748 results on '"Rovere Querini, P."'
Search Results
2. Preferential and sustained platelet activation in COVID-19 survivors with mental disorders
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Maugeri, Norma, De Lorenzo, Rebecca, Mazza, Mario Gennaro, Palladini, Mariagrazia, Ciceri, Fabio, Rovere-Querini, Patrizia, Manfredi, Angelo A., and Benedetti, Francesco
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- 2024
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3. Low-molecular-weight heparin in the prevention of unexplained recurrent miscarriage: a systematic review and meta-analysis
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Scarrone, Margherita, Salmeri, Noemi, Buzzaccarini, Giovanni, Canti, Valentina, Pasi, Federica, Papaleo, Enrico, Rovere-Querini, Patrizia, Candiani, Massimo, Alteri, Alessandra, Busnelli, Andrea, and Vanni, Valeria Stella
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- 2024
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4. Correction: Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19
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Matuozzo, Daniela, Talouarn, Estelle, Marchal, Astrid, Zhang, Peng, Manry, Jeremy, Seeleuthner, Yoann, Zhang, Yu, Bolze, Alexandre, Chaldebas, Matthieu, Milisavljevic, Baptiste, Gervais, Adrian, Bastard, Paul, Asano, Takaki, Bizien, Lucy, Barzaghi, Federica, Abolhassani, Hassan, Tayoun, Ahmad Abou, Aiuti, Alessandro, Darazam, Ilad Alavi, Allende, Luis M., Alonso-Arias, Rebeca, Arias, Andrés Augusto, Aytekin, Gokhan, Bergman, Peter, Bondesan, Simone, Bryceson, Yenan T., Bustos, Ingrid G., Cabrera-Marante, Oscar, Carcel, Sheila, Carrera, Paola, Casari, Giorgio, Chaïbi, Khalil, Colobran, Roger, Condino-Neto, Antonio, Covill, Laura E., Delmonte, Ottavia M., Zein, Loubna El, Flores, Carlos, Gregersen, Peter K., Gut, Marta, Haerynck, Filomeen, Halwani, Rabih, Hancerli, Selda, Hammarström, Lennart, Hatipoğlu, Nevin, Karbuz, Adem, Keles, Sevgi, Kyheng, Christèle, Leon-Lopez, Rafael, Franco, Jose Luis, Mansouri, Davood, Martinez-Picado, Javier, Akcan, Ozge Metin, Migeotte, Isabelle, Morange, Pierre-Emmanuel, Morelle, Guillaume, Martin-Nalda, Andrea, Novelli, Giuseppe, Novelli, Antonio, Ozcelik, Tayfun, Palabiyik, Figen, Pan-Hammarström, Qiang, de Diego, Rebeca Pérez, Planas-Serra, Laura, Pleguezuelo, Daniel E., Prando, Carolina, Pujol, Aurora, Reyes, Luis Felipe, Rivière, Jacques G., Rodriguez-Gallego, Carlos, Rojas, Julian, Rovere-Querini, Patrizia, Schlüter, Agatha, Shahrooei, Mohammad, Sobh, Ali, Soler-Palacin, Pere, Tandjaoui-Lambiotte, Yacine, Tipu, Imran, Tresoldi, Cristina, Troya, Jesus, van de Beek, Diederik, Zatz, Mayana, Zawadzki, Pawel, Al-Muhsen, Saleh Zaid, Alosaimi, Mohammed Faraj, Alsohime, Fahad M., Baris-Feldman, Hagit, Butte, Manish J., Constantinescu, Stefan N., Cooper, Megan A., Dalgard, Clifton L., Fellay, Jacques, Heath, James R., Lau, Yu-Lung, Lifton, Richard P., Maniatis, Tom, Mogensen, Trine H., von Bernuth, Horst, Lermine, Alban, Vidaud, Michel, Boland, Anne, Deleuze, Jean-François, Nussbaum, Robert, Kahn-Kirby, Amanda, Mentre, France, Tubiana, Sarah, Gorochov, Guy, Tubach, Florence, Hausfater, Pierre, Meyts, Isabelle, Zhang, Shen-Ying, Puel, Anne, Notarangelo, Luigi D., Boisson-Dupuis, Stephanie, Su, Helen C., Boisson, Bertrand, Jouanguy, Emmanuelle, Casanova, Jean-Laurent, Zhang, Qian, Abel, Laurent, and Cobat, Aurélie
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- 2024
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5. Pentraxin 3 in Myocarditis: Proof-of-Principle Assessment as a Diagnostic and Prognostic Biomarker
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Villatore, Andrea, Monno, Antonella, Sciorati, Clara, Rovere-Querini, Patrizia, Sala, Simone, Carino, Davide, De Bonis, Michele, Cianflone, Domenico, Manfredi, Angelo A., and Peretto, Giovanni
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- 2024
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6. Choroid plexus and perivascular space enlargement in neuropsychiatric systemic lupus erythematosus
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Gueye, Mor, Preziosa, Paolo, Ramirez, Giuseppe A., Bozzolo, Enrica P., Canti, Valentina, Margoni, Monica, Meani, Alessandro, Moiola, Lucia, Rovere-Querini, Patrizia, Manfredi, Angelo A., Filippi, Massimo, and Rocca, Maria A.
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- 2024
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7. Sarcopenic obesity and pre-sarcopenia contribute to frailty in community-dwelling Italian older people: data from the FRASNET study
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Sarah Damanti, Lorena Citterio, Laura Zagato, Elena Brioni, Cristiano Magnaghi, Marco Simonini, Rebecca De Lorenzo, Mariapia Ruggiero, Simona Santoro, Eleonora Senini, Marco Messina, Giordano Vitali, Paolo Manunta, Angelo A. Manfredi, Chiara Lanzani, and Patrizia Rovere Querini
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Body composition ,Frailty index ,Sarcopenia ,Sarcopenic obesity ,Geriatrics ,RC952-954.6 - Abstract
Abstract Background The ageing process is characterized by a change of body composition with an increase of fat mass and a reduction of muscle mass. Above a certain threshold these alterations configure a condition named sarcopenic obesity (SO). SO is associated with physical frailty in Asian and Brazilian populations. SO impacts on physical frailty in other ethnic groups but its influence on general frailty which is multidimensional and includes cognitive, social and physical factors, remain insufficiently explored in the Italian population. Methods Frailty was measured in community dwelling Italian older adults enrolled in the FRASNET study with the frailty index (FI). The FI quantifies frailty as the ratio of the number of present health deficits to the total number of health deficits considered. Regression analyses were performed to assess the association between body composition categories and frailty. Classification and regression tree models were run to evaluate the frailty predictors. Results One Thousand One Hundred Fourteen participants of the FRASNET study were included in the present analysis. The sample was composed for the 60.5% by females and its median age was 72 years. The median FI score was 0.11 (IQR 0.07–0.20); 234 individuals (21%) were frail (FI ≥ 0.25). SO (B 0.074, 95% C.I. 0.05–0.1, p
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- 2024
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8. Preferential and sustained platelet activation in COVID-19 survivors with mental disorders
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Norma Maugeri, Rebecca De Lorenzo, Mario Gennaro Mazza, Mariagrazia Palladini, Fabio Ciceri, Patrizia Rovere-Querini, Angelo A. Manfredi, and Francesco Benedetti
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Mood disorders ,Platelet activation ,COVID-19 ,Medicine ,Science - Abstract
Abstract Pre-existing mental disorders are considered a risk factor for severe COVID-19 outcomes, possibly because of higher vascular burden. Moreover, an unconventional platelet activation characterizes COVID-19 and contributes to inflammatory and thrombotic manifestations. In the light of the inflammation theory of mental disorders, we hypothesized that patients with mental disorders could be sensitive to the SARS-CoV-2 elicited platelet activation. We investigated platelet activation in 141 COVID-19 survivors at one month after clearance of the virus, comparing subjects with or without an established pre-existing diagnosis of mental disorder according to the DSM-5. We found that platelets from patients with a positive history of psychiatric disorder underwent unconventional activation more frequently than conventional activation or no activation at all. Such preferential activation was not detected when platelets from patients without a previous psychiatric diagnosis were studied. When testing the effects of age, sex, and psychiatric history on the platelet activation, GLZM multivariate analysis confirmed the significant effect of diagnosis only. These findings suggest a preferential platelet activation during acute COVID-19 in patients with a pre-existing psychiatric disorder, mediated by mechanisms associated with thromboinflammation. This event could have contributed to the higher risk of severe outcome in the psychiatric population.
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- 2024
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9. Low-molecular-weight heparin in the prevention of unexplained recurrent miscarriage: a systematic review and meta-analysis
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Margherita Scarrone, Noemi Salmeri, Giovanni Buzzaccarini, Valentina Canti, Federica Pasi, Enrico Papaleo, Patrizia Rovere-Querini, Massimo Candiani, Alessandra Alteri, Andrea Busnelli, and Valeria Stella Vanni
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Medicine ,Science - Abstract
Abstract The etiology of recurrent pregnancy loss (RPL) is complex and multifactorial and in half of patients it remains unexplained (U-RPL). Recently, low-molecular-weight heparin (LMWH) has gained increasing relevance for its therapeutic potential. On this regard, the aim of this systematic review and meta-analysis is to analyze the efficacy of low molecular weight heparin (LMWH) from the beginning of pregnancy in terms of live birth rates (LBR) in U-RPL. Registered randomized controlled trials (RCTs) were included. We stratified findings based on relevant clinical factors including number of previous miscarriages, treatment type and control type. Intervention or exposure was defined as the administration of LMWH alone or in combination with low-dose aspirin (LDA). A total of 6 studies involving 1016 patients were included. The meta-analysis results showed that LMWH used in the treatment of U-RPL was not associated with an increase in LBR with a pooled OR of 1.01, a medium heterogeneity (26.42%) and no publication bias. Results of other sub-analyses according to country, treatment type, and control type showed no significant effect of LMWH on LBR in all subgroups, with a high heterogeneity. The results highlight a non-significant effect of LMWH in U-RPL on LBR based on moderate quality evidence. Registration number: PROSPERO: ( https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022326433 ).
