a Fast Grant from Emergent Ventures, Mercatus Center at George Mason University, the Yale Center for Mendelian Genomics and the GSP Coordinating Center funded by the National Human Genome Research Institute (NHGRI) (UM1HG006504 and U24HG008956), the Yale High Performance Computing Center (S10OD018521), the Fisher Center for Alzheimer’s Research Foundation, the Meyer Foundation, the JPB Foundation, the French National Research Agency (ANR) under the “Investments for the Future” program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the French Foundation for Medical Research (FRM) (EQU201903007798), the FRM and ANR GENCOVID project (ANR-20-COVI-0003), ANRS Nord-Sud (ANRS-COV05), ANR GENVIR (ANR-20-CE93-003) and ANR AABIFNCOV (ANR-20-CO11-0001) projects, the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 824110 (EASI-Genomics), the Square Foundation, Grandir–Fonds de solidarité pour l’Enfance, the Fondation du Souffle, the SCOR Corporate Foundation for Science, Institut National de la Santé et de la Recherche Médicale (INSERM), REACTing-INSERM; and the University of Paris. P.B. was supported by the FRM (EA20170638020). P.B., J.R., and T.L.V. were supported by the MD-PhD program of the Imagine Institute (with the support of the Fondation Bettencourt Schueller). Work in the Laboratory of Virology and Infectious Disease was supported by the NIH (P01AI138398-S1, 2U19AI111825, and R01AI091707-10S1), a George Mason University Fast Grant, and the G. Harold and Leila Y. Mathers Charitable Foundation. The French COVID Cohort study group was sponsored by INSERM and supported by the REACTing consortium and by a grant from the French Ministry of Health (PHRC 20-0424). The Cov-Contact Cohort was supported by the REACTing consortium, the French Ministry of Health, and the European Commission (RECOVER WP 6). This work was also partly supported by the Intramural Research Program of the NIAID and NIDCR, NIH (grants ZIA AI001270 to L.D.N. and 1ZIAAI001265 to H.C.S.). This program is supported by the Agence Nationale de la Recherche (reference ANR-10-LABX-69-01). K.K.’s group was supported by the Estonian Research Council grants PRG117 and PRG377. R.H. was supported by an Al Jalila Foundation Seed Grant (AJF202019), Dubai, UAE, and a COVID-19 research grant (CoV19-0307) from the University of Sharjah, UAE. S.G.T. is supported by Investigator and Program Grants awarded by the National Health and Medical Research Council of Australia and a UNSW Sydney COVID Rapid Response Initiative Grant. L.I. reported funding from Regione Lombardia, Italy (project “Risposta immune in pazienti con COVID-19 e co-morbidità”). L.I. and G. L. Marseglia reported funding from Regione Lombardia, Italy (project Risposta immune in pazienti con COVID-19 e co-morbidità). This research was partially supported by the Instituto de Salud Carlos III (COV20/0968). J.R.H. reported funding from Biomedical Advanced Research and Development Authority HHSO10201600031C. S.O. reports funding Research Program on Emerging and Re-emerging Infectious Diseases from Japan Agency for Medical Research and Development, AMED (grant number JP20fk0108531). G.G. was supported by ANR Flash COVID-19 program and SARS-CoV-2 Program of the Faculty of Medicine from Sorbonne University iCOVID programs. The Three-City (3C) Study was conducted under a partnership agreement among the INSERM, the Victor Segalen Bordeaux 2 University, and Sanofi-Aventis. The Fondation pour la Recherche Médicale funded the preparation and initiation of the study. The 3C Study was also supported by the Caisse Nationale d’Assurance Maladie des Travailleurs Salariés, Direction générale de la Santé, Mutuelle Générale de l’Education Nationale (MGEN), Institut de la Longévité, Conseils Régionaux of Aquitaine and Bourgogne, Fondation de France, and Ministry of Research–INSERM Programme “Cohortes et collections de données biologiques”. S. Debette was supported by the University of Bordeaux Initiative of Excellence. P.K.G. reports funding from the National Cancer Institute, NIH, under contract no. 75N91019D00024, task order no. 75N91021F00001. J.W. is supported by an FWO Fundamental Clinical Mandate (1833317N). Sample processing at IrsiCaixa was possible thanks to the crowdfunding initiative YoMeCorono. Work at Vall d’Hebron was also partly supported by research funding from Instituto de Salud Carlos III grant PI17/00660 cofinanced by the European Regional Development Fund (ERDF). C.R.-G. and colleagues of the Canarian Health System Sequencing Hub were supported by the Instituto de Salud Carlos III (COV20_01333 and COV20_01334, Spanish Ministry for Science and Innovation RTC-2017-6471-1; AEI/FEDER, UE), Fundación DISA (OA18/017 and OA20/024), and Cabildo Insular de Tenerife (CGIEU0000219140 and “Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19”). C.M.B. is supported by a MSFHR Health Professional-Investigator Award. P.Q.H. and L.H. were funded by the European Union’s Horizon 2020 research and innovation program (ATAC, 101003650). Work at Y.-L.L.’s laboratory in the University of Hong Kong (HKU) was supported by the Society for the Relief of Disabled Children. MBBS/PhD study of D.L. in HKU was supported by the Croucher Foundation. J.L.F. was supported in part by the Coopération Scientifique France-Colciencias (ECOS-Nord/COLCIENCIAS/MEN/ICETEX (806-2018) and Colciencias contract 713-2016 (code 111574455633)]. A.K. was in part supported by grants NU20-05-00282 and NV18-05-00162 issued by the Czech Health Research Council and Ministry of Health, Czech Republic. L.P. was funded by Program Project COVID-19 OSR-UniSR and Ministero della Salute (COVID-2020-12371617). I.M. is a Senior Clinical Investigator at the Research Foundation–Flanders and is supported by the CSL Behring Chair of Primary Immunodeficiencies; by the KU Leuven C1 grant C16/18/007; by a VIB-GC PID grant; by the FWO frants G0C8517N, G0B5120N, and G0E8420N; and by the Jeffrey Modell Foundation. I.M. has received funding under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 948959). E.A. received funding from the Hellenic Foundation for Research and Innovation (INTERFLU, no. 1574). M.Vi received funding from the São Paulo Research Foundation (FAPESP) (grant number 2020/09702-1) and JBS SA (grant number 69004). The NH-COVAIR study group consortium was supported by a grant from the Meath Foundation
