Benefit and risk associated with interleukin-6 receptor inhibitor administration during severe COVID-19: a retrospective multicentric study none

Benefit and risk associated with interleukin-6 receptor inhibitor administration during severe COVID-19: a retrospective multicentric study none | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Benefit and risk associated with interleukin-6 receptor inhibitor administration during severe COVID-19: a retrospective multicentric study none Charlène Lefèvre, Théo Funck-Brentano, Marine Cachanado, Alexia Plocque, and 17 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6785789/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 22 Jan, 2026 Read the published version in Scientific Reports → Version 1 posted 11 You are reading this latest preprint version Abstract Purpose During severe and critical COVID-19, therapeutic options remain scarce. Among interventions, the use of interleukin-6 receptor inhibitor (IL-6Ri) is especially controversial due to persistent uncertainty about their efficacy and safety. Methods We conducted a multicentric retrospective French observational study. All severe or critical COVID-19 requiring hospital admission were included from march 1st 2020 to December 31th 2021. Our main aim was to compare the occurrence of secondary infections function of the administration of IL-6Ri. Digestive, hematological complications and survival were also analyzed. Results Among 2587 patients requiring hospital admission, 1603 had a severe COVID-19 and 984 a critical one requiring ICU admission. 224 received at least one dose of tocilizumab or sarilumab. Incidence of secondary infection was 29.5% in the IL-6Ri group vs. 19.5% without IL-6Ri (unadjusted OR: 1.73 [1.27;2.34]; p = 0.0004) in the whole population. This result remained consistent after adjustment, without multiple imputation (MI) (adjusted OR: 2.12 [1.51; 2.97]; p < 0.0001) and after MI (adjusted OR: 1.47 [1.25; 1.72]; p < 0.0001)). Incidence of hematological or digestive complication were similar between groups. Mortality of patients admitted in ward was higher in the IL-6Ri group (18.7% vs 10.5%, p = 0.0155). No difference in 28 days, ICU, hospital of 90 days mortality was noticed among ICU patients. Conclusion in this population, administration of IL-6Ri was associated with a higher risk of secondary infection in the whole population and with a higher mortality among patients who spent their whole stay in ward. Registration NCT05017441 (January 31st 2024) Health sciences/Diseases/Infectious diseases Health sciences/Diseases/Infectious diseases/Viral infection Health sciences/Medical research/Outcomes research Health sciences/Medical research/Study design/Clinical trials/Phase iv trials Covid-19 tocilizumab nosocomial infections ventilator-associated pneumonia neutropenia mortality Figures Figure 1 Introduction Since the onset of Coronavirus disease 2019 (COVID-19), numerous therapeutic interventions have been proposed, particularly for severe manifestations of the disease. The efficacy of corticosteroids in severe and critical COVID-19 cases has been swiftly established [ 1 – 3 ]. Concurrently, the pronounced inflammatory response observed in severe cases [ 4 ] has prompted exploration of cytokine pathway inhibitors as potential therapeutic targets. Elevated levels of circulating interleukin-6 (IL-6) in critically ill patients, and its correlation with severe hypoxemia, have highlighted the IL-6 pathway as a promising target for intervention [ 5 , 6 ]. However, randomized trials investigating IL-6 receptor inhibitors have yielded conflicting results, leading to ongoing uncertainty about their clinical relevance [ 7 ], despite numerous meta-analyses [ 7 – 10 ]. Moreover, the safety of targeting the IL-6 pathway in septic patients remains to be specifically investigated. IL-6 receptor (IL-6R) antagonists have been extensively used in chronic inflammatory diseases such as rheumatoid arthritis, juvenile idiopathic arthritis, and Castleman's disease [ 11 , 12 ]. Long-term experience with IL-6 pathway inhibition has highlighted an increased risk of infectious diseases, estimated at approximately 5.5 events per 100 patient-years [ 7 , 11 ]. Additionally, altering the IL-6 pathway may compromise digestive mucosa regeneration, mediated by signal transduction through the gp130 protein [ 12 , 13 ]. This could potentially lead to upper digestive tract hemorrhage, especially when combined with systemic corticosteroids. Conversely, the potential risks associated with the acute administration of IL-6 inhibitors are not yet well-documented. This is particularly true in cases of cytokine release syndrome following chimeric antigen receptor T-cell (CAR-T) therapy, or in severe and critical COVID-19 cases [ 7 , 14 , 15 ]. While recent meta-analyses of therapeutic trials have not reported an increased risk of infections [ 16 – 18 ], this remains a topic of debate [ 7 , 14 ]. The aim of our study was to highlight the potential complications associated with the IL-6 receptor inhibitors in use at the time, specifically tocilizumab and sarilumab. Methods Study design We conducted a retrospective, multicenter cohort study from March 1st, 2020, to December 31st, 2021. The study adhered to the STROBE (STrengthening the Reporting of Observational Studies in Epidemiology) guidelines for reporting observational studies. Settings and participants Eight medical (3 internal medicine and 2 pulmonary departments) and 4 critical care wards of three regional university hospitals in Paris were involved in this study. All consecutive adult patients admitted for a documented severe COVID-19, as defined by the IDSA guidelines [ 19 ] were included in the study. COVID-19 was confirmed by a positive SARS-CoV-2 real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay from nasal or oropharyngeal swabs, or lower respiratory tract samples (in invasively ventilated patients). Patients without laboratory-confirmed COVID-19 were excluded from the study. Patients were categorized into two groups: the "ward group," who spent their entire hospital stay in a ward, and the "ICU group," who required ICU admission at any point during their hospital stay. Patients were admitted to the ICU if they required noninvasive or invasive mechanical ventilation or if they experienced any other acute organ failure. Details are provided in the supplementary material. Data collection and proceeding Data were collected using a standardized electronic form. Major adverse event included nosocomial infections, myelotoxicity and digestive tract hemorrhage. Hospital acquired and ventilator-associated pneumonia were defined according to the European [ 20 , 21 ] and American guidelines [ 22 ]. Other ICU-acquired infections were diagnosed by the attending physician following established guidelines [ 23 ]. Primary bacterial bloodstream infection and central line associated bloodstream infection were defined as in the EUROBACT study [ 24 ]. Upper digestive tract hemorrhage was confirmed by endoscopic demonstration of an esophageal, gastric or duodenal lesion [ 25 – 27 ]. Lower intestinal hemorrhage was defined by the presence of melena or hematochezia and confirmed by colonoscopy [ 27 ]. Thrombopenia was defined as a platelet count below 150 G/l; neutropenia was defined as a neutrophils count below 1 500 /mm 3 , with severe neutropenia below 500 /mm 3 . The primary outcome was the proportion of hospital-acquired infectious episodes during the hospital stay. Secondary outcomes included the occurrence of leukopenia, thrombocytopenia, digestive hemorrhage or perforation, as well as the length of stay in the intensive care unit (ICU) and hospital, and the duration of mechanical ventilation. The exposure variable was the administration of tocilizumab or sarilumab during the hospital stay. Details are provided in the supplementary material. Ethical considerations The study was carried out in accordance with the Declaration of Helsinki and French law and was approved by our institutional review board (GERM; IRB n°00012157). Patients were informed about the study and their non-opposition ( they were informed and consent ) to the collection and use of non-identifying data for research purposes was obtained. The processing of patient data complied with the reference methodology 004 of the French Commission Nationale de l'Informatique et des Libertés (French National Data Protection Agency). Statistical analysis Patient characteristics were described for the entire population and stratified by the use of IL-6 inhibitors (tocilizumab or sarilumab). Categorical variables are presented as counts (percentages), and continuous variables as mean (± standard deviation) or median with interquartile range [Q1; Q3], depending on their distribution. Categorical variables were compared between groups using the Pearson Chi-squared test or Fisher’s exact test, while continuous variables were compared using the Student’s t-test or the Wilcoxon rank-sum test. As there were no formal recommendations for the use of tocilizumab or sarilumab, their prescription was based on patient-specific characteristics and the judgment of the attending physician. To address potential bias introduced by these prescription methods, a logistic regression model was employed to examine the relationship between the use of these medications and hospital-acquired infectious episodes. Details are provided in the supplementary material. Results Participants A total of 2587 patients were included in the study over a 22-month period. Of these, 1603 were admitted to a medical ward (referred to as the “Ward group”), while 984 required an ICU admission at some point during their hospital stay (Fig. 1 ). The populations are described in Table 1 and supplementary Tables 1 and 2. Table 1 Characteristics of the population Total (N = 2587) No IL-6R inhibitor (n = 2363) Tocilizumab or Sarilmab (n = 224) OR [IC95%] p Global population Center of inclusion Center 1 1361 (52.9%) 1243 (52.9%) 118 (52.9%) 1 0.0007 Center 2 955 (37.1%) 857 (36.5%) 98 (43.9%) 1.20 [0.91;1.60] Center 3 257 (10.0%) 250 (10.6%) 7 (3.1%) 0.29 [0.14;0.64] Age (years) Mean (SD) 63.60 (15.6) 63.5 (15.7) 64.1 (14.4) 0.72 Sex Female 963 (37.3%) 874 (37.1%) 89 (39.9%) 1 0.4 BMI (kg/m 2 ) Median [Q1;Q3] 27.6 [24.2;31.5] BMI (kg/m 2 ) Mean (SD) 30 728 (33.9%) 637 (32.8%) 91 (43.3%) 2.03 [1.39;2.96] Smoking (current of former) 459 (17.8%) 433 (20.4%) 26 (12.3%) 0.55 [0.36;0.83] 0.0045 Alcohol habits 183 (7.1%) 172 (8.4%) 11 (5.2%) 0.59 [0.32;1.11] 0.1 Hypertension 1245 (48.2%) 1136 (48.1%) 109 (48.7%) 1.02 [0.78;1.34] 0.88 Ischemic cardiopathy 260 (10.1%) 240 (10.2%) 20 (8.9%) 0.87 [0.54;1.40] 0.57 Chronic heart failure 88 (3.4%) 78 (3.3%) 10 (4.5%) 1.37 [0.70;2.68] 0.36 Diabetes mellitus 649 (25.1%) 589 (25.0%) 60 (26.8%) 1.10 [0.81;1.50] 0.55 Immunosuppressive treatment 143 (5.5%) 137 (5.8%) 6 (2.7%) 0.45 [0.19;1.02] 0.05 Infectious immunodepression 35 (1.3%) 33 (1.4%) 2 (0.9%) 0.64 [0.15;2.67] 0.76 Gastric or duodenal peptic ucler 54 (2.1%) 52 (2.2%) 2 (0.9%) 0.40 [0.10;1.65] 0.32 COPD/SAS/Asthma 475 (18.4%) 430 (18.2%) 45 (20.1%) 1.13 [0.80;1.59] 0.49 Long-term oxygen therapy 16 (0.6%) 16 (0.7%) 0 (0.00%) - 0.39 Chronic renal failure 211 (8.17%) 195 (8.26%) 16 (7.1%) 0.85 [0.50;1.45] 0.56 Chronic diialysis 47 (1.8%) 44 (1.9%) 3 (1.3%) 0.71 [0.22;2.32] 0.79 Malignant hemopathy / Cancer 313 (12.1%) 294 (12.5%) 19 (8.5%) 0.65 [0.40;1.06] 0.08 Stroke 173 (6.7%) 164 (6.9%) 9 (4.0%) 0.56 [0.28;1.11] 0.09 Proton pump inhibitor 518 (20.2%) 476 (20.3%) 42 (18.8%) 0.91 [0.64;1.29] 0.59 Anticoagulation 284 (11.1%) 266 (11.4%) 18 (8.1%) 0.69 [0.42;1.13] 0.14 Antiaggregant treatment 504 (19.71%) 461 (19.7%) 43 (19.3%) 0.97 [0.69;1.37] 0.87 Ward group Inclusion center Center 1 927 (58.2%) 888 (59.0%) 39 (43.3%) 1 0.0083 Center 2 666 (41.8%) 615 (40.9%) 51 (56.7%) 1.89 [1.23; 2.90] Center 3 1 (0.06%) 1 (0.07%) 0 (0.00%) - Age (years) Mean (SD) 64.99 (16.8) 64.77 (16.9) 68.69 (15.3) 0.0299 Sex (Female) 657 (41.1%) 620 (41.1%) 37 (41.1%) 1.00 [0.65; 1.54] > 0.99 BMI (kg/m 2 ) Median [Q1;Q3] 27.1 [23.83;31.00] 27.1[23.72;30.86] 27.8 [25.39;31.99] 0.08 BMI (kg/m 2 ) 30 367 (30.3%) 341 (30.1%) 26 (32.9%) 2.32 [1.27;3.59] Smoking habits (Yes) 271 (17.0%) 263 (17.5%) 8 (8.9%) 0.60 [0.21; 1.68] 0.08 Alcohol habits 121 (7.6%) 116 (7.7%) 5 (5.5%) 1.18 [0.36; 3.79] 0.24 Hypertension 740 (46.2%) 687 (45.5%) 53 (58.2%) 1.67 [1.09; 2.57] 0.0176 Ischemic cardiopathy 174 (10.9%) 162 (10.7%) 12 (13.3%) 1.28 [0.68; 2.40] 0.44 Chronic heart failure 71 (4.4%) 65 (4.3%) 6 (6.6%) 1.57 [0.66; 3.73] 0.29 Diabetes mellitus 355 (22.2%) 329 (21.8%) 26 (28.6%) 1.44 [0.90; 2.30] 0.13 Immunosuppressive treatment 84 (5.2%) 83 (5.5%) 1 (1.1%) 0.19 [0.03; 1.39] 0.09 Infectious immunodepression 22 (1.4%) 22 (1.5%) 0 (0.00%) - 0.63 Gastric or duodenal peptic ucler 39 (2.4%) 37 (2.4%) 2 (2.2%) 0.90 [0.21; 3.77] > 0.99 COPD/SAS/Asthma 301 (18.8%) 279 (18.5%) 22 (24.2%) 1.41 [0.86; 2.31] 0.18 Long-term oxygen therapy 12 (0.7%) 12 (0.8%) 0 (0.00%) > 0.99 Chronic renal failure 124 (7.7%) 115 (7.6%) 9 (9.9%) 1.33 [0.65; 2.72] 0.43 Dialysis 15 (0.9%) 15 (1.0%) 0 (0.00%) > 0.99 Cancer / malignant hemopathy 212 (13.2%) 201 (13.3%) 11 (12.1%) 0.89 [0.47; 1.71] 0.74 Stroke 124 (7.7%) 118 (7.8%) 6 (6.6%) 0.83 [0.36; 1.95] 0.67 Proton pump inhibitors 339 (21.3%) 318 (21.2%) 21 (23.3%) 1.13 [0.68; 1.87] 0.64 Anticoagulation 198 (12.5%) 186 (12.4%) 12 (13.3%) 1.08 [0.58; 2.03] 0.81 Antiaggregant therapy 325 (20.5%) 306 (20.5%) 19 (20.9%) 1.02 [0.61; 1.72] 0.93 ICU Group Center of inclusion Center 1 434 (44.3%) 355 (42.0%) 79 (59.4%) 1 < 0.0001 Center 2 289 (29.5%) 242 (28.6%) 47 (35.3%) 0.87 [0.59;1.30] Center 3 256 (26.1%) 249 (29.4%) 7 (5.3%) 0.13 [0.06;0.28] Age (years) Mean (SD) 61.3 (13.15) 61.4 (13.19) 60.9 (12.89) 0.62 Sex Female 306 (31.1%) 254 (29.9%) 52 (39.1%) 0.66 [0.45;0.97] 0.0328 BMI (kg/m2) Median [Q1;Q3] 28.28 [24.98;32.28] 28.07 [24.90;31.83] 29.90 [25.39;34.55] 0.0078 BMI (kg/m2) 30 361 (38.5%) 296 (36.7%) 65 (49.6%) 1.73 [1.07;2.81] Smoking habits 188 (19.1%) 170 (20.0%) 18 (13.5%) 2.51 [0.83;7.65] 0.0011 Alcohol habits 62 (6.3%) 56 (6.6%) 6 (4.5%) 2.68 [0.78;9.15] 0.0011 Hypertension 505 (51.4%) 449 (52.8%) 56 (42.1%) 0.65 [0.45;0.94] 0.0215 Ischemic cardiopathy 86 (8.7%) 78 (9.2%) 8 (6.0%) 0.63 [0.30;1.34] 0.23 Chronic heart failure 17 (1.7%) 13 (1.5%) 4 (3.0%) 2.00 [0.64;6.22] 0.27 Diabetes mellitus 294 (29.9%) 260 (30.6%) 34 (25.6%) 0.78 [0.51;1.18] 0.24 Immunosuppressive treatment 59 (6.0%) 54 (6.3%) 5 (3.8%) 0.58 [0.23;1.47] 0.24 Infection immunodepression 13 (1.3%) 11 (1.3%) 2 (1.5%) 1.16 [0.26;5.31] 0.69 Gastric or duodenal peptic ucler 15 (1.5%) 15 (1.8%) 0 (0.0%) - 0.24 COPD/SAS/Asthma 174 (17.7%) 151 (17.8%) 23 (17.3%) 0.97 [0.60;1.57] 0.89 Long-term oxygen therapy 4 (0.4%) 4 (0.5%) 0 (0.0%) - > 0.99 Chronic renal failure 87 (8.9%) 80 (9.4%) 7 (5.3%) 0.53 [0.24;1.18] 0.12 Chronic dialysis 32 (3.3%) 29 (3.4%) 3 (2.3%) 0.65 [0.20;2.18] 0.61 Cancer/malignant hemopathy 101 (10.3%) 93 (10.9%) 8 (6.1%) 0.53 [0.25;1.11] 0.09 Stroke 49 (4.9%) 46 (5.4%) 3 (2.3%) 0.40 [0.12;1.32] 0.12 Proton pump inhibitor 179 (18.4%) 158 (18.8%) 21 (15.8%) 0.81 [0.49;1.33] 0.41 Anticoagulation 86 (8.9%) 80 (9.5%) 6 (4.5%) 0.45 [0.19;1.06] 0.06 Antiaggregant therapy 179 (18.4%) 155 (18.4%) 24 (18.2%) 0.98 [0.61;1.58] 0.94 BMI : Body mass index; COPD: chronic obstructive pulmonary diseases; SAS: sleep apnoea syndrome Table 2 Evolution during hospital stay: Ward group Total (N = 1603) No IL-6R inhibitor (N = 1512) Tocilizumab or Sarilmab (N = 91) OR [IC95%] p Type of IL-6R inhibitor Sarilumab 11 (0.7%) 0 (0.00%) 11 (12.1%) - - Tocilizumab 80 (5.0%) 0 (0.00%) 80 (87.9%) - - New anticoagulation 1461 (91.5%) 1370 (91.03%) 91 (100.0%) 1 0.0028 Anticoagulation. type Curative 367 (25.1%) 346 (25.26%) 21 (23.1%) 1 < 0.0001 Preventive 652 (44.6%) 635 (46.35%) 17 (18.7%) 0.44 [0.23; 0.85] Intermediate dose preventive 442 (30.2%) 389 (28.39%) 53 (58.2%) 2.24 [1.33; 3.80] Corticosteroids 857 (53.5%) 778 (51.46%) 79 (86.8%) 6.21 [3.36; 11.49] < 0.0001 Proton pump inhibitors 126 (7.9%) 97 (6.42%) 29 (31.9%) 6.82 [4.19; 11.10] 0.99 Standard supplemental oxygen (days) Median [Q1;Q3] 4.00 [2.00; 8.00] 4.00 [2.00; 7.00] 7.50 [5.00; 11.00] < 0.0001 High flow nasal oxygen 122 (7.6%) 99 (6.58%) 23 (25.6%) 4.88 [2.91; 8.16] < 0.0001 If HFNO. length(days) Median [Q1;Q3] 5.00 [3.00; 8.00] 5.00 [2.00; 7.00] 7.00 [4.00; 10.00] 0.0186 Length of hospital stay (days) Median [Q1;Q3] 7.00 [4.00; 11.00] 7.00 [4.00; 11.00] 10.00 [7.00; 15.00] < 0.0001 COVID-19 severity HNFO was required in 81 (10.9%) cases, non-invasive ventilation in 122 (12.5%) of ICU patients and invasive mechanical ventilation in 565 (57.5%) (Tables 2 and 3 , and supplementary table 3–5). Median hospital length of stay (LOS) was 7.0 [4.0; 11.0] days for the ward group and 19.0 [11.0; 33.0] days for the ICU group. Among ICU patients, the median time from hospital admission to ICU admission was 1.0 day [IQR 1.0–4.0], and the median ICU LOS was 9.0 [IQR 4.0; 20.3] days (Table 3 , Supplementary Tables 3–5). In the ward group, the median duration of standard oxygen therapy was 4.0 days [IQR 2.0–8.0], and of HFNO was 5.0 days [IQR 3.0; 8.0] (Table 2 , Supplementary Table 4). Median duration of invasive mechanical ventilation was 14.0 days [7.5; 29.0]. Neuromuscular blockade was administered to 52.1% (n = 512) of patients, prone positioning was required in 42.4% (n = 416) and ECMO support was required in 6.5% (n = 64) of patients (Table 3 , Supplementary Table 6). Table 3 Evolution during hospital stay: ICU Group Total (N = 984) No IL-6R inhibitor (N = 851) Tocilizumab or Sarilmab (N = 133) OR [IC95%] p Type of IL-6R inhibitor Sarilumab 112 (11.4%) 0 (0.0%) 112 (84.2%) - - Tocilizumab 21 (2.1%) 0 (0.0%) 21 (15.8%) - - Anticoagulation No 170 (17.4%) 169 (20.0%) 1 (0.7%) 1 < 0.0001 Yes 806 (82.6%) 674 (79.9%) 132 (99.2%) 33.10 [4.59; 238.43] Anticoagulation. type Curative 262 (32.5%) 229 (34.0%) 33 (25.0%) 1 4.00 x 10 − 4 Preventive 122 (15.1%) 112 (16.6%) 10 (7.6%) 0.62 [0.29; 1.30] Intermediate dose preventive 422 (52.4%) 333 (49.4%) 89 (67.4%) 1.85 [1.20; 2.86] Corticosteroids 620 (63.0%) 508 (59.7%) 112 (84.2%) 3.60 [2.22; 5.85] < 0.0001 Proton pump inhibitors 123 (12.5%) 74 (8.7%) 49 (36.8%) 6.12 [4.00; 9.36] < 0.0001 Chloroquine / hydroxychloroquine 41 (4.2%) 39 (4.6%) 2 (1.5%) 0.32 [0.08; 1.33] 0.1 If invasive mechanical ventilation. length (days) Median [Q1;Q3] 14.00 [7.50;29.00] 14.00 [7.00;29.00] 17.00 [8.00;29.00] 0.55 Prone position 416 (42.4%) 359 (42.3%) 57 (42.9%) 1.02 [0.71;1.48] 0.9 Muscular blockers 512 (52.1%) 450 (52.9%) 62 (46.6%) 0.78 [0.54;1.12] 0.17 VV or VA ECMO (N = 982) 64 (6.5%) 52 (6.1%) 12 (9.0%) 1.52 [0.79;2.93] 0.21 Cardiac arrest (N = 972) 72 (7.4%) 63 (7.5%) 9 (6.8%) 0.90 [0.44;1.86] 0.78 Catecholamines (N = 980) 399 (40.7%) 348 (41.1%) 51 (38.3%) 0.89 [0.61;1.30] 0.55 Dialysis (N = 978) 165 (16.9%) 150 (17.7%) 15 (11.4%) 0.60 [0.34;1.06] 0.08 Total length of ward stay (days) Median [Q1;Q3] 7.00 [2.00;13.00] 6.00 [2.0013.00] 9.00 [4.00; 14.00] 0.0132 Length of ward stay before ICU admission (days) Median [Q1;Q3] 1.00 [1.00;4.00] 1.00 [1.004.00] 2.00 [1.00; 4.00] 0.0335 Length of ICU stay (days) Median [Q1;Q3] 9.00 [4.00;20.25] 9.00 [4.0021.00] 9.00 [4.00; 20.00] 0.88 Length of hospital stay (days) Median [Q1;Q3] 19.00 [11.00;33.00] 18.00 [11.0033.00] 20.00 [13.00; 33.00] 0.29 SAPS II (N = 961) Mean (SD) 40.5 (18.32) 41.6 (18.80) 33.70 (13.0) < 0.0001 COVID-19 Specific Therapeutic Interventions Corticosteroids were prescribed in 857 patients (53.5%) in the ward group and 620 patients (63.0%) in the ICU group. Other treatments are detailed in Table 3 and supplementary Table 5. With the exception of corticosteroids, COVID-19-specific treatments were initiated during the patient’s ward stay. A total of 224 patients (8.7%) received at least one dose of tocilizumab or sarilumab. Tocilizumab was administered to 192 patients (7.4%) and sarilumab to 32 patients (1.2%) (Tables 2 and 3 , Fig. 1 , Supplementary Tables 1–5). Both IL-6R inhibitors were initiated prior to ICU transfer in the majority of cases (9 out of 133 cases (6.7%) during ICU stay). Patients treated with IL-6R inhibitors received significantly more corticosteroids (85.3% vs. 54.4%, p < 0.0001), proton pump inhibitors (34.8% vs . 