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Infliximab, a chimeric, monoclonal, anti-TNF antibody has been shown to be safe and efficacious for refractory sarcoidosis, we investigated whether adalimumab, a fully human, anti-TNF monoclonal antibody, is similarly safe and efficacious in refractory pulmonary sarcoidosis.An open-label, single-center study was conducted in 11 patients with refractory pulmonary sarcoidosis. Patients received adalimumab 40 mg weekly for 45 weeks, with a final follow-up at Week 52. The primary endpoint was the percent change in predicted forced vital capacity (FVC) at 24 weeks. Secondary efficacy parameters included the 6-minute walk test (6MWT), Borg dyspnea score, and Physician's (PGA) and Patient's (PaGA) Global Assessments. A successful outcome of the study was defined as reduction in immunosuppressive therapy (prednisone to 10 mg or less), improvement in FVC of 5% or greater, improvement in 6-minute walk test distance (6MWD) of 50 meter or greater at the end of weeks 24 and 52.Eleven patients received adalimumab and had 24-week follow-ups. Only ten patients had a Week 52 evaluation. FVC stabilized in seven patients, and four patients showed improvement in FVC. Five patients had improved 6MWD, and nine had lower Borg dyspnea scores. PGA and PaGA improved at weeks 24 and 52 for all patients (Plt;0.008 for all comparisons). Among 11 patients who underwent adalimumab treatment, 9 (82%) and 8(80%) had a successful outcome at the end of 24 and 52 weeks respectively. No severe adverse incidents were reported.In this small, open-label study, adalimumab improved refractory pulmonary sarcoidosis and was well tolerated (ClinicalTrials.gov identifier NCT00311246).

Background: Platelets are inflammatory cells with an important role in antimicrobial host defenses. We speculate that an abnormal platelet count may be a marker of severity in patients with community-acquired pneumonia (CAP). The objectives of this study were to evaluate if abnormal platelet count in hospitalized patients with CAP was associated with 30-day mortality and to compare platelet count and leukocyte count as predictors of 30-day mortality. Methods: We performed a retrospective cohort study of 500 consecutive patients hospitalized with CAP at the Veterans Hospital of Louisville, Kentucky, between June 2001 and March 2006 to investigate the association of platelet count and leukocyte count with 30-day mortality. Predictor variables were platelet count and leukocyte count. Abnormal platelet count was < 100,000/L (thrombocytopenia) and > 400,000/L (thrombocytosis). The outcome variable was 30-day mortality. To control for potential confounding, a propensity score that incorporated 33 variables was used. Results: Platelet count was strongly associated ( P = .0009) with 30-day mortality, whereas no association was observed for leukocyte count ( P = .5114). High platelet counts resulted in a significantly increased risk of mortality. Conclusions: Thrombocytopenia and thrombocytosis are associated with mortality in patients hospitalized with CAP. When evaluating an initial CBC test in patients with CAP, an abnormal platelet count is a better predictor of outcome than an abnormal leukocyte count. © 2010 American College of Chest Physicians.

The natural resistance-associated macrophage protein (NRAMP1), Vitamin-D receptor (VDR) and Tumor necrosis factor (TNF-alpha) have been associated in susceptibility to tuberculosis, but the results have been inconsistent. This study aimed to determine the association of NRAMP1, VDR, and TNF-á variant with development of pulmonary tuberculosis (PTB) among Iranian patients. The single nucleotide polymorphisms (SNPs) at INT4, D543, 3'UTR of NRAMP1 gene, SNPs in restriction sites of BsmI, and FokI of the VDR gene and SNPs of TNF-alpha at -238,-308, -244,857,-863 positions were analyzed by PCR-RFLP among two groups of individual; patients with PTB (n=117) and healthy controls (n=60). Thereafter, the frequencies of extended haplotypes and diplotypes were estimated. No statistically significant differences were observed in allele frequencies of INT4, D543, 3'UTR of NRAMPI, FokI of VDR and TNF-alpha at -238, -244,-863 and -857 position. Although, the frequency of b allele of BsmI [ORs: 0.24 CI95% (0.07-0.67 (p=0.001)] and -308 A variant in TNF-alpha promoter region [ORs:0.26 CI95%( 0.07-0.77) (p=0.006)] were significantly more in PTB patients than healthy controls. The frequency of extended diplotypes of NRAMP [GG TGTG++GA; 0.02(0.001-0.0035)], VDR [FFBB; 0.2(0.6-0.6] and TNF-alpha [CCCCGGGGGG; 0.49(0.25-0.97)] were statistically different in patients and control subjects (p0.05). This study confirmed the association of SNPs in BsmI (B/b + b/b) of VDR and SNPs in -308A (G/A +G/G) of TNF-alpha genes with susceptibility to tuberculosis in Iranian PTB patients. Furthermore, the extended haplotypes and diplotypes analysis can be considered as an alternative way to determine the host susceptibility to TB.

Background In this study, we intended to find the prevalence of nontuberculosis mycobacteria (NTM) among patients who are referred as suspected multidrug-resistant tuberculosis (MDR-TB) cases to the only referral center in Iran. Methods All patients referred to our center in 2002–2006 as MDR-TB with histories of treatment with standard and CAT II World Health Organization regimens were included in the study. Sputum smear and culture for acid-fast bacilli were performed for all patients 3 times. Sputum polymerase chain reaction was also performed for all patients. Mycobacterial identification was performed via polymerase chain reaction and routine identification tests for all culture-positive cases. Results Of the 105 patients in the study, 12 (11.43%) were identified to have NTM infection. The identified mycobacteria were classified in order of prevalence as Chelonae (8 cases), Simiae (2 cases), Aloei (1 case), and Farcinogen (1 case). Based on radiologic findings, most of the cases demonstrated bilateral nodularity (83.3%) and also multifocal bronchiectasis (75%). Notably, cavitary lesions were present in 41.7% of the cases. Conclusion Based on the findings of this study, it is essential that such cases be identified before commencing MDR-TB treatment.

Background An epidemiological link between respiratory infection and acute myocardial infarction (AMI) has been suggested, and recent data indicate that there is an association between AMI and pneumococcal community-acquired pneumonia (CAP) in hospitalized patients. The objective of this study was to investigate the association of AMI with the severity of pneumonia at hospitalization and clinical failure during hospitalization among patients with CAP. Methods An observational, retrospective study involving consecutive patients hospitalized with CAP was performed at the Veterans Hospital of Louisville, Kentucky. Patients admitted to the intensive care unit were defined as having severe CAP. Clinical failure was defined as the development of respiratory failure or shock. AMI was diagnosed on the basis of abnormal troponin levels and electrocardiogram findings. Propensity-adjusted models that controlled for clinical and nonclinical factors were used to investigate the association between AMI and pneumonia severity index and between AMI and clinical failure. Results Data for a total of 500 patients were studied. At hospital admission, AMI was present in 13 (15%) of 86 patients with severe CAP. During hospitalization, AMI was present in 13 (20%) of 65 patients who experienced clinical failure. Following risk adjustment, significant associations were discovered between AMI and the pneumonia severity index score (modeled with a restricted cubic spline) (P = .05) and between AMI and clinical failure (P = .04). Conclusions A combined diagnosis of CAP and AMI is common among hospitalized patients with severe CAP. In cases in which the clinical course of a hospitalized patient with CAP is complicated by clinical failure, AMI should be considered as a possible etiology.

Background Hemolysis is common in all extracorporeal circuits as evident by the elevated plasma free hemoglobin (PFHb) level. We investigated whether increased hemolysis during extracorporeal membrane oxygenation (ECMO) is an independent mortality predictor. Methods We performed a retrospective observational study of consecutive subjects who received ECMO at a tertiary care facility from 2007-2013 to investigate independent predictors of in-hospital mortality. We examined variables related to patient demographics, comorbidities, markers of hemolysis, ECMO characteristics, transfusion requirements, and complications. 24-hour PFHb> 50 mg/dL was used as a marker of severe hemolysis. Results 154 patients received ECMO for cardiac (n= 115) or pulmonary (n=39) indications. Patients’ mean age was 51 years and 75.3% were males. Compared to nonsurvivors, survivors had lower pre-ECMO lactic acid (p=0.026), lower 24-hour lactic acid (p=0.023), shorter ECMO duration (P=0.01), fewer RBC transfusions on ECMO (p=0.008) and lower level of PFHb 24-hours post ECMO implantation (p=0.029). 24-hour PFHb> 50 mg/dL occurred in 3.9 % versus 15.5% of survivors and nonsurvivors, respectively, p=0.002. A Cox proportional hazard analysis identified PFHb> 50 mg/dL 24-hours post ECMO as an independent predictor of mortality (OR= 3.4, 95% confidence interval: 1.3 – 8.8, p= 0.011). Conclusion PFHb> 50 mg/dL checked 24-hour post ECMO implantation is a useful tool to predict mortality. We propose the routine checking of PFHb 24-hours after ECMO initiation for early identification and treatment of the cause of hemolysis.

Background Non-tuberculous mycobacteria (NTM) are ubiquitous environmental organisms. Data about NTM in patients with non-CF bronchiectasis are limited. Methods In a retrospective study, data was collected on patients with bronchiectasis and patients who were diagnosed with NTM were identified. All patients diagnosed with bronchiectasis (code 494) using the International Classification of Diseases, ninth revision (ICD-9), between 1999 and 2006, were identified. Clinical data including radiology findings, lung function, progression of disease, and the presence of NTM in sputum were collected for those who met the study criteria. Results 300 patients with ICD code for bronchiectasis were found in the data. Of these, 182 patients were enrolled in the study after confirmation of the radiology findings of bronchiectasis by CT scanning. Patients were divided into two groups: bronchiectasis with NTM isolates ( n = 68) and bronchiectasis without NTM isolates ( n = 114). The clinical data was reviewed to define the clinical characteristics of these patients; 12% of the patients were found to have NTM from their sputum or BAL. Of the total patients, 55 (30%) of these met the American Thoracic Society criteria for the diagnosis of NTM disease. Mycobacterium avium complex (MAC) was the most common isolate. It was found that the probability of NTM isolation was significantly higher in elderly female patients ( p = 0.04) with a low body mass index (BMI) ( p = 0.002). Additionally, it was found that gram-negative rods were frequently isolated in these patients, and the frequency of exacerbations was significantly higher in patients with NTM infections. Conclusions NTM infections are common in non-CF bronchiectasis. MAC is the most frequently isolated NTM in these patients. Elderly female patients with a low BMI are a high-risk group for NTM infection in non-CF bronchiectasis. Furthermore, these patients are prone to secondary infections and frequent exacerbations. This study suggests a strong correlation between non-CF bronchiectasis and NTM. Thus, these patients should be routinely screened for NTM infections.