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- 2024
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10. Monoclonal antibodies against SARS-CoV-2 to prevent COVID-19 worsening in a large multicenter cohort
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Alessandro Soria, Francesca Graziano, Giulia Ghilardi, Giuseppe Lapadula, Daniela Dalla Gasperina, Simone Vasilij Benatti, Eugenia Quiros-Roldan, Maurizio Milesi, Francesca Bai, Marco Merli, Davide Minisci, Marco Franzetti, Erika Asperges, Filippo Chiabrando, Daria Pocaterra, Alessandro Pandolfo, Fabio Zanini, Domenico Lombardi, Anna Cappelletti, Alban Rugova, Maria Lucia Borghesi, Nicola Squillace, Luigi Pusterla, Stefania Piconi, Paola Morelli, Patrizia Rovere Querini, Raffaele Bruno, Stefano Rusconi, Salvatore Casari, Alessandra Bandera, Fabio Franzetti, Giovanna Travi, Antonella D'Arminio Monforte, Giulia Marchetti, Angelo Pan, Francesco Castelli, Marco Rizzi, Francesco Dentali, Maria Mallardo, Emanuela Rossi, Maria Grazia Valsecchi, Stefania Galimberti, and Paolo Bonfanti
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Monoclonal antibodies ,COVID-19 ,SARS-CoV-2 ,Hospitalization ,Immunodeficiency ,Omicron variant ,Science (General) ,Q1-390 ,Social sciences (General) ,H1-99 - Abstract
Objective: Monoclonal antibodies (mAbs) against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) reduced Coronavirus Disease 2019 (COVID-19) hospitalizations in people at risk of clinical worsening. Real-world descriptions are limited. Methods: CONDIVIDIAMO, a two-year multicenter observational study, consecutively enrolled SARS-CoV-2 outpatients with ≥1 risk factor for COVID-19 progression receiving mAbs. Demographic data, underlying medical condition, type of mAbs combination received, duration of symptoms before mAbs administration, COVID-19 vaccination history, were collected upon enrolment and centrally recorded. Data on outcomes (hospitalizations, reasons of hospitalization, deaths) were prospectively collected. The primary endpoint was the rate of hospitalization or death in a 28-day follow-up, whichever occurred first; subjects were censored at the day of last follow-up or up to 28 days. The Kaplan-Meier method was used to estimate the incidence rate curve in time. The Cox regression model was used to assess potential risk factors for unfavorable outcome. Results were shown as hazard ratio (HR) along with the corresponding 95 % Confidence Interval (95%CI). Results: Among 1534 subjects (median [interquartile range, IQR] age 66.5 [52.4–74.9] years, 693 [45.2 %] women), 632 (41.2 %) received bamlanivimab ± etesevimab, 209 (13.6 %) casirivimab/imdevimab, 586 (38.2 %) sotrovimab, 107 (7.0 %) tixagevimab/cilgavimab. After 28-day follow-up, 87/1534 (5.6 %, 95%CI: 4.4%–6.8 %) met the primary outcome (85 hospitalizations, 2 deaths). Hospitalizations for COVID-19 (52, 3.4 %) occurred earlier than for other reasons (33, 2.1 %), after a median (IQR) of 3.5 (1–7) versus 8 (3–15) days (p = 0.006) from mAbs administration.In a multivariable Cox regression model, factors independently associated with increased hospitalization risk were age (hazard ratio [HR] 1.02, 95%CI 1.00–1.03, p = 0.021), immunodeficiency (HR 1.78, 95%CI 1.11–2.85, p = 0.017), pre-Omicron calendar period (HR 1.66, 95%CI 1.02–2.69, p = 0.041). Conclusions: MAbs real-world data over a 2-year changing pandemic landscape showed the feasibility of the intervention, although the hospitalization rate was not negligible. Immunosuppressed subjects remain more at risk of clinical worsening.
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- 2024
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11. Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19
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Matuozzo, Daniela, Talouarn, Estelle, Marchal, Astrid, Zhang, Peng, Manry, Jeremy, Seeleuthner, Yoann, Zhang, Yu, Bolze, Alexandre, Chaldebas, Matthieu, Milisavljevic, Baptiste, Gervais, Adrian, Bastard, Paul, Asano, Takaki, Bizien, Lucy, Barzaghi, Federica, Abolhassani, Hassan, Abou Tayoun, Ahmad, Aiuti, Alessandro, Alavi Darazam, Ilad, Allende, Luis M, Alonso-Arias, Rebeca, Arias, Andrés Augusto, Aytekin, Gokhan, Bergman, Peter, Bondesan, Simone, Bryceson, Yenan T, Bustos, Ingrid G, Cabrera-Marante, Oscar, Carcel, Sheila, Carrera, Paola, Casari, Giorgio, Chaïbi, Khalil, Colobran, Roger, Condino-Neto, Antonio, Covill, Laura E, Delmonte, Ottavia M, El Zein, Loubna, Flores, Carlos, Gregersen, Peter K, Gut, Marta, Haerynck, Filomeen, Halwani, Rabih, Hancerli, Selda, Hammarström, Lennart, Hatipoğlu, Nevin, Karbuz, Adem, Keles, Sevgi, Kyheng, Christèle, Leon-Lopez, Rafael, Franco, Jose Luis, Mansouri, Davood, Martinez-Picado, Javier, Metin Akcan, Ozge, Migeotte, Isabelle, Morange, Pierre-Emmanuel, Morelle, Guillaume, Martin-Nalda, Andrea, Novelli, Giuseppe, Novelli, Antonio, Ozcelik, Tayfun, Palabiyik, Figen, Pan-Hammarström, Qiang, de Diego, Rebeca Pérez, Planas-Serra, Laura, Pleguezuelo, Daniel E, Prando, Carolina, Pujol, Aurora, Reyes, Luis Felipe, Rivière, Jacques G, Rodriguez-Gallego, Carlos, Rojas, Julian, Rovere-Querini, Patrizia, Schlüter, Agatha, Shahrooei, Mohammad, Sobh, Ali, Soler-Palacin, Pere, Tandjaoui-Lambiotte, Yacine, Tipu, Imran, Tresoldi, Cristina, Troya, Jesus, van de Beek, Diederik, Zatz, Mayana, Zawadzki, Pawel, Al-Muhsen, Saleh Zaid, Alosaimi, Mohammed Faraj, Alsohime, Fahad M, Baris-Feldman, Hagit, Butte, Manish J, Constantinescu, Stefan N, Cooper, Megan A, Dalgard, Clifton L, Fellay, Jacques, Heath, James R, Lau, Yu-Lung, Lifton, Richard P, Maniatis, Tom, Mogensen, Trine H, von Bernuth, Horst, Lermine, Alban, and Vidaud, Michel
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Clinical Research ,Infectious Diseases ,Pneumonia & Influenza ,Genetics ,Human Genome ,Prevention ,2.1 Biological and endogenous factors ,Aetiology ,Humans ,Young Adult ,Adult ,Middle Aged ,COVID-19 ,SARS-CoV-2 ,Toll-Like Receptor 3 ,Toll-Like Receptor 7 ,Interferon Type I ,Autoantibodies ,COVID Human Genetic Effort ,COVIDeF Study Group ,French COVID Cohort Study Group ,CoV-Contact Cohort ,COVID-STORM Clinicians ,COVID Clinicians ,Orchestra Working Group ,Amsterdam UMC Covid-19 Biobank ,NIAID-USUHS COVID Study Group ,Immunity ,Rare variants ,Type I interferon ,Clinical Sciences - Abstract
BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P = 1.1 × 10-4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3-8.2], P = 2.1 × 10-4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1-2635.4], P = 3.4 × 10-3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3-8.4], P = 7.7 × 10-8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10-5).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old.
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- 2023
12. The longitudinal characterization of immune responses in COVID-19 patients reveals novel prognostic signatures for disease severity, patients’ survival and long COVID
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Maddalena Noviello, Rebecca De Lorenzo, Raniero Chimienti, Norma Maugeri, Claudia De Lalla, Gabriel Siracusano, Nicola Ivan Lorè, Paola Maria Vittoria Rancoita, Federica Cugnata, Elena Tassi, Stefania Dispinseri, Danilo Abbati, Valeria Beretta, Eliana Ruggiero, Francesco Manfredi, Aurora Merolla, Elisa Cantarelli, Cristina Tresoldi, Claudia Pastori, Roberta Caccia, Francesca Sironi, Ilaria Marzinotto, Fabio Saliu, Silvia Ghezzi, Vito Lampasona, Elisa Vicenzi, Paola Cinque, Angelo Andrea Manfredi, Gabriella Scarlatti, Paolo Dellabona, Lucia Lopalco, Clelia Di Serio, Mauro Malnati, Fabio Ciceri, Patrizia Rovere-Querini, and Chiara Bonini
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COVID-19 severity ,COVID-19 patients’ survival ,SARS-CoV-2 innate immunity ,SARS-CoV-2 adaptive immunity ,long COVID ,Immunologic diseases. Allergy ,RC581-607 - Abstract
IntroductionSARS-CoV-2 pandemic still poses a significant burden on global health and economy, especially for symptoms persisting beyond the acute disease. COVID-19 manifests with various degrees of severity and the identification of early biomarkers capable of stratifying patient based on risk of progression could allow tailored treatments.MethodsWe longitudinally analyzed 67 patients, classified according to a WHO ordinal scale as having Mild, Moderate, or Severe COVID-19. Peripheral blood samples were prospectively collected at hospital admission and during a 6-month follow-up after discharge. Several subsets and markers of the innate and adaptive immunity were monitored as putative factors associated with COVID-19 symptoms.ResultsMore than 50 immunological parameters were associated with disease severity. A decision tree including the main clinical, laboratory, and biological variables at admission identified low NK-cell precursors and CD14+CD91+ monocytes, and high CD8+ Effector Memory T cell frequencies as the most robust immunological correlates of COVID-19 severity and reduced survival. Moreover, low regulatory B-cell frequency at one month was associated with the susceptibility to develop long COVID at six months, likely due to their immunomodulatory ability.DiscussionThese results highlight the profound perturbation of the immune response during COVID-19. The evaluation of specific innate and adaptive immune-cell subsets allows to distinguish between different acute and persistent COVID-19 symptoms.