7.2%, p < 0.0001), and intermediate-dose preventive anticoagulation (63.7% vs . 35.3%, p < 0.0001). These results were consistent in both the ward group (Table 2 , Supplementary Table 4) and the ICU group (Table 3 , Supplementary Table 5). Outcomes A total of 2 144 (82.9%) patients were discharged alive (1427 (89.0%) in the ward group and 717 (72.9%) in the ICU group). In the ward group, mortality was higher in patients receiving IL-6R inhibitors (17 (18.7%) vs . 159 (10.5%); p < 0.02). In the ICU group, hospital mortality was similar in both groups (23.3% vs . 27.7% ; p = 0.29) (Table 4 , Supplementary Table 7). In the ward group, the length of hospital stay was significantly longer in patients receiving IL-6R inhibitors compared to those who did not (10.0 [7.0; 15.0] vs . 7.0 [4.0; 11.0]; p < 0.0001) (Table 2 , Supplementary Table 4). In the ICU group, no difference in the length of ICU or hospital stay was observed (20.0 [13.0; 33.0] vs. 18.0 [11.0; 33.0]; p = 0.29) (Table 3 , Supplementary Table 5). Table 4 Outcome Total (N = 2587) No IL-6R inhibitor Tocilizumab or Sarilmab OR [IC95%] p Total population survival 2144 (82.9%) 1968 (83.3%) 176 (78.6%) 1 0.07 Ward group (n = 1603) Hospital mortality 176 (11.0%) 159 (9.9%) 17 (18.7%) 1.95 [1.13;3.40] 0.0155 Day 90 mortality 180 (1.4%) 161 (10.0%) 17(18.7%) - ICU group (n = 984) D 28 mortality 8 (3.0%) 8 (3.4%) 0 (0%) - ICU mortality 248 (25.2%) 217 (27.7%) 31 (23.3%) - Hospital mortality 267 (27.1%) 236 (27.7%) 31 (23.3%) 0.79 [0.52;1.22] 0.29 Day 90 mortality 271 (27.5%) 240 (24.4%) 31(23.3%) - 0,8 Infectious Complications During hospital stay, 97 patients (6.1%) in the ward group developed a documented infection. The most frequent were urinary tract infections (53; 3.3%), and pneumonias (6; 0.4%) (Table 5 a and 5 b, Supplementary Table 8). Patients who received IL-6R inhibitors developed more hospital-acquired infections than those who did not (unadjusted OR: 1.73 [1.27; 2.34]; p = 0.0004). This result remained consistent after adjustment both with and without multiple imputation (adjusted OR: 2.12 [1.51; 2.97]; p < 0.0001 and adjusted OR: 1.47 [1.25; 1.72]; p < 0.0001, respectively) (Tables 5 a, 5 b and 6 , Supplementary Tables 8 and 14). No such difference was observed based on patient severity (medical ward vs. ICU). In the ICU group, the incidence of hospital-acquired infections was similar with or without prior treatment with IL-6R inhibitors (43.7% vs . 42.9%; OR: 0.97 [0.67; 1.40]; p = 0.85) (Table 6 , Supplementary Tables 9 and 13). The combination of IL-6R inhibitors and corticosteroids did not modify the risk of secondary infection compared to corticosteroids alone, neither in the "ward group" nor in the "ICU group" (Table 7 ). No difference was observed based on the number of initial comorbidities (Supplementary Table 11). However, the risk of infection during ICU stay was associated with the background severity (Supplementary Table 12). Table 5 a: Clinical course complications: Ward grou Total (N = 1603) No IL-6R inhibitor (N = 1512) Tocilizumab or Sarilmab (N = 91) OR [IC95%] p Infection during hospital stay 97 (6.0%) 88 (5.8%) 9 (9.9%) 1.78 [0.86;3.65] 0.11 Fungal infection 2 (0.1%) 2 (0.1%) 0 (0.0%) > 0.99 Viral infection 1 (0.1%) 0 (0.0%) 1 (1.1%) 0.06 Number of infectious episode (N = 95) Mean (SD) 1.05 (0.3) 1.07 (0.3) 0.89 (0.3) 0.06 Urinary tract infection (N = 1602) 53 (3.3%) 50 (3.3%) 3 (3.3%) 1.00 [0.30;3.26] > 0.99 Primitive bacteremia (N = 1600) 5 (0.3%) 5 (0.3%) 0 (0.0%) > 0.99 Secondary bacteremia (N = 1600) 10 (0.6%) 9 (0.6%) 1 (1.1%) 1.85 [0.23;14.78] 0.44 Catheter related infection (N = 1599) 1 (0.1%) 1 (0.1%) 0 (0.0%) > 0.99 Pneumonia 6 (0.4%) 6 (0.4%) 0 (0.0%) > 0.99 Any adverse event Number of non-infectious adverse event (Median [Q1;Q3]) Hematological complication 33 (2.1%) 29 (1.9%) 4 (4.4%) 2.35 [0.81;6.84] 0.11 - Thrombopenia (N = 32) 30 (93.7%) 26 (92.9%) 4 (100.0%) > 0.99 - Length of thrombopenia (days) Median [Q1;Q3] 2.00 [1.00;4.75] 2.50 [1.00;5.75] 1.50 [1.00;2.00] 0.2 - Neutropenia 5 (15.1%) 5 (17.2%) 0 (0.0%) > 0.99 - Severe neutropenia 1 (3.0%) 1 (3.4%) 0 (0.0%) > 0.99 Bleeding - Number of bleeding episodes Mean (SD) 12 (0.7%) 11 (0.7%) 1 (1.1%) 1.52 [0.19;11.87] 0.51 - Gastroduodenal bleeding 1 (8.3%) 1 (9.1%) 0 (0.0%) Digestive perforation (N = 76) 1 (8.3%) 0 (0.0%) 1 (100.0%) 0.08 Table 5 b: Clinical course complications: ICU group Total (N = 984) No IL-6R inhibitor (N = 851) Tocilizumab or Sarilmab (N = 133) OR [IC95%] p Infection during hospital stay 429 (43.6%) 372 (43.7%) 57 (42.9%) 0.97 [0.67;1.40] 0.85 Fungal infection 32 (3.2%) 27 (3.2%) 5 (3.8%) 1.19 [0.45;3.15] 0.79 Viral infection 30 (3.1%) 26 (3.1%) 4 (3.0%) 0.98 [0.34;2.87] > 0.99 Number of infectious episode Median [Q1;Q3] 2.00 [1.00;3.00] 2.00 [1.00;2.00] 2.00 [1.00;3.00] 0.82 Urinary tract infection 42 (4.3%) 38 (4.5%) 4 (3.0%) 0.66 [0.23;1.87] 0.43 Primitive bacteremia 75 (7.7%) 68 (8.0%) 7 (5.3%) 0.63 [0.29;1.41] 0.26 Secondary bacteremia 50 (5.1%) 42 (5.0%) 8 (6.1%) 1.23 [0.57;2.69] 0.6 Catheter-related infection 30 (3.1%) 29 (3.4%) 1 (0.8%) 0.21 [0.03;1.59] 0.11 Ventilator-associated pneumonia 356 (36.2%) 305 (35.8%) 51 (38.3%) 1.11 [0.76;1.62] 0.58 Hematological complication 30 (3.1%) 25 (2.9%) 5 (3.8%) 1.29 [0.49;3.43] 0.59 - Thrombopenia 28 (93.3%) 23 (92.0%) 5 (100.0%) - > 0.99 - Length of thrombopenia (days) Median [Q1;Q3] 5.00 [3.00;10.50] 5.00 [2.25;10.75] 10.00 [10.00;10.00] - 0.13 - Neutropenia 3 (10.0%) 3 (12.0%) 0 (0.0%) - > 0.99 - Severe neutropenia 2 (6.9%) 2 (8.3%) 0 (0.0%) - > 0.99 Bleeding - Number of bleeding episodes Mean (SD) 64 (6.5%) 60 (7.1%) 4 (3.0%) 0.41 [0.15;1.15] 0.08 - Gastroduodenal bleeding (confirmed by oesogastric endoscopy) 20 (31.2%) 20 (33.3%) 0 (0.0%) - 0.3 - Lower digestive tract bleeding 7 (10.9%) - Digestive perforation 1 (1.6%) 1 (1.7%) 0 (0.0%) - > 0.99 Other complications No difference in hematological abnormalities or digestive complication was observed between groups (Table 5 , 6 , Supplementary Table 10). Table 6: Infectious complication: Multiple imputation Table 7: Effect of IL-6R inhibitor and corticosteroids on infection and survival Total (N=224) No IL-6R inhibitor and corticosteroids (N=191) Tocilizumab or Sarilmab without corticosteroids (N=33) OR [IC95%] p Infection during hospital stay 66 (29.5%) 10 (30.3%) 56 (29.3%) 0.95 [0.43;2.13] 0.91 Fungal infection 5 (2.2%) 1 (3.0%) 4 (2.1%) 0.68 [0.07;6.32] 0.55 Viral infection 5 (2.2%) 0 (0.0%) 5 (2.6%) >0.99 Number of infectious episode Mean (SD) 1.00 [1.00;2.00] 1.50 [1.00;2.75] 1.00 [1.00;2.00] 0.62 Urinary tract infection 7 (3.1%) 0 (0.0%) 7 (3.7%) 0.60 Primitive bacteremia 7 (3.1%) 1 (3.0%) 6 (3.1%) 1.04 [0.12;8.91] >0.99 Secondary bacteremia 9 (4.0%) 2 (6.1%) 7 (3.7%) 0.59 [0.12;2.99] 0.62 Catheter related infection 1 (0.4%) 1 (3.0%) 0 (0.0%) - 0.15 Ventilator-associated pneumonia 51 (22.8%) 9 (27.3%) 42 (22.0%) 0.75 [0.32;1.74] 0.5 ICU admission 133 (59.4%) 21 (63.6%) 112 (58.6%) 0.81 [0.38;1.74] 0.59 Hospital mortality 48 (21.4%) 5 (15.1%) 43 (22.5%) 1.63 [0.59;4.47] 0.34 Discussion In our multicenter study, an IL-6R inhibitors were prescribed in 8.6%. The prolonged uncertainty regarding the relevance of IL-6 pathway inhibition [ 7 ] led to variable administration during the study period, resulting in a low percentage of patients who actually received an IL-6R inhibitor. This was particularly noticeable in the ICU, where the delayed onset of inflammation and relatively low levels of IL-6 compared to typical acute respiratory distress syndrome or septic shock [ 28 , 29 ] often prevented the administration of these IL-6R inhibitors. As more studies emerged, guidelines were modified based on recent syntheses [ 19 , 30 ]. Both suggest the use of tocilizumab in severe COVID-19, but, balance the potential improvements and the prevention of adverse events [ 19 ]. However, the incidence and severity of these complications remain unclear [ 7 ]. We found an increased risk of secondary infections associated with the administration of IL-6R inhibitor in the overall patient population (OR: 1.73 [1.27; 2.34]; p = 0.0004). Impairment of immune defenses due to the disruption of the IL-6 pathway is well-documented during long-term treatment of moderate chronic inflammatory diseases [ 11 , 31 ]. Conversely, the effect of a short period of treatment, remains poorly documented. The inability of a single dose to sufficiently dampen the cytokine response seems probable [ 32 ] but previous smaller observational studies yielded divergent results. Marco Ripa et al. found an increased risk of infections. However, the involvement of IL-6R inhibitors was uncertain, and the multivariate analysis did not confirm this link [ 33 ]. In another early study in Chicago, the administration of tocilizumab was associated with the risk of secondary bacterial infections [ 34 ]. Unfortunately, the groups were highly heterogeneous, leading to a disequilibrium that blurred the conclusions. Recent meta-analyses offer similarly conflicting conclusions [ 16 , 35 – 37 ]. Many secondary episodes were of viral origin. The central role of IL-6 in viral infection control, by reducing the production of acute phase proteins and modifying B lymphocytes differentiation and T cell maturation, may explain these results [ 31 , 38 ]. The absence of observed SARS-CoV-2 clearance compromise during clinical use of tocilizumab [ 39 ] tends to reduce the relevance of this hypothesis. However, the timing of use, potential exhaustion of the inflammatory response, and alteration of the respiratory tract mucosa by the initial viral aggression may secondarily favor a new respiratory viral disease. The delay between admission and tocilizumab administration may play a role in the infectious risk [ 40 ]. Moreover, the association between IL-6R inhibition and specific visceral infections remains unclear. We observed a raw difference in secondary bacteremia that did not reach statistical significance that aligns with previous observations [ 41 , 42 ]. Unexpectedly, while previous studies demonstrated an increased risk of infection in ICU patients [ 40 – 42 ], we did not identify such a difference in our critical care patients. Administration beyond two days of hospital admission or two days of HFNO requirement has been associated with infectious complications [ 43 ]. In our study, IL-6R inhibitors were all administered on the first day of hospital admission. This may partly explain the discrepancy in the reported infectious risk between studies and may have contributed to the absence of infections during ICU stay. Conversely, as previously discussed [ 7 ], the absence of a deleterious effect is often associated with a lack of beneficial effect in the same studies [ 7 , 39 ]. A recent meta-analysis reached a similar conclusion [ 8 ]. The absence of beneficial effects on survival, organ support requirements during ICU stay, or duration of mechanical ventilation observed in our study may partly explain the lack of deleterious effects from IL-6 pathway inhibition. Most patients concurrently received corticosteroids, making it challenging to evaluate the separate effects of these drugs [ 44 ]. The absence of systematic corticosteroid use allowed for an adjustment that confirmed the involvement of tocilizumab, independent of its potential synergistic effect on the immune response [ 44 ]. The limited clinical effect of IL-6 pathway inhibitors in our severe and critical population is further supported by the absence of deleterious digestive and hematological effects widely described in chronic inflammatory diseases and COVID-19 [ 17 , 45 ]. Our study has several limitations. First, the retrospective design may result in less comprehensive side effect documentation. However, the severity of the complications of interest makes it unlikely that they were omitted from patient files. Furthermore, the incidence of adverse events in our cohort is similar to previous studies and higher than in many randomized trials. Second, the small number of patients treated with IL-6R inhibitors limits the conclusions that can be drawn. This usage however, reflected clinical reality and uncertainty about the benefits and risks of tocilizumab and sarilumab. Third, the lack of information on HFNO use or ICU admission during this critical pandemic period, along with the absence of data on ICU or tracheal intubation withholding, prevents us from drawing conclusions about the potential efficacy of IL-6R inhibition. Conversely, our cohort has several strengths. The multicenter recruitment of severe patients from both wards and ICUs enabled the inclusion of the largest group of patients who received an IL-6R inhibitor in a tolerability study. The retrospective design minimized bias in the reporting of adverse events associated with the administration of controversial therapies. A specific analysis of tocilizumab allowed for the distinction of adverse events associated with the only IL-6R inhibitor shown to have a benefit during severe COVID-19. The multivariate analysis highlighted risk factors associated with an increased probability of secondary infection during IL-6R inhibitor treatment, which should be considered in the risk-benefit analysis of IL-6R inhibitor therapy in this context. Conclusion In this multicenter French cohort study, the administration of an IL-6R inhibitor to severe COVID-19 patients was associated with an increased incidence of secondary infections in ward patients, particularly viral infections. Conversely, in critical cases requiring ICU admission and even invasive mechanical ventilation, no infectious, digestive, or hematological complications were associated with IL-6R inhibitor administration. Broader international studies are needed to confirm these findings. Declarations Funding: This work was supported by the Groupe Hospitalier Paris Saint‑Joseph Acknowledgement This work was supported by the Groupe Hospitalier Paris Saint‑Joseph All data generated or analyzed during this study are included in this study or its supplementary material files. Further inquiries can be directed to the corresponding author. Authors contributions : Conceptualization: CL, TFB, AP, MT, FP. Methodology: MC, AF, GC, FP. Inclusions, review and editing: CL, TFB, AP, FP, LS, DM, OV, FB, LW, AP, SL, NR, PRB, MT, CB, JD. First draft: CL, TFB, FP. Conflicts of interest: Charlène Lefèvre: No conflict Théo Funck-Brentano: No conflict Marine Cachanado: No conflict Alexia Plocque: No conflict Audrey Fels: No conflict Frederic Pène: No conflict Laurent Savale: No conflict David Montani: No conflict Olivier Voisin: No conflict Flore Bintein: No conflict Lucille Wildenberg: No conflict Axel Philippe: No conflict Stephane Legriel: No conflict Nicolas Roche: No conflict: Dr Roche reported receiving grant funding from Boehringer Ingelheim, Novartis AG, Pfizer Inc, and GSK PLC and personal fees from Boehringer Ingelheim, Novartis AG, Pfizer Inc, GSK PLC, Austral Pharma, Biosency, MSD, AstraZeneca, Chiesi Farmaceutici SpA, Menarini Group, Nuvaira, Sanofi SA, and Zambon outside the submitted work. Pierre-Régis Burgel: No conflict Marc Tran: No conflict Christophe Baillard: No conflict Jacques Duranteau: No conflict Gilles Chatellier: No conflict Francois Philippart: No conflict All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. Ethics approval : The study was carried out in accordance with the Declaration of Helsinki and French law. The TOCSIN study was approved by our institutional review board (GERM; IRB n°00012157). Patients were informed about the study and their non-opposition to the collection and use of non-identifying data for research purposes was obtained. The processing of patient data complied with the reference methodology 004 of the French Commission Nationale de l'Informatique et des Libertés (French National Data Protection Agency). 