Background Limited evidence showed the persistence of Mycobacterium tuberculosis (MTB) in soil and water of TB sanatoriums or hospitals, but no reports suggest the occurrence of MTB in nature. Here, this study investigates the probability of isolating MTB from the environment with no clear source of contamination. To further highlight the transmission vehicle from human to nature and vice versa, the typing patterns of isolated MTB strains from the environment was compared with clinical MTB isolates. Additionally, the viability of MTB after 3 and 6 months of contamination was investigated. Methods The soil ( n = 700) and water ( n = 800) from different locations of suburban towns of Tehran was examined for the presence of MTB. The digested and decontaminated samples were inoculated in three LJ (Lowenstein Jensen) mediums and incubated at 37 °C, 25 °C and 42 °C for 12 weeks. Spoligotypes and MIRU-VNTR typing methods were performed on DNA extracted from single colonies. Thereafter, the obtained typing patterns were compared with the genotyping of TB patients that were residents of Robat Karim ( n = 25), Firuzkuh ( n = 10), Shahr-e-Ray ( n = 20) and Tehran ( n = 413). Result MTB accounts for 14.4% of total mycobacterium that was isolated from soil and water in suburban towns of Tehran. Based on polymerase chain reaction (PCR) typing methods, T family (56/82; 68%) followed by Delhi/CAS (11/82; 13.4%) were the most frequent MTB super families in both water and soil samples. Overall, 27.7% of isolates in clusters were intra-connected strains, i.e., found in different regions; however, no similar typing pattern between soil, water and clinical isolates was observed. The most frequent super family of MTB in clinical isolates was Delhi/CAS (142; 30.3%) followed by NEW-1 (127; 27.1%). The environment and clinical isolates had a minimum of 2 and a maximum of 10 loci difference (5–7 difference on average). The bacilli in contaminated soil (36%) and damp water (8.4%) remained alive for a considerable period of time, i.e., up to 9 months . Conclusion Persistence of MTB in soil and water highlights the risk of transmission, which needs further investigation. This study was supported by the National Research Institute of Tuberculosis and Lung Disease of Iran, Iran.

Introduction Nontuberculous mycobacteria (NTM) are ubiquitous in the environment and exist as important causes of pulmonary infections in human. Pulmonary involvement is the most common disease manifestation of NTM and the incidence of NTM is growing in the North America. Susceptibility to NTM infection is incompletely understood and, therefore preventative tools are not well defined. Treatment of pulmonary nontuberculous mycobacterial (NTM) infection is difficult and entails multiple antibiotics and an extended treatment course. Also, there is a considerable variation in treatment management that should be considered before initiating treatment. Material and methods A literature search was conducted using search keywords “nontuberculous mycobacteria,” “MAC,” “ M. abscessus ,” “epidemiology,” “treatment,” “North America,” “mortality,” “cystic fibrosis,” “transplantation,” “prevention,” and “diagnosis” from studies that have been published between the years 2009 and 2014. PubMed, Cinahl, Scopus, Embase, and the Cochrane Library were searched. A total of 382 articles were reviewed from which 65 papers met our selection criteria. Titles of interest were further reviewed by all authors. Reference lists of relevant studies were hand-searched in order to identify other potentially relevant articles. Studies included in this review met the following criteria: (i) study populations included patients with NTM; (ii) articles were full reports, case reports or reviews; (iii) articles were in English and published from the US based institutes; (iv) articles were published in peer-reviewed journals. Results Nontuberculous mycobacteria (NTM) are an important cause of morbidity and mortality, often in the form of progressive lung disease. Few reports are accessible on NTM disease prevalence in the United States; however based on the recent data the incidence and mortality rates of pulmonary NTM have been reported to be rising in North America. We highlight the new findings in the epidemiology, diagnosis and treatment of mycobacterial infections. We debate new advances regarding NTM infection in cystic fibrosis patients and solid organ transplant recipients. Finally, we introduce a new epidemiologic model for NTM disease based on virulence–exposure–host factors. Conclusion It is critical that NTM is recognized as an important public health issue with potentially significant consequences for affected patients. Finally, the applicability of the virulence–exposure–host model in NTM disease should be investigated.

An approved treatment regimen for multi-drug resistant tuberculosis (MDR-TB) patients during pregnancy does not exist to this day. The main reason for the lack of information in this area is the small number of patients and insufficient studies regarding the safety of the second-line drugs during pregnancy on the mother and the fetus [1]. This case report highlights the difficulties associated with MDR-TB. In December 2003, an 18-year-old Afghan woman was admitted to our center on complaints of cough, sputum, and dyspnea. The patient had a history of two periods of anti-TB treatments (Cat I and Cat II) in the past two years. Despite two years of anti-TB treatment the patient’s mother died secondary to TB. The patient’s chest X-ray demonstrated opacity accompanied by a cavity in the middle-upper lobe of the right lung, and alveolar infiltration together with nodular densities in the lower lobe of the left lung. Sputum smear was positive for Koch’s Bacillus (BK). An empirical regimen for MDR-TB was commenced because of a positive smear of sputum for BK (Ofloxacin, high-dose Isoniazid, Amikacin, Clofazimin, Pyrazinamid, and B6). After completion of five months of therapy, sputum smear and culture results were negative again. The performed chest X-ray at this stage demonstrated a decrease in the size of the right cavitary lesion. Considering the results of the patient’s drug susceptibility test, which demonstrated resistance to the four drugs Isoniazid, Rifampin, Ethambutol, and Streptomycin, and sensitivity to Pyrazinamid, the treatment regimen was continued. Earlier in the treatment the patient was advised to refrain from becoming pregnant and educated regarding the potential teratogenic side effects of anti-TB medications on the fetus and the need for up to 18 months

This survey identified the spoligopatterns of Mycobacterium tuberculosis strains with an international designation responsible for transmission and prevalence of TB (2000 to 2005) among native and immigrant populations of Tehran. The spacer oligonucleotides typing was performed on 1742 Mycobacterium tuberculosis strains isolated from verified cases of TB. Clinical and demographic data of patients were collected using traditional methods. A total of 133 distinct spoligopatterns was observed. 1679 clinical isolates were clustered in 70 clusters (52.5%) and 63 isolates were defined as orphans pattern (47.3%). Based on an international spoligotype database, the east African-Indian (EAI, 24%), central Asian (CAS, 20.8%), T clade (20.7%), Haarlem I (4.4%), Beijing (3.2%) and shared type 253 (3.1%) were the major identified M. tuberculosis superfamilies. Our results showed that the intra-community TB transmission was 13.7%, whereas the inter-community transmission was 39.3% for Afghanis and 20.3% for Iranians. The study highlighted the epidemic potential of specific genotypes (EAI, CAS, T clades) among tuberculosis cases in the Tehran territory. We also confirmed that the impact of transmission through immigration is low.

Mycobacterium tuberculosis-specific CD8+ and CD4+ T lymphocyte responses restrict the spread of extracellular pathogens by limiting M.tuberculosis replication. Alterations in cytolytic function, inappropriate maturation/differentiation, and limited proliferation could reduce their ability to control M.tuberculosis replication.In an attempt to further characterize the immune responses during M.tuberculosis infection, we enumerated gamma-delta and alpha-beta receptor-bearing T cells expressing CD8 or CD4 phenotype and analyzed the differentiation phenotypes of CD8+ and CD4+ T lymphocyte subpopulations in 47 cases (23 new cases and 24 multidrug resistant patients) and 20 control subjects, using flowcytometry.We found that the CD4/CD8 ratio was significantly lower in newly-diagnosed M.tuberculosis patients compared to multidrug resistant and control subjects (P0.003). Also, we found that a large proportion of CD8+ T lymphocytes in newly-diagnosed patients was defined by increased surface expression of CD57 as compared to the two other settings (P0.002). This increase was more profound in patients with an inverted CD4/CD8 ratio. Analysis of the late activation antigen revealed that this was predominantly HLA-DR+ (P0.003). No significant changes were observed in the percentages of CD8+CD57+ T cells between the different settings. Moreover, the co-stimulatory molecule CD28+ tended to be underexpressed by CD8+ T cells in multidrug resistant patients when compared to newly-diagnosed subjects (P0.002), but not to the control subjects. In contrast, the frequency of CD28+ marker on CD4+ T cells was higher in the setting of multidrug resistant compared with those of new cases (P0.0001). No significant changes were observed in percentages of gamma-delta receptor-bearing T cells between different groups.We suggest that the increase in the proportion of CD57+ within CD8+ T cells in newly-diagnosed patients results from M.tuberculosis antigenic stimulation, which is a hallmark of many infections and that the protracted accumulation of CD57+ T lymphocytes might reflect an end-stage differentiation phenotype.

Introduction While NTM infection is mainly acquired from environmental exposure, monitoring of environmental niches for NTM is not a routine practice. This study aimed to find the prevalence of environmental NTM in soil and water in four highly populated suburbs of Tehran, Iran. Material and Methods A total of 4014 samples from soil and water resources were collected and studied. Sediments of each treated sample were cultured in Lowenstein-Jensen medium and observed twice per week for growth rate, colony morphology, and pigmentation. Colonies were studied with phenotypic tests. Molecular analysis was performed on single colonies derived from subculture of original isolates. Environmental samples were compared with 34 NTM isolates from patients who were residents of the study locations. Results Out of 4014 samples, mycobacteria were isolated from 862 (21.4%) specimens; 536 (62.1%) belonged to slow growing mycobacteria (SGM) and 326 (37.8%) were rapid growing mycobacteria (RGM). The five most frequent NTM were M. farcinogens (105/862; 12.1%), M. fortuitum (72/862; 8.3%), M. senegalense (58/862; 6.7%), M. kansasii (54/862; 6.2%), and M. simiae (46/862; 5.3%). In total, 62.5% (539/862) of mycobacterial positive samples were isolated from water and only 37.4% (323/862) of them were isolated from soil samples (P

Summary Objectives This survey identified the spoligopatterns of Mycobacterium tuberculosis strains with an international designation responsible for transmission and prevalence of Multi-Drug Resistance Tuberculosis (MDR-TB) among native and immigrant population of Tehran (2000–2005). Methods The spacer oligonucleotides typing was performed on 263 M. tuberculosis strains isolated from verified cases of MDR-TB. Clinical and demographical data of patients were collected using traditional methods. Results Classical epidemiological investigation revealed that out of 263 MDR-TB cases, 175, 66.5% were isolated from Afghan immigrants. In both communities, majority of MDR-TB cases had either previous history of TB (107, 40.6%) or had a close contact (84, 31.9%). By spoligotyping, 27 distinct patterns were observed, 253 clinical isolates were grouped in 17 clusters (62.9%) and 10 isolates displayed an orphan pattern (37%). Based on an international spoligotype database, Haarlem I (85, 33.5%), Beijing (52, 20.5%), Central Asia (32, 12.1%), and EAI (21, 8.3%) were the major identified super families. Although, 76.9% of the Beijing genotypes and 100% of ST 253 strains (that was prevalent through former Soviet Union) were isolated from Afghan patients only. The linkage patterns between 30 Iranian and Afghan patients were observed. Conclusion The study highlighted the epidemic potential of Haarlem I and Beijing genotypes among MDR-TB cases in Tehran territory.

On December 31, 2012, the FDA approved the first new tuberculosis drug in four decades. SIRTURO™ (bedaquiline) was approved on the basis of phase two efficacy and safety data to treat multidrug-resistant tuberculosis (MDR-TB). Bedaquiline is manufactured by Johnson and Johnson and is the first medication exclusively manufactured for MDR-TB [1].

Chronic pulmonary diseases describe chronic diseases that affect the airways and lung parenchyma. Examples of common chronic pulmonary diseases include asthma, bronchiectasis, chronic obstructive lung disease, lung fibrosis, sarcoidosis, pulmonary hypertension and cor pulmonale. Pulmonary infection is considered a significant cause of mortality in patients with chronic pulmonary diseases. Streptococcus pneumoniae is the leading isolated bacteria from adult patients with community-acquired pneumonia, the most common pulmonary infection. Vaccination against S. pneumoniae can reduce the risk of mortality especially from more serious infections in both immunocompetent and immunocompromised patients. Patients with chronic pulmonary diseases who take steroids or immunomodulating therapy (e.g., methotrexate, anti-TNF inhibitors), having concurrent sickle cell disease or other hemoglobinopathies, primary immunodeficiency disorders, human immunodeficiency virus infection / acquired immunodeficiency syndrome (HIV/AIDS), nephrotic syndrome, and hematologic or solid malignancies should be vaccinated with both 13-valent pneumococcal conjugate vaccine (PCV13) and the pneumococcal polysaccharide vaccine 23-valent (PPSV23).