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- 2021
139. Innate Immunity Mediated Inflammation and Beta Cell Function: Neighbors or Enemies?
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Antonio Citro, Francesco Campo, Erica Dugnani, Lorenzo Piemonti, Citro, A., Campo, F., Dugnani, E., and Piemonti, L.
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insulin secretion ,type 1 diabetes ,Mini Review ,Endocrinology, Diabetes and Metabolism ,Inflammation ,Biology ,lcsh:Diseases of the endocrine glands. Clinical endocrinology ,Endocrinology ,Insulin-Secreting Cells ,medicine ,Animals ,Humans ,Secretion ,innate immunity ,Tissue homeostasis ,Autoimmune disease ,lcsh:RC648-665 ,Innate immune system ,Acquired immune system ,medicine.disease ,Immunity, Innate ,cytokines ,Diabetes Mellitus, Type 1 ,inflammation ,Immunology ,Beta cell ,medicine.symptom ,Insulitis - Abstract
Type 1 diabetes (T1D) is still considered a huge burden because the available treatments are not effective in preventing the onset or progression of the disease. Recently, the idea that diabetes is an autoimmune disease mediated exclusively by T cells has been reshaped. In fact, T cells are not the only players with an active role in beta cell destruction. Macrophages and neutrophils, which physiologically reside in pancreatic tissue, can also participate in tissue homeostasis and damage by promoting innate immune responses and modulating inflammation. During the development of the pancreatic islet inflammation there is a strong interplay of both adaptive and innate immune cells, and the presence of innate immune cells has been demonstrated both in exocrine and endocrine pancreatic compartments during the earliest stages of insulitis. Innate immune cell populations secrete cytokines, which must be considered both as physiological and pathological mediators. In fact, it has been demonstrated that cytokines could regulate directly and indirectly insulin secretion and, simultaneously, trigger inflammatory reaction. Indeed, cytokines pathways could represent targets both to improve glucose metabolism and to prevent autoimmune damage. Concordantly, the combination of immunomodulatory strategies against both innate and adaptive immunity should be tested in the next future, as they can be more efficient to prevent or delay islet damage and T1D onset.
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- 2021
140. Young infants exhibit robust functional antibody responses and restrained IFN-γ production to SARS-CoV-2
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Kapil Gupta, Andrew D. Davidson, Michaela Gregorova, Adam Finn, Amy Thomas, Anu Goenka, Vito Lampasona, Holly Baum, Maia Kavanagh Williamson, Alice Halliday, Kathleen M Gillespie, Elizabeth Oliver, Barry Vipond, Emily Milodowski, Laura Rivino, Lorenzo Piemonti, Imre Berger, Mick Bailey, Ashley M. Toye, Alistair J K Williams, Peter Muir, Anna E. Long, Natalie D. Di Bartolo, Linda Wooldridge, Lea Knezevic, Jolanta Bernatoniene, Goenka, A., Halliday, A., Gregorova, M., Milodowski, E., Thomas, A., Williamson, M. K., Baum, H., Oliver, E., Long, A. E., Knezevic, L., Williams, A. J. K., Lampasona, V., Piemonti, L., Gupta, K., Di Bartolo, N., Berger, I., Toye, A. M., Vipond, B., Muir, P., Bernatoniene, J., Bailey, M., Gillespie, K. M., Davidson, A. D., Wooldridge, L., Rivino, L., and Finn, A.
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Adult ,Male ,Saliva ,T cell ,BrisSynBio ,Peripheral blood mononuclear cell ,General Biochemistry, Genetics and Molecular Biology ,Interferon-gamma ,Young Adult ,Immune system ,Immunity ,Report ,antibody ,Medicine ,Humans ,Functional ability ,Respiratory system ,biology ,business.industry ,Bristol BioDesign Institute ,Infant, Newborn ,COVID-19 ,Infant ,Covid19 ,infant ,immunity ,Immunoglobulin A ,medicine.anatomical_structure ,Immunoglobulin G ,Immunology ,Antibody Formation ,Spike Glycoprotein, Coronavirus ,biology.protein ,Leukocytes, Mononuclear ,Female ,Antibody ,business - Abstract
Severe COVID-19 appears rare in children. This is unexpected, especially in young infants, who are vulnerable to severe disease caused by other respiratory viruses. We evaluate convalescent immune responses in 4 infants under 3 months old with confirmed COVID-19 who presented with mild febrile illness, alongside their parents, and adult controls recovered from confirmed COVID-19. Although not statistically significant, compared to seropositive adults, infants have high serum levels of IgG and IgA to SARS-CoV-2 spike protein, with a corresponding functional ability to block SARS-CoV-2 cellular entry. Infants also exhibit robust saliva anti-spike IgG and IgA responses. Spike-specific IFN-γ production by infant peripheral blood mononuclear cells appears restrained, but the frequency of spike-specific IFN-γ- and/or TNF-α-producing T cells is comparable between infants and adults. On principal-component analysis, infant immune responses appear distinct from their parents. Robust functional antibody responses alongside restrained IFN-γ production may help protect infants from severe COVID-19., Graphical abstract, Goenka et al. demonstrate that the SARS-CoV-2 immune response of young infants appears distinct compared with their parents. They show that infants exhibit relatively high serum (and saliva) levels of anti-spike IgG associated with robust SARS-CoV-2 neutralization but restrained cellular spike-specific IFN-γ production.