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6785789","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":471547678,"identity":"39753f99-79d1-46eb-b75b-0af994f5960b","order_by":0,"name":"Charlène Lefèvre","email":"","orcid":"","institution":"Groupe hospitalier Paris Saint Joseph","correspondingAuthor":false,"prefix":"","firstName":"Charlène","middleName":"","lastName":"Lefèvre","suffix":""},{"id":471547679,"identity":"0f238295-de50-4313-877b-e15a7516b344","order_by":1,"name":"Théo Funck-Brentano","email":"","orcid":"","institution":"Groupe hospitalier Paris Saint Joseph","correspondingAuthor":false,"prefix":"","firstName":"Théo","middleName":"","lastName":"Funck-Brentano","suffix":""},{"id":471547680,"identity":"f1e2d051-e09f-4a95-8bd1-c44cd10804fb","order_by":2,"name":"Marine Cachanado","email":"","orcid":"","institution":"Groupe hospitalier Paris Saint Joseph","correspondingAuthor":false,"prefix":"","firstName":"Marine","middleName":"","lastName":"Cachanado","suffix":""},{"id":471547681,"identity":"61bda683-799a-49ef-bdde-5fa054db9876","order_by":3,"name":"Alexia Plocque","email":"","orcid":"","institution":"Groupe hospitalier Paris Saint Joseph","correspondingAuthor":false,"prefix":"","firstName":"Alexia","middleName":"","lastName":"Plocque","suffix":""},{"id":471547682,"identity":"adf233df-9fbf-48b2-8ea9-4fa831e13290","order_by":4,"name":"Audrey Fels","email":"","orcid":"","institution":"Groupe hospitalier Paris Saint Joseph","correspondingAuthor":false,"prefix":"","firstName":"Audrey","middleName":"","lastName":"Fels","suffix":""},{"id":471547683,"identity":"bc58c9ac-bed2-4de6-a675-b1d2f1a0ba85","order_by":5,"name":"Fréderic Pène","email":"","orcid":"","institution":"Hôpital Cochin, Université Paris Cité","correspondingAuthor":false,"prefix":"","firstName":"Fréderic","middleName":"","lastName":"Pène","suffix":""},{"id":471547684,"identity":"021238ee-d31d-4998-a2e0-4dcd3c21510a","order_by":6,"name":"Laurent Savale","email":"","orcid":"","institution":"Bicêtre Hospital","correspondingAuthor":false,"prefix":"","firstName":"Laurent","middleName":"","lastName":"Savale","suffix":""},{"id":471547685,"identity":"d2fed2bf-ef73-4c2b-a20d-180826676f17","order_by":7,"name":"David Montani","email":"","orcid":"","institution":"Bicêtre Hospital","correspondingAuthor":false,"prefix":"","firstName":"David","middleName":"","lastName":"Montani","suffix":""},{"id":471547686,"identity":"2b3db83a-f84b-4f8d-a80f-a87ac38bb30a","order_by":8,"name":"Olivier Voisin","email":"","orcid":"","institution":"Groupe hospitalier Paris Saint Joseph","correspondingAuthor":false,"prefix":"","firstName":"Olivier","middleName":"","lastName":"Voisin","suffix":""},{"id":471547687,"identity":"55dc7897-3620-4875-80c9-ccaf193dfecc","order_by":9,"name":"Flore Bintein","email":"","orcid":"","institution":"Groupe hospitalier Paris Saint Joseph","correspondingAuthor":false,"prefix":"","firstName":"Flore","middleName":"","lastName":"Bintein","suffix":""},{"id":471547688,"identity":"e989dcc8-1809-427b-94d2-1de403a87383","order_by":10,"name":"Lucille Wildenberg","email":"","orcid":"","institution":"Bicêtre Hospital","correspondingAuthor":false,"prefix":"","firstName":"Lucille","middleName":"","lastName":"Wildenberg","suffix":""},{"id":471547689,"identity":"ec99ba72-ee8c-4ecd-8dee-0c25bc3f824c","order_by":11,"name":"Axel Philippe","email":"","orcid":"","institution":"Hôpital Cochin, Assistance Publique-Hôpitaux de Paris","correspondingAuthor":false,"prefix":"","firstName":"Axel","middleName":"","lastName":"Philippe","suffix":""},{"id":471547690,"identity":"6388a4ba-5205-4050-bffb-ccf486e22910","order_by":12,"name":"Stéphane Legriel","email":"","orcid":"","institution":"Versailles Hospital","correspondingAuthor":false,"prefix":"","firstName":"Stéphane","middleName":"","lastName":"Legriel","suffix":""},{"id":471547691,"identity":"859695fa-c533-4cc3-90e2-bb50f08aec74","order_by":13,"name":"Nicolas Roche","email":"","orcid":"","institution":"Assistance Publique - Hopitaux de Paris, Hôpital Cochin","correspondingAuthor":false,"prefix":"","firstName":"Nicolas","middleName":"","lastName":"Roche","suffix":""},{"id":471547692,"identity":"51540418-9f21-41e4-8e52-7f4995197ebb","order_by":14,"name":"Pierre-Régis Burgel","email":"","orcid":"","institution":"Hôpital Cochin, Université Paris Cité","correspondingAuthor":false,"prefix":"","firstName":"Pierre-Régis","middleName":"","lastName":"Burgel","suffix":""},{"id":471547693,"identity":"4f92ee05-0e5c-4cf6-9744-390c1758af05","order_by":15,"name":"Marc Tran","email":"","orcid":"","institution":"Groupe hospitalier Paris Saint Joseph","correspondingAuthor":false,"prefix":"","firstName":"Marc","middleName":"","lastName":"Tran","suffix":""},{"id":471547694,"identity":"c9d7943c-fe75-4cb5-ad99-c81399c0a904","order_by":16,"name":"Nicolas Noël","email":"","orcid":"","institution":"Bicêtre Hospital","correspondingAuthor":false,"prefix":"","firstName":"Nicolas","middleName":"","lastName":"Noël","suffix":""},{"id":471547695,"identity":"afac0134-51a3-417b-a6b8-6724df049455","order_by":17,"name":"Christophe Baillard","email":"","orcid":"","institution":"Hôpital Cochin, Assistance Publique-Hôpitaux de Paris","correspondingAuthor":false,"prefix":"","firstName":"Christophe","middleName":"","lastName":"Baillard","suffix":""},{"id":471547696,"identity":"64c07ac6-3fae-4896-b2b7-06467d65c8fc","order_by":18,"name":"Jacques Duranteau","email":"","orcid":"","institution":"Assistance Publique Hôpitaux de Paris, Paris Saclay University","correspondingAuthor":false,"prefix":"","firstName":"Jacques","middleName":"","lastName":"Duranteau","suffix":""},{"id":471547697,"identity":"b9b3a417-b916-4bb6-aacf-ab4af4e6b32b","order_by":19,"name":"Gilles Chatellier","email":"","orcid":"","institution":"Groupe hospitalier Paris Saint Joseph","correspondingAuthor":false,"prefix":"","firstName":"Gilles","middleName":"","lastName":"Chatellier","suffix":""},{"id":471547698,"identity":"6ae35338-2afa-41c2-8ea8-07e74224314c","order_by":20,"name":"Francois Philippart","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA70lEQVRIie3RvYrCQBDA8R0GYhOwjcSPV9iQB8irrFwrcmBltyEQG68XLHwFS8scgasW7wFMkWusYyEoWDiuWNjsWgq3/2KY5gc7LGMu1xvWkj4raq53qEHSlFAbiV8QEZog8jtBbiVM6BW94EZosZDw67sQn9W4vfz9mR43VYISvcZIultBD9tPgu2Ht+up/TCViAsTSYIRJ1IOpUJv18lLAbJdmh/2ICsiEyIJnY+vkTUROOQlpFbSVVzfEimMQ8jplsxGwnncNJdq3FfwdzjnVRLNMjNhgZ6FuE2kb2VRZgbPBE5EBjbhcrlc/64rTgVRVftwQRIAAAAASUVORK5CYII=","orcid":"","institution":"Groupe hospitalier Paris Saint Joseph","correspondingAuthor":true,"prefix":"","firstName":"Francois","middleName":"","lastName":"Philippart","suffix":""}],"badges":[],"createdAt":"2025-05-30 14:53:27","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6785789/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6785789/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41598-026-36864-w","type":"published","date":"2026-01-22T15:57:17+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":84810962,"identity":"fd5a4a82-7e94-4e4b-961a-8daea63cd228","added_by":"auto","created_at":"2025-06-17 14:52:54","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":174865,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6785789/v1/82fa9156c14879c60b281d41.jpeg"},{"id":101151969,"identity":"5cf1ad74-96c3-44b0-b3d5-f438f67227e6","added_by":"auto","created_at":"2026-01-26 16:08:52","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2299969,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6785789/v1/4d5d6f67-2662-49d1-81aa-ee5f6611eeda.pdf"},{"id":84809911,"identity":"f9ee0e4e-3e3d-4e4d-9533-8001bef680a0","added_by":"auto","created_at":"2025-06-17 14:44:54","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":118720,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementarymaterial.docx","url":"https://assets-eu.researchsquare.com/files/rs-6785789/v1/7409d411ff2bc41f10fe5393.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Benefit and risk associated with interleukin-6 receptor inhibitor administration during severe COVID-19: a retrospective multicentric study none","fulltext":[{"header":"Introduction","content":"\u003cp\u003eSince the onset of Coronavirus disease 2019 (COVID-19), numerous therapeutic interventions have been proposed, particularly for severe manifestations of the disease. The efficacy of corticosteroids in severe and critical COVID-19 cases has been swiftly established [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Concurrently, the pronounced inflammatory response observed in severe cases [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] has prompted exploration of cytokine pathway inhibitors as potential therapeutic targets.\u003c/p\u003e \u003cp\u003eElevated levels of circulating interleukin-6 (IL-6) in critically ill patients, and its correlation with severe hypoxemia, have highlighted the IL-6 pathway as a promising target for intervention [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. However, randomized trials investigating IL-6 receptor inhibitors have yielded conflicting results, leading to ongoing uncertainty about their clinical relevance [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], despite numerous meta-analyses [\u003cspan additionalcitationids=\"CR8 CR9\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Moreover, the safety of targeting the IL-6 pathway in septic patients remains to be specifically investigated.\u003c/p\u003e \u003cp\u003eIL-6 receptor (IL-6R) antagonists have been extensively used in chronic inflammatory diseases such as rheumatoid arthritis, juvenile idiopathic arthritis, and Castleman's disease [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Long-term experience with IL-6 pathway inhibition has highlighted an increased risk of infectious diseases, estimated at approximately 5.5 events per 100 patient-years [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Additionally, altering the IL-6 pathway may compromise digestive mucosa regeneration, mediated by signal transduction through the gp130 protein [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. This could potentially lead to upper digestive tract hemorrhage, especially when combined with systemic corticosteroids.\u003c/p\u003e \u003cp\u003eConversely, the potential risks associated with the acute administration of IL-6 inhibitors are not yet well-documented. This is particularly true in cases of cytokine release syndrome following chimeric antigen receptor T-cell (CAR-T) therapy, or in severe and critical COVID-19 cases [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. While recent meta-analyses of therapeutic trials have not reported an increased risk of infections [\u003cspan additionalcitationids=\"CR17\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], this remains a topic of debate [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe aim of our study was to highlight the potential complications associated with the IL-6 receptor inhibitors in use at the time, specifically tocilizumab and sarilumab.\u003c/p\u003e "},{"header":"Methods","content":"\n\u003ch3\u003eStudy design\u003c/h3\u003e\n\u003cp\u003eWe conducted a retrospective, multicenter cohort study from March 1st, 2020, to December 31st, 2021.\u003c/p\u003e \u003cp\u003e The study adhered to the STROBE (STrengthening the Reporting of Observational Studies in Epidemiology) guidelines for reporting observational studies.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eSettings and participants\u003c/h2\u003e \u003cp\u003e Eight medical (3 internal medicine and 2 pulmonary departments) and 4 critical care wards of three regional university hospitals in Paris were involved in this study. All consecutive adult patients admitted for a documented severe COVID-19, as defined by the IDSA guidelines [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] were included in the study.\u003c/p\u003e \u003cp\u003eCOVID-19 was confirmed by a positive SARS-CoV-2 real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay from nasal or oropharyngeal swabs, or lower respiratory tract samples (in invasively ventilated patients). Patients without laboratory-confirmed COVID-19 were excluded from the study.\u003c/p\u003e \u003cp\u003ePatients were categorized into two groups: the \"ward group,\" who spent their entire hospital stay in a ward, and the \"ICU group,\" who required ICU admission at any point during their hospital stay.\u003c/p\u003e \u003cp\u003ePatients were admitted to the ICU if they required noninvasive or invasive mechanical ventilation or if they experienced any other acute organ failure. Details are provided in the supplementary material.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eData collection and proceeding\u003c/h3\u003e\n\u003cp\u003eData were collected using a standardized electronic form. Major adverse event included nosocomial infections, myelotoxicity and digestive tract hemorrhage. Hospital acquired and ventilator-associated pneumonia were defined according to the European [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] and American guidelines [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Other ICU-acquired infections were diagnosed by the attending physician following established guidelines [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Primary bacterial bloodstream infection and central line associated bloodstream infection were defined as in the EUROBACT study [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eUpper digestive tract hemorrhage was confirmed by endoscopic demonstration of an esophageal, gastric or duodenal lesion [\u003cspan additionalcitationids=\"CR26\" citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Lower intestinal hemorrhage was defined by the presence of melena or hematochezia and confirmed by colonoscopy [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Thrombopenia was defined as a platelet count below 150 G/l; neutropenia was defined as a neutrophils count below 1 500 /mm\u003csup\u003e3\u003c/sup\u003e, with severe neutropenia below 500 /mm\u003csup\u003e3\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe primary outcome was the proportion of hospital-acquired infectious episodes during the hospital stay. Secondary outcomes included the occurrence of leukopenia, thrombocytopenia, digestive hemorrhage or perforation, as well as the length of stay in the intensive care unit (ICU) and hospital, and the duration of mechanical ventilation. The exposure variable was the administration of tocilizumab or sarilumab during the hospital stay. Details are provided in the supplementary material.\u003c/p\u003e\n\u003ch3\u003eEthical considerations\u003c/h3\u003e\n\u003cp\u003e The study was carried out in accordance with the Declaration of Helsinki and French law and was approved by our institutional review board (GERM; IRB n\u0026deg;00012157). Patients were informed about the study and their non-opposition (\u003cem\u003ethey were informed and consent\u003c/em\u003e) to the collection and use of non-identifying data for research purposes was obtained. The processing of patient data complied with the reference methodology 004 of the French Commission Nationale de l'Informatique et des Libert\u0026eacute;s (French National Data Protection Agency).\u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003ePatient characteristics were described for the entire population and stratified by the use of IL-6 inhibitors (tocilizumab or sarilumab). Categorical variables are presented as counts (percentages), and continuous variables as mean (\u0026plusmn;\u0026thinsp;standard deviation) or median with interquartile range [Q1; Q3], depending on their distribution. Categorical variables were compared between groups using the Pearson Chi-squared test or Fisher\u0026rsquo;s exact test, while continuous variables were compared using the Student\u0026rsquo;s t-test or the Wilcoxon rank-sum test. As there were no formal recommendations for the use of tocilizumab or sarilumab, their prescription was based on patient-specific characteristics and the judgment of the attending physician. To address potential bias introduced by these prescription methods, a logistic regression model was employed to examine the relationship between the use of these medications and hospital-acquired infectious episodes. Details are provided in the supplementary material.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\n \u003ch2\u003eParticipants\u003c/h2\u003e\n \u003cp\u003eA total of 2587 patients were included in the study over a 22-month period. Of these, 1603 were admitted to a medical ward (referred to as the \u0026ldquo;Ward group\u0026rdquo;), while 984 required an ICU admission at some point during their hospital stay (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). The populations are described in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e and supplementary Tables 1 and 2.