Background Environmental nontuberculous mycobacteria (NTM) are ubiquitous organisms with which humans commonly interact. The epidemiologic characteristics of NTM diseases including mortality rate and its associated factors remain largely unknown. In this study, we explored the geographical area of exposure and mortality and comorbid conditions of affected persons to determine environment, host, and host-pathogen interactive factors. Methods We analyzed mortality related to nontuberculous mycobacterial infections from 1999 through 2010 by examining multiple-cause-of-death data from the National Center for Health Statistics. Among those who died with these diseases, we analyzed age-adjusted mortality rates, trends, associations with demographic variables, and comorbid conditions and correlated this information with similar data for tuberculosis-related mortality during the same time. Measurements and Mean Results From 1999 through 2010, nontuberculous mycobacterial disease was reported as an immediate cause of death in 2,990 people in the United States with a combined overall mean age-adjusted mortality rate of 0.1 per 100,000 person-years. A significant increase in the number of NTM related deaths was seen from 1999 through 2010 (R2 = 0.72, p

A 28-year-old HIV-negative black male from Ethiopia, with no significant medical history, presented for a lump on the left side of his neck since 5 months ago. Associated symptoms were fever, night sweats and a 4.5-kg weight loss (15% of weight). He had immigrated to the USA 5 years before presentation and had not left the country since he moved. He was not using any drugs and was in a monogamous relationship with his wife. Physical examination was unremarkable except for multiple large spongy and rubbery lymph nodes on the left side of the neck, bilateral axillaries and multiple insignificant inguinal lymph nodes bilaterally. Hepatosplenomegaly and tenderness in the left upper quadrant were appreciated. Computed tomography (CT) of the neck, thorax and abdomen with contrast revealed multiple cystic lymph nodes in the neck, chest and abdomen, and multiple cystic lesions in the spleen and liver. A left axillary lymph node excisional biopsy showed caseating granuloma. Acid-fast and fungal stains of the specimen were negative. Mycobacterium tuberculosis complex was isolated from a biopsied lymph node 2 months later. It was reported pan-susceptible to all four first-line anti-tuberculosis (TB) drugs. Following 6 months of treatment, the patient made a full recovery (Figures 1 and 2). Splenic involvement in TB is a rare clinical condition and is difficult to diagnose. Although the TB case rate has decreased

Background: There are number of patients who are unable to expectorate sputum specimens. In this study, we used gastric lavage (GL) test for diagnosis of tuberculosis (TB) in patients who were unable to produce sputum. Materials and Methods: Patients who were unable to produce sputum specimens were included in the study to confirm TB disease. Gastric lavage sampling was performed and sent for acid fast bacillus smear and culture under special laboratory conditions and sterilized methods. Further bronchoscopy for broncho-alveolar lavage was done on patients with negative GL smear results. Drug susceptibility tests were performed on 48 GL culture positive cases. Results: Eighty-five patients were included in the study; who were hospitalized at our referral center for suspected TB. GL smears were reported to be positive in 37 cases (66.07%) and culture in 85.7%. The total number of smear and culture-positive cases in this study was 48 (85.7%). Forty cases (87%) of drug-sensitive, 1 case (2.2%) of isoniazid and rifampin-resistant TB (multi-drug resistant; MDR), and 5 cases of resistant to one drug were detected. There have not been observed any complications after the GL method. Conclusion: It seems that regarding the high number of positive GL cultures (85.7%), GL can be effective for diagnosis of patients who have suspicious tuberculosis symptoms and are unable to produce sputum especially in resource limited areas.

Summary Background Non-tuberculous mycobacteria (NTM) are ubiquitous environmental organisms. Cystic fibrosis (CF) patients are susceptible to NTM, but data about NTM in patients with non-CF bronchiectasis are limited. Methods We conducted a retrospective, descriptive study at the University of Illinois Medical Center. All patients diagnosed with bronchiectasis (code 494) using the International Classification of Diseases, ninth revision (ICD-9), between 1999 and 2006, were identified. Clinical data including lung function, radiology studies, and presence of NTM in sputum were abstracted for those who met the study criteria. Results One hundred eighty-two patients were enrolled in the study. Patients were divided into two groups: bronchiectasis with NTM isolates ( n = 68) and bronchiectasis without isolates ( n =114), and compared for clinical characteristics and underlying diseases. Mycobacterium avium complex (MAC) was the most common isolate. Fifty-five patients (30%) met the American Thoracic Society criteria for diagnosis of NTM disease. Gram-negative rods were commonly co-isolated. The probability of NTM isolation was significantly higher in elderly female patients ( p = 0.04). Moreover, the probability of NTM isolation was significantly higher in the female group with low body mass index (BMI) ( p = 0.002). Conclusions NTM infections are common in non-CF bronchiectasis. MAC is the most frequently isolated NTM in these patients. There is also great variability in age and sex characteristics for NTM in non-CF bronchiectasis patients. Female patients with a low BMI are a high risk group for NTM infection in non-CF bronchiectasis. Routine screening for NTM is strongly recommended in this patient population.

The following is a case of multidrug-resistant pulmonary tuberculosis (MDR-TB) that was treated successfully with a linezolid-containing regimen. It was found that linezolid is an efficient medicine for MDR-TB treatment with an acceptable side effect profile. Treatment was maintained for 18months, and closely monitoring toxicities did not reveal evidence of any neurologic adverse effects. However, despite our expectation, thrombocytopenia was seen after 2years follow-up.

Nontuberculous mycobacteria (NTM) are a diverse group of bacterial species that are distributed in the environment. Many of these environmental bacteria can cause disease in humans. The identification of NTM in environmental sources is important for both clinical and epidemiological purposes. In this study, the distribution of NTM species from environmental and clinical samples in the Middle East was reviewed. In order to provide an overview of NTM, as well as recent epidemiological trends, all studies addressing NTM in the Middle East from 1984 to 2014 were reviewed.A total of 96 articles were found, in which 1751 NTM strains were isolated and 1084 of which were obtained from clinical samples, 619 from environmental samples and 48 were cited by case reports.Mycobacterium fortuitum was the most common rapid growing mycobacteria (RGM) isolated from both clinical (269 out of 447 RGM; 60.1%) and environmental (135 out of 289 RGM; 46.7%) samples. Mycobacterium avium complex (MAC) was the most common slow growing mycobacteria (SGM) isolated from clinical samples (140 out of 637 SGM; 21.9%). An increasing trend in NTM isolation from the Middle East was noted over the last 5years. This review demonstrates the increasing concern regarding NTM disease in the Middle East, emphasizing the need for regional collaboration and coordination in order to respond appropriately.

Mycobacterial diseases are a group of illnesses that cause a considerable number of deaths throughout the world, regardless of years of public health control efforts. Personalized medicine is a new but rapidly advancing field of healthcare. Personalized medicine in the field of mycobacteriology may be applied in the different levels of management such as prevention, diagnosis, treatment and prognosis. A genetic predisposition and a protein dysfunction study are recommended to tailor an individual approach in mycobacterial diseases.

We compared the effectiveness of 2 treatment regimens for isoniazid-resistant tuberculosis (TB) in 42 patients attending a TB referral centre in the Islamic Republic of Iran. The patients were divided into 2 treatment groups: 26 received the 6-month standard HRZE treatment and 16 received a modified treatment of RZE for 6 months. There were no significant differences in age or sex of the groups. With the standard method of treatment, 21 (80.8%) patients were cured, 4 (15.4%) resulted in treatment failure, and 1 (3.8%) died. In the modified treatment group, 16 (100%) patients were cured, These differences were not statistically significantly different (P = 0.194).

Objectives Nontuberculous mycobacterial (NTM) infections are frequently reported as a cause of bone and soft-tissue infection of the upper extremity, primarily in the hand and wrist. Limited information exists on clinical characteristics and treatment outcomes of patients with NTM infection of the upper extremity. The clinical and radiological characteristic of these infections in a large group of patients with upper extremity NTM infections are described herein. Methods A retrospective analysis was conducted of NTM infections of the upper extremity at Mayo Clinic Florida from December 2000 through December 2012. Only patients with positive mycobacterial cultures from the upper extremities were included. Data collection included demographics, radiologic and clinical characteristics, mycobacterial culture results, time to diagnosis and treatment outcomes. Results Forty-two patients were included; 71% were male and the mean age was 60 ± 18 years. Eighteen (43%) patients were diagnosed with skin/soft tissue infections and 15 (36%) had tenosynovitis. Twenty-six (62%) patients were immunosuppressed. The most common underlying medical conditions were rheumatologic disorders (40%) and diabetes mellitus (17%). Sixteen (38%) patients were taking glucocorticosteroids, and 11 (26%) patients were receiving tumor necrosis factor alpha (TNF-α) inhibitors at the time of diagnosis. Injuries to the affected extremity were reported in 62% of patients. Fishing (21%) and gardening (14%) were the most common reported exposures. Signs and symptoms of infection were localized to the skin in 62% and extended to the joints in 52%. Mycobacterium marinum (36%) and Mycobacterium chelonae / abscessus (33%) were the two most commonly identified organisms. Radiologic studies were available in 30 (71%) patients. Average time to clinical evaluation from onset of symptoms was 2.6 (±3.5) months and time to diagnosis from initial clinical evaluation was 4.5 (±4.5) months. Forty-one (98%) patients were treated. Twenty-eight (68%) patients were treated with both antimicrobial and surgical debridement, nine (21%) with antimicrobial treatment alone, and four (10%) with surgical debridement alone. Twenty-six (62%) patients were cured, four (9%) relapsed after the first round of treatment, two (5%) failed all treatment modalities, and three (7%) patients died. Conclusion Diagnosis of NTM infection of the upper extremity is often delayed due to its indolent presentation and lack of clinical suspicion. Healthcare professionals should be aware of the increasing incidence of soft tissue NTM infection after percutaneous injury, especially in immunosuppressed patients, to improve diagnostic promptness and treatment outcome.