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- 2024
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13. Use of defibrotide in COVID-19 pneumonia: comparison of a phase II study and a matched real-world cohort control
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Annalisa Ruggeri, Francesco Corrado, Antonio Voza, Lee-Jen Wei, Gloria Catalano, Carmine Liberatore, Rosamaria Nitti, Carlo Fedeli, Alessandro Bruno, Eleonora Calabretta, Fabio Giglio, Fabio Sciutti, Francesca Lunghi, Giovanni Landoni, Alessio Aghemo, Massimo Iacobelli, Patrizia Rovere Querini, Paul G. Richardson, Andrea Assanelli, Jacopo Peccatori, Fabio Ciceri, and Carmelo Carlo-Stella
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
The coronavirus disease 2019 (COVID-19) pandemic led to an unprecedented burden on healthcare systems around the world and a severe global socioeconomic crisis, with more than 750 million confirmed cases and at least 7 million deaths reported by 31st December 2023. The DEFI-VID19 study (ClinicalTrials.gov NCT04335201), a phase II, single-arm, multicenter, open-label trial was designed in mid-2020 to assess the safety and efficacy of defibrotide in treating patients with COVID-19 pneumonia. Defibrotide was administered at a dose of 25 mg/kg/d intravenously, divided into four daily doses over a planned 14-day period for patients with COVID-19 pneumonia receiving non-invasive ventilation. The primary endpoint was Respiratory Failure Free Survival (RFFS); Overall Survival (OS), the number of post-recovery days, and adverse events were the secondary endpoints. For comparison, a contemporaneous control cohort receiving standard of care only was retrospectively selected by applying the eligibility criteria of the DEFI-VID19 trial. To adjust for the imbalance between the two cohorts in terms of baseline variable distributions, an outcome regression analysis was conducted. In adjusted analysis, patients receiving defibrotide reported a trend towards higher RFFS (HR=0.71[0.95CI: 0.34 to 1.29, P= .138]) and OS (HR=0.78[0.95CI: 0.33 to 1.53, P= .248]) and showed a significantly increased number of post-recovery days (difference in means: 3.61[ 0.95CI: 0.97 to 6.26, P= .0037]). Despite concomitant thromboprophylaxis with low molecular weight heparin, the safety profile of defibrotide proved to be favorable. Taken together, our findings suggest that defibrotide may represent a valuable addition to the COVID-19 therapeutic options.
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- 2024
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14. Management of pregnancy in autoimmune rheumatic diseases: maternal disease course, gestational and neonatal outcomes and use of medications in the prospectiveItalian P-RHEUM.it study
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Carlo Alberto Scirè, Alessandra Bortoluzzi, Andrea Doria, Micaela Fredi, Marcello Govoni, Chiara Tani, Angela Tincani, Maurizio Cutolo, Marta Mosca, Florenzo Iannone, Elena Elefante, Margherita Zen, Maddalena Larosa, Paola Conigliaro, Maria Sole Chimenti, Veronica Codullo, Cecilia Nalli, Veronique Ramoni, Carlomaurizio Montecucco, Marco Taglietti, Valentina Picerno, Greta Carrara, Laura Andreoli, Chiara Marvisi, Carlo Salvarani, Serena Guiducci, Antonio Luca Brucato, Franco Franceschini, Giandomenico Sebastiani, Marta Tonello, Silvia Bellando-Randone, Dina Zucchi, Giovanna Cuomo, Maria Letizia Urban, Maria Gerosa, Ettore Silvagni, Elisa Bellis, Francesca Bellisai, Alessandra Milanesi, Patrizia Rovere-Querini, Ariela Hoxha, Salvatore D'Angelo, Sonia Zatti, Emanuele Bizzi, Gianpiero Landolfi, Bernd Raffeiner, Leonardo Santo, Teresa Del Ross, Maria Stefania Cutro, Giulia Pazzola, Oscar Massimiliano Epis, Sara Benedetti, Maria Favaro, Antonia Calligaro, Annamaria Iuliano, Sabrina Gori, Francesca Crisafulli, Matteo Filippini, Maria Chiara Gerardi, Maria Grazia Lazzaroni, Cecilia Beatrice Chighizola, Laura Trespidi, Maria Chiara Ditto, Cristina Zanardini, Roberta Erra, Melissa Padovan, Irene Mattioli, Davide Rozza, Claudia Lomater, Daniele Lini, Valentina Canti, Rebecca De Lorenzo, Francesca Ruffilli, Giulia Carrea, Ludovica Cavallo, Alessandra Zambon, Claudia Barison, Francesca Serale, Paolo Semeraro, Chiara Loardi, Rossana Orabona, Francesca Ramazzotto, Giulia Fontana, Giorgia Gozzoli, Paola Bizioli, Roberto Felice Caporali, Manuela Wally Ossola, Beatrice Maranini, Danila Morano, Rosita Verteramo, Maria Grazia Anelli, Marlea Lavista, Anna Abbruzzese, Carlo Giuseppe Fasano, Teresa Carbone, Angela Anna Padula, Giuseppina Comitini, Giuseppina Di Raimondo, Clizia Gagliardi, Gloria Crepaldi, Estrella Garcia Gonzalez, Anna Paola Pata, Martina Zerbinati, and Sara Tonetta
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Medicine - Abstract
Objectives To investigate pregnancy outcomes in women with autoimmune rheumatic diseases (ARD) in the Italian prospective cohort study P-RHEUM.it.Methods Pregnant women with different ARD were enrolled for up to 20 gestational weeks in 29 Rheumatology Centres for 5 years (2018–2023). Maternal and infant information were collected in a web-based database.Results We analysed 866 pregnancies in 851 patients (systemic lupus erythematosus was the most represented disease, 19.6%). Maternal disease flares were observed in 135 (15.6%) pregnancies. 53 (6.1%) pregnancies were induced by assisted reproduction techniques, 61 (7%) ended in miscarriage and 11 (1.3%) underwent elective termination. Obstetrical complications occurred in 261 (30.1%) pregnancies, including 2.3% pre-eclampsia. Two cases of congenital heart block were observed out of 157 pregnancies (1.3%) with anti-Ro/SSA. Regarding treatments, 244 (28.2%) pregnancies were treated with glucocorticoids, 388 (44.8%) with hydroxychloroquine, 85 (9.8%) with conventional synthetic disease-modifying anti-rheumatic drugs and 122 (14.1%) with biological disease-modifying anti-rheumatic drugs. Live births were 794 (91.7%), mostly at term (84.9%); four perinatal deaths (0.5%) occurred. Among 790 newborns, 31 (3.9%) were small-for-gestational-age and 169 (21.4%) had perinatal complications. Exclusive maternal breast feeding was received by 404 (46.7%) neonates. The Edinburgh Postnatal Depression Scale was compiled by 414 women (52.4%); 89 (21.5%) scored positive for emotional distress.Conclusions Multiple factors including preconception counselling and treat-to-target with pregnancy-compatible medications may have contributed to mitigate disease-related risk factors, yielding limited disease flares, good pregnancy outcomes and frequency of complications which were similar to the Italian general obstetric population. Disease-specific issues need to be further addressed to plan preventative measures.
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- 2024
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15. Multimodal deep learning for COVID-19 prognosis prediction in the emergency department: a bi-centric study
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Dipaola, Franca, Gatti, Mauro, Giaj Levra, Alessandro, Menè, Roberto, Shiffer, Dana, Faccincani, Roberto, Raouf, Zainab, Secchi, Antonio, Rovere Querini, Patrizia, Voza, Antonio, Badalamenti, Salvatore, Solbiati, Monica, Costantino, Giorgio, Savevski, Victor, and Furlan, Raffaello
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- 2023
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16. Correction: Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19
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Daniela Matuozzo, Estelle Talouarn, Astrid Marchal, Peng Zhang, Jeremy Manry, Yoann Seeleuthner, Yu Zhang, Alexandre Bolze, Matthieu Chaldebas, Baptiste Milisavljevic, Adrian Gervais, Paul Bastard, Takaki Asano, Lucy Bizien, Federica Barzaghi, Hassan Abolhassani, Ahmad Abou Tayoun, Alessandro Aiuti, Ilad Alavi Darazam, Luis M. Allende, Rebeca Alonso-Arias, Andrés Augusto Arias, Gokhan Aytekin, Peter Bergman, Simone Bondesan, Yenan T. Bryceson, Ingrid G. Bustos, Oscar Cabrera-Marante, Sheila Carcel, Paola Carrera, Giorgio Casari, Khalil Chaïbi, Roger Colobran, Antonio Condino-Neto, Laura E. Covill, Ottavia M. Delmonte, Loubna El Zein, Carlos Flores, Peter K. Gregersen, Marta Gut, Filomeen Haerynck, Rabih Halwani, Selda Hancerli, Lennart Hammarström, Nevin Hatipoğlu, Adem Karbuz, Sevgi Keles, Christèle Kyheng, Rafael Leon-Lopez, Jose Luis Franco, Davood Mansouri, Javier Martinez-Picado, Ozge Metin Akcan, Isabelle Migeotte, Pierre-Emmanuel Morange, Guillaume Morelle, Andrea Martin-Nalda, Giuseppe Novelli, Antonio Novelli, Tayfun Ozcelik, Figen Palabiyik, Qiang Pan-Hammarström, Rebeca Pérez de Diego, Laura Planas-Serra, Daniel E. Pleguezuelo, Carolina Prando, Aurora Pujol, Luis Felipe Reyes, Jacques G. Rivière, Carlos Rodriguez-Gallego, Julian Rojas, Patrizia Rovere-Querini, Agatha Schlüter, Mohammad Shahrooei, Ali Sobh, Pere Soler-Palacin, Yacine Tandjaoui-Lambiotte, Imran Tipu, Cristina Tresoldi, Jesus Troya, Diederik van de Beek, Mayana Zatz, Pawel Zawadzki, Saleh Zaid Al-Muhsen, Mohammed Faraj Alosaimi, Fahad M. Alsohime, Hagit Baris-Feldman, Manish J. Butte, Stefan N. Constantinescu, Megan A. Cooper, Clifton L. Dalgard, Jacques Fellay, James R. Heath, Yu-Lung Lau, Richard P. Lifton, Tom Maniatis, Trine H. Mogensen, Horst von Bernuth, Alban Lermine, Michel Vidaud, Anne Boland, Jean-François Deleuze, Robert Nussbaum, Amanda Kahn-Kirby, France Mentre, Sarah Tubiana, Guy Gorochov, Florence Tubach, Pierre Hausfater, COVID Human Genetic Effort, COVIDeF Study Group, French COVID Cohort Study Group, CoV-Contact Cohort, COVID Clinicians, Orchestra Working Group, Amsterdam UMC Covid-19 Biobank, NIAID-USUHS COVID Study Group, Isabelle Meyts, Shen-Ying Zhang, Anne Puel, Luigi D. Notarangelo, Stephanie Boisson-Dupuis, Helen C. Su, Bertrand Boisson, Emmanuelle Jouanguy, Jean-Laurent Casanova, Qian Zhang, Laurent Abel, and Aurélie Cobat
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Medicine ,Genetics ,QH426-470 - Published
- 2024
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17. Inflammatory Markers Predict Blood Neurofilament Light Chain Levels in Acute COVID-19 Patients
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Rebecca De Lorenzo, Nicola I. Loré, Annamaria Finardi, Alessandra Mandelli, Federico Calesella, Mariagrazia Palladini, Daniela M. Cirillo, Cristina Tresoldi, Fabio Ciceri, Patrizia Rovere-Querini, Angelo A. Manfredi, Mario G. Mazza, Francesco Benedetti, and Roberto Furlan
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COVID-19 ,neurofilament light chain ,inflammatory markers ,neuroCOVID ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Acute coronavirus disease 2019 (COVID-19) is paralleled by a rise in the peripheral levels of neurofilament light chain (NfL), suggesting early nervous system damage. In a cohort of 103 COVID-19 patients, we studied the relationship between the NfL and peripheral inflammatory markers. We found that the NfL levels are significantly predicted by a panel of circulating cytokines/chemokines, including CRP, IL-4, IL-8, IL-9, Eotaxin, and MIP-1ß, which are highly up-regulated during COVID-19 and are associated with clinical outcomes. Our findings show that peripheral cytokines influence the plasma levels of the NfL, suggesting a potential role of the NfL as a marker of neuronal damage associated with COVID-19 inflammation.