\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u0026nbsp;\u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eCharacteristics of the population\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTotal (N\u0026thinsp;=\u0026thinsp;2587)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eNo IL-6R inhibitor (n\u0026thinsp;=\u0026thinsp;2363)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTocilizumab or Sarilmab (n\u0026thinsp;=\u0026thinsp;224)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOR [IC95%]\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ep\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGlobal population\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCenter of inclusion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCenter 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1361 (52.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1243 (52.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e118 (52.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.0007\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCenter 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e955 (37.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e857 (36.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e98 (43.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.20 [0.91;1.60]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCenter 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e257 (10.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e250 (10.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7 (3.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.29 [0.14;0.64]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e63.60 (15.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e63.5 (15.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e64.1 (14.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.72\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e963 (37.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e874 (37.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e89 (39.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMedian [Q1;Q3]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e27.6 [24.2;31.5]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e) Mean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;=25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e653 (30.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e610 (31.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e43 (20.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.0011\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e]25\u0026ndash;30]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e768 (35.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e692 (35.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e76 (36.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.56 [1.06;2.30]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e728 (33.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e637 (32.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e91 (43.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.03 [1.39;2.96]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking (current of former)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e459 (17.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e433 (20.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e26 (12.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.55 [0.36;0.83]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.0045\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAlcohol habits\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e183 (7.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e172 (8.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e11 (5.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.59 [0.32;1.11]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHypertension\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1245 (48.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1136 (48.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e109 (48.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.02 [0.78;1.34]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.88\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIschemic cardiopathy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e260 (10.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e240 (10.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e20 (8.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.87 [0.54;1.40]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.57\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChronic heart failure\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e88 (3.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e78 (3.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e10 (4.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.37 [0.70;2.68]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.36\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDiabetes mellitus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e649 (25.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e589 (25.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e60 (26.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.10 [0.81;1.50]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.55\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eImmunosuppressive treatment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e143 (5.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e137 (5.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6 (2.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.45 [0.19;1.02]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.05\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eInfectious immunodepression\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e35 (1.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e33 (1.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2 (0.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.64 [0.15;2.67]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.76\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGastric or duodenal peptic ucler\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e54 (2.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e52 (2.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2 (0.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.40 [0.10;1.65]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.32\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCOPD/SAS/Asthma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e475 (18.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e430 (18.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e45 (20.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.13 [0.80;1.59]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.49\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLong-term oxygen therapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e16 (0.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e16 (0.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0 (0.00%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.39\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChronic renal failure\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e211 (8.17%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e195 (8.26%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e16 (7.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.85 [0.50;1.45]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.56\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChronic diialysis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e47 (1.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e44 (1.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3 (1.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.71 [0.22;2.32]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.79\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMalignant hemopathy / Cancer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e313 (12.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e294 (12.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e19 (8.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.65 [0.40;1.06]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.08\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eStroke\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e173 (6.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e164 (6.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9 (4.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.56 [0.28;1.11]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.09\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eProton pump inhibitor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e518 (20.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e476 (20.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e42 (18.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.91 [0.64;1.29]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.59\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAnticoagulation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e284 (11.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e266 (11.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e18 (8.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.69 [0.42;1.13]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.14\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAntiaggregant treatment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e504 (19.71%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e461 (19.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e43 (19.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.97 [0.69;1.37]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.87\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWard group\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eInclusion center\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCenter 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e927 (58.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e888 (59.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e39 (43.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.0083\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCenter 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e666 (41.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e615 (40.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e51 (56.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.89 [1.23; 2.90]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCenter 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1 (0.06%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1 (0.07%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0 (0.00%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge (years) Mean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e64.99 (16.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e64.77 (16.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e68.69 (15.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.0299\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSex (Female)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e657 (41.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e620 (41.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e37 (41.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00 [0.65; 1.54]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e) Median [Q1;Q3]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e27.1 [23.83;31.00]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e27.1[23.72;30.86]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e27.8 [25.39;31.99]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.08\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;=25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e413 (34.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e397 (35.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e16 (20.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.0192\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e]25\u0026ndash;30]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e432 (35.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e395 (34.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e37 (46.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.32 [1.27; 4.25]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e367 (30.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e341 (30.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e26 (32.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.32 [1.27;3.59]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking habits (Yes)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e271 (17.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e263 (17.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8 (8.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.60 [0.21; 1.68]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.08\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAlcohol habits\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e121 (7.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e116 (7.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5 (5.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.18 [0.36; 3.79]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.24\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHypertension\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e740 (46.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e687 (45.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e53 (58.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.67 [1.09; 2.57]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.0176\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIschemic cardiopathy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e174 (10.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e162 (10.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e12 (13.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.28 [0.68; 2.40]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.44\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChronic heart failure\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e71 (4.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e65 (4.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6 (6.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.57 [0.66; 3.73]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.29\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDiabetes mellitus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e355 (22.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e329 (21.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e26 (28.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.44 [0.90; 2.30]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eImmunosuppressive treatment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e84 (5.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e83 (5.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1 (1.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.19 [0.03; 1.39]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.09\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eInfectious immunodepression\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e22 (1.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e22 (1.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0 (0.00%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.63\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGastric or duodenal peptic ucler\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e39 (2.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e37 (2.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2 (2.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.90 [0.21; 3.77]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCOPD/SAS/Asthma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e301 (18.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e279 (18.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e22 (24.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.41 [0.86; 2.31]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.18\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLong-term oxygen therapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e12 (0.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e12 (0.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0 (0.00%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChronic renal failure\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e124 (7.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e115 (7.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9 (9.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.33 [0.65; 2.72]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.43\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDialysis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e15 (0.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e15 (1.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0 (0.00%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCancer / malignant hemopathy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e212 (13.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e201 (13.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e11 (12.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.89 [0.47; 1.71]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.74\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eStroke\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e124 (7.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e118 (7.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6 (6.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.83 [0.36; 1.95]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.67\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eProton pump inhibitors\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e339 (21.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e318 (21.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e21 (23.