Introduction: Pulmonary mycobacterial diseases describe both tuberculosis (TB) and nontuberculous mycobacteria (NTM). TB is an established public health issue and a reportable disease. Efforts in treatment and surveillance have resulted in the incidence of TB to decrease in recent years. However, the incidence of NTM is increasing, classifying NTM as an emerging public health problem in the US. Despite the increasing importance of pulmonary mycobacterial diseases, few data are available measuring the cost burden of mycobacterial diseases at the national level. The purpose of this study was to evaluate the cost burden and measure emerging trends in hospitalization of pulmonary TB and NTM in the US from 2001 through 2012. Methods: This study was a retrospective community-based cost analysis of hospitalized patients with a principal diagnosis of pulmonary mycobacterial diseases from 2001 through 2012. Data for pulmonary TB and NTM were retrieved from the Healthcare Cost and Utilization Project (HCUP), US Department of Health and Human services. Data included in this analysis were national hospital costs, payer sources, hospital lengths of stay, in-hospital mortality, and discharge information. The statistical significance of observed trends of NTM and TB national hospital costs were calculated using Poisson log-linear regression. National hospital costs for NTM and TB were projected in relation to health care inflation for each year. A regression model was applied to test the correlation between historic and projected national hospital costs. Results: From a total of 36,484,846 admissions, 20,049 hospital admissions were reported for pulmonary NTM and 69,257 for pulmonary TB in the US from 2001 through 2012. The total associated costs of these admissions was $1,337,939,745,325, an estimated $970,643,222 of which was directly associated with pulmonary NTM and $3,390,013,793 for pulmonary TB. During the study period, the national hospital costs of pulmonary NTM increased at a statistically significant rate in the US over each year (p = 0.001). A linear regression analysis demonstrated a high degree of correlation between NTM historic and projected national hospital costs (R=0.938, p

