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Abstract
Although male Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) patients have higher Intensive Care Unit (ICU) admission rates and a worse disease course, a comprehensive analysis of female and male ICU survival and underlying factors such as comorbidities, risk factors, and/or anti-infection/inflammatory therapy administration is currently lacking. Therefore, we investigated the association between sex and ICU survival, adjusting for these and other variables. In this multicenter observational cohort study, all patients with SARS-CoV-2 pneumonia admitted to seven ICUs in one region across Belgium, The Netherlands, and Germany, and requiring vital organ support during the first pandemic wave were included. With a random intercept for a center, mixed-effects logistic regression was used to investigate the association between sex and ICU survival. Models were adjusted for age, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, comorbidities, and anti-infection/inflammatory therapy. Interaction terms were added to investigate effect modifications by sex with country and sex with obesity. A total of 551 patients (29% were females) were included. Mean age was 65.4 ± 11.2 years. Females were more often obese and smoked less frequently than males (p-value 0.001 and 0.042, respectively). APACHE II scores of females and males were comparable. Overall, ICU mortality was 12% lower in females than males (27% vs 39% respectively, p-value < 0.01) with an odds ratio (OR) of 0.62 (95%CI 0.39–0.96, p-value 0.032) after adjustment for age and APACHE II score, 0.63 (95%CI 0.40–0.99, p-value 0.044) after additional adjustment for comorbidities, and 0.63 (95%CI 0.39–0.99, p-value 0.047) after adjustment for anti-infection/inflammatory therapy. No effect modifications by sex with country and sex with obesity were found (p-values for interaction > 0.23 and 0.84, respectively). ICU survival in female SARS-CoV-2 patients was higher than in male patients, independent of age, disease severity, smoking, obesity, comorbidities, anti-infection/inflammatory therapy, and country. Sex-specific biological mechanisms may play a role, emphasizing the need to address diversity, such as more sex-specific prediction, prognostic, and therapeutic approach strategies.
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Details
1 Maastricht University Medical Center + (Maastricht UMC+), Department of Intensive Care Medicine, Maastricht, the Netherlands (GRID:grid.412966.e) (ISNI:0000 0004 0480 1382); Laurentius Ziekenhuis, Department of Intensive Care Medicine, Roermond, the Netherlands (GRID:grid.415842.e) (ISNI:0000 0004 0568 7032)
2 Maastricht University Medical Center + (Maastricht UMC+), Department of Intensive Care Medicine, Maastricht, the Netherlands (GRID:grid.412966.e) (ISNI:0000 0004 0480 1382); Care and Public Health Research Institute (CAPHRI), Maastricht University, Maastricht, the Netherlands (GRID:grid.5012.6) (ISNI:0000 0001 0481 6099)
3 Jessa Hospital, Department of Intensive Care Medicine, Hasselt, Belgium (GRID:grid.414977.8) (ISNI:0000 0004 0578 1096); UHasselt, Faculty of Medicine and Life Sciences, Diepenbeek, Belgium (GRID:grid.12155.32) (ISNI:0000 0001 0604 5662)
4 VieCuri Medisch Centrum, Department of Intensive Care Medicine, Venlo, the Netherlands (GRID:grid.416856.8) (ISNI:0000 0004 0477 5022)
5 Laurentius Ziekenhuis, Department of Intensive Care Medicine, Roermond, the Netherlands (GRID:grid.415842.e) (ISNI:0000 0004 0568 7032)
6 Zuyderland Medisch Centrum, Department of Intensive Care Medicine, Heerlen/Sittard, the Netherlands (GRID:grid.416905.f)
7 University Medical Center Utrecht, Julius Center for Health Sciences and Primary Care, Utrecht, the Netherlands (GRID:grid.7692.a) (ISNI:0000000090126352); The George Institute for Global Health, Imperial College London, London, United Kingdom (GRID:grid.7445.2) (ISNI:0000 0001 2113 8111); The George Institute for Global Health, University of New South Wales, Sydney, Australia (GRID:grid.415508.d) (ISNI:0000 0001 1964 6010)
8 Maastricht University Medical Center + (Maastricht UMC+), Department of Intensive Care Medicine, Maastricht, the Netherlands (GRID:grid.412966.e) (ISNI:0000 0004 0480 1382); Maastricht UMC+ Academy for Postgraduate Medical Education, Maastricht, the Netherlands (GRID:grid.412966.e) (ISNI:0000 0004 0480 1382); Cardiovascular Research Institute Maastricht (CARIM), Maastricht, the Netherlands (GRID:grid.5012.6) (ISNI:0000 0001 0481 6099)
9 Maastricht University Medical Center + (Maastricht UMC+), Department of Intensive Care Medicine, Maastricht, the Netherlands (GRID:grid.412966.e) (ISNI:0000 0004 0480 1382); Cardiovascular Research Institute Maastricht (CARIM), Maastricht, the Netherlands (GRID:grid.5012.6) (ISNI:0000 0001 0481 6099)
10 University Hospital Rheinisch Westfälische Hochschule (RWTH) Aachen, Department of Intensive Care Medicine, Aachen, Germany (GRID:grid.412301.5) (ISNI:0000 0000 8653 1507)
11 Ziekenhuis Oost-Limburg, Department of Intensive Care Medicine, Genk, Belgium (GRID:grid.470040.7) (ISNI:0000 0004 0612 7379); UHasselt, Faculty of Medicine and Life Sciences, Diepenbeek, Belgium (GRID:grid.12155.32) (ISNI:0000 0001 0604 5662)
12 Maastricht University Medical Center + (Maastricht UMC+), Department of Intensive Care Medicine, Maastricht, the Netherlands (GRID:grid.412966.e) (ISNI:0000 0004 0480 1382); Cardiovascular Research Institute Maastricht (CARIM), Maastricht, the Netherlands (GRID:grid.5012.6) (ISNI:0000 0001 0481 6099); Maastricht UMC+, Department of Cardiology, Maastricht, the Netherlands (GRID:grid.412966.e) (ISNI:0000 0004 0480 1382); Maastricht UMC+, School for Oncology and Developmental Biology, Maastricht, the Netherlands (GRID:grid.412966.e) (ISNI:0000 0004 0480 1382)
13 Maastricht University Medical Center + (Maastricht UMC+), Department of Intensive Care Medicine, Maastricht, the Netherlands (GRID:grid.412966.e) (ISNI:0000 0004 0480 1382)
14 Maastricht UMC+, Department of Cardiology, Maastricht, the Netherlands (GRID:grid.412966.e) (ISNI:0000 0004 0480 1382)
15 Care and Public Health Research Institute (CAPHRI), Maastricht University, Maastricht, the Netherlands (GRID:grid.5012.6) (ISNI:0000 0001 0481 6099); Maastricht UMC+, Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht, the Netherlands (GRID:grid.412966.e) (ISNI:0000 0004 0480 1382)
16 Ziekenhuis Oost-Limburg, Department of Intensive Care Medicine, Genk, Belgium (GRID:grid.470040.7) (ISNI:0000 0004 0612 7379)
17 Maastricht University Medical Center + (Maastricht UMC+), Department of Intensive Care Medicine, Maastricht, the Netherlands (GRID:grid.412966.e) (ISNI:0000 0004 0480 1382); Zuyderland Medisch Centrum, Department of Intensive Care Medicine, Heerlen/Sittard, the Netherlands (GRID:grid.416905.f)