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.13 [0.68; 1.87]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.64\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAnticoagulation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e198 (12.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e186 (12.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e12 (13.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.08 [0.58; 2.03]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.81\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAntiaggregant therapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e325 (20.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e306 (20.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e19 (20.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.02 [0.61; 1.72]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.93\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eICU Group\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCenter of inclusion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCenter 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e434 (44.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e355 (42.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e79 (59.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCenter 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e289 (29.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e242 (28.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e47 (35.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.87 [0.59;1.30]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCenter 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e256 (26.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e249 (29.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7 (5.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.13 [0.06;0.28]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge (years) Mean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e61.3 (13.15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e61.4 (13.19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e60.9 (12.89)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.62\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSex Female\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e306 (31.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e254 (29.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e52 (39.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.66 [0.45;0.97]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.0328\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBMI (kg/m2) Median [Q1;Q3]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e28.28 [24.98;32.28]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e28.07 [24.90;31.83]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e29.90 [25.39;34.55]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.0078\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBMI (kg/m2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;=25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e240 (25.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e213 (26.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e27 (20.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.019\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e]25\u0026ndash;30]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e336 (35.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e297 (36.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e39 (29.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.04 [0.62;1.74]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e361 (38.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e296 (36.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e65 (49.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.73 [1.07;2.81]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking habits\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e188 (19.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e170 (20.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e18 (13.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.51 [0.83;7.65]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.0011\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAlcohol habits\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e62 (6.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e56 (6.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6 (4.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.68 [0.78;9.15]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.0011\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHypertension\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e505 (51.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e449 (52.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e56 (42.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.65 [0.45;0.94]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.0215\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIschemic cardiopathy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e86 (8.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e78 (9.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8 (6.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.63 [0.30;1.34]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.23\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChronic heart failure\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e17 (1.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e13 (1.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4 (3.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.00 [0.64;6.22]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.27\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDiabetes mellitus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e294 (29.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e260 (30.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e34 (25.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.78 [0.51;1.18]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.24\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eImmunosuppressive treatment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e59 (6.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e54 (6.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5 (3.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.58 [0.23;1.47]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.24\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eInfection immunodepression\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e13 (1.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e11 (1.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2 (1.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.16 [0.26;5.31]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.69\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGastric or duodenal peptic ucler\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e15 (1.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e15 (1.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.24\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCOPD/SAS/Asthma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e174 (17.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e151 (17.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e23 (17.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.97 [0.60;1.57]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.89\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLong-term oxygen therapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4 (0.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4 (0.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChronic renal failure\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e87 (8.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e80 (9.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7 (5.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.53 [0.24;1.18]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.12\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChronic dialysis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e32 (3.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e29 (3.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3 (2.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.65 [0.20;2.18]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.61\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCancer/malignant hemopathy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e101 (10.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e93 (10.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8 (6.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.53 [0.25;1.11]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.09\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eStroke\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e49 (4.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e46 (5.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3 (2.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.40 [0.12;1.32]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.12\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eProton pump inhibitor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e179 (18.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e158 (18.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e21 (15.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.81 [0.49;1.33]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.41\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAnticoagulation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e86 (8.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e80 (9.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6 (4.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.45 [0.19;1.06]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.06\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAntiaggregant therapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e179 (18.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e155 (18.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e24 (18.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.98 [0.61;1.58]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.94\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003eBMI : Body mass index; COPD: chronic obstructive pulmonary diseases; SAS: sleep apnoea syndrome\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u0026nbsp;\u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eEvolution during hospital stay: Ward group\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTotal (N\u0026thinsp;=\u0026thinsp;1603)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eNo IL-6R inhibitor (N\u0026thinsp;=\u0026thinsp;1512)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTocilizumab or Sarilmab (N\u0026thinsp;=\u0026thinsp;91)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOR [IC95%]\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ep\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eType of IL-6R inhibitor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSarilumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e11 (0.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0 (0.00%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e11 (12.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTocilizumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e80 (5.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0 (0.00%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e80 (87.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNew anticoagulation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1461 (91.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1370 (91.03%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e91 (100.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0028\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAnticoagulation. type\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCurative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e367 (25.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e346 (25.26%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e21 (23.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePreventive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e652 (44.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e635 (46.35%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e17 (18.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.44 [0.23; 0.85]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIntermediate dose preventive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e442 (30.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e389 (28.39%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e53 (58.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.24 [1.33; 3.80]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCorticosteroids\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e857 (53.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e778 (51.46%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e79 (86.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.21 [3.36; 11.49]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eProton pump inhibitors\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e126 (7.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e97 (6.42%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e29 (31.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.82 [4.19; 11.10]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChloroquine/ Hydroxychloroquine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e76 (4.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e76 (5.03%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0195\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAnakinra\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e58 (3.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e58 (3.85%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.07\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLopinavir/ritonavir\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4 (0.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4 (0.27%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eStandard supplemental oxygen (days) Median [Q1;Q3]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4.00 [2.00; 8.00]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4.00 [2.00; 7.00]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7.50 [5.00; 11.00]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHigh flow nasal oxygen\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e122 (7.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e99 (6.58%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e23 (25.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.88 [2.91; 8.16]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIf HFNO. length(days)\u003c/p\u003e\n \u003cp\u003eMedian [Q1;Q3]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5.00 [3.00; 8.00]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5.00 [2.00; 7.00]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7.00 [4.00; 10.00]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0186\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLength of hospital stay (days) Median [Q1;Q3]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7.00 [4.00; 11.00]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7.00 [4.00; 11.00]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e10.00 [7.00; 15.00]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003ch3\u003eCOVID-19 severity\u003c/h3\u003e\n\u003cp\u003eHNFO was required in 81 (10.9%) cases, non-invasive ventilation in 122 (12.5%) of ICU patients and invasive mechanical ventilation in 565 (57.5%) (Tables \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e and \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e, and supplementary table 3\u0026ndash;5).\u003c/p\u003e\n\u003cp\u003eMedian hospital length of stay (LOS) was 7.0 [4.0; 11.0] days for the ward group and 19.0 [11.0; 33.0] days for the ICU group. Among ICU patients, the median time from hospital admission to ICU admission was 1.0 day [IQR 1.0\u0026ndash;4.0], and the median ICU LOS was 9.0 [IQR 4.0; 20.3] days (Table \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e, Supplementary Tables\u0026nbsp;3\u0026ndash;5).\u003c/p\u003e\n\u003cp\u003eIn the ward group, the median duration of standard oxygen therapy was 4.0 days [IQR 2.0\u0026ndash;8.0], and of HFNO was 5.0 days [IQR 3.0; 8.0] (Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e, Supplementary Table 4). Median duration of invasive mechanical ventilation was 14.0 days [7.5; 29.0]. Neuromuscular blockade was administered to 52.1% (n\u0026thinsp;=\u0026thinsp;512) of patients, prone positioning was required in 42.4% (n\u0026thinsp;=\u0026thinsp;416) and ECMO support was required in 6.5% (n\u0026thinsp;=\u0026thinsp;64) of patients (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e, Supplementary Table 6).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u0026nbsp;\u003ctable id=\"Tab3\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eEvolution during hospital stay: ICU Group\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTotal (N\u0026thinsp;=\u0026thinsp;984)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eNo IL-6R inhibitor (N\u0026thinsp;=\u0026thinsp;851)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTocilizumab or Sarilmab (N\u0026thinsp;=\u0026thinsp;133)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOR [IC95%]\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ep\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eType of IL-6R inhibitor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSarilumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e112 (11.