HGID Lab Andrés Augusto Arias1,3, Bertrand Boisson1,2, Soraya Boucherit2, Jacinta Bustamante1,2, Marwa Chbihi2, Jie Chen1, Maya Chrabieh2, Tatiana Kochetkov1, Tom Le Voyer2, Dana Liu1, Yelena Nemirovskaya1, Masato Ogishi1, Dominick Papandrea1, Cécile Patissier2, Franck Rapaport1, Manon Roynard2, Natasha Vladikine2, Mark Woollett1, Peng Zhang1 1St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University. 2Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children. 3School of Microbiology and Group of Primary Immunodeficiencies, University of Antioquia UdeA, Medellin, Colombia., NIAID-USUHS Immune Response to COVID Group Anuj Kashyap1, Li Ding1, Marita Bosticardo1, Qinlu Wang2, Sebastian Ochoa1, Hui Liu1, Samuel D. Chauvin3, Michael Stack1, Galina Koroleva4, Neha Bansal5, Clifton L. Dalgard6,7, Andrew L. Snow8 1Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research, NIAID, NIH, Bethesda, MD, USA. 2Bioinformatics and Computational Biosciences Branch, NIAID Office of Cyber Infrastructure and Computational Biology, NIAID, NIH, Bethesda, MD, USA. 3Laboratory of Immune System Biology, Division of Intramural Research, NIAID, NIH, Bethesda, MD, USA. 4NIH Center for Human Immunology, NIH, Bethesda, MD, USA. 5Multiscale Systems Biology Section, Laboratory of Immune System Biology, NIAID, NIH, Bethesda, MD, USA. 6PRIMER, Uniformed Services University of the Health Sciences, Bethesda, MD, USA. 7Department of Anatomy, Physiology & Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA. 8Department of Pharmacology & Molecular Therapeutics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA., COVID Clinicians Jorge Abad1, Sergio Aguilera-Albesa2, Ozge Metin Akcan3, Ilad Alavi Darazam4, Juan C. Aldave5, Miquel Alfonso Ramos6, Seyed Alireza Nadji7, Gulsum Alkan8, Jerome Allardet-Servent9, Luis M. Allende10, Laia Alsina11, Marie-Alexandra Alyanakian12, Blanca Amador-Borrero13, Zahir Amoura14, Arnau Antolí15, Sevket Arslan16, Sophie Assant17, Terese Auguet18, Axelle Azot19, Fanny Bajolle20, Aurélie Baldolli21, Maite Ballester22, Hagit Baris Feldman23, Benoit Barrou24, Alexandra Beurton25, Agurtzane Bilbao26, Geraldine Blanchard-Rohner27, Ignacio Blanco1, Adeline Blandinières28, Daniel Blazquez-Gamero29, Marketa Bloomfield30, Mireia Bolivar-Prados31, Raphael Borie32, Ahmed A. Bousfiha33, Claire Bouvattier34, Oksana Boyarchuk35, Maria Rita P. Bueno36, Jacinta Bustamante20, Juan José Cáceres Agra37, Semra Camli38, Ruggero Capra39, Maria Carrabba40, Carlos Casasnovas41, Marion Caseris42, Martin Castelle43, Francesco Castelli44, Martín Castillo de Vera45, Mateus V. Castro36, Emilie Catherinot46, Martin Chalumeau47, Bruno Charbit48, Matthew P. Cheng49, Père Clavé31, Bonaventura Clotet50, Anna Codina51, Fatih Colkesen52, Fatma Colkesen53, Roger Colobran 54, Cloé Comarmond55, Angelo G. Corsico56, David Dalmau57, David Ross Darley58, Nicolas Dauby59, Stéphane Dauger60, Loic de Pontual61, Amin Dehban62, Geoffroy Delplancq63, Alexandre Demoule64, Antonio Di Sabatino65, Jean-Luc Diehl66, Stephanie Dobbelaere67, Sophie Durand68, Waleed Eldars69, Mohamed Elgamal70, Marwa H. Elnagdy71, Melike Emiroglu72, Emine Hafize Erdeniz73, Selma Erol Aytekin74, Romain Euvrard75, Recep Evcen76, Giovanna Fabio40, Laurence Faivre77, Antonin Falck42, Muriel Fartoukh78, Morgane Faure79, Miguel Fernandez Arquero80, Carlos Flores81, Bruno Francois82, Victoria Fumadó83, Francesca Fusco84, Blanca Garcia Solis85, Pascale Gaussem86, Juana Gil-Herrera87, Laurent Gilardin88, Monica Girona Alarcon89, Mónica Girona-Alarcón89, Jean-Christophe Goffard90, Funda Gok91, Rafaela González-Montelongo92, Antoine Guerder93, Yahya Gul94, Sukru Nail Guner94, Marta Gut95, Jérôme Hadjadj96, Filomeen Haerynck97, Rabih Halwani98, Lennart Hammarström99, Nevin Hatipoglu100, Elisa Hernandez-Brito101, María Soledad Holanda-Peña102, Juan Pablo Horcajada103, Sami Hraiech104, Linda Humbert105, Alejandro D. Iglesias106, Antonio Íñigo-Campos92, Matthieu Jamme107, María Jesús Arranz108, Iolanda Jordan109, Fikret Kanat110, Hasan Kapakli111, Iskender Kara112, Adem Karbuz113, Kadriye Kart Yasar114, Sevgi Keles115, Yasemin Kendir Demirkol116, Adam Klocperk117, Zbigniew J. Król118, Paul Kuentz119, Yat Wah M. Kwan120, Jean-Christophe Lagier121, Yu-Lung Lau122, Fleur Le Bourgeois60, Yee-Sin Leo123, Rafael Leon Lopez124, Daniel Leung122, Michael Levin125, Michael Levy60, Romain Lévy20, Zhi Li48, Agnes Linglart126, José M. Lorenzo-Salazar92, Céline Louapre127, Catherine Lubetzki127, Charles-Edouard Luyt128, David C. Lye129, Davood Mansouri130, Majid Marjani131, Jesus Marquez Pereira132, Andrea Martin133, David Martínez Pueyo134, Javier Martinez-Picado135, Iciar Marzana136, Alexis Mathian14, Larissa R. B. Matos36, Gail V. Matthews137, Julien Mayaux138, Jean-Louis Mège139, Isabelle Melki140, Jean-François Meritet141, Ozge Metin142, Isabelle Meyts143, Mehdi Mezidi144, Isabelle Migeotte145, Maude Millereux146, Tristan Mirault147, Clotilde Mircher68, Mehdi Mirsaeidi148, Abián Montesdeoca Melián149, Antonio Morales Martinez150, Pierre Morange151, Demence Mordacq105, Guillaume Morelle152, Stéphane Mouly13, Adrián Muñoz-Barrera92, Cyril Nafati153, João Farela Neves154, Lisa F. P. Ng155, Yeray Novoa Medina156, Esmeralda Nuñez Cuadros157, J. Gonzalo Ocejo-Vinyals158, Zerrin Orbak159, Mehdi Oualha20, Tayfun Özçelik160, Qiang Pan Hammarström161, Christophe Parizot138, Tiffany Pascreau162, Estela Paz-Artal163, Sandra Pellegrini48, Rebeca Pérez de Diego85, Aurélien Philippe164, Quentin Philippot78, Laura Planas-Serra165, Dominique Ploin166, Julien Poissy167, Géraldine Poncelet42, Marie Pouletty168, Paul Quentric138, Didier Raoult139, Anne-Sophie Rebillat68, Ismail Reisli169, Pilar Ricart170, Jean-Christophe Richard171, Nadia Rivet28, Jacques G. Rivière172, Gemma Rocamora Blanch15, Carlos Rodrigo1, Carlos Rodriguez-Gallego173, Agustí Rodríguez-Palmero174, Carolina Soledad Romero175, Anya Rothenbuhler176, Flore Rozenberg177, Maria Yolanda Ruiz del Prado178, Joan Sabater Riera15, Oliver Sanchez179, Silvia Sánchez-Ramón180, Agatha Schluter165, Matthieu Schmidt181, Cyril E. Schweitzer182, Francesco Scolari183, Anna Sediva184, Luis M. Seijo185, Damien Sene13, Sevtap Senoglu114, Mikko Seppänen186, Alex Serra Ilovich187, Mohammad Shahrooei62, David Smadja188, Ali Sobh189, Xavier Solanich Moreno15, Jordi Solé-Violán190, Catherine Soler191, Pere Soler-Palacín133, Yuri Stepanovskiy192, Annabelle Stoclin193, Fabio Taccone145, Yacine Tandjaoui-Lambiotte194, Jean-Luc Taupin195, Simon J. Tavernier196, Benjamin Terrier197, Caroline Thumerelle105, Gabriele Tomasoni198, Julie Toubiana47, Josep Trenado Alvarez199, Sophie Trouillet-Assant200, Jesús Troya201, Alessandra Tucci202, Matilde Valeria Ursini‬84, Yurdagul Uzunhan203, Pierre Vabres204, Juan Valencia-Ramos205, Ana Maria Van Den Rym85, Isabelle Vandernoot206, Hulya Vatansev207, Valentina Vélez-Santamaria41, Sébastien Viel166, Cédric Vilain208, Marie E. Vilaire68, Audrey Vincent34, Guillaume Voiriot209, Fanny Vuotto105, Alper Yosunkaya91, Barnaby E. Young123, Fatih Yucel210, Faiez Zannad211, Mayana Zatz36, Alexandre Belot212* 1University Hospital and Research Institute “Germans Trias i Pujol”, Badalona, Spain. 2Navarra Health Service Hospital, Pamplona, Spain. 3Division of Pediatric Infectious Diseases, Necmettin Erbakan University, Meram Medical Faculty, Konya, Turkey. 4Department of Infectious Diseases, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 5Hospital Nacional Edgardo Rebagliati Martins, Lima, Peru. 6Parc Sanitari Sant Joan de Déu, Sant Boi de Llobregat Spain. 7Virology Research Center, National institutes of Tuberculosis and Lung diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 8Division of Pediatric Infectious Diseases, Faculty of Medicine, Selcuk University, Konya, Turkey. 9Intensive care unit, Hôpital Européen, Marseille, France. 10Immunology Department, University Hospital 12 de Octubre. Research Institute imas12. Complutense University, Madrid, Spain. 11Hospital Sant Joan de Déu, Barcelona, Spain. 12Department of Biological Immunology, Necker Hospital for Sick Children, APHP and INEM, Paris, France. 13Internal medicine department, Hôpital Lariboisière, APHP; Université de Paris, Paris, France. 14Internal medicine department, Pitié-Salpétrière Hospital, Paris, France. 15Hospital Universitari de Bellvitge, Barcelona, Spain. 16Division of Clinical Immunology and Allergy, Necmettin Erbakan University, Meram Medical Faculty, Konya, Turkey. 17Joint Research Unit, Hospices Civils de Lyon-bio Mérieux, Hospices Civils de Lyon, Lyon Sud Hospital, Lyon, France. 18Hospital U. de Tarragona Joan XXIII. Universitat Rovira i Virgili (URV). IISPV, Tarragona, Spain. 19Private practice, Paris, France. 20Necker Hospital for Sick Children, AP-HP, Paris, France. 21Department of Infectious Diseases, CHU de Caen, Caen, France. 22Consorcio Hospital General Universitario, Valencia, Spain. 23The Genetics Institute, Tel Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. 24Dept Urology, Nephrology, Transplantation, APHP-SU, Sorbonne Université, INSERM U 1082, Paris, France. 25Service de Médecine Intensive–Réanimation et Pneumologie, APHP Hôpital Pitié–Salpêtrière, Paris, France. 26Cruces University Hospital, Bizkaia, Spain. 27Paediatric Immunology and Vaccinology Unit, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland. 28Hematology, Georges Pompidou Hospital, APHP, Paris, France. 29Pediatric Infectious Diseases Unit. Instituto de Investigación 12 de Octubre (imas12). Hospital Universitario 12 de Octubre, Madrid, Spain. 30Department of Immunology, Motol University Hospital, 2nd Faculty of Medicine, Charles University, Department of Pediatrics, Thomayer’s Hospital, 1st Faculty of Medicine, Charles University, Prague, Czech Republic. 31Centro de Investigación Biomédica en Red de Enfermedades Hepàticas y Digestivas (Ciberehd). Hospital de Mataró, Consorci Sanitari del Maresme, Mataró, Spain. 32Service de Pneumologie, Hopital Bichat, APHP, Paris, France. 33Clinical immunology unit, pediatric infectious disease departement, Faculty of Medicine and Pharmacy, Averroes University Hospital. LICIA Laboratoire d'immunologie clinique, d'inflammation et d'allergie, Hassann Ii University, Casablanca, Morocco. 34Endocrinology unit, APHP Hôpitaux Universitaires Paris-Sud, Le Kremlin-Bicêtre, France. 35Department of Children's Diseases and Pediatric Surgery, I.Horbachevsky Ternopil National Medical University, Ternopil, Ukraine. 36Human Genome and stem-cell research center- University of São Paulo, São Paulo, Brazil. 37Hospital Insular, Las Palmas de Gran Canaria, Spain. 38Division of Critical Care Medicine, Department of Anesthesiology and Reanimation, Konya State Hospital, Konya, Turkey. 39MS Center, Spedali Civili, Brescia, Italy. 40Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. 41Bellvitge University Hospital, L'Hospitalet de Llobregat, Barcelona, Spain. 42Hopital Robert Debré, Paris, France. 43Pediatric Immuno-hematology Unit, Necker Enfants Malades Hospital, AP-HP, Paris, France. 44Department of Infectious and Tropical Diseases, University of Brescia, ASST Spedali Civili di Brescia, Brescia, Italy. 45Doctoral Health Care Center, Canarian Health System, Las Palmas de Gran Canaria, Spain. 46Hôpital Foch, Suresnes, France. 47Necker Hospital for Sick Children, Paris University, AP-HP, Paris, France. 48Pasteur Institute, Paris, France. 49McGill University Health Centre, Montreal, Canada. 50University Hospital and Research Institute “Germans Trias i Pujol”, IrsiCaixa AIDS Research Institute, UVic-UCC, Badalona, Spain. 51Clinical Biochemistry, Pathology, Paediatric Neurology and Molecular Medicine Departments and Biobank, Institut de Recerca Sant Joan de Déu and CIBERER-ISCIII, Esplugues, Spain. 52Division of Clinical Immunology and Allergy, Department of Internal Medicine, Necmettin Erbakan University, Meram Medical Faculty, Konya, Turkey. 53Department of Infectious Diseases and Clinical Microbiology, Konya Training and Research Hospital, Konya, Turkey. 54Hospital Universitari Vall d’Hebron, Barcelona, Spain. 55Pitié-Salpêtrière Hospital, Paris, France. 56Respiratory Diseases Division, IRCCS Policlinico San Matteo Foundation and University of Pavia, Pavia, Italy. 57Fundació Docència i Recerca Mútua Terrassa, Barcelona, Spain. 