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- 2021
141. Total pancreatectomy sequelae and quality of life: results of islet autotransplantation as a possible mitigation strategy
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Francesca Aleotti, Rita Nano, Gianpaolo Balzano, Massimo Falconi, Lorenzo Piemonti, Aleotti, F., Nano, R., Piemonti, L., Falconi, M., and Balzano, G.
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medicine.medical_specialty ,Total pancreatectomy ,medicine.medical_treatment ,Islets of Langerhans Transplantation ,Transplantation, Autologous ,Pancreatectomy ,Diabetes mellitus ,Pancreatitis, Chronic ,medicine ,Endocrine system ,Humans ,Islet transplantation ,Exocrine pancreatic insufficiency ,geography ,geography.geographical_feature_category ,business.industry ,Pancreatic islets ,medicine.disease ,Islet ,Autotransplantation ,Surgery ,medicine.anatomical_structure ,Treatment Outcome ,Quality of Life ,Pancreatitis ,Pancreas ,business ,Autologous - Abstract
Total pancreatectomy (TP) is a procedure weighed down not only by postoperative morbidity and mortality but also by long-term effects as a consequence of endocrine and exocrine pancreatic insufficiency. While the latter is now managed quite effectively with pancreatic enzyme replacement therapy, the former remains a challenge. The diabetes resulting after TP, with the complete loss of endogenous insulin and contraregulatory hormones, is characterized by important glycemic variations and is, therefore, frequently referred to as "brittle diabetes". One method to reduce the impact of brittle diabetes in patients undergoing TP is the re-infusion of autologous pancreatic islets isolated from the resected pancreas. Indications to islet autotransplantation (IAT), originally described for patients undergoing TP for chronic pancreatitis, have since been extended to selected patients with other benign and malignant diseases of pancreas. This review recaps on the literature regarding long-term postoperative complications, their impact on quality of life after TP and the role of IAT.
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- 2021
142. Inhibiting glycolysis rescues memory impairment in an intellectual disability Gdi1-null mouse
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Maja Malnar, Angela Bachi, Helena H. Chowdhury, Anemari Horvat, Patrizia D’Adamo, Antonia Gurgone, Saša Trkov Bobnar, Marko Muhič, Lorenzo Piemonti, Maria Lidia Mignogna, Michela Masetti, Jelena Velebit, Veronica Bianchi, Robert Zorec, Matjaž Stenovec, Alessia Mercalli, Katja Fink, Sara Belloli, Stefano Taverna, Maja Potokar, Marko Kreft, Rosa Maria Moresco, Nina Vardjan, Maddalena Ripamonti, Umberto Restuccia, D'Adamo, Patrizia, Horvat, Anemari, Gurgone, Antonia, Mignogna, Maria Lidia, Bianchi, Veronica, Masetti, Michela, Ripamonti, Maddalena, Taverna, Stefano, Velebit, Jelena, Malnar, Maja, Muhič, Marko, Fink, Katja, Bachi, Angela, Restuccia, Umberto, Belloli, Sara, Moresco, Rosa Maria, Mercalli, Alessia, Piemonti, Lorenzo, Potokar, Maja, Bobnar, Saša Trkov, Kreft, Marko, Chowdhury, Helena H, Stenovec, Matjaž, Vardjan, Nina, Zorec, R, D'Adamo, P, Horvat, A, Gurgone, A, Mignogna, M, Bianchi, V, Masetti, M, Ripamonti, M, Taverna, S, Velebit, J, Malnar, M, Muhic, M, Fink, K, Bachi, A, Restuccia, U, Belloli, S, Moresco, R, Mercalli, A, Piemonti, L, Potokar, M, Bobnar, S, Kreft, M, Chowdhury, H, Stenovec, M, and Vardjan, N
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0301 basic medicine ,CTX, context memory ,Male ,Endocrinology, Diabetes and Metabolism ,Glucose uptake ,Intellectual disability ,FRET, Förster Resonance Energy Transfer ,SV, synaptic vesicle ,XLID, X-linked intellectual disability ,Mice ,0302 clinical medicine ,Endocrinology ,Basic Science ,GDI1 knockout mice ,Aerobic glycolysis ,Astrocytes ,cAMP ,Glycolysis ,Gdi1 KO, full knockout of Gdi1 ,Cells, Cultured ,Guanine Nucleotide Dissociation Inhibitors ,NA, noradrenaline ,Mice, Knockout ,Cultured ,3-Cl-5-OH-BA, 3-chloro-5-hydroxybenzoic acid ,Animals ,Brain ,Deoxyglucose ,Down-Regulation ,Glucose ,Intellectual Disability ,Maze Learning ,Memory ,Memory Disorders ,[18F]-FDG, [18F]-fluoro-2-deoxy-d-glucose ,Aerobic glycolysi ,cAMP, cyclic adenosine monophosphate ,GlastGdi1flox/Y, GLAST:CreERT2+/Gdi1lox/Y inducible astrocyte-specific Gdi1 KO male mice ,medicine.anatomical_structure ,intellectual disability ,Knockout mouse ,Astrocyte ,Gdi1 WT, wild type ,medicine.medical_specialty ,Cells ,Knockout ,030209 endocrinology & metabolism ,Biology ,2-DG, 2-deoxy-d-glucose ,sEPSCs, spontaneous excitatory postsynaptic currents ,CNS, central nervous system ,SEM, standard error of the mean ,03 medical and health sciences ,αGDI, α guanosine dissociation inhibitor protein coded by GDI1 gene ,CFP, cyan fluorescent protein ,Downregulation and upregulation ,Internal medicine ,medicine ,aerobic glycolysis ,GlastGdi1X/Y, male mice (Gdi1X/Y) carrying the GLAST:CreERT2 transgene ,GLUT1, d-glucose transporter ,Wild type ,astrocytes ,GFAP, glial fibrillary acidic protein ,PSD, postsynaptic density ,GDI1, guanosine dissociation inhibitor 1 gene ,YFP, yellow fluorescent protein ,030104 developmental biology ,GPCR, G-protein coupled receptor ,Anaerobic glycolysis ,GPR81, G-protein receptor 81 ,CS, conditional stimulus, tone ,PKA, protein kinase A ,MCTs, monocarboxylate transporters ,Homeostasis - Abstract