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e112 (84.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTocilizumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e21 (2.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e21 (15.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAnticoagulation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e170 (17.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e169 (20.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1 (0.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e806 (82.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e674 (79.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e132 (99.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33.10 [4.59; 238.43]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAnticoagulation. type\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCurative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e262 (32.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e229 (34.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e33 (25.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.00 x 10\u003csup\u003e\u0026minus;\u0026thinsp;4\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePreventive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e122 (15.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e112 (16.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e10 (7.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.62 [0.29; 1.30]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIntermediate dose preventive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e422 (52.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e333 (49.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e89 (67.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.85 [1.20; 2.86]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCorticosteroids\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e620 (63.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e508 (59.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e112 (84.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.60 [2.22; 5.85]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eProton pump inhibitors\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e123 (12.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e74 (8.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e49 (36.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.12 [4.00; 9.36]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChloroquine / hydroxychloroquine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e41 (4.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e39 (4.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2 (1.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.32 [0.08; 1.33]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIf invasive mechanical ventilation. length (days) Median [Q1;Q3]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e14.00 [7.50;29.00]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e14.00 [7.00;29.00]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e17.00 [8.00;29.00]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.55\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eProne position\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e416 (42.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e359 (42.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e57 (42.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.02 [0.71;1.48]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMuscular blockers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e512 (52.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e450 (52.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e62 (46.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.78 [0.54;1.12]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.17\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eVV or VA ECMO (N\u0026thinsp;=\u0026thinsp;982)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e64 (6.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e52 (6.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e12 (9.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.52 [0.79;2.93]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.21\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCardiac arrest (N\u0026thinsp;=\u0026thinsp;972)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e72 (7.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e63 (7.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9 (6.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.90 [0.44;1.86]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.78\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCatecholamines (N\u0026thinsp;=\u0026thinsp;980)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e399 (40.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e348 (41.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e51 (38.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.89 [0.61;1.30]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.55\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDialysis (N\u0026thinsp;=\u0026thinsp;978)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e165 (16.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e150 (17.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e15 (11.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.60 [0.34;1.06]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.08\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTotal length of ward stay (days) Median [Q1;Q3]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7.00 [2.00;13.00]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6.00 [2.0013.00]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9.00 [4.00; 14.00]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0132\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLength of ward stay before ICU admission (days)\u003c/p\u003e\n \u003cp\u003eMedian [Q1;Q3]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.00 [1.00;4.00]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.00 [1.004.00]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.00 [1.00; 4.00]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0335\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLength of ICU stay (days) Median [Q1;Q3]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9.00 [4.00;20.25]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9.00 [4.0021.00]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9.00 [4.00; 20.00]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.88\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLength of hospital stay (days) Median [Q1;Q3]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e19.00 [11.00;33.00]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e18.00 [11.0033.00]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e20.00 [13.00; 33.00]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.29\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSAPS II (N\u0026thinsp;=\u0026thinsp;961)\u003c/p\u003e\n \u003cp\u003eMean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e40.5 (18.32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e41.6 (18.80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e33.70 (13.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eCOVID-19 Specific Therapeutic Interventions\u003c/p\u003e\n\u003cp\u003eCorticosteroids were prescribed in 857 patients (53.5%) in the ward group and 620 patients (63.0%) in the ICU group. Other treatments are detailed in Table \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e and supplementary Table 5. With the exception of corticosteroids, COVID-19-specific treatments were initiated during the patient\u0026rsquo;s ward stay.\u003c/p\u003e\n\u003cp\u003eA total of 224 patients (8.7%) received at least one dose of tocilizumab or sarilumab. Tocilizumab was administered to 192 patients (7.4%) and sarilumab to 32 patients (1.2%) (Tables \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e and \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e, Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e, Supplementary Tables\u0026nbsp;1\u0026ndash;5). Both IL-6R inhibitors were initiated prior to ICU transfer in the majority of cases (9 out of 133 cases (6.7%) during ICU stay).\u003c/p\u003e\n\u003cp\u003ePatients treated with IL-6R inhibitors received significantly more corticosteroids (85.3% vs. 54.4%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001), proton pump inhibitors (34.8% \u003cem\u003evs\u003c/em\u003e. 7.2%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001), and intermediate-dose preventive anticoagulation (63.7% \u003cem\u003evs\u003c/em\u003e. 35.3%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001). These results were consistent in both the ward group (Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e, Supplementary Table 4) and the ICU group (Table \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e, Supplementary Table\u0026nbsp;5).\u003c/p\u003e\n\u003cp\u003eOutcomes\u003c/p\u003e\n\u003cp\u003eA total of 2 144 (82.9%) patients were discharged alive (1427 (89.0%) in the ward group and 717 (72.9%) in the ICU group). In the ward group, mortality was higher in patients receiving IL-6R inhibitors (17 (18.7%) \u003cem\u003evs\u003c/em\u003e. 159 (10.5%); p\u0026thinsp;\u0026lt;\u0026thinsp;0.02). In the ICU group, hospital mortality was similar in both groups (23.3% \u003cem\u003evs\u003c/em\u003e. 27.7% ; p\u0026thinsp;=\u0026thinsp;0.29) (Table \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e, Supplementary Table\u0026nbsp;7).\u003c/p\u003e\n\u003cp\u003eIn the ward group, the length of hospital stay was significantly longer in patients receiving IL-6R inhibitors compared to those who did not (10.0 [7.0; 15.0] \u003cem\u003evs\u003c/em\u003e. 7.0 [4.0; 11.0]; p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) (Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e, Supplementary Table 4). In the ICU group, no difference in the length of ICU or hospital stay was observed (20.0 [13.0; 33.0] vs. 18.0 [11.0; 33.0]; p\u0026thinsp;=\u0026thinsp;0.29) (Table \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e, Supplementary Table 5).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u0026nbsp;\u003ctable id=\"Tab4\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eOutcome\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTotal (N\u0026thinsp;=\u0026thinsp;2587)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eNo IL-6R inhibitor\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTocilizumab or Sarilmab\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOR [IC95%]\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ep\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTotal population survival\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2144 (82.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1968 (83.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e176 (78.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.07\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWard group (n\u0026thinsp;=\u0026thinsp;1603)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHospital mortality\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e176 (11.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e159 (9.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17 (18.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.95 [1.13;3.40]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.0155\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDay 90 mortality\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e180 (1.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e161 (10.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17(18.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eICU group (n\u0026thinsp;=\u0026thinsp;984)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eD 28 mortality\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8 (3.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8 (3.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eICU mortality\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e248 (25.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e217 (27.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e31 (23.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHospital mortality\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e267 (27.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e236 (27.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e31 (23.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.79 [0.52;1.22]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.29\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDay 90 mortality\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e271 (27.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e240 (24.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e31(23.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0,8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eInfectious Complications\u003c/p\u003e\n\u003cp\u003eDuring hospital stay, 97 patients (6.1%) in the ward group developed a documented infection. The most frequent were urinary tract infections (53; 3.3%), and pneumonias (6; 0.4%) (Table \u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003ea and \u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003eb, Supplementary Table 8). Patients who received IL-6R inhibitors developed more hospital-acquired infections than those who did not (unadjusted OR: 1.73 [1.27; 2.34]; p\u0026thinsp;=\u0026thinsp;0.0004). This result remained consistent after adjustment both with and without multiple imputation (adjusted OR: 2.12 [1.51; 2.97]; p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001 and adjusted OR: 1.47 [1.25; 1.72]; p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001, respectively) (Tables \u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003ea, \u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003eb and \u003cspan class=\"InternalRef\"\u003e6\u003c/span\u003e, Supplementary Tables\u0026nbsp;8 and 14). No such difference was observed based on patient severity (medical ward vs. ICU).\u003c/p\u003e\n\u003cp\u003eIn the ICU group, the incidence of hospital-acquired infections was similar with or without prior treatment with IL-6R inhibitors (43.7% \u003cem\u003evs\u003c/em\u003e. 42.9%; OR: 0.97 [0.67; 1.40]; p\u0026thinsp;=\u0026thinsp;0.85) (Table \u003cspan class=\"InternalRef\"\u003e6\u003c/span\u003e, Supplementary Tables\u0026nbsp;9 and 13).\u003c/p\u003e\n\u003cp\u003eThe combination of IL-6R inhibitors and corticosteroids did not modify the risk of secondary infection compared to corticosteroids alone, neither in the \u0026quot;ward group\u0026quot; nor in the \u0026quot;ICU group\u0026quot; (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e7\u003c/span\u003e). No difference was observed based on the number of initial comorbidities (Supplementary Table 11). However, the risk of infection during ICU stay was associated with the background severity (Supplementary Table 12).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable id=\"Tab5\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003ea: Clinical course complications: Ward grou\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTotal (N\u0026thinsp;=\u0026thinsp;1603)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eNo IL-6R inhibitor (N\u0026thinsp;=\u0026thinsp;1512)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTocilizumab or Sarilmab (N\u0026thinsp;=\u0026thinsp;91)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOR [IC95%]\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ep\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eInfection during hospital stay\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e97 (6.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e88 (5.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9 (9.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.78 [0.86;3.65]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.11\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFungal infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2 (0.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2 (0.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eViral infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1 (0.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1 (1.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.06\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNumber of infectious episode (N\u0026thinsp;=\u0026thinsp;95) Mean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.05 (0.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.07 (0.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.89 (0.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.06\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUrinary tract infection (N\u0026thinsp;=\u0026thinsp;1602)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e53 (3.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e50 (3.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3 (3.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.00 [0.30;3.26]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePrimitive bacteremia (N\u0026thinsp;=\u0026thinsp;1600)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5 (0.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5 (0.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSecondary bacteremia (N\u0026thinsp;=\u0026thinsp;1600)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e10 (0.