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- 2024
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18. Multimodal deep learning for COVID-19 prognosis prediction in the emergency department: a bi-centric study
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Franca Dipaola, Mauro Gatti, Alessandro Giaj Levra, Roberto Menè, Dana Shiffer, Roberto Faccincani, Zainab Raouf, Antonio Secchi, Patrizia Rovere Querini, Antonio Voza, Salvatore Badalamenti, Monica Solbiati, Giorgio Costantino, Victor Savevski, and Raffaello Furlan
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Medicine ,Science - Abstract
Abstract Predicting clinical deterioration in COVID-19 patients remains a challenging task in the Emergency Department (ED). To address this aim, we developed an artificial neural network using textual (e.g. patient history) and tabular (e.g. laboratory values) data from ED electronic medical reports. The predicted outcomes were 30-day mortality and ICU admission. We included consecutive patients from Humanitas Research Hospital and San Raffaele Hospital in the Milan area between February 20 and May 5, 2020. We included 1296 COVID-19 patients. Textual predictors consisted of patient history, physical exam, and radiological reports. Tabular predictors included age, creatinine, C-reactive protein, hemoglobin, and platelet count. TensorFlow tabular-textual model performance indices were compared to those of models implementing only tabular data. For 30-day mortality, the combined model yielded slightly better performances than the tabular fastai and XGBoost models, with AUC 0.87 ± 0.02, F1 score 0.62 ± 0.10 and an MCC 0.52 ± 0.04 (p
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- 2023
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19. Profiling Covid-19 patients with respect to level of severity: an integrated statistical approach
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Federica Cugnata, Maria Giovanna Scarale, Rebecca De Lorenzo, Marco Simonini, Lorena Citterio, Patrizia Rovere Querini, Antonella Castagna, Clelia Di Serio, and Chiara Lanzani
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Medicine ,Science - Abstract
Abstract A full understanding of the characteristics of Covid-19 patients with a better chance of experiencing poor vital outcomes is critical for implementing accurate and precise treatments. In this paper, two different advanced data-driven statistical approaches along with standard statistical methods have been implemented to identify groups of patients most at-risk for death or severity of respiratory distress. First, the tree-based analysis allowed to identify profiles of patients with different risk of in-hospital death (by Survival Tree-ST analysis) and severity of respiratory distress (by Classification and Regression Tree-CART analysis), and to unravel the role on risk stratification of highly dependent covariates (i.e., demographic characteristics, admission values and comorbidities). The ST analysis identified as the most at-risk group for in-hospital death the patients with age > 65 years, creatinine $$\ge$$ ≥ 1.2 mg/dL, CRP $$\ge$$ ≥ 25 mg/L and anti-hypertensive treatment. Based on the CART analysis, the subgroups most at-risk of severity of respiratory distress were defined by patients with creatinine level $$\ge$$ ≥ 1.2 mg/dL. Furthermore, to investigate the multivariate dependence structure among the demographic characteristics, the admission values, the comorbidities and the severity of respiratory distress, the Bayesian Network analysis was applied. This analysis confirmed the influence of creatinine and CRP on the severity of respiratory distress.
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- 2023
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20. Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19
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Daniela Matuozzo, Estelle Talouarn, Astrid Marchal, Peng Zhang, Jeremy Manry, Yoann Seeleuthner, Yu Zhang, Alexandre Bolze, Matthieu Chaldebas, Baptiste Milisavljevic, Adrian Gervais, Paul Bastard, Takaki Asano, Lucy Bizien, Federica Barzaghi, Hassan Abolhassani, Ahmad Abou Tayoun, Alessandro Aiuti, Ilad Alavi Darazam, Luis M. Allende, Rebeca Alonso-Arias, Andrés Augusto Arias, Gokhan Aytekin, Peter Bergman, Simone Bondesan, Yenan T. Bryceson, Ingrid G. Bustos, Oscar Cabrera-Marante, Sheila Carcel, Paola Carrera, Giorgio Casari, Khalil Chaïbi, Roger Colobran, Antonio Condino-Neto, Laura E. Covill, Ottavia M. Delmonte, Loubna El Zein, Carlos Flores, Peter K. Gregersen, Marta Gut, Filomeen Haerynck, Rabih Halwani, Selda Hancerli, Lennart Hammarström, Nevin Hatipoğlu, Adem Karbuz, Sevgi Keles, Christèle Kyheng, Rafael Leon-Lopez, Jose Luis Franco, Davood Mansouri, Javier Martinez-Picado, Ozge Metin Akcan, Isabelle Migeotte, Pierre-Emmanuel Morange, Guillaume Morelle, Andrea Martin-Nalda, Giuseppe Novelli, Antonio Novelli, Tayfun Ozcelik, Figen Palabiyik, Qiang Pan-Hammarström, Rebeca Pérez de Diego, Laura Planas-Serra, Daniel E. Pleguezuelo, Carolina Prando, Aurora Pujol, Luis Felipe Reyes, Jacques G. Rivière, Carlos Rodriguez-Gallego, Julian Rojas, Patrizia Rovere-Querini, Agatha Schlüter, Mohammad Shahrooei, Ali Sobh, Pere Soler-Palacin, Yacine Tandjaoui-Lambiotte, Imran Tipu, Cristina Tresoldi, Jesus Troya, Diederik van de Beek, Mayana Zatz, Pawel Zawadzki, Saleh Zaid Al-Muhsen, Mohammed Faraj Alosaimi, Fahad M. Alsohime, Hagit Baris-Feldman, Manish J. Butte, Stefan N. Constantinescu, Megan A. Cooper, Clifton L. Dalgard, Jacques Fellay, James R. Heath, Yu-Lung Lau, Richard P. Lifton, Tom Maniatis, Trine H. Mogensen, Horst von Bernuth, Alban Lermine, Michel Vidaud, Anne Boland, Jean-François Deleuze, Robert Nussbaum, Amanda Kahn-Kirby, France Mentre, Sarah Tubiana, Guy Gorochov, Florence Tubach, Pierre Hausfater, COVID Human Genetic Effort, COVIDeF Study Group, French COVID Cohort Study Group, CoV-Contact Cohort, COVID-STORM Clinicians, COVID Clinicians, Orchestra Working Group, Amsterdam UMC Covid-19 Biobank, NIAID-USUHS COVID Study Group, Isabelle Meyts, Shen-Ying Zhang, Anne Puel, Luigi D. Notarangelo, Stephanie Boisson-Dupuis, Helen C. Su, Bertrand Boisson, Emmanuelle Jouanguy, Jean-Laurent Casanova, Qian Zhang, Laurent Abel, and Aurélie Cobat
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Rare variants ,COVID-19 ,Immunity ,Type I interferon ,Medicine ,Genetics ,QH426-470 - Abstract
Abstract Background We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15–20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases. Methods We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. Results No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5–528.7, P = 1.1 × 10−4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3–8.2], P = 2.1 × 10−4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1–2635.4], P = 3.4 × 10−3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3–8.4], P = 7.7 × 10−8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10−5). Conclusions Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old.
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- 2023
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21. Higher Seasonal Variation of Systemic Inflammation in Bipolar Disorder
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Sara Dallaspezia, Vincenzo Cardaci, Mario Gennaro Mazza, Rebecca De Lorenzo, Patrizia Rovere Querini, Cristina Colombo, and Francesco Benedetti
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bipolar disorder ,obsessive compulsive disorder ,season ,inflammation ,neutrophil ,lymphocyte ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Seasonal rhythms affect the immune system. Evidence supports the involvement of immuno-inflammatory mechanisms in bipolar disorder (BD), with the neutrophil to lymphocyte ratio (NLR), and the systemic immune-inflammatory index (SII; platelets × neutrophils/lymphocytes) consistently reported to be higher in patients with BD than in HC, but seasonal rhythms of innate and adaptive immunity have never been studied. We retrospectively studied NLR and SII in 824 participants divided into three groups: 321 consecutively admitted inpatients affected by a major depressive episode in course of BD, and 255 consecutively admitted inpatients affected by obsessive–compulsive disorder (OCD; positive psychiatric control), and 248 healthy controls (HC). Patients with BD showed markedly higher markers of systemic inflammation in autumn and winter, but not in spring and summer, in respect to both HC and patients with OCD, thus suggesting a specific effect of season on inflammatory markers in BD, independent of a shared hospital setting and drug treatment. Given that systemic inflammation is emerging as a new marker and as target for treatment in depressive disorders, we suggest that seasonal rhythms should be considered for tailoring antidepressant immuno-modulatory treatments in a precision medicine approach.