Objectives GDI1 gene encodes for αGDI, a protein controlling the cycling of small GTPases, reputed to orchestrate vesicle trafficking. Mutations in human GDI1 are responsible for intellectual disability (ID). In mice with ablated Gdi1, a model of ID, impaired working and associative short-term memory was recorded. This cognitive phenotype worsens if the deletion of αGDI expression is restricted to neurons. However, whether astrocytes, key homeostasis providing neuroglial cells, supporting neurons via aerobic glycolysis, contribute to this cognitive impairment is unclear. Methods We carried out proteomic analysis and monitored [18F]-fluoro-2-deoxy-d-glucose uptake into brain slices of Gdi1 knockout and wild type control mice. d-Glucose utilization at single astrocyte level was measured by the Förster Resonance Energy Transfer (FRET)-based measurements of cytosolic cyclic AMP, d-glucose and L-lactate, evoked by agonists selective for noradrenaline and L-lactate receptors. To test the role of astrocyte-resident processes in disease phenotype, we generated an inducible Gdi1 knockout mouse carrying the Gdi1 deletion only in adult astrocytes and conducted behavioural tests. Results Proteomic analysis revealed significant changes in astrocyte-resident glycolytic enzymes. Imaging [18F]-fluoro-2-deoxy-d-glucose revealed an increased d-glucose uptake in Gdi1 knockout tissue versus wild type control mice, consistent with the facilitated d-glucose uptake determined by FRET measurements. In mice with Gdi1 deletion restricted to astrocytes, a selective and significant impairment in working memory was recorded, which was rescued by inhibiting glycolysis by 2-deoxy-d-glucose injection. Conclusions These results reveal a new astrocyte-based mechanism in neurodevelopmental disorders and open a novel therapeutic opportunity of targeting aerobic glycolysis, advocating a change in clinical practice., Highlights • Mutations in human Gdi1, encoding αGDI, a protein controlling vesicle traffic, are responsible for Intellectual Disability. • Gdi1 knockout revealed significant changes in astrocyte-resident glycolytic enzymes and facilitated D-glucose utilization. • Astrocyte-selective Gdi1 deletion impairs working memory, which can be rescued by administration of 2-deoxy-D-glucose. • Astrocyte-based glycolysis is a new target to treat Intellectual Disability.
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- 2021
143. Pre-existing diabetes and covid-associated hyperglycaemia in patients with covid-19 pneumonia
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Cristina Brigatti, Fabio Ciceri, Chiara Molinari, Alessia Mercalli, Vito Lampasona, Rita Nano, Andrea Laurenzi, Lorenzo Piemonti, Elena Bazzigaluppi, Ilaria Marzinotto, Raffaella Melzi, Cristina Tresoldi, Giovanni Landoni, Marina Scavini, Amelia Caretto, Laurenzi, A., Caretto, A., Molinari, C., Bazzigaluppi, E., Brigatti, C., Marzinotto, I., Mercalli, A., Melzi, R., Nano, R., Tresoldi, C., Landoni, G., Ciceri, F., Lampasona, V., Scavini, M., and Piemonti, L.
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medicine.medical_specialty ,Coronavirus disease 2019 (COVID-19) ,QH301-705.5 ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Glutamate decarboxylase ,clinical outcome ,Biology ,Article ,General Biochemistry, Genetics and Molecular Biology ,Internal medicine ,Diabetes mellitus ,medicine ,In patient ,Humoral response ,Biology (General) ,General Immunology and Microbiology ,diabetes ,Clinical outcome ,SARS-CoV-2 ,Diabetes ,Autoantibody ,COVID-19 ,medicine.disease ,Pneumonia ,Cohort ,General Agricultural and Biological Sciences ,humoral response - Abstract
Aim. The aim of the current study was to compare clinical characteristics, laboratory findings, and major outcomes of patients hospitalized for COVID-19 pneumonia with COVID-associated hyperglycaemia or pre-existing diabetes. Methods. A cohort of 176 adult patients with a diagnosis of pre-existing diabetes (n = 112) or COVID-associated hyperglycaemia (n = 55) was studied. Results. Patients with COVID-associated hyperglycaemia had lower BMI, significantly less comorbidities, and higher levels of inflammatory markers and indicators of multi-organ injury than those with pre-existing diabetes. No differences between pre-existing diabetes and COVID-associated hyperglycaemia were evident for symptoms at admission, the humoral response against SARS-CoV-2, or autoantibodies to glutamic acid decarboxylase or interferon alpha-4. COVID-associated hyperglycaemia was independently associated with the risk of adverse clinical outcome, which was defined as ICU admission or death (HR 2.11, 95% CI 1.34–3.31, p = 0.001), even after adjustment for age, sex, and other selected variables associated with COVID-19 severity. Furthermore, at the same time, we documented a negative association (HR 0.661, 95% CI 0.43–1.02, p = 0.063) between COVID-associated hyperglycaemia to swab negativization. Conclusions. Recognizing hyperglycaemia as a specific clinical entity associated with COVID-19 pneumonia is relevant for early and appropriate patient management and close monitoring for the progression of disease severity.