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9 (0.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1 (1.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.85 [0.23;14.78]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.44\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCatheter related infection (N\u0026thinsp;=\u0026thinsp;1599)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1 (0.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1 (0.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePneumonia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6 (0.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6 (0.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAny adverse event\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNumber of non-infectious adverse event (Median [Q1;Q3])\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHematological complication\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e33 (2.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e29 (1.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4 (4.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.35 [0.81;6.84]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.11\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e- Thrombopenia (N\u0026thinsp;=\u0026thinsp;32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e30 (93.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e26 (92.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4 (100.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e- Length of thrombopenia (days) Median [Q1;Q3]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.00 [1.00;4.75]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.50 [1.00;5.75]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.50 [1.00;2.00]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e- Neutropenia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5 (15.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5 (17.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e- Severe neutropenia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1 (3.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1 (3.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBleeding\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e- Number of bleeding episodes Mean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e12 (0.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e11 (0.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1 (1.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.52 [0.19;11.87]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.51\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e- Gastroduodenal bleeding\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1 (8.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1 (9.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDigestive perforation (N\u0026thinsp;=\u0026thinsp;76)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1 (8.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1 (100.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.08\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003ctable id=\"Tab8\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eb: Clinical course complications: ICU group\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTotal (N\u0026thinsp;=\u0026thinsp;984)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eNo IL-6R inhibitor (N\u0026thinsp;=\u0026thinsp;851)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTocilizumab or Sarilmab (N\u0026thinsp;=\u0026thinsp;133)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOR [IC95%]\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ep\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eInfection during hospital stay\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e429 (43.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e372 (43.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e57 (42.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.97 [0.67;1.40]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.85\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFungal infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e32 (3.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e27 (3.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5 (3.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.19 [0.45;3.15]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.79\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eViral infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e30 (3.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e26 (3.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4 (3.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.98 [0.34;2.87]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNumber of infectious episode Median [Q1;Q3]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.00 [1.00;3.00]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.00 [1.00;2.00]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.00 [1.00;3.00]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.82\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUrinary tract infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e42 (4.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e38 (4.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4 (3.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.66 [0.23;1.87]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.43\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePrimitive bacteremia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e75 (7.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e68 (8.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7 (5.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.63 [0.29;1.41]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.26\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSecondary bacteremia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e50 (5.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e42 (5.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8 (6.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.23 [0.57;2.69]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCatheter-related infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e30 (3.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e29 (3.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1 (0.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.21 [0.03;1.59]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.11\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eVentilator-associated pneumonia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e356 (36.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e305 (35.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e51 (38.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.11 [0.76;1.62]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.58\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHematological complication\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e30 (3.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e25 (2.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5 (3.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.29 [0.49;3.43]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.59\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e- Thrombopenia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e28 (93.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e23 (92.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5 (100.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e- Length of thrombopenia (days) Median [Q1;Q3]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5.00 [3.00;10.50]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5.00 [2.25;10.75]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e10.00 [10.00;10.00]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e- Neutropenia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3 (10.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3 (12.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e- Severe neutropenia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2 (6.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2 (8.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBleeding\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e- Number of bleeding episodes Mean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e64 (6.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e60 (7.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4 (3.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.41 [0.15;1.15]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.08\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e- Gastroduodenal bleeding (confirmed by oesogastric endoscopy)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e20 (31.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e20 (33.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e- Lower digestive tract bleeding\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7 (10.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDigestive perforation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1 (1.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1 (1.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eOther complications\u003c/p\u003e\n\u003cp\u003eNo difference in hematological abnormalities or digestive complication was observed between groups (Table \u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e, \u003cspan class=\"InternalRef\"\u003e6\u003c/span\u003e, Supplementary Table\u0026nbsp;10).\u003c/p\u003e\n\u003cp\u003eTable 6: Infectious complication: Multiple imputation\u003c/p\u003e\n\u003cp\u003e\u003cimg src=\"https://myfiles.space/user_files/69519_bce2c0439cd956a6/69519_custom_files/img1750059005.png\" alt=\"\" /\u003e\u003c/p\u003e\n\u003cp\u003eTable 7: Effect of IL-6R inhibitor and corticosteroids on infection and survival\u003c/p\u003e\n\u003ctable class=\"fr-table-selection-hover\" border=\"1\" width=\"738\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 30.8424%;\" valign=\"top\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 15.3533%;\" valign=\"top\"\u003e\n\u003cp\u003e\u003cstrong\u003eTotal (N=224)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 15.3533%;\" valign=\"top\"\u003e\n\u003cp\u003e\u003cstrong\u003eNo IL-6R inhibitor and corticosteroids (N=191)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 15.3533%;\" valign=\"top\"\u003e\n\u003cp\u003e\u003cstrong\u003eTocilizumab \u0026nbsp;or Sarilmab without corticosteroids (N=33)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 15.3533%;\" valign=\"top\"\u003e\n\u003cp\u003e\u003cstrong\u003eOR [IC95%]\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 7.74457%;\" valign=\"top\"\u003e\n\u003cp\u003e\u003cstrong\u003ep\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 30.8424%;\" valign=\"top\"\u003e\n\u003cp\u003e\u003cstrong\u003eInfection during hospital stay\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 15.3533%;\" valign=\"top\"\u003e\n\u003cp\u003e66 (29.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 15.3533%;\" valign=\"top\"\u003e\n\u003cp\u003e10 (30.3%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 15.3533%;\" valign=\"top\"\u003e\n\u003cp\u003e56 (29.3%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 15.3533%;\" valign=\"top\"\u003e\n\u003cp\u003e0.95 [0.43;2.13]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 7.74457%;\" valign=\"top\"\u003e\n\u003cp\u003e0.91\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 30.8424%;\" valign=\"top\"\u003e\n\u003cp\u003e\u003cstrong\u003eFungal infection\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 15.3533%;\" valign=\"top\"\u003e\n\u003cp\u003e5 (2.2%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 15.3533%;\" valign=\"top\"\u003e\n\u003cp\u003e1 (3.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 15.3533%;\" valign=\"top\"\u003e\n\u003cp\u003e4 (2.1%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 15.3533%;\" valign=\"top\"\u003e\n\u003cp\u003e0.68 [0.07;6.32]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 7.74457%;\" valign=\"top\"\u003e\n\u003cp\u003e0.55\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 30.8424%;\" valign=\"top\"\u003e\n\u003cp\u003e\u003cstrong\u003eViral infection\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 15.3533%;\" valign=\"top\"\u003e\n\u003cp\u003e5 (2.2%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 15.3533%;\" valign=\"top\"\u003e\n\u003cp\u003e0 (0.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 15.3533%;\" valign=\"top\"\u003e\n\u003cp\u003e5 (2.6%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 15.3533%;\" valign=\"top\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 7.74457%;\" valign=\"top\"\u003e\n\u003cp\u003e\u0026gt;0.99\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 30.8424%;\" valign=\"top\"\u003e\n\u003cp\u003e\u003cstrong\u003eNumber of infectious episode Mean (SD)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 15.3533%;\" valign=\"top\"\u003e\n\u003cp\u003e1.00 [1.00;2.00]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 15.3533%;\" valign=\"top\"\u003e\n\u003cp\u003e1.50 [1.00;2.75]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 15.3533%;\" valign=\"top\"\u003e\n\u003cp\u003e1.00 [1.00;2.00]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 15.3533%;\" valign=\"top\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 7.74457%;\" valign=\"top\"\u003e\n\u003cp\u003e0.62\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 30.8424%;\" valign=\"top\"\u003e\n\u003cp\u003e\u003cstrong\u003eUrinary tract infection\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 15.3533%;\" valign=\"top\"\u003e\n\u003cp\u003e7 (3.1%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 15.3533%;\" valign=\"top\"\u003e\n\u003cp\u003e0 (0.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 15.3533%;\" valign=\"top\"\u003e\n\u003cp\u003e7 (3.7%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 15.3533%;\" valign=\"top\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 7.74457%;\" valign=\"top\"\u003e\n\u003cp\u003e0.60\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 30.8424%;\" valign=\"top\"\u003e\n\u003cp\u003e\u003cstrong\u003ePrimitive bacteremia\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 15.3533%;\" valign=\"top\"\u003e\n\u003cp\u003e7 (3.1%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 15.3533%;\" valign=\"top\"\u003e\n\u003cp\u003e1 (3.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 15.3533%;\" valign=\"top\"\u003e\n\u003cp\u003e6 (3.1%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 15.3533%;\" valign=\"top\"\u003e\n\u003cp\u003e1.04 [0.12;8.91]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 7.74457%;\" valign=\"top\"\u003e\n\u003cp\u003e\u0026gt;0.99\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 30.8424%;\" valign=\"top\"\u003e\n\u003cp\u003e\u003cstrong\u003eSecondary bacteremia \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 15.3533%;\" valign=\"top\"\u003e\n\u003cp\u003e9 (4.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 15.3533%;\" valign=\"top\"\u003e\n\u003cp\u003e2 (6.1%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 15.3533%;\" valign=\"top\"\u003e\n\u003cp\u003e7 (3.7%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 15.3533%;\" valign=\"top\"\u003e\n\u003cp\u003e0.59 [0.12;2.99]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 7.74457%;\" valign=\"top\"\u003e\n\u003cp\u003e0.62\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 30.8424%;\" valign=\"top\"\u003e\n\u003cp\u003e\u003cstrong\u003eCatheter related infection\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 15.3533%;\" valign=\"top\"\u003e\n\u003cp\u003e1 (0.4%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 15.3533%;\" valign=\"top\"\u003e\n\u003cp\u003e1 (3.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 15.3533%;\" valign=\"top\"\u003e\n\u003cp\u003e0 (0.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 15.3533%;\" valign=\"top\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 7.74457%;\" valign=\"top\"\u003e\n\u003cp\u003e0.15\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 30.8424%;\" valign=\"top\"\u003e\n\u003cp\u003e\u003cstrong\u003eVentilator-associated pneumonia\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 15.3533%;\" valign=\"top\"\u003e\n\u003cp\u003e51 (22.8%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 15.3533%;\" valign=\"top\"\u003e\n\u003cp\u003e9 (27.3%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 15.3533%;\" valign=\"top\"\u003e\n\u003cp\u003e42 (22.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 15.3533%;\" valign=\"top\"\u003e\n\u003cp\u003e0.75 [0.32;1.74]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 7.74457%;\" valign=\"top\"\u003e\n\u003cp\u003e0.5\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 30.8424%;\" valign=\"top\"\u003e\n\u003cp\u003e\u003cstrong\u003eICU admission\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 15.3533%;\" valign=\"top\"\u003e\n\u003cp\u003e133 (59.4%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 15.3533%;\" valign=\"top\"\u003e\n\u003cp\u003e21 (63.6%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 15.3533%;\" valign=\"top\"\u003e\n\u003cp\u003e112 (58.6%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 15.3533%;\" valign=\"top\"\u003e\n\u003cp\u003e0.81 [0.38;1.74]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 7.74457%;\" valign=\"top\"\u003e\n\u003cp\u003e0.59\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 30.8424%;\" valign=\"top\"\u003e\n\u003cp\u003e\u003cstrong\u003eHospital mortality\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 15.3533%;\" valign=\"top\"\u003e\n\u003cp\u003e48 (21.4%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 15.3533%;\" valign=\"top\"\u003e\n\u003cp\u003e5 (15.1%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 15.3533%;\" valign=\"top\"\u003e\n\u003cp\u003e43 (22.