TY - JOUR
T1 - Better COVID-19 Intensive Care Unit survival in females, independent of age, disease severity, comorbidities, and treatment
AU - Meijs, D.A.M.
AU - van Bussel, B.C.T.
AU - Stessel, B.
AU - Mehagnoul-Schipper, J.
AU - Hana, A.
AU - Scheeren, C.I.E.
AU - Peters, S.A.E.
AU - van Mook, W.N.K.A.
AU - van der Horst, I.C.C.
AU - Marx, G.
AU - Mesotten, D.
AU - Ghossein-Doha, C.
AU - CoDaP Investigators
AU - Heijnen, N.F.L.
AU - Raafs, A.
AU - van Kuijk, S.M.J.
AU - Smits, L.J.M.
AU - Janssen, E.B.N.J.
AU - Mulder, M.M.G.
AU - Koelmann, M.
AU - Bels, J.L.M.
AU - Florack, M.C.D.M.
N1 - Funding Information:
Our study was supported by the "Interreg Euregio Meuse-Rhine" (Covid Data Platform (CoDaP) Grant: Interreg-EMR 187). Funding sources were not involved in the study design, data collection, data analysis, data interpretation, writing process, and decision to submit for publication. Researchers were independent of funders, and all authors had full data access.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/1/14
Y1 - 2022/1/14
N2 - 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.
AB - 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.
KW - ACE2
KW - BIAS
KW - MISSING DATA
KW - RECEPTOR
KW - RESPIRATORY SYNDROME
KW - SEX-DIFFERENCES
KW - OUTCOMES
U2 - 10.1038/s41598-021-04531-x
DO - 10.1038/s41598-021-04531-x
M3 - Article
C2 - 35031644
SN - 2045-2322
VL - 12
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 734
ER -