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- 2021
144. Neonatal diabetes mutations disrupt a chromatin pioneering function that activates the human insulin gene
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Sian Ellard, Jorge Ferrer, Javier García-Hurtado, Sarah E. Flanagan, Philippe Ravassard, Miguel A. Maestro, Elisa De Franco, Ildem Akerman, Gerhard Mittler, Andrew T. Hattersley, Lorenzo Piemonti, Vanessa Grau, University of Birmingham [Birmingham], Centre for Genomic Regulation [Barcelona] (CRG), Universitat Pompeu Fabra [Barcelona] (UPF)-Centro Nacional de Analisis Genomico [Barcelona] (CNAG), University of Exeter Medical School, University of Exeter, Max Planck Institute of Immunobiology and Epigenetics (MPI-IE), Max-Planck-Gesellschaft, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), IRCCS Ospedale San Raffaele [Milan, Italy], Gestionnaire, Hal Sorbonne Université, Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Akerman, I., Maestro, M. A., De Franco, E., Grau, V., Flanagan, S., Garcia-Hurtado, J., Mittler, G., Ravassard, P., Piemonti, L., Ellard, S., Hattersley, A. T., Ferrer, J., and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
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0301 basic medicine ,Transcription, Genetic ,[SDV]Life Sciences [q-bio] ,Endocrinology, Diabetes and Metabolism ,medicine.disease_cause ,Sulfonylurea Receptors ,Bioinformatics ,Infant, Newborn, Diseases ,Mice ,0302 clinical medicine ,Endocrinology ,Transcription (biology) ,Insulina ,Human insulin ,Insulin ,Protein Isoforms ,Medicine ,Biology (General) ,Promoter Regions, Genetic ,health care economics and organizations ,Genetics ,Mutation ,GLIS3 ,Diabetis ,Gene Expression Regulation, Developmental ,Chromatin ,3. Good health ,Cell biology ,[SDV] Life Sciences [q-bio] ,DNA-Binding Proteins ,neonatal diabetes ,QH301-705.5 ,Neonatal diabetes ,mouse model ,education ,MEDLINE ,Mice, Transgenic ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Article ,Gene product ,03 medical and health sciences ,Text mining ,Diabetes Mellitus ,Animals ,Humans ,Point Mutation ,Transcription factor ,Pancreas ,Gene ,Alleles ,regulatory element ,HIP ,INS promoter ,business.industry ,Point mutation ,Infants nadons -- Malalties ,Infant, Newborn ,Embryo, Mammalian ,Noncoding DNA ,Repressor Proteins ,030104 developmental biology ,Trans-Activators ,business ,030217 neurology & neurosurgery ,Function (biology) ,Genètica - Abstract
Summary Despite the central role of chromosomal context in gene transcription, human noncoding DNA variants are generally studied outside of their genomic location. This limits our understanding of disease-causing regulatory variants. INS promoter mutations cause recessive neonatal diabetes. We show that all INS promoter point mutations in 60 patients disrupt a CC dinucleotide, whereas none affect other elements important for episomal promoter function. To model CC mutations, we humanized an ∼3.1-kb region of the mouse Ins2 gene. This recapitulated developmental chromatin states and cell-specific transcription. A CC mutant allele, however, abrogated active chromatin formation during pancreas development. A search for transcription factors acting through this element revealed that another neonatal diabetes gene product, GLIS3, has a pioneer-like ability to derepress INS chromatin, which is hampered by the CC mutation. Our in vivo analysis, therefore, connects two human genetic defects in an essential mechanism for developmental activation of the INS gene., Graphical abstract, Highlights • Mutations of a CC dinucleotide in the human INS promoter cause neonatal diabetes • We humanized ∼3.1 kb of mouse Ins2 and created a CC mutant version • Humanized Ins2, but not the CC mutant, recapitulates developmental chromatin activation • GLIS3, also mutated in diabetes, activates INS chromatin and requires an intact CC, Mutations in the CC element of the INS promoter or the transcription factor GLIS3 cause neonatal diabetes. Akerman et al. humanize a 3.1-kb region upstream of the mouse Ins2 gene and show that GLIS3 and the CC element form a pioneering mechanism that activates INS chromatin during pancreas development.
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- 2021
145. Circulating CXCL10 and IL-6 in solid organ donors after brain death predict graft outcomes
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Marina Scavini, Lorenzo Piemonti, Andrea Gianelli Castiglione, Valeria Sordi, Massimo Cardillo, G. Scotti, Viviana Sioli, Silvia Pellegrini, Piemonti, L., Sordi, V., Pellegrini, S., Scotti, G. M., Scavini, M., Sioli, V., Gianelli Castiglione, A., and Cardillo, M.
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Brain Death ,medicine.medical_specialty ,Graft failure ,medicine.medical_treatment ,Science ,Delayed Graft Function ,Kaplan-Meier Estimate ,Disease ,030230 surgery ,Article ,law.invention ,Prognostic markers ,03 medical and health sciences ,Medical research ,0302 clinical medicine ,law ,Internal medicine ,medicine ,Humans ,CXCL10 ,Interleukin 6 ,Proportional Hazards Models ,Cause of death ,Heart transplantation ,Kidney ,Multidisciplinary ,biology ,Interleukin-6 ,business.industry ,Graft Survival ,Prognosis ,Intensive care unit ,Tissue Donors ,Chemokine CXCL10 ,medicine.anatomical_structure ,biology.protein ,Cytokines ,Medicine ,030211 gastroenterology & hepatology ,business - Abstract
We tested the hypothesis that circulating CXCL10 and IL-6 in donor after brain death provide independent additional predictors of graft outcome. From January 1, 2010 to June 30, 2012 all donors after brain death managed by the NITp (n = 1100) were prospectively included in this study. CXCL10 and IL-6 were measured on serum collected for the crossmatch at the beginning of the observation period. Graft outcome in recipients who received kidney (n = 1325, follow-up 4.9 years), liver (n = 815, follow-up 4.3 years) and heart (n = 272, follow-up 5 years) was evaluated. Both CXCL-10 and IL-6 showed increased concentration in donors after brain death. The intensive care unit stay, the hemodynamic instability, the cause of death, the presence of risk factors for cardiovascular disease and the presence of ongoing infection resulted as significant determinants of IL-6 and CXCL10 donor concentrations. Both cytokines resulted as independent predictors of Immediate Graft Function. Donor IL-6 or CXCL10 were associated with graft failure after liver transplant, and acted as predictors of recipient survival after kidney, liver and heart transplantation. Serum donor IL-6 and CXCL10 concentration can provide independent incremental prediction of graft outcome among recipients followed according to standard clinical practice.