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- 2024
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22. Autoantibody status according to multiparametric assay accurately estimates connective tissue disease classification and identifies clinically relevant disease clusters
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Micaela Fredi, Nicola Bizzaro, Margherita Zen, Chiara Baldini, Ilaria Cavazzana, Roberto Giacomelli, Valeria Riccieri, Marco Fornaro, Franco Franceschini, Roberto Gerli, Anna Ghirardello, Paola Migliorini, Maurizio Benucci, Maria Infantino, Mariangela Manfredi, Elena Bartoloni, Antonella Fioravanti, Amelia Rigon, Silvia Piantoni, Onelia Bistoni, Francesca Bellisai, Carlo Perricone, Giacomo Cafaro, Danilo Villalta, Stefania Masneri, Paola Parronchi, Boaz Palterer, Stefania Del Rosso, Fabiana Topini, Manuela Sebastiano, Emirena Garrafa, Sara Cheleschi, Maria-Romana Bacarelli, Marilina Tampoia, Daniele Cammelli, Luisa Arcarese, Patrizia Rovere Querini, and Valentina Canti
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Medicine - Abstract
Objective Assessment of circulating autoantibodies represents one of the earliest diagnostic procedures in patients with suspected connective tissue disease (CTD), providing important information for disease diagnosis, identification and prediction of potential clinical manifestations. The purpose of this study was to evaluate the ability of multiparametric assay to correctly classify patients with multiple CTDs and healthy controls (HC), independent of clinical features, and to evaluate whether serological status could identify clusters of patients with similar clinical features.Methods Patients with systemic lupus erythematosus (SLE), systemic sclerosis (SSc), Sjogren’s syndrome (SjS), undifferentiated connective tissue disease (UCTD), idiopathic inflammatory myopathies (IIM) and HC were enrolled. Serum was tested for 29 autoantibodies. An XGBoost model, exclusively based on autoantibody titres was built and classification accuracy was evaluated. A hierarchical clustering model was subsequently developed and clinical/laboratory features compared among clusters.Results 908 subjects were enrolled. The classification model showed a mean accuracy of 60.84±4.05% and a mean area under the receiver operator characteristic curve of 88.99±2.50%, with significant discrepancies among groups. Cluster analysis identified four clusters (CL). CL1 included patients with typical features of SLE. CL2 included most patients with SjS, along with some SLE and UCTD patients with SjS-like features. CL4 included anti-Jo1 patients only. CL3 was the largest and most heterogeneous, including all the remaining subjects, overall characterised by low titre or lower-prevalence autoantibodies.Conclusion Extended multiparametric autoantibody assay allowed an accurate classification of CTD patients, independently of clinical features. Clustering according to autoantibody titres is able to identify clusters of CTD subjects with similar clinical features, independently of their final diagnosis.
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- 2023
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23. P1572: COVID-19 MORTALITY IN HIGH-RISK PATIENTS AFTER ALLO-HSCT AND CAR-T: IMPROVED OUTCOME THROUGH A PANDEMIC.
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Daniele Sannipoli, Gariazzo Camilla, Francesca Farina, Elisa Diral, Alessandro Bruno, Daniela Clerici, Sarah Marktel, Luca Canziani, Gloria Catalano, Paolo Fiore, Chiara Oltolini, Patrizia Rovere Querini, Consuelo Corti, Fabio Ciceri, Giordano Vitali, and Maria Teresa Lupo-Stanghellini
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2023
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24. P1638: CLONAL HEMATOPOIESIS OF INDETERMINATE POTENTIAL (CHIP) IS A RISK FACTOR FOR PULMONARY VASCULAR THROMBOSIS IN PATIENTS WITH COVID-19.
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Federico Mario Aletti, Annalisa Ruggeri, Piera Angelillo, Sara Mastaglio, Federico Erbella, Diego Palumbo, Giliola Calori, Matteo G. Carrabba, Patrizia Rovere Querini, Fabio Ciceri, Cristina Tresoldi, Gabriele Fragasso, Francesco De Cobelli, Matteo Zampini, Matteo Giovanni Della Porta, and Massimo Bernardi
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2023
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25. Long-term consequences of COVID-19 on cognitive functioning up to 6 months after discharge: role of depression and impact on quality of life
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Poletti, Sara, Palladini, Mariagrazia, Mazza, Mario Gennaro, De Lorenzo, Rebecca, Furlan, Roberto, Ciceri, Fabio, Rovere-Querini, Patrizia, and Benedetti, Francesco
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- 2022
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26. Vertebral fractures at hospitalization predict impaired respiratory function during follow-up of COVID-19 survivors
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di Filippo, Luigi, Compagnone, Nicola, Frara, Stefano, Allora, Agnese, Doga, Mauro, Rovere Querini, Patrizia, Cremona, George, and Giustina, Andrea
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- 2022
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27. Impact of Remdesivir on SARS-CoV-2 Clearance in a Real-Life Setting: A Matched-Cohort Study
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Spagnuolo V, Voarino M, Tonelli M, Galli L, Poli A, Bruzzesi E, Racca S, Clementi N, Oltolini C, Tresoldi M, Rovere Querini P, Dagna L, Zangrillo A, Ciceri F, Clementi M, and Castagna A
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covid-19 ,remdesivir ,sars-cov-2 ,viral clearance ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Vincenzo Spagnuolo,1 Marta Voarino,2 Marco Tonelli,2,3 Laura Galli,1 Andrea Poli,1 Elena Bruzzesi,2 Sara Racca,3 Nicola Clementi,2,3 Chiara Oltolini,1 Moreno Tresoldi,4 Patrizia Rovere Querini,2,5 Lorenzo Dagna,2,6 Alberto Zangrillo,2,7 Fabio Ciceri,2,8 Massimo Clementi,2,3 Antonella Castagna1,2 On behalf of the COVID-BioB Study Group1Unit of Infectious Diseases, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), San Raffaele Scientific Institute, Milan, Italy; 2Faculty of Medicine and Surgery, Vita-Salute San Raffaele University, Milan, Italy; 3Unit of Microbiology and Virology, IRCCS San Raffaele Scientific Institute, Milan, Italy; 4General Medicine and Advanced Care Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy; 5Internal Medicine, Diabetes, and Endocrinology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy; 6Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy; 7Anesthesia and Intensive Care Department, IRCCS San Raffaele Scientific Institute, Milan, Italy; 8Hematology and Bone Marrow Transplant Unit, IRCCS San Raffaele Scientific Institute, Milan, ItalyCorrespondence: Vincenzo Spagnuolo, Unit of Infectious Diseases, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), San Raffaele Scientific Institute, Milan, Italy, Tel +390226437907, Fax +390226437903, Email spagnuolo.vincenzo@hsr.itBackground: Evidence regarding the impact of remdesivir (RDV) on SARS-CoV-2 viral clearance (VC) is scarce. The aim of this study was to compare VC timing in hospitalized COVID-19 patients who did or did not receive RDV.Methods: This was a matched-cohort study of patients hospitalized with pneumonia, a SARS-CoV-2-positive nasopharyngeal swab (NPS) at admission, and at least one NPS during follow-up. Patients who received RDV (cases) and those who did not (controls) were matched in a 1:2 ratio by age, sex, and PaO2/FiO2 (P/F) values at admission. NPSs were analyzed using real-time polymerase chain reaction. Time to VC (within 30 days after hospital discharge) was estimated using the Kaplan–Meier curve. A multivariable Cox proportional hazard model was fitted to determine factors associated with VC.Results: There were 648 patients enrolled in the study (216 cases and 432 controls). VC was observed in 490 patients (75.6%), with a median time of 25 (IQR 16– 34) days. Overall, time to VC was similar between cases and controls (p = 0.519). However, time to VC was different when considering both RDV treatment status and age (p = 0.007). A significant finding was also observed when considering both RDV treatment status and P/F values at admission (p = 0.007). A multivariate analysis showed that VC was associated with a younger age (aHR = 0.990, 95% CI 0.983– 0.998 per every 10-year increase in age; p = 0.009) and a higher baseline P/F ratio (aHR=1.275, 95% CI 1.029– 1.579; p=0.026), but not with RDV treatment status.Conclusion: Time to VC was similar in cases and controls. However, there was a benefit associated with using RDV in regard to time to VC in younger patients and in those with a P/F ratio ≤ 200 mmHg at hospital admission.Keywords: COVID-19, remdesivir, SARS-CoV-2, viral clearance
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- 2022
28. POS0895 FAMILY PLANNING IN WOMEN AFFECTED BY RHEUMATOLOGICAL DISEASES: REAL-LIFE DATA FROM ITALY
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Carrea, G., primary, Gerosa, M., additional, Mosca, M., additional, Padovan, M., additional, Paolino, S., additional, Anelli, M. G., additional, Ramonda, R., additional, Nalli, C., additional, Rovere-Querini, P., additional, Bellis, E., additional, D’angelo, S., additional, Fusaro, E., additional, Chimenti, M. S., additional, Santo, L., additional, Gabini, M., additional, Pazzola, G., additional, Serale, F., additional, Montecucco, C., additional, Conti, F., additional, and Caporali, R. F., additional
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- 2024
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29. AB1405 ADVERSE PREGNANCY OUTCOMES BEYOND THE ANTIPHOSPHOLIPID ANTIBODY SYNDROME: THE ROLE OF COMPLEMENT ACTIVATION
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Cavallo, L., primary, Canti, V., additional, De Lorenzo, R., additional, Pasi, F., additional, Girardelli, S., additional, Castiglioni, M. T., additional, and Rovere-Querini, P., additional
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- 2024
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30. Exploring the Association between Delirium and Malnutrition in COVID-19 Survivors: A Geriatric Perspective
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Sarah Damanti, Marta Cilla, Giordano Vitali, Valeria Tiraferri, Chiara Pomaranzi, Giulia De Rubertis, Rebecca De Lorenzo, Giuseppe Di Lucca, Raffaella Scotti, Emanuela Messina, Raffaele Dell’Acqua, Monica Guffanti, Paola Cinque, Antonella Castagna, Patrizia Rovere-Querini, and Moreno Tresoldi
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delirium ,malnutrition ,frailty ,COVID-19 survivors ,geriatric syndromes ,Nutrition. Foods and food supply ,TX341-641 - Abstract
Older individuals face an elevated risk of developing geriatric syndromes when confronted with acute stressors like COVID-19. We assessed the connection between in-hospital delirium, malnutrition, and frailty in a cohort of COVID-19 survivors. Patients aged ≥65, hospitalized in a tertiary hospital in Milan for SARS-CoV-2 pneumonia, were enrolled and screened for in-hospital delirium with the 4 ‘A’s Test (4AT) performed twice daily (morning and evening) during hospital stay. Malnutrition was assessed with the malnutrition universal screening tool (MUST) at hospital admission and with the mini-nutritional assessment short-form (MNA-SF) one month after hospital discharge. Frailty was computed with the frailty index one month after hospital discharge. Fifty patients (median age 78.5, 56% male) were enrolled. At hospital admission, 10% were malnourished. The 13 patients (26%) who developed delirium were frailer (7 vs. 4), experienced a higher in-hospital mortality (5 vs. 3), and were more malnourished one month after discharge (3 of the 4 patients with delirium vs. 6 of the 28 patients without delirium who presented at follow up). The 4AT scores correlated with the MNA-SF scores (r = −0.55, p = 0.006) and frailty (r = 0.35, p = 0.001). Frailty also correlated with MUST (r = 0.3, p = 0.04), MNA-SF (r = −0.42, p = 0.02), and hospitalization length (r = 0.44, p = 0.001). Delirium, malnutrition, and frailty are correlated in COVID-19 survivors. Screening for these geriatric syndromes should be incorporated in routine clinical practice.