58UNSW Medicine, St Vincent's Clinical School; Department of Thoracic Medicine, St Vincent's Hospital Darlinghurst, Sidney, Australia. 59CHU Saint-Pierre, Université Libre de Bruxelles (ULB), Brussels, Belgium. 60Pediatric Intensive Care Unit, Robert-Debré University Hospital, APHP, Paris, France. 61Sorbonne Paris Nord, Hôpital Jean Verdier, APHP, Bondy, France. 62Specialized Immunology Laboratory of Dr. Shahrooei, Sina Medical Complex, Ahvaz, Iran. 63Centre de génétique humaine, CHU Besançon, Besançon, France. 64Sorbonne Université médecine and APHP Sorbonne université site Pitié-Salpêtrière, Paris, France. 65Department of Internal Medicine, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy. 66Intensive Care unit, Georges Pompidou Hospital, APHP, Paris, France. 67Department of Pneumology, AZ Delta, Roeselare, Belgium. 68Institut Jérôme Lejeune, Paris, France. 69Department of Microbiology and Immunology, Faculty of Medicine, Mansoura University, Mansoura, Egypt. 70Department of Chest, Faculty of Medicine, Mansoura University, Mansoura, Egypt. 71Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Mansoura University, Mansoura, Egypt. 72Faculty of Medicine, Division of Pediatric Infectious Diseases, Selcuk University, Konya, Turkey. 73Division of Pediatric Infectious Diseases, Ondokuz Mayıs University, Samsun, Turkey. 74Necmettin Erbakan University, Meram Medical Faculty, Division of Pediatric Allergy and Immunology, Konya, Turkey. 75Centre Hospitalier Fleyriat, Bourg-en-Bresse, France. 76Division of Clinical Immunology and Allergy, Department of Internal Medicine, Necmettin Erbakan University, Meram Medical Faculty, Konya, Turkey. 77Centre de Génétique, CHU Dijon, Dijon, France. 78APHP Tenon Hospital, Paris, France. 79Sorbonne Universités, UPMC University of Paris, Paris, France. 80Department of Clinical Immunology, Hospital Clínico San Carlos, Madrid, Spain. 81Genomics Division, Instituto Tecnológico y de Energías Renovables (ITER), Santa Cruz de Tenerife, Spain; CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain; Research Unit, Hospital Universitario N.S. de Candelaria, Santa Cruz de Tenerife, Spain; Instituto de Tecnologías Biomédicas (ITB), Universidad de La Laguna, San Cristóbal de La Laguna, Spain. 82CHU Limoges and Inserm CIC 1435 & UMR 1092, Limoges, France. 83Infectious Diseases Unit, Department of Pediatrics, Hospital Sant Joan de Déu, Barcelona, Spain; Institut de Recerca Sant Joan de Déu, Spain; Universitat de Barcelona (UB), Barcelona, Spain. 84Institute of Genetics and Biophysics ‘Adriano Buzzati-Traverso’, IGB-CNR, Naples, Italy. 85Laboratory of Immunogenetics of Human Diseases, IdiPAZ Institute for Health Research, La Paz Hospital, Madrid, Spain. 86Hematology, APHP, Hopital Européen Georges Pompidou and Inserm UMR-S1140, Paris, France. 87Hospital General Universitario and Instituto de Investigación Sanitaria "Gregorio Marañón", Madrid, Spain. 88Bégin military Hospital, Bégin, France. 89Pediatric Intensive Care Unit, Hospital Sant Joan de Déu, Barcelona, Spain. 90Department of Internal Medicine, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium. 91Division of Critical Care Medicine, Department of Anesthesiology and Reanimation, Necmettin Erbakan University, Meram Medical Faculty, Konya, Turkey. 92Genomics Division, Instituto Tecnológico y de Energías Renovables (ITER), Santa Cruz de Tenerife, Spain. 93Assistance Publique Hôpitaux de Paris, Paris, France. 94Division of Allergy and Immunology, Necmettin Erbakan University, Meram Medical Faculty, Konya, Turkey. 95CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST); Universitat Pompeu Fabra (UPF), Barcelona, Spain. 96Department of Internal Medicine, National Reference Center for Rare Systemic Autoimmune Diseases, AP-HP, APHP-CUP, Hôpital Cochin, Paris, France. 97Ghent University Hospital, Ghent, Belgium. 98Sharjah Institute of Medical Research, College of Medicine, University of Sharjah, Sharjah, UAE. 99Department of Biosciences and Nutrition, SE14183, Huddinge, Karolinska Institutet, Stockholm, Sweden. 100Pediatric Infectious Diseases Unit, Bakirkoy Dr. Sadi Konuk Training and Research Hospital, University of Health Sciences, Istanbul, Turkey. 101Department of Immunology, Hospital Universitario de Gran Canaria Dr. Negrín, Canarian Health System, Las Palmas de Gran Canaria, Spain. 102IntensivenCare Unit. Marqués de Valdecilla Hospital, Santander, Spain. 103Hospital del Mar, Parc de Salut Mar, Barcelona, Spain. 104Intensive care unit, APHM, Marseille, France. 105CHU Lille, Lille, France. 106Department of Pediatrics, Columbia University, New York, NY, USA. 107Centre hospitalier intercommunal Poissy Saint Germain en Laye, Poissy, France. 108Division of Respiratory Diseases, Fundació Docència i Recerca Mútua Terrassa, Barcelona, Spain. 109Hospital Sant Joan de Déu, Kids Corona Platfform, Barcelona, Spain. 110Selcuk University, Faculty of Medicine, Chest Diseases Department, Konya, Turkey. 111Division of Allergy and Immunology, Balikesir Ataturk City Hospital, Balikesir, Turkey. 112Division of Critical Care Medicine, Selcuk University, Faculty of Medicine, Konya, Turkey. 113Division of Pediatric Infectious Diseases, Prof. Dr. Cemil Tascıoglu City Hospital, Istanbul, Turkey. 114Departments of Infectious Diseases and Clinical Microbiology, Bakirkoy Dr. Sadi Konuk Training and Research Hospital, University of Health Sciences, Istanbul, Turkey. 115Meram Medical Faculty, Necmettin Erbakan University, Meram Medical Faculty, Konya, Turkey. 116Health Sciences University, Umraniye Education and Research Hospital, Istanbul, Turkey. 117Department of Immunology, 2nd Faculty of Medicine, Charles University and University Hospital in Motol, Prague, Czech Republic. 118Central Clinical Hospital of Ministry of the Interior and Administration in Warsaw, Warsaw, Poland. 119Oncobiologie Génétique Bioinformatique, PC Bio, CHU Besançon, Besançon, France. 120Paediatric Infectious Disease Unit, Hospital Authority Infectious Disease Center, Princess Margaret Hospital, Hong Kong (Special Administrative Region), China. 121Aix Marseille Univ, IRD, MEPHI, IHU Méditerranée Infection, Marseille, France. 122Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, China. 123National Centre for Infectious Diseases, Singapore. 124Hospital Universitario Reina Sofía, Cordoba, Spain. 125Imperial College, London, England. 126Endocrinology and diabetes for children, AP-HP, Bicêtre Paris-Saclay hospital, Le Kremlin-Bicêtre, France. 127Neurology unit, APHP Pitié-Salpêtrière Hospital, Paris University, Paris, France. 128Intensive care unit, APHP Pitié-Salpêtrière Hospital, Paris University, Paris, France. 129National Centre for Infectious Diseases; Tan Tock Seng Hospital; Yong Loo Lin School of Medicine; Lee Kong Chian School of Medicine, Singapore. 130Department of Clinical Immunology and Infectious Diseases, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 131Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran. 132Hospital Sant Joan de Déu and University of Barcelona, Barcelona, Spain. 133Pediatric Infectious Diseases and Immunodeficiencies Unit, Hospital Universitari Vall d’Hebron, Vall d'Hebron Research Institute, Vall d’Hebron Barcelona Hospital Campus. Universitat Autònoma de Barcelona (UAB), Barcelona, Spain. 134Hospital Universitari Mutua de Terrassa, Universitat de Barcelona, Barcelona, Spain. 135IrsiCaixa AIDS Research Institute, ICREA, UVic-UCC, Research Institute “Germans Trias i Pujol”, Badalona, Spain. 136Department of Laboratory, Cruces University Hospital, Barakaldo, Bizkaia, Spain. 137University of New South Wales, Australia. 138APHP Pitié-Salpêtrière Hospital, Paris, France. 139Aix-Marseille University, APHM, Marseille, France. 140Robert Debré Hospital, Paris, France. 141APHP Cohin Hospital, Paris, France. 142Necmettin Erbakan University Meram Faculty of Medicine Department of Pediatric Infectious Diseases, Konya, Turkey. 143University Hospitals Leuven, Leuven, Belgium. 144Hospices Civils de Lyon, Hôpital de la Croix-Rousse, Lyon, France. 145Hôpital Erasme, Brussels, Belgium. 146CH Gonesse, Gonesse, France. 147Vascular Medicine, Georges Pompidou Hospital, APHP, Paris, France. 148Division of Pulmonary and Critical Care, University of Miami, Miami, USA. 149Guanarteme Health Care Center, Canarian Health System, Las Palmas de Gran Canaria, Spain. 150Regional University Hospital of Malaga, Malaga, Spain. 151Aix-Marseille Université, Marseille, France. 152Department of General Paediatrics, Hôpital Bicêtre, AP-HP, University of Paris Saclay, Le Kremlin-Bicêtre, France. 153CHU de La Timone, Marseille, France. 154Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal. 155Infectious Diseases Horizontal Technlogy Centre, A*STAR; Singapore Immunology Network, A*STAR, Singapore. 156Department of Pediatrics, Complejo Hospitalario Universitario Insular-Materno Infantil, Canarian Health System, Las Palmas de Gran Canaria, Spain. 157Regional Universitary Hospital of Malaga, Málaga, Spain. 158Hospital Universitario Marqués de Valdecilla, Santander, Spain. 159Ataturk University Medical Faculty, Erzurum, Turkey. 160Bilkent University, Department of Molecular Biology and Genetics, Ankara, Turkey. 161Department of Laboratory Medicine, Karolinska Institutet, SE14186, Stockholm, Sweden. 162L'Hôpital Foch, Suresnes, France. 163Department of Immunology, Hospital Universitario 12 de Octubre, Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Madrid, Spain. 164APHP Hôpitaux Universitaires Paris-Sud, Le Kremlin-Bicêtre, France. 165Neurometabolic Diseases Laboratory, IDIBELL-Hospital Duran i Reynals, Barcelona; CIBERER U759, ISCiii Madrid, Spain. 166Hospices Civils de Lyon, Lyon, France. 167Université de Lille, Inserm U1285, CHU Lille, Paris, France. 168Departement of General Pediatrics, University Hospital Robert Debré, APHP, Paris, France. 169Necmettin Erbakan University, Konya, Turkey. 170Germans Trias i Pujol Hospital, Badalona, Spain. 171Medical intensive care unit. Hopital de la Croix-Rousse. Hospices Civils de Lyon, Lyon, France. 172Pediatric Infectious Diseases and Immunodeficiencies Unit, Hospital Universitari Vall d’Hebron, Vall d'Hebron Research Institute, Vall d’Hebron Barcelona Hospital Campus., Barcelona, Spain. 173Department of Immunology, Hospital Universitario de Gran Canaria Dr. Negrín, Canarian Health System, Las Palmas de Gran Canaria, Spain, EU. University Fernando Pessoa Canarias, Las Palmas de Gran Canaria, Spain. 174Neurometabolic Diseases Laboratory, IDIBELL-Hospital Duran i Reynals, Barcelona, Spain. 175Consorcio Hospital General Universitario, Valencia, Spain. 176APHP Hôpitaux Universitaires Paris-Sud, Paris, France. 177Virology unit, Université de Paris, Cohin Hospital, APHP, Paris, France. 178Hospital San Pedro, Logroño, Spain. 179Respiratory medicine, Georges Pompidou Hospital, APHP, Paris, France. 180Dept. Immunology, Hospital Clínico San Carlos, Madrid, Spain. 181Service de Médecine Intensive Réanimation, Institut de Cardiologie, Hopital Pitié-Salpêtrière, Paris, France. 182CHRU de Nancy, Hôpital d'Enfants, Vandoeuvre, France. 183Chair of Nephrology, University of Brescia, Brescia, Italy. 184Department of Immunology, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic. 185Clínica Universidad de Navarra, Madrid, Spain. 186HUS Helsinki University Hospital, Children and Adolescents, Rare Disease Center, and Inflammation Center, Adult Immunodeficiency Unit, Majakka, Helsinki, Finland. 187Fundació Docència i Recerca Mútua Terrassa, Terrassa, Spain. 188Hopital Européen Georges Pompidou, Paris, France. 189Department of Pediatrics, Faculty of Medicine, Mansoura University, Mansoura, Egypt. 190Critical Care Unit, Hospital Universitario de Gran Canaria Dr. Negrín, Canarian Health System, Las Palmas de Gran Canaria, Spain. 191CHU de Saint Etienne, Saint-Priest-en-Jarez, France. 192Shupyk National Medical Academy for Postgraduate Education, Kiev, Ukraine. 193Gustave Roussy Cancer Campus, Villejuif, France. 194Intensive Care Unit, Avicenne Hospital, APHP, Bobigny, France. 195Laboratory of Immunology and Histocompatibility, Saint-Louis Hospital, Paris University, Paris, France. 196Department of Internal Diseases and Pediatrics, Primary Immune Deficiency Research Lab, Centre for Primary Immunodeficiency Ghent, Jeffrey Modell Diagnosis and Research Centre, Ghent University Hospital, Ghent, Belgium. 