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- 2021
146. Standardized GMP-compliant scalable production of human pancreas organoids
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Francesco Pampaloni, Alessandro Cherubini, Lorenzo Piemonti, Francesca Salanitro, Mario Barilani, Marta Dossena, Erica Dugnani, Lorenza Lazzari, Roberta Piras, Till Moreth, Dossena, M., Piras, R., Cherubini, A., Barilani, M., Dugnani, E., Salanitro, F., Moreth, T., Pampaloni, F., Piemonti, L., and Lazzari, L.
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Cell ,Medicine (miscellaneous) ,Regenerative Medicine ,Biochemistry, Genetics and Molecular Biology (miscellaneous) ,Regenerative medicine ,Flow cytometry ,lcsh:Biochemistry ,03 medical and health sciences ,Tissue culture ,0302 clinical medicine ,medicine ,Organoid ,Humans ,lcsh:QD415-436 ,Progenitor cell ,Pancreas ,030304 developmental biology ,lcsh:R5-920 ,0303 health sciences ,medicine.diagnostic_test ,Chemistry ,Research ,Pancreatic Ducts ,Cell Biology ,3. Good health ,Cell biology ,Culture Media ,Organoids ,medicine.anatomical_structure ,Molecular Medicine ,Stem cell ,lcsh:Medicine (General) ,030217 neurology & neurosurgery - Abstract
Background Organoids are three-dimensional in vitro-grown cell clusters that recapitulate key features of native organs. In regenerative medicine, organoid technology represents a promising approach for the replacement of severely damaged organs, such as the pancreas in patients with type 1 diabetes. Isolation human pancreas organoids (hPOs) in chemically defined serum-free culture media would be a major milestone for this approach. Methods Starting from discarded pancreatic tissues, we developed a large-scale process for obtaining clinically relevant quantities of undifferentiated organoids, obviating enzymatic digestion and operator-dependent pancreatic ducts picking steps. hPO identity was characterized by molecular and flow cytometry analysis. Results This work demonstrates that it is possible to obtain a large-scale production of organoids. We introduced some innovations in the isolation, expansion, and freezing of hPOs from five donors. First of all, the choice of the starting material (islet-depleted pancreas) that allows obtaining a high quantity of hPOs at low passages. On the other hand, we introduced mechanical dissociation and we eliminated the picking step to exclude the operator-depending steps, without affecting the success of the culture (100% success rate). Another important improvement was to replace R-spondin-1 (Rspo1) conditioned medium with Rspo1 recombinant molecule to obtain a well-defined composition of the expansion medium. Finally, we implemented a GMP-compliant freezing protocol. hPOs showed exponential growth with diameter and area that increased three- and eight-fold in 7 days, respectively. Immunophenotypic profile and gene expression analysis revealed that hPOs were composed of ductal (82.33 ± 8.37%), acinar (2.80 ± 1.25%) cells, and pancreatic progenitors (5.81 ± 2.65%). Conclusion This work represents a milestone for a GMP-compliance hPO production and, ultimately, their clinical application as a type 1 diabetes therapy.
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- 2020
147. B lymphocytes contribute to stromal reaction in pancreatic ductal adenocarcinoma
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Takashi Maehara, Elena Rigamonti, Shiv Pillai, Marco Lanzillotta, Paolo Giorgio Arcidiacono, Emanuel Della-Torre, Massimo Falconi, Lucrezia Rovati, Maria Pia Protti, Erica Dugnani, Naoki Kaneko, Antonella Monno, Claudia Minici, Cristina Scielzo, Lucia De Monte, Stefano Crippa, Vikram Deshpande, Lorenzo Piemonti, Angelo A. Manfredi, Minici, C., Rigamonti, E., Lanzillotta, M., Monno, A., Rovati, L., Maehara, T., Kaneko, N., Deshpande, V., Protti, M. P., De Monte, L., Scielzo, C., Crippa, S., Arcidiacono, P. G., Dugnani, E., Piemonti, L., Falconi, M., Pillai, S., Manfredi, A. A., and Della-Torre, E.