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- 2023
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31. Cognitive, EEG, and MRI features of COVID-19 survivors: a 10-month study
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Cecchetti, Giordano, Agosta, Federica, Canu, Elisa, Basaia, Silvia, Barbieri, Alessandra, Cardamone, Rosalinda, Bernasconi, Maria Paola, Castelnovo, Veronica, Cividini, Camilla, Cursi, Marco, Vabanesi, Marco, Impellizzeri, Matteo, Lazzarin, Serena Marita, Fanelli, Giovanna Franca, Minicucci, Fabio, Giacalone, Giacomo, Falini, Andrea, Falautano, Monica, Rovere-Querini, Patrizia, Roveri, Luisa, and Filippi, Massimo
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- 2022
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32. Chitinase-3-like protein-1 at hospital admission predicts COVID-19 outcome: a prospective cohort study
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Rebecca De Lorenzo, Clara Sciorati, Nicola I. Lorè, Annalisa Capobianco, Cristina Tresoldi, Daniela M. Cirillo, Fabio Ciceri, Patrizia Rovere-Querini, and Angelo A. Manfredi
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Medicine ,Science - Abstract
Abstract Infectious and inflammatory stimuli elicit the generation of chitinase-3-like protein-1 (CHI3L1), involved in tissue damage, repair and remodeling. We evaluated whether plasma CHI3L1 at disease onset predicts clinical outcome of patients with Coronavirus 2019 (COVID-19) disease. Blood from 191 prospectively followed COVID-19 patients were collected at hospital admission between March 18th and May 5th, 2020. Plasma from 80 survivors was collected one month post-discharge. Forty age- and sex-matched healthy volunteers served as controls. Primary outcome was transfer to intensive care unit (ICU) or death. CHI3L1 was higher in COVID-19 patients than controls (p
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- 2022
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33. Inflammatory signature of post-COVID-19 depression
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M. Palladini, M. G. Mazza, V. Aggio, S. Spadini, F. Calesella, S. Poletti, P. Rovere-Querini, and F. Benedetti
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Psychiatry ,RC435-571 - Abstract
Introduction Persisting and disabling depressive symptomatology represent a prominent feature of the post-acute COVID-19 syndrome. Sars-CoV-2-induced immune system dysregulation mainly result in a cytokine storm. Once in the brain, inflammatory mediators negatively affect neurotransmission, microglia activation, and oxidative stress, possibly disrupting critical brain neurocircuits which underpin depressive symptoms. So far, only inflammatory markers based on leukocyte counts have been linked to depressive outcome in COVID survivors. However, an accurate immune profile of post-COVID depression has yet to be elucidated. Objectives Identify inflammatory mediators that predict post-COVID depression among a panel of cytokines, chemokines, and growth factors, with a machine learning routine. Methods 88 COVID age- and sex-matched survivors’ (age 52.01 ± 9.32) were screened for depressive symptomatology one month after the virus clearance through the Beck Depression Inventory (BDI-13), with 12.5% of the individuals scoring in the clinical range (BDI-13 ≥ 9). Immune assay was performed through Luminex system on blood sampling obtained in the same context. We entered 42 analytes into an elastic net penalized regression model predicting presence of clinical depression, applied within a 5-fold nested cross-validation machine learning routine running in MATLAB. Significance of predictors was evaluated according to variable inclusion probability (VIP), as returned by 5000 bootstraps. Socio-demographics, previous psychiatric history, hospitalization, time after discharge were used as covariates. Results The model reached a balance accuracy of 73% and AUC of 77%, correctly identifying 73% of people suffering from clinically relevant depressive symptoms (Figure1). Depressive symptomatology was predicted by high levels of CCL17, ICAM-1, MIF, whereas CXCL13, CXCL12, CXCL10, CXCL5, CXCL2, CCL23, CCL15, CCL8, GM-CSF showed a protective effect (Figure2). Image: Image 2: Conclusions This is the first study highlighting a putative inflammatory signature of post-COVID depression. Consistently to the immune profile of Major Depressive disorder, upregulation of innate immunity mediators seems to foster depressive symptoms in the aftermath of COVID. Interestingly, recruiters of B and T cells promoting a physiological adaptive response to viral infection also mitigate its psychiatric sequelae. Understanding the biological basis of post-COVID depression could pave the way for personalized treatments capable of reducing its add-on burden. Disclosure of InterestNone Declared
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- 2023
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34. The exploration of interoception construct in COVID-19 survivors
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G. D’Orsi, M. Palladini, A. Scalabrini, M. G. Mazza, S. Poletti, P. Rovere-Querini, and F. Benedetti
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Psychiatry ,RC435-571 - Abstract
Introduction The new coronavirus disease (COVID-19) has important physical and mental health implications at short and long term. Some inflammatory parameters are implicated in the maintenance of psychiatric symptoms, especially those of anxiety and depression. Additionally, growing literature attributes a role to interoception in several mental health conditions. Objectives We investigated the involvement of the interoception in COVID-19 survivors and its possible associations with psychopathological and inflammatory variables. Methods Our study included 57 people surviving COVID-19 at one month follow-up after recovery. Individual interoceptive accuracy (IA) measure was obtained through heart-beat perception task. A measure of accuracy in external time perception (TA) was also obtained asking people to mentally produce a duration of 10s. Each participant completed State-Trait Anxiety Inventory - STAI-Y; Zung Self-Rating Depression Scale - ZSDS; Beck Depression Inventory - BDI-II; Impact of Events Scale - IES-R and Multidimensional Assessment of Interoceptive Awareness - MAIA. Peripheral inflammation markers were obtained in a subsample of 40 people by a blood sampling conducted at the time of admission and discharge from hospital. Correlation, regression and GLM analyses were performed with SPSS. Mediation analysis were performed with Hayes’ Process tool. Results TA is not associated with IA, symptomatological measures and bodily awareness. Trusting is the only aspect of body awareness associated with IA (p=.021). Noticing (p=.010), Not-distracting (p=.009), Not-worrying (p=.012) and Trusting (p=.001) predict anxiety psychopathology. Poor IA predict anxiety symptomatology (p=.004) and part of this effect is mediated by Trusting [Fig.1]. In the end, platelets count at the time of hospitalization negatively correlates with anxiety symptoms (p=.003). Image: Conclusions COVID-19 hospitalization could be considered a psychophysical traumatic experience which involved mental and physical health and the connection and integration between them. It’s necessary to deepen the different facets of body awareness and IA in post-covid stages and to study how interoceptive dimensions change over time. Further research is needed to investigate the specific role of platelets in prominent anxiety psychopathology detected in COVID-19 survivors, wondering about their possible involvement in the dysfunctional interoception process too. Disclosure of Interest None Declared
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- 2023
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35. A longitudinal analysis of humoral, T cellular response and influencing factors in a cohort of healthcare workers: Implications for personalized SARS-CoV-2 vaccination strategies
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Eleonora Sabetta, Maddalena Noviello, Clara Sciorati, Marco Viganò, Rebecca De Lorenzo, Valeria Beretta, Veronica Valtolina, Chiara Di Resta, Giuseppe Banfi, Davide Ferrari, Massimo Locatelli, Fabio Ciceri, Chiara Bonini, Patrizia Rovere-Querini, and Rossella Tomaiuolo
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COVID-19 ,T-cell response ,SARS-CoV-2 vaccination ,serological tests and risk factors ,influencing factors (variables) ,Immunologic diseases. Allergy ,RC581-607 - Abstract
IntroductionSARS-CoV-2 mRNA vaccinations elicit both virus-specific humoral and T-cell responses, but a complex interplay of different influencing factors, such as natural immunity, gender, and age, guarantees host protection. The present study aims to assess the immune dynamics of humoral, T-cell response, and influencing factors to stratify individual immunization status up to 10 months after Comirnaty-vaccine administration.MethodsTo this aim, we longitudinally evaluated the magnitude and kinetics of both humoral and T-cell responses by serological tests and enzyme-linked immunospot assay at 5 time points. Furthermore, we compared the course over time of the two branches of adaptive immunity to establish an eventual correlation between adaptive responses. Lastly, we evaluated putative influencing factors collected by an anonymized survey administered to all participants through multiparametric analysis. Among 984 healthcare workers evaluated for humoral immunity, 107 individuals were further analyzed to describe SARS-CoV-2-specific T-cell responses. Participants were divided into 4 age groups:
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- 2023
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36. Chitinase-3-like protein-1 at hospital admission predicts COVID-19 outcome: a prospective cohort study
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De Lorenzo, Rebecca, Sciorati, Clara, Lorè, Nicola I., Capobianco, Annalisa, Tresoldi, Cristina, Cirillo, Daniela M., Ciceri, Fabio, Rovere-Querini, Patrizia, and Manfredi, Angelo A.