197Department of Internal Medicine, Université de Paris, INSERM, U970, PARCC, F-75015, Paris, France. 198First Division of Anesthesiology and Critical Care Medicine, University of Brescia, ASST Spedali Civili di Brescia, Brescia, Italy. 199Intensive Care Department, Hospital Universitari MutuaTerrassa, Universitat Barcelona, Terrassa, Spain. 200Hospices Civils de Lyon, Lyon Sud Hospital, Lyon, France. 201Infanta Leonor University Hospital, Madrid, Spain. 202Hematology Department, ASST Spedali Civili di Brescia, Brescia, Italy. 203Pneumologie, Hôpital Avicenne, APHP, INSERM U1272, Université Sorbonne Paris Nord, Bobigny, France. 204Dermatology unit, Laboratoire GAD, INSERM UMR1231 LNC, université de Bourgogne, Dijon, France. 205University Hospital of Burgos, Burgos, Spain. 206Center of Human Genetics, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium. 207Department of Chest Diseases, Necmettin Erbakan University, Meram Medical Faculty, Konya, Turkey. 208CHU de Caen, Caen, France. 209Sorbonne Université, Service de Médecine Intensive Réanimation, Hôpital Tenon, Assistance Publique-Hôpitaux de Paris, Paris, France. 210General Intensive Care Unit, Konya Training and Research Hospital, Konya, Turkey. 211CHU de Nancy, Nancy, France. 212University of Lyon, CIRI, INSERM U1111, National referee centre RAISE, Pediatric Rheumatology, HFME, Hospices Civils de Lyon, Lyon, France. *Leader of the COVID-clinicians group., COVID-STORM Clinicians Giuseppe Foti1, Giacomo Bellani1, Giuseppe Citerio1, Ernesto Contro1, Alberto Pesci2, Maria Grazia Valsecchi3, Marina Cazzaniga4 1Department of Emergency, Anesthesia and Intensive Care, School of Medicine and Surgery, University of Milano-Bicocca, San Gerardo Hospital, Monza IT. 2Department of Pneumology, School of Medicine and Surgery, University of Milano-Bicocca, San Gerardo Hospital, Monza IT. 3Center of Bioinformatics and Biostatistics, School of Medicine and Surgery, University of Milano-Bicocca, San Gerardo Hospital, Monza IT. 4Phase I Research Center, School of Medicine and Surgery, University of Milano-Bicocca, San Gerardo Hospital, Monza IT., Imagine COVID Group Christine Bole-Feysot1, Stanislas Lyonnet1*, Cécile Masson1, Patrick Nitschke1, Aurore Pouliet1, Yoann Schmitt1, Frederic Tores1, Mohammed Zarhrate1 1Imagine Institute, Université de Paris, INSERM UMR 1163, Paris, France. *Leader of the Imagine COVID group., French COVID Cohort Study Group Laurent Abel1, Claire Andrejak2, François Angoulvant3, Delphine Bachelet4, Romain Basmaci5, Sylvie Behillil6, Marine Beluze7, Dehbia Benkerrou8, Krishna Bhavsar4, François Bompart9, Lila Bouadma4, Maude Bouscambert10, Mireille Caralp11, Minerva Cervantes-Gonzalez12, Anissa Chair4, Alexandra Coelho13, Camille Couffignal4, Sandrine Couffin-Cardiergues14, Eric D’ortenzio12, Charlene Da Silveira4, Marie-Pierre Debray4, Dominique Deplanque15, Diane Descamps16, Mathilde Desvallées17, Alpha Diallo18, Alphonsine Diouf13, Céline Dorival8, François Dubos19, Xavier Duval4, Philippine Eloy4, Vincent V. E. Enouf20, Hélène Esperou21, Marina Esposito-Farese4, Manuel Etienne22, Nadia Ettalhaoui4, Nathalie Gault4, Alexandre Gaymard10, Jade Ghosn4, Tristan Gigante23, Isabelle Gorenne4, Jérémie Guedj24, Alexandre Hoctin13, Isabelle Hoffmann4, Salma Jaafoura21, Ouifiya Kafif4, Florentia Kaguelidou25, Sabina Kali4, Antoine Khalil4, Coralie Khan17, Cédric Laouénan4, Samira Laribi4, Minh Le4, Quentin Le Hingrat4, Soizic Le Mestre18, Hervé Le Nagard24, François-Xavier Lescure4, Yves Lévy26, Claire Levy-Marchal27, Bruno Lina10, Guillaume Lingas24, Jean Christophe Lucet4, Denis Malvy28, Marina Mambert13, France Mentré4, Noémie Mercier18, Amina Meziane8, Hugo Mouquet20, Jimmy Mullaert4, Nadège Neant24, Marion Noret29, Justine Pages30, Aurélie Papadopoulos21, Christelle Paul18, Nathan Peiffer-Smadja4, Ventzislava Petrov-Sanchez18, Gilles Peytavin4, Olivier Picone31, Oriane Puéchal12, Manuel Rosa-Calatrava10, Bénédicte Rossignol23, Patrick Rossignol32, Carine Roy4, Marion Schneider4, Caroline Semaille12, Nassima Si Mohammed4, Lysa Tagherset4, Coralie Tardivon4, Marie-Capucine Tellier4, François Téoulé8, Olivier Terrier10, Jean-François Timsit4, Théo Treoux4, Christelle Tual33, Sarah Tubiana4, Sylvie van der Werf34, Noémie Vanel35, Aurélie Veislinger33, Benoit Visseaux16, Aurélie Wiedemann26, Yazdan Yazdanpanah36 1Inserm UMR 1163, Paris, France. 2CHU Amiens, France. 3Hôpital Necker, Paris, France. 4Hôpital Bichat, Paris, France. 5Hôpital Louis Mourrier, Colombes, France. 6Institut Pasteur, Paris, France. 7F-CRIN Partners Platform, AP-HP, Université de Paris, Paris, France. 8Inserm UMR 1136, Paris, France. 9Drugs for Neglected Diseases initiative, Geneva, Switzerland. 10Inserm UMR 1111, Lyon, France. 11Inserm Transfert, Paris, France. 12REACTing, Paris, France. 13Inserm UMR 1018, Paris, France. 14Inserm, Pôle Recherche Clinique, France. 15CIC 1403 Inserm-CHU Lille, Paris, France. 16Université de Paris, IAME, INSERM UMR 1137, AP-HP, University hospital Bichat Claude Bernard, Virology, F-75018 Paris, France. 17Inserm UMR 1219, Bordeaux, France. 18ANRS, Paris, France. 19CHU Lille, France. 20Pasteur Institute, Paris, France. 21Inserm sponsor, Paris, France. 22Rouen - SMIT, France. 23FCRIN INI-CRCT, Nancy, France. 24Inserm UMR 1137, Paris, France. 25Centre d'Investigation Clinique, Inserm CIC1426, Hôpital Robert Debré, Paris, France. 26Inserm UMR 955, Créteil, France; Vaccine Research Instiute (VRI), Paris, France. 27F-CRIN INI-CRCT, Paris, France. 28Bordeaux - SMIT, France. 29RENARCI, Annecy, France. 30Hôpital Robert Debré, Paris, France. 31Colombes - Louis Mourier - Gynécologie, France. 32University of Lorraine, Plurithematic Clinical Investigation Centre Inserm CIC-P; 1433, Inserm U1116, CHRU Nancy Hopitaux de Brabois, F-CRIN INI-CRCT; (Cardiovascular and Renal Clinical Trialists), Nancy, France. 33Inserm CIC-1414, Rennes, France. 34Institut Pasteur, UMR 3569 CNRS, Université de Paris, Paris, France. 35hôpital la timone, Marseille, France. 36Paris - Bichat - SMIT, France., The Milieu Intérieur Consortium Laurent Abel1, Andres Alcover2, Hugues Aschard2, Kalla Astrom3, Philippe Bousso2, Pierre Bruhns2, Ana Cumano2, Caroline Demangel2, Ludovic Deriano2, James Di Santo2, Françoise Dromer2, Gérard Eberl2, Jost Enninga2, Jacques Fellay4, Ivo Gomperts-Boneca2, Milena Hasan2, Serge Hercberg5, Olivier Lantz6, Hugo Mouquet2, Etienne Patin2, Sandra Pellegrini2, Stanislas Pol7, Antonio Rausell8, Lars Rogge2, Anavaj Sakuntabhai2, Olivier Schwartz2, Benno Schwikowski2, Spencer Shorte2, Frédéric Tangy2, Antoine Toubert9, Mathilde Touvier10, Marie-Noëlle Ungeheuer2, Matthew L. Albert11*, Darragh Duffy2*, Lluis Quintana-Murci2* 1INSERM U1163, University of Paris, Imagine Institute, Paris, France. 2Pasteur Institute, Paris, France. 3Lund University, Lund, Sweden. 4EPFL, Lausanne, Switzerland. 5Université Paris 13, Paris, France. 6Curie Institute, Paris, France. 7Cochin Hospital, Paris, France. 8INSERM UMR 1163 – Institut Imagine. 9Hôpital Saint-Louis, Paris, France. 10Université Paris 13, Paris, France. 11In Sitro. *Co-coordinators of the Milieu Intérieur Consortium. Additional information can be found at: https://www.pasteur.fr/labex/milieu-interieur., CoV-Contact Cohort Loubna Alavoine1, Karine K. A. Amat2, Sylvie Behillil3, Julia Bielicki4, Patricia Bruijning5, Charles Burdet6, Eric Caumes7, Charlotte Charpentier8, Bruno Coignard9, Yolande Costa1, Sandrine Couffin-Cardièrgues10, Florence Damond8, Aline Dechanet11, Christelle Delmas10, Diane Descamps8, Xavier Duval1, Jean-Luc Ecobichon1, Vincent Enouf3, Hélène Espérou10, Wahiba Frezouls1, Nadhira Houhou11, Emila Ilic-Habensus1, Ouifiya Kafif11, John Kikoine11, Quentin Le Hingrat8, David Lebeaux12, Anne Leclercq1, Jonathan Lehacaut1, Sophie Letrou1, Bruno Lina13, Jean-Christophe Lucet14, Denis Malvy15, Pauline Manchon11, Milica Mandic1, Mohamed Meghadecha16, Justina Motiejunaite17, Mariama Nouroudine1, Valentine Piquard11, Andreea Postolache11, Caroline Quintin1, Jade Rexach1, Layidé Roufai10, Zaven Terzian11, Michael Thy18, Sarah Tubiana1, Sylvie van der Werf3, Valérie Vignali1, Benoit Visseaux8, Yazdan Yazdanpanah14 1Centre d'Investigation Clinique, Inserm CIC 1425, Hôpital Bichat Claude Bernard, APHP, Paris, France. 2IMEA Fondation Léon M'Ba, Paris, France. 3Institut Pasteur, UMR 3569 CNRS, Université de Paris, Paris, France. 4University of Basel Children’s Hospital. 5Julius Center for Health Sciences and Primary Care, Utrecht. 6Université de Paris, IAME, Inserm UMR 1137, F-75018, Paris, France, Hôpital Bichat Claude Bernard, APHP, Paris, France. 7Hôpital Pitiè Salpétriere, APHP, Paris. 8Université de Paris, IAME, INSERM UMR 1137, AP-HP, University hospital Bichat Claude Bernard, Virology, F-75018 Paris, France. 9Santé Publique France, Saint Maurice, France. 10Pole Recherche Clinique, Inserm, Paris France. 11Hôpital Bichat Claude Bernard, APHP, Paris, France. 12APHP, Paris, France. 13Virpath Laboratory, International Center of Research in Infectiology, Lyon University, INSERM U1111, CNRS UMR 5308, ENS, UCBL, Lyon, France . 14IAME Inserm UMR 1138, Hôpital Bichat Claude Bernard, APHP, Paris, France. 15Service des Maladies Infectieuses et Tropicales; Groupe Pellegrin-Place Amélie-Raba-Léon, BORDEAUX. 16Hôpital Hotel Dieu, APHP, Paris, France. 17ervice des explorations fonctionnelles, Hôpital Bichat- Claude Bernard, APHP, Paris, France. 18Center for Clinical Investigation, Assistance Publique-Hôpitaux de Paris, Bichat-Claude Bernard University Hospital., Amsterdam UMC Covid-19 Biobank Michiel van Agtmael1, Anne Geke Algera2, Frank van Baarle2, Diane Bax3, Martijn Beudel4, Harm Jan Bogaard5, Marije Bomers1, Lieuwe Bos2, Michela Botta2, Justin de Brabander6, Godelieve Bree6, Matthijs C. Brouwer4, Sanne de Bruin2, Marianna Bugiani7, Esther Bulle2, O. Chouchane1, Alex Cloherty3, Paul Elbers2, Lucas Fleuren2, Suzanne Geerlings1, Bart Geerts8, Theo Geijtenbeek9, Armand Girbes2, Bram Goorhuis1, Martin P. Grobusch1, Florianne Hafkamp9, Laura Hagens2, Jorg Hamann10, Vanessa Harris1, Robert Hemke11, Sabine M. Hermans1, Leo Heunks2, Markus Hollmann8, Janneke Horn2, Joppe W. Hovius1, Menno de Jong12, Rutger Koning4, Mourik van Mourik2, Jeaninne Nellen1, Frederique Paulus2, Edgar Peters1, Tom van der Poll1, Bennedikt Preckel8, Jan M. Prins1, Jorinde Raasveld2, Tom Reijnders1, Michiel Schinkel1, Marcus Schultz2, Alex Schuurman13, Kim Sigaloff1, Marry Smit2, Cornelis S. Stijnis1, Willemke Stilma2, Charlotte Teunissen14, Patrick Thoral2, Anissa Tsonas2, Marc van der Valk1, Denise Veelo8, Alexander P. J. Vlaar15, Heder de Vries2, Michèle van Vugt1, W. Joost Wiersinga1, Dorien Wouters16, A. H. (Koos) Zwinderman17, Diederik van de Beek18* 1Department of Infectious Diseases, Amsterdam UMC, Netherlands. 2Department of Intensive Care, Amsterdam UMC, Netherlands. 3Experimental Immunology, Amsterdam UMC, Netherlands. 4Department of Neurology, Amsterdam UMC, Netherlands. 5Department of Pulmonology, Amsterdam UMC, Netherlands. 6Department of Infectious Diseases, Amsterdam UMC, Netherlands. 7Department of Pathology, Amsterdam UMC, Netherlands. 8Department of Anesthesiology, Amsterdam UMC, Netherlands. 9Department of Experimental Immunology, Amsterdam UMC, Netherlands. 10Amsterdam UMC, THE NETHERLANDS Biobank Core Facility, Amsterdam UMC, Netherlands. 11Department of Radiology, Amsterdam UMC, Netherlands. 12Department of Medical Microbiology, Amsterdam UMC, Netherlands. 13Department of Internal Medicine, Amsterdam UMC, Netherlands. 14Neurochemical Laboratory, Amsterdam UMC, Netherlands. 15Deparment of Intensive Care, Amsterdam UMC, Netherlands. 16Department of Clinical Chemistry, Amsterdam UMC, Netherlands. 17Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam UMC, Netherlands. 