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0301 basic medicine ,Stromal cell ,endocrine system diseases ,Immunology ,B-cells ,Pancreatic Ductal Adenocarcinoma ,plasmablasts ,Extracellular matrix ,03 medical and health sciences ,0302 clinical medicine ,Pancreatic cancer ,fibroblasts ,medicine ,Humans ,Immunology and Allergy ,pancreas ,Fibroblast ,RC254-282 ,Original Research ,B-Lymphocytes ,LOXL2 ,Chemistry ,fibrosis ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC581-607 ,IGG4-related disease ,PDGF ,medicine.disease ,digestive system diseases ,Desmoplasia ,Pancreatic Neoplasms ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Prominent Stromal Reaction ,Cancer research ,Immunologic diseases. Allergy ,Stromal Cells ,medicine.symptom ,Pancreas ,Research Article ,Carcinoma, Pancreatic Ductal - Abstract
Pancreatic ductal adenocarcinoma (PDAC) is characterized by a prominent stromal reaction that has been variably implicated in both tumor growth and tumor suppression. B-lymphocytes have been recently implicated in PDAC progression but their contribution to the characteristic stromal desmoplasia has never been assessed before. In the present work, we aimed to verify whether B-lymphocytes contribute to stromal cell activation in PDAC. CD19+ B-lymphocytes purified from peripheral blood of patients with PDAC were cultivated in the presence of human pancreatic fibroblasts and cancer-associated fibroblasts. Released pro-fibrotic soluble factors and collagen production were assessed by ELISA and Luminex assays. Quantitative RT-PCR was used to assess fibroblast activation in the presence of B cells. The expression of selected pro-fibrotic and inflammatory molecules was confirmed on PDAC tissue sections by multi-color immunofluorescence studies. We herein demonstrate that B-cells from PDAC patients (i) produce the pro-fibrotic molecule PDGF-B and stimulate collagen production by fibroblasts; (ii) express enzymes implicated in extracellular matrix remodeling including LOXL2; and (iii) produce the chemotactic factors CCL-4, CCL-5, and CCL-11. In addition we demonstrate that circulating plasmablasts are expanded in the peripheral blood of patients with PDAC, stimulate collagen production by fibroblasts, and infiltrate pancreatic lesions. Our results indicate that PDAC is characterized by perturbations of the B-cell compartment with expansion of B-lymphocyte subsets that directly contribute to the stromal reaction observed at disease site. These findings provide an additional rationale for modulating B-cell activity in patients with pancreatic cancer.
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- 2020
148. Mild SARS-CoV-2 Infection After Gene Therapy in a Child With Wiskott-Aldrich Syndrome: A Case Report
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Sabina Cenciarelli, Valeria Calbi, Federica Barzaghi, Maria Ester Bernardo, Chiara Oltolini, Maddalena Migliavacca, Vera Gallo, Francesca Tucci, Federico Fraschetta, Elena Albertazzi, Elena Sophia Fratini, Giulia Consiglieri, Stefania Giannelli, Francesca Dionisio, Claudia Sartirana, Sara Racca, Chiara Camesasca, Giovanni Peretto, Rita Daverio, Antonio Esposito, Francesco De Cobelli, Paolo Silvani, Marco Rabusin, Andrea Cara, Daria Trabattoni, Stefania Dispinseri, Gabriella Scarlatti, Lorenzo Piemonti, Vito Lampasona, Maria Pia Cicalese, Alessandro Aiuti, Francesca Ferrua, Cenciarelli, S., Calbi, V., Barzaghi, F., Bernardo, M. E., Oltolini, C., Migliavacca, M., Gallo, V., Tucci, F., Fraschetta, F., Albertazzi, E., Fratini, E. S., Consiglieri, G., Giannelli, S., Dionisio, F., Sartirana, C., Racca, S., Camesasca, C., Peretto, G., Daverio, R., Esposito, A., De Cobelli, F., Silvani, P., Rabusin, M., Cara, A., Trabattoni, D., Dispinseri, S., Scarlatti, G., Piemonti, L., Lampasona, V., Cicalese, M. P., Aiuti, A., and Ferrua, F.
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lcsh:Immunologic diseases. Allergy ,severe acute respiratory syndrome Coronavirus 2 (2019-nCoV) ,Male ,Wiskott–Aldrich syndrome ,Genetic enhancement ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Immunology ,Case Report ,macromolecular substances ,Antibodies, Viral ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Immunology and Allergy ,Medicine ,Humans ,030212 general & internal medicine ,Autoinflammatory disease ,Gene ,Specific immunoglobulins ,business.industry ,SARS-CoV-2 ,fungi ,Infant ,COVID-19 ,immune reconstitution ,Genetic Therapy ,medicine.disease ,gene therapy ,Antibodies, Neutralizing ,Wiskott-Aldrich Syndrome ,030220 oncology & carcinogenesis ,lcsh:RC581-607 ,business ,After treatment ,Wiskott-Aldrich Syndrome Protein ,primary immunodeficiencies - Abstract
In this work we present the case of SARS-CoV-2 infection in a 1.5-year-old boy affected by severe Wiskott-Aldrich Syndrome with previous history of autoinflammatory disease, occurring 5 months after treatment with gene therapy. Before SARS-CoV-2 infection, the patient had obtained engraftment of gene corrected cells, resulting in WASP expression restoration and early immune reconstitution. The patient produced specific immunoglobulins to SARS-CoV-2 at high titer with neutralizing capacity and experienced a mild course of infection, with limited inflammatory complications, despite pre-gene therapy clinical phenotype.