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- 2022
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37. Longitudinal Changes in Physical Function and Their Impact on Health Outcomes in COVID-19 Patients
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Rebecca De Lorenzo, Luigi Di Filippo, Sabrina Scelfo, Aurora Merolla, Andrea Giustina, Caterina Conte, and Patrizia Rovere-Querini
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SARS-CoV-2 ,COVID-19 ,muscle strength ,sarcopenia ,physical function ,Nutrition. Foods and food supply ,TX341-641 - Abstract
Background: Coronavirus disease (COVID-19) is correlated with a variety of long-term sequelae that affect different aspects of health, including physical function. This study investigated the longitudinal changes in handgrip strength (HGS) over six months post-hospital discharge in COVID-19 patients and explores the associations between HGS, health-related quality of life, dyspnoea, exercise capacity, and body mass index (BMI). Methods: Adult COVID-19 patients were followed up at one, three, and six months after hospital discharge. HGS, BMI, exercise capacity, and health-related quality of life were assessed. Data from patients with HGS measurements at all three time points were analysed. Results: Low HGS was prevalent one month post-discharge (35%). Participants with low HGS exhibited more severe disease (30.5% vs. 5.9% were admitted to the intensive care unit, p < 0.01), longer hospital stays (median [IQR] 21 [10.0; 40.5] vs. 12.0 [8.0; 20.0] days, p < 0.01), greater weight loss (−5.7 [−9.1; −0.6] vs. −3.2 [−5.7; −0.0] kg, p = 0.004), and reduced exercise capacity (6 min walking test [6 MWT], 95.7 [84.0; 102.0] vs. 100.0 [92.9; 105.0]% predicted, p = 0.007). Those with persistently low HGS (40% of the initial low HGS group) had worse exercise capacity (6-MWT 93.3 [78.3; 101.0] vs. 101.0 [95.0; 107.0]% predicted, p < 0.001), more dyspnoea (29.0% vs. 2.0% of participants, p < 0.001), poorer quality of life (visual analogue scale score, 75 [50; 75] vs. 85 [75; 95], p < 0.001), and higher rates of problems in various health dimensions. HGS at 1 month was the only significant predictor of HGS improvement from 1 month to 6 months (odds ratio [95% CI] 1.11 [1.03; 1.20], p = 0.008). Conclusions: This study highlights the prevalence of reduced physical function among COVID-19 survivors and emphasises the importance of early identification and intervention to optimise their long-term health. Monitoring HGS, a simple and reliable tool, can provide valuable insights into patients’ overall physical function, aiding in tailored care and improved outcomes.
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- 2023
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38. Acute Kidney Injury at Hospital Admission for SARS-CoV-2 Infection as a Marker of Poor Prognosis: Clinical Implications for Triage Risk Stratification
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Carlo Andrea Bravi, Walter Cazzaniga, Marco Simonini, Alessandro Larcher, Elisabetta Messaggio, Laura Zagato, Cristina Carenzi, Roberto Bertini, Alberto Briganti, Paolo Manunta, Giuseppe Vezzoli, Andrea Salonia, Chiara Lanzani, Umberto Capitanio, Alberto Zangrillo, Giovanni Landoni, Patrizia Rovere-Querini, Moreno Tresoldi, Francesco Montorsi, and Fabio Ciceri
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coronavirus disease-19 ,severe acute respiratory syndrome coronavirus 2 ,urology ,acute kidney injury ,risk stratification ,triage ,Dermatology ,RL1-803 ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 ,Diseases of the genitourinary system. Urology ,RC870-923 - Abstract
Background/Aims: The new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a wide spectrum of effects, including acute kidney injury (AKI) in up to 40% of hospitalized patients. Given the established relationship between AKI and poor prognosis, whether AKI might be a prognostic indicator for patients admitted to the hospital for SARS-CoV-2 infection would allow for a straightforward risk stratification of these patients. Methods: We analyzed data of 623 patients admitted to San Raffaele Hospital (Milan, IT) between February 25 and April 19, 2020, for laboratory-confirmed SARS-CoV-2 infection. Incidence of AKI at hospital admission was calculated, with AKI defined according to the KDIGO criteria. Multivariable Cox regression models assessed the association between AKI and overall mortality and admission to the intensive care unit (ICU). Results: Overall, 108 (17%) patients had AKI at hospital admission for SARS-CoV-2 infection. After a median follow-up for survivors of 14 days (interquartile range: 8, 23), 123 patients died, while 84 patients were admitted to the ICU. After adjusting for confounders, patients who had AKI at hospital admission were at increased risk of overall mortality compared to those who did not have AKI (hazards ratio [HR]: 2.00; p = 0.0004), whereas we did not find evidence of an association between AKI and ICU admission (HR: 0.95; p = 0.9). Conclusions: These data suggest that AKI might be an indicator of poor prognosis for patients with SARS-CoV-2 infection, and as such, given its readily availability, it might be used to improve risk stratification at hospital admission.
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- 2022
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39. Blood neurofilament light chain and total tau levels at admission predict death in COVID-19 patients
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De Lorenzo, Rebecca, Loré, Nicola I., Finardi, Annamaria, Mandelli, Alessandra, Cirillo, Daniela M., Tresoldi, Cristina, Benedetti, Francesco, Ciceri, Fabio, Rovere-Querini, Patrizia, Comi, Giancarlo, Filippi, Massimo, Manfredi, Angelo A., and Furlan, Roberto
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- 2021
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40. 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, and Piemonti, Lorenzo
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- 2021
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41. Hypocalcemia in COVID-19 is associated with low vitamin D levels and impaired compensatory PTH response
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di Filippo, Luigi, Allora, Agnese, Locatelli, Massimo, Rovere Querini, Patrizia, Frara, Stefano, Banfi, Giuseppe, and Giustina, Andrea
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- 2021
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42. Patients with COVID-19: in the dark-NETs of neutrophils
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Ackermann, Maximilian, Anders, Hans-Joachim, Bilyy, Rostyslav, Bowlin, Gary L., Daniel, Christoph, De Lorenzo, Rebecca, Egeblad, Mikala, Henneck, Timo, Hidalgo, Andrés, Hoffmann, Markus, Hohberger, Bettina, Kanthi, Yogendra, Kaplan, Mariana J., Knight, Jason S., Knopf, Jasmin, Kolaczkowska, Elzbieta, Kubes, Paul, Leppkes, Moritz, Mahajan, Aparna, Manfredi, Angelo A., Maueröder, Christian, Maugeri, Norma, Mitroulis, Ioannis, Muñoz, Luis E., Narasaraju, Teluguakula, Naschberger, Elisabeth, Neeli, Indira, Ng, Lai Guan, Radic, Marko Z., Ritis, Konstantinos, Rovere-Querini, Patrizia, Schapher, Mirco, Schauer, Christine, Simon, Hans-Uwe, Singh, Jeeshan, Skendros, Panagiotis, Stark, Konstantin, Stürzl, Michael, van der Vlag, Johan, Vandenabeele, Peter, Vitkov, Ljubomir, von Köckritz-Blickwede, Maren, Yanginlar, Cansu, Yousefi, Shida, Zarbock, Alexander, Schett, Georg, and Herrmann, Martin
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- 2021
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43. CXCL10 levels at hospital admission predict COVID-19 outcome: hierarchical assessment of 53 putative inflammatory biomarkers in an observational study
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Nicola I. Lorè, Rebecca De Lorenzo, Paola M. V. Rancoita, Federica Cugnata, Alessandra Agresti, Francesco Benedetti, Marco E. Bianchi, Chiara Bonini, Annalisa Capobianco, Caterina Conte, Angelo Corti, Roberto Furlan, Paola Mantegani, Norma Maugeri, Clara Sciorati, Fabio Saliu, Laura Silvestri, Cristina Tresoldi, Bio Angels for COVID-BioB Study Group, Fabio Ciceri, Patrizia Rovere-Querini, Clelia Di Serio, Daniela M. Cirillo, and Angelo A. Manfredi
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COVID-19 severity predictors ,Biomarkers ,Decision tree ,CXCL10 ,Therapeutics. Pharmacology ,RM1-950 ,Biochemistry ,QD415-436 - Abstract
Abstract Background Host inflammation contributes to determine whether SARS-CoV-2 infection causes mild or life-threatening disease. Tools are needed for early risk assessment. Methods We studied in 111 COVID-19 patients prospectively followed at a single reference Hospital fifty-three potential biomarkers including alarmins, cytokines, adipocytokines and growth factors, humoral innate immune and neuroendocrine molecules and regulators of iron metabolism. Biomarkers at hospital admission together with age, degree of hypoxia, neutrophil to lymphocyte ratio (NLR), lactate dehydrogenase (LDH), C-reactive protein (CRP) and creatinine were analysed within a data-driven approach to classify patients with respect to survival and ICU outcomes. Classification and regression tree (CART) models were used to identify prognostic biomarkers. Results Among the fifty-three potential biomarkers, the classification tree analysis selected CXCL10 at hospital admission, in combination with NLR and time from onset, as the best predictor of ICU transfer (AUC [95% CI] = 0.8374 [0.6233–0.8435]), while it was selected alone to predict death (AUC [95% CI] = 0.7334 [0.7547–0.9201]). CXCL10 concentration abated in COVID-19 survivors after healing and discharge from the hospital. Conclusions CXCL10 results from a data-driven analysis, that accounts for presence of confounding factors, as the most robust predictive biomarker of patient outcome in COVID-19. Graphic abstract
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- 2021
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44. Weight trajectories and abdominal adiposity in COVID-19 survivors with overweight/obesity
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Di Filippo, Luigi, De Lorenzo, Rebecca, Cinel, Elena, Falbo, Elisabetta, Ferrante, Marica, Cilla, Marta, Martinenghi, Sabina, Vitali, Giordano, Bosi, Emanuele, Giustina, Andrea, Rovere-Querini, Patrizia, and Conte, Caterina
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- 2021
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45. Case Report: Consistent disease manifestations with a staggered time course in two identical twins affected by adenosine deaminase 2 deficiency
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Federica Barzaghi, Maria Pia Cicalese, Matteo Zoccolillo, Immacolata Brigida, Matteo Barcella, Ivan Merelli, Claudia Sartirana, Monica Zanussi, Valeria Calbi, Maria Ester Bernardo, Francesca Tucci, Maddalena Migliavacca, Fabio Giglio, Matteo Doglio, Daniele Canarutto, Francesca Ferrua, Giulia Consiglieri, Giulia Prunotto, Francesco Saettini, Sonia Bonanomi, Patrizia Rovere-Querini, Giulia Di Colo, Tatiana Jofra, Georgia Fousteri, Federica Penco, Marco Gattorno, Michael S. Hershfield, Lucia Bongiovanni, Maurilio Ponzoni, Sarah Marktel, Raffaella Milani, Jacopo Peccatori, Fabio Ciceri, Alessandra Mortellaro, and Alessandro Aiuti
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ADA2 ,adenosine deaminase 2 deficiency ,neutropenia ,T large granular lymphocytes ,TLGL ,HSCT ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Deficiency of adenosine deaminase 2 (DADA2) is an autosomal recessive disease associated with a highly variable clinical presentation, including vasculitis, immunodeficiency, and hematologic manifestations, potentially progressing over time. The present study describes the long-term evolution of the immuno-hematological features and therapeutic challenge of two identical adult twin sisters affected by DADA2. The absence of plasmatic adenosine deaminase 2 (ADA2) activity in both twins suggested the diagnosis of DADA2, then confirmed by genetic analysis. Exon sequencing revealed a missense (p.Leu188Pro) mutation on the paternal ADA2 allele. While, whole genome sequencing identified an unreported deletion (IVS6_IVS7del*) on the maternal allele predicted to produce a transcript missing exon 7. The patients experienced the disease onset during childhood with early strokes (Patient 1 at two years, Patient 2 at eight years of age), subsequently followed by other shared DADA2-associated features, including neutropenia, hypogammaglobulinemia, reduced switched memory B cells, inverted CD4:CD8 ratio, increased naïve T cells, reduced follicular regulatory T cells, the almost complete absence of NK cells, T-large granular cell leukemia, and osteoporosis. Disease evolution differed: clinical manifestations presented several years earlier and were more pronounced in Patient 1 than in Patient 2. Due to G-CSF refractory life-threatening neutropenia, Patient 1 successfully underwent an urgent hematopoietic stem cell transplantation (HSCT) from a 9/10 matched unrelated donor. Patient 2 experienced a similar, although delayed, disease evolution and is currently on anti-TNF therapy and anti-infectious prophylaxis. The unique cases confirmed that heterozygous patients with null ADA2 activity deserve deep investigation for possible structural variants on a single allele. Moreover, this report emphasizes the importance of timely recognizing DADA2 at the onset to allow adequate follow-up and detection of disease progression. Finally, the therapeutic management in these identical twins raises significant concerns as they share a similar phenotype, with a delayed but almost predictable disease evolution in one of them, who could benefit from a prompt definitive treatment like elective allogeneic HSCT. Additional data are required to assess whether the absence of enzymatic activity at diagnosis is associated with hematological involvement and is also predictive of bone marrow dysfunction, encouraging early HSCT to improve functional outcomes.