18Department of Neurology, Amsterdam UMC, Netherlands. *Leader of the AMC consortium., COVID Human Genetic Effort Laurent Abel1, Alessandro Aiuti2, Saleh Al Muhsen3, Fahd Al-Mulla4, Mark S. Anderson5, Andrés Augusto Arias6, Hagit Baris Feldman7, Dusan Bogunovic8, Alexandre Bolze9, Anastasiia Bondarenko10, Ahmed A. Bousfiha11, Petter Brodin12, Yenan Bryceson12, Carlos D. Bustamante13, Manish Butte14, Giorgio Casari15, Samya Chakravorty16, John Christodoulou17, Elizabeth Cirulli9, Antonio Condino Neto18, Megan A. Cooper19, Clifton L. Dalgard20, Joseph L. DeRisi21, Murkesh Desai22, Beth A. Drolet23, Sara Espinosa24, Jacques Fellay25, Carlos Flores26, Jose Luis Franco27, Peter K. Gregersen28, Filomeen Haerynck29, David Hagin30, Rabih Halwani​31, Jim Heath32, Sarah E. Henrickson33, Elena Hsieh34, Kohsuke Imai35, Yuval Itan8, Timokratis Karamitros36, Kai Kisand37, Cheng-Lung Ku38, Yu-Lung Lau39, Yun Ling40, Carrie L. Lucas41, Tom Maniatis42, Davoud Mansouri43, Laszlo Marodi44, Isabelle Meyts45, Joshua Milner46, Kristina Mironska47, Trine Mogensen48, Tomohiro Morio49, Lisa P. Ng50, Luigi D. Notarangelo51, Giuseppe Novelli52, Antonio Novelli53, Cliona O'Farrelly54, Satoshi Okada55, Tayfun Ozcelik56, Rebeca Perez de Diego57, Anna M. Planas58, Carolina Prando59, Aurora Pujol60, Lluis Quintana-Murci61, Laurent Renia62, Alessandra Renieri63, Carlos Rodríguez-Gallego64, Vanessa Sancho-Shimizu65, Vijay Sankaran66, Kelly Schiabor Barrett9, Mohammed Shahrooei67, Andrew Snow68, Pere Soler-Palacín69, András N. Spaan70, Stuart Tangye71, Stuart Turvey72, Furkan Uddin73, Mohammed J. Uddin74, Diederik van de Beek75, Sara E. Vazquez76, Donald C. Vinh77, Horst von Bernuth78, Nicole Washington9, Pawel Zawadzki79, Helen C. Su51*, Jean-Laurent Casanova80* 1INSERM U1163, University of Paris, Imagine Institute, Paris, France. 2San Raffaele Telethon Institute for Gene Therapy, IRCCS Ospedale San Raffaele, Milan, Italy. 3King Saud University, Riyadh, Saudi Arabia. 4Kuwait University, Kuwait City, Kuwait. 5University of California, San Francisco, San Francisco, CA, USA. 6Universidad de Antioquia, Group of Primary Immunodeficiencies, Antioquia, Colombia. 7The Genetics Institute, Tel Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. 8Icahn School of Medicine at Mount Sinai, New York, NY, USA. 9Helix, San Mateo, CA, USA. 10Shupyk National Medical Academy for Postgraduate Education, Kiev, Ukraine. 11Clinical immunology unit, pediatric infectious disease departement, Faculty of Medicine and Pharmacy, Averroes University Hospital. LICIA Laboratoire d'immunologie clinique, d'inflammation et d'allergie, Hassann Ii University., Casablanca, Morocco. 12Karolinska Institute, Stockholm, Sweden. 13Stanford University, Stanford, CA, USA. 14University of California, Los Angeles, CA, USA. 15Medical Genetics, IRCCS Ospedale San Raffaele, Milan, Italy. 16Emory, Atlanta, GA, USA. 17Murdoch Children's Research Institute, Victoria, Australia. 18University of São Paulo, São Paulo, Brazil. 19Washington University School of Medicine, St. Louis, MO, USA. 20The American Genome Center; Uniformed Services University of the Health Sciences, Bethesda, MD, USA. 21University of California San Francisco; Chan Zuckerberg Biohub, San Francisco, CA, United States. 22Bai Jerbai Wadia Hospital for Children, Mumbai, India. 23 School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA. 24Instituto Nacional de Pediatria (National Institute of Pediatrics), Mexico City, Mexico. 25Swiss Federal Institute of Technology Lausanne, Lausanne, Switzerland. 26Research Unit, Hospital Universitario Nuestra Señora de Candelaria, Canarian Health System, Santa Cruz de Tenerife, Spain. 27University of Antioquia, Medellín, Colombia. 28Feinstein Institute for Medical Research, Northwell Health USA, Manhasset, NY, USA. 29Department of Paediatric Immunology and Pulmonology, Centre for Primary Immunodeficiency Ghent (CPIG), PID research lab, Jeffrey Modell Diagnosis and Research Centre, Ghent University Hospital, Edegem, Belgium. 30The Genetics Institute Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. 31Sharjah Institute of Medical Research, College of Medicine, University of Sharjah, Sharjah, UAE. 32Institute for Systems Biology, Seattle, WA, USA. 33Children's Hospital of Philadelphia, Philadelphia, PA, USA. 34Anschutz Medical Campus, Aurora, CO, USA. 35Riken, Tokyo, Japan. 36Hellenic Pasteur Institute, Athens, Greece. 37University of Tartu, Tartu, Estonia. 38Chang Gung University, Taoyuan County, Taiwan. 39The University of Hong Kong, Hong Kong, China. 40Shanghai Public Health Clinical Center, Fudan University, Shanghai, China. 41Yale School of Medicine, New Haven, CT, USA. 42New York Genome Center, New York, NY, USA. 43Shahid Beheshti University of Medical Sciences, Tehran, Iran. 44Semmelweis University Budapest, Budapest, Hungary. 45KU Leuven, Department of Immunology, Microbiology and Transplantation, Leuven, Belgium. 46Columbia University Medical Center, New York, NY, USA. 47University Clinic for Children's Diseases, Skopje, North Macedonia. 48Aarhus University, Aarhus, Denmark. 49Tokyo Medical & Dental University Hospital, Tokyo, Japan. 50Singapore Immunology Network, Singapore. 51National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. 52Bambino Gesù Children's Hospital, Rome, Italy; Dept. Biomedicine and Prevention, University of Rome “Tor Vergata”, Rome, Italy. 53Bambino Gesù Children's Hospital, Rome, Italy, Rome, Italy, Italy. 54Trinity College, Dublin, Ireland. 55Hiroshima University, Hiroshima, Japan. 56Bilkent University, Ankara, Turkey. 57Laboratory of Immunogenetics of Human Diseases, Innate Immunity Group, IdiPAZ Institute for Health Research, La Paz Hospital, Madrid 28046, Spain, EU, Madrid, Spain, Spain. 58IIBB-CSIC, IDIBAPS, Barcelona, Spain. 59Faculdades Pequeno Príncipe e Instituto de Pesquisa Pelé Pequeno Príncipe, Curitiba, Brazil. 60Neurometabolic Diseases Laboratory, IDIBELL- Hospital Duran I Reynals; Catalan Institution for Research and Advanced Studies (ICREA); CIBERER U759, ISCiii Madrid Spain, Barcelona, Spain. 61Institut Pasteur (CNRS UMR2000) and Collège de France, Paris, France. 62Infectious Diseases Horizontal Technology Center and Singapore Immunology Network, Agency for Science Technology (A*STAR), Singapore. 63University of Siena, Siena, Italy. 64Hospital Universitario de Gran Canaria Dr Negrín, Canarian Health System, Canary Islands, Spain. 65Imperial College London, London, UK. 66Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. 67Saeed Pathobiology and Genetic Lab, Tehran, Iran. 68Uniformed Services University of the Health Sciences (USUHS), Bethesda, MD, USA. 69Hospital Universitari Vall d'Hebron, Barcelona, Spain. 70University Medical Center Utrecht, Amsterdam, Netherlands. 71Garvan Institute of Medical Research, Sydney, Australia. 72The University of British Columbia, Vancouver, Canada. 73Holy Family Red Crescent Medical College; Centre for Precision Therapeutics, NeuroGen Children's Healthcare; Genetics and Genomic Medicine Centre, NeuroGen Children's Healthcare, Dhaka, Bangladesh. 74Mohammed Bin Rashid University of Medicine and Health Sciences, College of Medicine, Dubai, UAE; The Centre for Applied Genomics, Department of Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada, Dhaka, Bangladesh. 75Amsterdam UMC, Amsterdam, Netherlands. 76University of California, San Francisco, San Francisco, CA, United States. 77McGill University Health Centre, Montreal, Canada. 78Charité - Berlin University Hospital Center, Berlin, Germany. 79Molecular Biophysics Division, Faculty of Physics, A. Mickiewicz University, Uniwersytetu Poznanskiego 2, Poznań, Poland. 80Rockefeller University, Howard Hughes Medical Institute, Necker Hospital, New York, NY, USA. *Leaders of the COVID Human Genetic Effort., Interindividual clinical variability in the course of SARS-CoV-2 infection is immense. We report that at least 101 of 987 patients with life-threatening COVID-19 pneumonia had neutralizing IgG auto-Abs against IFN-ω (13 patients), the 13 types of IFN-α (36), or both (52), at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1,227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 were men. A B cell auto-immune phenocopy of inborn errors of type I IFN immunity underlies life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men., 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 Award (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 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, ANRS-COV05, the Square Foundation, Grandir - Fonds de solidarité pour l’enfance, the SCOR Corporate Foundation for Science, Institut Institut National de la Santé et de la Recherche Médicale (INSERM) and the University of Paris. Samples from San Raffaele Hospital were obtained within the Covid-BioB project and healthcare personnel of San Raffaele Hospital, San Raffaele Telethon Institute for Gene Therapy (SR-TIGET) clinical lab and clinical research Unit; funded by the Program Project COVID-19 OSR-UniSR and Fondazione Telethon. 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). The “Milieu Intérieur” cohort was supported by was supported by the French Government’s Investissement d’Avenir Program, Laboratoire d’Excellence “Milieu Intérieur” Grant (ANR-10-LABX-69-01) (PI: L QuintanaMurci & D Duffy). The Simoa experiment was supported by the PHRC-20-0375 COVID-19 grant “DIGITAL COVID” (PI: G Gorochov). SGT is supported by a Leadership 3 Investigator Grant awarded by the National Health and Medical Research Council of Australia, and a COVID19 Rapid Response Grant awarded by UNSW Sydney. CRG and colleagues were supported by Instituto de Salud Carlos III (COV20_01333 and COV20_01334, Spanish Ministry of Science and Innovation -RTC-2017-6471-1; AEI/FEDER, UE), and Cabildo Insular de Tenerife (CGIEU0000219140 and “Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19”). SA and AB were supported by ANR-20-COVI-0064 (PI: A Belot). This work is supported by the French Ministry of Health “Programme Hospitalier de Recherche Clinique Inter regional 2013”, by the Contrat de Plan Etat-Lorraine and FEDER Lorraine, and a public grant overseen by the French National Research Agency (ANR) as part of the second “Investissements d’Avenir” program FIGHT-HF (reference: ANR-15-RHU-0004) and by the French PIA project “Lorraine Université d’Excellence”, reference ANR15-IDEX-04-LUE (45) and biobanking is performed by the Biological Resource Center Lorrain BB-0033-00035. This study was supported by the Fonds IMMUNOV, for Innovation in Immunopathology and by a grant from the Agence National de la Recherche (ANR-flash Covid19 “AIROCovid” to FRL), and by the FAST Foundation (French Friends of Sheba Tel Hashomer Hospital). Work in the Laboratory of Virology and Infectious Disease was supported by 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 Amsterdam UMC Covid-19 Biobank was supported by grants of the Amsterdam Corona Research Fund, Dr. C.J. Vaillant Fund, and Netherlands Organization for Health Research and Development (ZonMw; NWO-Vici-Grant [grant number 918·19·627 to DvdB]. This work was also supported by the Division of Intramural Research of the National Institute of Dental Craniofacial Research and National Institute of Allergy and Infectious Diseases, National Institutes of Health, and by Regione Lombardia, Italy (project “Risposta immune in pazienti con COVID-19 e comorbidita”). The opinions and assertions expressed herein are those of the author(s) and do not necessarily reflect the official policy or position of the Uniformed Services University or the Department of Defense. JH holds an Institut Imagine MD-PhD fellowship from the Fondation Bettencourt Schueller. JR is supported by the Inserm PhD program (“poste d’accueil Inserm”). PB was supported by the French Foundation for Medical Research (FRM, EA20170638020) and the MD-PhD program of the Imagine Institute (with the support of the Fondation Bettencourt-Schueller). We thank the Association “Turner et vous” for their help and support. Sample processing at IrsiCaixa was possible thanks to the crowdfunding initiative YoMeCorono. DCV is supported by the Fonds de la recherche en santé du Québec clinician-scientist scholar program. K. Kisand was supported by the Estonian Research Council grant PUT1367. We thank the GEN-COVID Multicenter Study (https://sites.google.com/dbm.unisi.it/gen-covid). We thank the NIAID Office of Cyber Infrastructure and Computational Biology, Bioinformatics and Computational Biosciences Branch (Contract HHSN316201300006W/HHSN27200002 to MSC, Inc) and Operations Engineering Branch for developing the HGRepo system to enable streamlined access to the data and the NCI Advanced Biomedical Computational Science (ABCS) for data transformation support.