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- 2020
149. The first 142 amino acids of glutamate decarboxylase do not contribute to epitopes recognized by autoantibodies associated with Type 1 diabetes
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Peter Achenbach, Benjamin Thomas Gillard, Rebecca Wyatt, Anna E. Long, Cristina Brigatti, Lorenzo Piemonti, Deborah K. Shoemark, Ilaria Marzinotto, Kathleen M Gillespie, Kyla Chandler, Alistair J K Williams, Daniela Liberati, Vito Lampasona, Sian Grace, Wyatt, R C, Brigatti, C, Liberati, D, Grace, S L, Gillard, B T, Long, A E, Marzinotto, I, Shoemark, D, Chandler, K A, Achenbach, P, Gillespie, K M, Piemonti, L, Lampasona, V, and Williams, A J K
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Adult ,Male ,0301 basic medicine ,endocrine system ,Adolescent ,endocrine system diseases ,Endocrinology, Diabetes and Metabolism ,Glutamate decarboxylase ,Radioimmunoassay ,Enzyme-Linked Immunosorbent Assay ,030209 endocrinology & metabolism ,Sensitivity and Specificity ,Epitope ,Epitopes ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Diabetes mellitus ,Internal Medicine ,medicine ,Humans ,Family ,Child ,Aged ,Autoantibodies ,Type 1 diabetes ,Predictive marker ,biology ,Glutamate Decarboxylase ,business.industry ,Autoantibody ,Infant ,nutritional and metabolic diseases ,Middle Aged ,medicine.disease ,Peptide Fragments ,Diabetes Mellitus, Type 1 ,030104 developmental biology ,Child, Preschool ,Immunology ,Type 1 Diabetes ,biology.protein ,Female ,Antibody ,Prediction ,business - Abstract
Aims: Glutamate decarboxylase (GAD) antibodies are the most widely used predictive marker for Type 1 diabetes, but many individuals currently found to be GAD antibody-positive are unlikely to develop diabetes. We have shown previously that radioimmunoassays using N-terminally truncated 35S-GAD65(96–585) offer better disease specificity with similar sensitivity to full-length 35S-GAD65(1–585). To determine whether assay performance could be improved further, we evaluated a more radically truncated 35S-GAD65(143–585) radiolabel. Methods: Samples from people with recent-onset Type 1 diabetes (n = 157) and their first-degree relatives (n = 745) from the Bart's–Oxford family study of childhood diabetes were measured for GAD antibodies using 35S-labelled GAD65(143–585). These were screened previously using a local radioimmunoassay with 35S-GAD65(1–585). A subset was also tested by enzyme-linked immunosorbent assay (ELISA), which performs well in international workshops, but requires 10 times more serum. Results were compared with GAD antibody measurements using 35S-GAD65(1–585) and 35S-GAD65(96–585). Results: Sensitivity of GAD antibody measurement was maintained using 35S-GAD65(143–585) compared with 35S-GAD65(1–585) and 35S-GAD65(96–585). Specificity for Type 1 diabetes was improved compared with 35S-GAD65(1–585), but was similar to 35S-GAD65(96–585). Relatives found to be GAD antibody-positive using these truncated labels were at increased risk of diabetes progression within 15 years, compared with those positive for GAD(1–585) antibody only, and at similar risk to those found GAD antibody-positive by ELISA. Conclusions: The first 142 amino acids of GAD65 do not contribute to epitopes recognized by Type 1 diabetes-associated GAD antibodies. Low-volume radioimmunoassays using N-terminally truncated 35S-GAD65 are more specific than those using full-length GAD65 and offer practical alternatives to the GAD antibody ELISA for identifying children at increased risk of Type 1 diabetes.
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- 2018
150. Inhibition of Eph/ephrin interaction with the small molecule UniPR500 improves glucose tolerance in healthy and insulin-resistant mice
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Lorenzo Piemonti, Fabio Manenti, Daniele Pala, Paola Chiodelli, Alessio Lodola, Francesca Ferlenghi, Marco Rusnati, Simona Bertoni, Carmine Giorgio, Philippe Ravassard, R. Di Lecce, Elisabetta Barocelli, Matteo Incerti, Massimiliano Tognolini, Simonetta Russo, Anna Maria Cantoni, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Giorgio, C, Incerti, M, Pala, D, Russo, S, Chiodelli, P, Rusnati, M, Cantoni, A M, Di Lecce, R, Barocelli, E, Bertoni, S, Ravassard, P, Manenti, F, Piemonti, L, Ferlenghi, F, Lodola, A, and Tognolini, M
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0301 basic medicine ,Male ,medicine.medical_treatment ,Pharmacology ,Cell Line ,03 medical and health sciences ,0302 clinical medicine ,Insulin resistance ,In vivo ,Insulin-Secreting Cells ,Insulin Secretion ,medicine ,Glucose homeostasis ,Ephrin ,Animals ,Humans ,Hypoglycemic Agents ,Insulin ,Protein Interaction Maps ,Eph/ephrins ,ComputingMilieux_MISCELLANEOUS ,Chemistry ,Pancreatic islets ,Diabetes ,Erythropoietin-producing hepatocellular (Eph) receptor ,Antagonist ,Glucose Tolerance Test ,medicine.disease ,3. Good health ,Mice, Inbred C57BL ,030104 developmental biology ,medicine.anatomical_structure ,Diabetes Mellitus, Type 1 ,Glucose ,[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics ,030220 oncology & carcinogenesis ,Insulin Resistance ,Ephrins - Abstract
Eph/ephrin interactions and their bidirectional signaling are integral part of the complex communication system between β-cells, essential for glucose homeostasis. Indeed, Eph/ephrin system was shown to be directly involved in the glucose-stimulated insulin secretion (GSIS) process occurring in the pancreatic islets. Here we tested the Eph antagonist UniPR500 as GSIS enhancer. UniPR500 was validated as EphA5-ephrin-A5 inhibitor in vitro and its efficacy as GSIS enhancer was assessed on EndoC-βH1 cells. The selectivity of UniPR500 was evaluated by testing this compound on a panel of well-known molecular targets responsible for the regulation of glucose homeostasis. Plasmatic levels of UniPR500 were measured by HPLC/MS approach after oral administration. Finally, UniPR500 was tested as hypoglycemic agent in healthy mice, in a non-genetic mouse model of insulin resistance (IR) and in a non-genetic mouse model of type 1 diabetes (T1D). The compound is an orally bioavailable and selective Eph antagonist, able to increase GSIS from EndoC-βH1 cells. When tested in vivo UniPR500 showed to improve glucose tolerance in healthy and IR mice. As expected by a GSIS enhancer acting on healthy β-cells, UniPR500 was ineffective when tested on a non-genetic mouse model of type 1 diabetes, where pancreatic function was severely compromised. In conclusion our findings suggest that Eph targeting is a new and valuable pharmacological strategy in the search of new hypoglycemic agents.
- Published
- 2019
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