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- 2022
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46. Concomitant Autoimmunity in Endometriosis Impairs Endometrium–Embryo Crosstalk at the Implantation Site: A Multicenter Case-Control Study
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Noemi Salmeri, Gianluca Gennarelli, Valeria Stella Vanni, Stefano Ferrari, Alessandro Ruffa, Patrizia Rovere-Querini, Luca Pagliardini, Massimo Candiani, and Enrico Papaleo
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endometriosis ,autoimmunity ,autoantibodies ,implantation ,embryo development ,pregnancy rate ,Medicine - Abstract
Endometriosis and autoimmune diseases share a hyper-inflammatory state that might negatively impact the embryo–endometrium crosstalk. Inflammatory and immune deregulatory mechanisms have been shown to impair both endometrial receptivity and embryo competence at the implantation site. The aim of this study was to investigate the potential additional impact of co-existing autoimmunity in women affected by endometriosis on the early stages of reproduction. This was a retrospective, multicenter case-control study enrolling N = 600 women with endometriosis who underwent in vitro fertilization–embryo transfer cycles between 2007 and 2021. Cases were women with endometriosis and concomitant autoimmunity matched based on age and body mass index to controls with endometriosis only in a 1:3 ratio. The primary outcome was the cumulative clinical pregnancy rate (cCPR). The study found significantly lower cleavage (p = 0.042) and implantation (p = 0.029) rates among cases. Autoimmunity (p = 0.018), age (p = 0.007), and expected poor response (p = 0.014) were significant negative predictors of cCPR, with an adjusted odds ratio of 0.54 (95% CI, 0.33–0.90) for autoimmunity. These results suggest that the presence of concomitant autoimmunity in endometriosis has a significant additive negative impact on embryo implantation. This effect might be due to several immunological and inflammatory mechanisms that interfere with both endometrial receptivity and embryo development and deserves further consideration.
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- 2023
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47. Low incidence of intrauterine growth restriction in pregnant patients with systemic lupus erythematosus taking hydroxychloroquine
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Valentina Canti, Margherita Scarrone, Rebecca De Lorenzo, Giuseppe A. Ramirez, Roberta Erra, Sara Bordoli, Sara Cella, Elena Schmit, Susanna Rosa, Maria T. Castiglioni, and Patrizia Rovere-Querini
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systemic lupus erythematosus ,hydroxychloroquine ,pregnancy ,adverse pregnancy outcomes ,systemic autoimmune diseases ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Systemic lupus erythematosus (SLE) preferentially affects women of childbearing age. Miscarriages or fetal death, intrauterine growth restriction (IUGR), preterm delivery, preeclampsia and disease flares complicate pregnancy in SLE patients. Treatment is challenging due to the need to prevent disease exacerbations and limit obstetrical complications, while showing an acceptable safety profile for both the mother and the fetus. We collected data from 74 pregnancies in 53 SLE patients prospectively followed in a dedicated ‘Pregnancy at risk’ outpatient clinic from 2003 to 2019. Out of 74, 45 pregnancies patients were treated with hydroxychloroquine (HCQ). Mothers under HCQ therapy (HCQ+ patients) and those who did not receive HCQ (HCQ−) were homogeneous in terms of age and comorbidities. Disease activity prior to conception was slightly higher in HCQ+ patients. No significant difference was observed in terms of obstetrical history. In patients achieving a viable pregnancy, the rate of IUGR (4/39, 10% in HCQ+ vs 8/25, 32%, in HCQ− patients, p
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- 2021
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48. Concomitant autoimmunity may be a predictor of more severe stages of endometriosis
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Vanni Valeria Stella, Villanacci Roberta, Salmeri Noemi, Papaleo Enrico, Delprato Diana, Ottolina Jessica, Rovere-Querini Patrizia, Ferrari Stefano, Viganò Paola, and Candiani Massimo
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Medicine ,Science - Abstract
Abstract Pathogenesis of endometriosis is still unclear and a role of both innate and adaptive immune system has been postulated. Some recent findings have revealed an increased risk to have concomitant autoimmune disease in women with endometriosis, but no study so far has investigated whether this association could affect endometriosis severity and stage. We retrospectively reviewed medical patients’ notes of women with a confirmed diagnosis of endometriosis who referred to our endometriosis outpatient clinic between January 2015 and December 2019. Cases (endometriosis and an autoimmune disease) were matched in a 1:3 ratio by age and study period with controls (endometriosis without history of autoimmunity). At univariate logistic analysis, concomitant autoimmunity (OR 2.63, 95% CI 1.64–4.21, p
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- 2021
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49. Resting state network functional connectivity abnormalities in systemic lupus erythematosus: correlations with neuropsychiatric impairment
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Bonacchi, Raffaello, Rocca, Maria A., Ramirez, Giuseppe A., Bozzolo, Enrica P., Canti, Valentina, Preziosa, Paolo, Valsasina, Paola, Riccitelli, Gianna C., Meani, Alessandro, Moiola, Lucia, Rovere-Querini, Patrizia, Manfredi, Angelo A., and Filippi, Massimo
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- 2021
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50. Prevalence of Long COVID-19 Symptoms After Hospital Discharge in Frail and Robust Patients
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Sarah Damanti, Marta Cilla, Maria Cilona, Aldo Fici, Aurora Merolla, Giacomo Pacioni, Rebecca De Lorenzo, Sabina Martinenghi, Giordano Vitali, Cristiano Magnaghi, Anna Fumagalli, Mario Gennaro Mazza, Francesco Benedetti, Moreno Tresoldi, and Patrizia Rovere Querini
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frailty ,COVID-19 ,long COVID-19 syndrome ,older people ,prevalence ,Medicine (General) ,R5-920 - Abstract
BackgroundA motley postacute symptomatology may develop after COVID-19, irrespective of the acute disease severity, age, and comorbidities. Frail individuals have reduced physiological reserves and manifested a worse COVID-19 course, during the acute setting. However, it is still unknown, whether frailty may subtend some long COVID-19 manifestations. We explored the prevalence of long COVID-19 disturbs in COVID-19 survivals.MethodsThis was an observational study. Patients aged 65 years or older were followed-up 1, 3, and 6 months after hospitalization for COVID-19 pneumonia.ResultsA total of 382 patients were enrolled. Frail patients were more malnourished (median Mini Nutritional Assessment Short Form score 8 vs. 9, p = 0.001), at higher risk of sarcopenia [median Strength, Assistance with walking, Rising from a chair, Climbing stairs, and Falls (SARC-F) score 3 vs. 1.5, p = 0.003], and manifested a worse physical performance [median Short Physical Performance Battery (SPPB) score 10 vs. 11, p = 0.0007] than robust individuals, after hospital discharge following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia. Frailty was significantly associated with: (i) confusion, as a presenting symptom of COVID-19 [odds ratio (OR) 77.84, 95% CI 4.23–1432.49, p = 0.003]; (ii) malnutrition (MNA-SF: adjusted B –5.63, 95% CI –8.39 to –2.87, p < 0.001), risk of sarcopenia (SARC-F: adjusted B 9.11, 95% CI 3.10–15.13, p = 0.003), impaired muscle performance (SPPB: B –3.47, 95% CI –6.33 to –0.61, p = 0.02), complaints in mobility (adjusted OR 1674200.27, 95% CI 4.52–619924741831.25, p = 0.03), in self-care (adjusted OR 553305.56, 95% CI 376.37–813413358.35, p < 0.001), and in performing usual activities of daily living (OR 71.57, 95% CI 2.87–1782.53, p = 0.009) at 1-month follow-up; (iii) dyspnea [modified Medical Research Council (mMRC): B 4.83, 95% CI 1.32–8.33, p = 0.007] and risk of sarcopenia (SARC-F: B 7.12, 95% CI 2.17–12.07, p = 0.005) at 3-month follow-up; and (iv) difficulties in self-care (OR 2746.89, 95% CI 6.44–1172310.83, p = 0.01) at the 6-month follow-up. In a subgroup of patients (78 individuals), the prevalence of frailty increased at the 1-month follow-up compared to baseline (p = 0.009).ConclusionThe precocious identification of frail COVID-19 survivors, who manifest more motor and respiratory complaints during the follow-up, could improve the long-term management of these COVID-19 sequelae.
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- 2022
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