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 15.3533%;\" valign=\"top\"\u003e\n\u003cp\u003e1.63 [0.59;4.47]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 7.74457%;\" valign=\"top\"\u003e\n\u003cp\u003e0.34\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn our multicenter study, an IL-6R inhibitors were prescribed in 8.6%. The prolonged uncertainty regarding the relevance of IL-6 pathway inhibition [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] led to variable administration during the study period, resulting in a low percentage of patients who actually received an IL-6R inhibitor. This was particularly noticeable in the ICU, where the delayed onset of inflammation and relatively low levels of IL-6 compared to typical acute respiratory distress syndrome or septic shock [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e] often prevented the administration of these IL-6R inhibitors. As more studies emerged, guidelines were modified based on recent syntheses [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Both suggest the use of tocilizumab in severe COVID-19, but, balance the potential improvements and the prevention of adverse events [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. However, the incidence and severity of these complications remain unclear [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWe found an increased risk of secondary infections associated with the administration of IL-6R inhibitor in the overall patient population (OR: 1.73 [1.27; 2.34]; p\u0026thinsp;=\u0026thinsp;0.0004). Impairment of immune defenses due to the disruption of the IL-6 pathway is well-documented during long-term treatment of moderate chronic inflammatory diseases [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Conversely, the effect of a short period of treatment, remains poorly documented. The inability of a single dose to sufficiently dampen the cytokine response seems probable [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e] but previous smaller observational studies yielded divergent results. Marco Ripa \u003cem\u003eet al.\u003c/em\u003e found an increased risk of infections. However, the involvement of IL-6R inhibitors was uncertain, and the multivariate analysis did not confirm this link [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. In another early study in Chicago, the administration of tocilizumab was associated with the risk of secondary bacterial infections [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. Unfortunately, the groups were highly heterogeneous, leading to a disequilibrium that blurred the conclusions. Recent meta-analyses offer similarly conflicting conclusions [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan additionalcitationids=\"CR36\" citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eMany secondary episodes were of viral origin. The central role of IL-6 in viral infection control, by reducing the production of acute phase proteins and modifying B lymphocytes differentiation and T cell maturation, may explain these results [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. The absence of observed SARS-CoV-2 clearance compromise during clinical use of tocilizumab [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e] tends to reduce the relevance of this hypothesis. However, the timing of use, potential exhaustion of the inflammatory response, and alteration of the respiratory tract mucosa by the initial viral aggression may secondarily favor a new respiratory viral disease. The delay between admission and tocilizumab administration may play a role in the infectious risk [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. Moreover, the association between IL-6R inhibition and specific visceral infections remains unclear. We observed a raw difference in secondary bacteremia that did not reach statistical significance that aligns with previous observations [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e, \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eUnexpectedly, while previous studies demonstrated an increased risk of infection in ICU patients [\u003cspan additionalcitationids=\"CR41\" citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e], we did not identify such a difference in our critical care patients. Administration beyond two days of hospital admission or two days of HFNO requirement has been associated with infectious complications [\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]. In our study, IL-6R inhibitors were all administered on the first day of hospital admission. This may partly explain the discrepancy in the reported infectious risk between studies and may have contributed to the absence of infections during ICU stay. Conversely, as previously discussed [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], the absence of a deleterious effect is often associated with a lack of beneficial effect in the same studies [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. A recent meta-analysis reached a similar conclusion [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. The absence of beneficial effects on survival, organ support requirements during ICU stay, or duration of mechanical ventilation observed in our study may partly explain the lack of deleterious effects from IL-6 pathway inhibition.\u003c/p\u003e \u003cp\u003eMost patients concurrently received corticosteroids, making it challenging to evaluate the separate effects of these drugs [\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e]. The absence of systematic corticosteroid use allowed for an adjustment that confirmed the involvement of tocilizumab, independent of its potential synergistic effect on the immune response [\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe limited clinical effect of IL-6 pathway inhibitors in our severe and critical population is further supported by the absence of deleterious digestive and hematological effects widely described in chronic inflammatory diseases and COVID-19 [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOur study has several limitations. First, the retrospective design may result in less comprehensive side effect documentation. However, the severity of the complications of interest makes it unlikely that they were omitted from patient files. Furthermore, the incidence of adverse events in our cohort is similar to previous studies and higher than in many randomized trials. Second, the small number of patients treated with IL-6R inhibitors limits the conclusions that can be drawn. This usage however, reflected clinical reality and uncertainty about the benefits and risks of tocilizumab and sarilumab. Third, the lack of information on HFNO use or ICU admission during this critical pandemic period, along with the absence of data on ICU or tracheal intubation withholding, prevents us from drawing conclusions about the potential efficacy of IL-6R inhibition.\u003c/p\u003e \u003cp\u003eConversely, our cohort has several strengths. The multicenter recruitment of severe patients from both wards and ICUs enabled the inclusion of the largest group of patients who received an IL-6R inhibitor in a tolerability study. The retrospective design minimized bias in the reporting of adverse events associated with the administration of controversial therapies. A specific analysis of tocilizumab allowed for the distinction of adverse events associated with the only IL-6R inhibitor shown to have a benefit during severe COVID-19. The multivariate analysis highlighted risk factors associated with an increased probability of secondary infection during IL-6R inhibitor treatment, which should be considered in the risk-benefit analysis of IL-6R inhibitor therapy in this context.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn this multicenter French cohort study, the administration of an IL-6R inhibitor to severe COVID-19 patients was associated with an increased incidence of secondary infections in ward patients, particularly viral infections. Conversely, in critical cases requiring ICU admission and even invasive mechanical ventilation, no infectious, digestive, or hematological complications were associated with IL-6R inhibitor administration. Broader international studies are needed to confirm these findings.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003eThis work was supported by the Groupe Hospitalier Paris Saint‑Joseph\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgement\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the Groupe Hospitalier Paris Saint‑Joseph\u003c/p\u003e\n\u003cp\u003eAll data generated or analyzed during this study are included in this study or its supplementary material files. Further inquiries can be directed to the corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors contributions\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003eConceptualization: CL, TFB, AP, MT, FP. Methodology: MC, AF, GC, FP. Inclusions, review and editing: CL, TFB, AP, FP, LS, DM, OV, FB, LW, AP, SL, NR, PRB, MT, CB, JD. First draft: CL, TFB, FP.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eConflicts of interest:\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCharlène Lefèvre: No conflict\u003c/p\u003e\n\u003cp\u003eThéo Funck-Brentano: No conflict\u003c/p\u003e\n\u003cp\u003eMarine Cachanado: No conflict\u003c/p\u003e\n\u003cp\u003eAlexia Plocque: No conflict\u003c/p\u003e\n\u003cp\u003eAudrey Fels: No conflict\u003c/p\u003e\n\u003cp\u003eFrederic Pène: No conflict\u003c/p\u003e\n\u003cp\u003eLaurent Savale: No conflict\u003c/p\u003e\n\u003cp\u003eDavid Montani: No conflict\u003c/p\u003e\n\u003cp\u003eOlivier Voisin: No conflict\u003c/p\u003e\n\u003cp\u003eFlore Bintein: No conflict\u003c/p\u003e\n\u003cp\u003eLucille Wildenberg: No conflict\u003c/p\u003e\n\u003cp\u003eAxel Philippe: No conflict\u003c/p\u003e\n\u003cp\u003eStephane Legriel: No conflict\u003c/p\u003e\n\u003cp\u003eNicolas Roche: No conflict: \u0026nbsp; Dr Roche reported receiving grant funding from Boehringer Ingelheim, Novartis AG, Pfizer Inc, and GSK PLC and personal fees from Boehringer Ingelheim, Novartis AG, Pfizer Inc, GSK PLC, Austral Pharma, Biosency, MSD, AstraZeneca, Chiesi Farmaceutici SpA, Menarini Group, Nuvaira, Sanofi SA, and Zambon outside the submitted work.\u003c/p\u003e\n\u003cp\u003ePierre-Régis Burgel: No conflict\u003c/p\u003e\n\u003cp\u003eMarc Tran: No conflict\u003c/p\u003e\n\u003cp\u003eChristophe Baillard: No conflict\u003c/p\u003e\n\u003cp\u003eJacques Duranteau: No conflict\u003c/p\u003e\n\u003cp\u003eGilles Chatellier: No conflict\u003c/p\u003e\n\u003cp\u003eFrancois Philippart: No conflict\u003c/p\u003e\n\u003cp\u003eAll authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval\u003c/strong\u003e: The study was carried out in accordance with the Declaration of Helsinki and French law. The TOCSIN study was approved by our institutional review board (GERM; IRB n°00012157). Patients were informed about the study and their non-opposition to the collection and use of non-identifying data for research purposes was obtained.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe processing of patient data complied with the reference methodology 004 of the French Commission Nationale de l'Informatique et des Libertés (French National Data Protection Agency).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e: Datasets used/analyzed in this study are accessible upon reasonable request to the corresponding author.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAbani, O. et al. Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. \u003cem\u003eLancet\u003c/em\u003e \u003cb\u003e397\u003c/b\u003e, 1637\u0026ndash;1645. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/S0140-6736(21)00676-0\u003c/span\u003e\u003cspan address=\"10.1016/S0140-6736(21)00676-0\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2021).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTomazini, B. M. et al. Effect of Dexamethasone on Days Alive and Ventilator-Free in Patients With Moderate or Severe Acute Respiratory Distress Syndrome and COVID-19: The CoDEX Randomized Clinical Trial. \u003cem\u003eJAMA\u003c/em\u003e \u003cb\u003e324\u003c/b\u003e, 1307\u0026ndash;1316. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1001/jama.2020.17021\u003c/span\u003e\u003cspan address=\"10.1001/jama.2020.17021\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2020).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group et al. 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Med.\u003c/em\u003e \u003cb\u003e383\u003c/b\u003e, 2333\u0026ndash;2344. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1056/NEJMoa2028836\u003c/span\u003e\u003cspan address=\"10.1056/NEJMoa2028836\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2020).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Covid-19, tocilizumab, nosocomial infections, ventilator-associated pneumonia, neutropenia, mortality","lastPublishedDoi":"10.21203/rs.3.rs-6785789/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6785789/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDuring severe and critical COVID-19, therapeutic options remain scarce. Among interventions, the use of interleukin-6 receptor inhibitor (IL-6Ri) is especially controversial due to persistent uncertainty about their efficacy and safety.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe conducted a multicentric retrospective French observational study. All severe or critical COVID-19 requiring hospital admission were included from march 1st 2020 to December 31th 2021. Our main aim was to compare the occurrence of secondary infections function of the administration of IL-6Ri. Digestive, hematological complications and survival were also analyzed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAmong 2587 patients requiring hospital admission, 1603 had a severe COVID-19 and 984 a critical one requiring ICU admission. 224 received at least one dose of tocilizumab or sarilumab. Incidence of secondary infection was 29.5% in the IL-6Ri group \u003cem\u003evs.\u003c/em\u003e 19.5% without IL-6Ri (unadjusted OR: 1.73 [1.27;2.34]; p = 0.0004) in the whole population. This result remained consistent after adjustment, without multiple imputation (MI) (adjusted OR: 2.12 [1.51; 2.97]; p \u0026lt; 0.0001) and after MI (adjusted OR: 1.47 [1.25; 1.72]; p \u0026lt; 0.0001)). Incidence of hematological or digestive complication were similar between groups. Mortality of patients admitted in ward was higher in the IL-6Ri group (18.7% \u003cem\u003evs\u003c/em\u003e 10.5%, p = 0.0155). No difference in 28 days, ICU, hospital of 90 days mortality was noticed among ICU patients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ein this population, administration of IL-6Ri was associated with a higher risk of secondary infection in the whole population and with a higher mortality among patients who spent their whole stay in ward.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRegistration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNCT05017441 (January 31st 2024)\u003c/p\u003e","manuscriptTitle":"Benefit and risk associated with interleukin-6 receptor inhibitor administration during severe COVID-19: a retrospective multicentric study none","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-17 14:44:49","doi":"10.21203/rs.3.rs-6785789/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-07-22T09:03:05+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-02T10:41:37+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-06-23T12:00:29+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"21614213495875623713159172980573289040","date":"2025-06-14T20:32:30+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"182002286221832588643026347050711667247","date":"2025-06-13T08:08:26+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"229386173029200890824798031455289814036","date":"2025-06-12T16:51:47+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-06-12T16:35:53+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-06-12T16:31:49+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-06-02T06:57:43+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-05-31T03:36:19+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2025-05-30T14:49:08+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"340fcfaf-aa91-47f8-86c7-06cfb2830465","owner":[],"postedDate":"June 17th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":50074701,"name":"Health sciences/Diseases/Infectious diseases"},{"id":50074702,"name":"Health sciences/Diseases/Infectious diseases/Viral infection"},{"id":50074703,"name":"Health sciences/Medical research/Outcomes research"},{"id":50074704,"name":"Health sciences/Medical research/Study design/Clinical trials/Phase iv trials"}],"tags":[],"updatedAt":"2026-01-26T16:05:23+00:00","versionOfRecord":{"articleIdentity":"rs-6785789","link":"https://doi.org/10.1038/s41598-026-36864-w","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2026-01-22 15:57:17","publishedOnDateReadable":"January 22nd, 2026"},"versionCreatedAt":"2025-06-17 14:44:49","video":"","vorDoi":"10.1038/s41598-026-36864-w","vorDoiUrl":"https://doi.org/10.1038/s41598-026-36864-w","workflowStages":[]},"version":"v1","identity":"rs-6785789","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6785789","identity":"rs-6785789","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}