Better COVID-19 Intensive Care Unit survival in females, independent of age, disease severity, comorbidities, and treatment

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.

Risk Factors of Severe COVID-19: A Review of Host, Viral and Environmental Factors

“…Males typically experience more frequent lower respiratory tract infections [ 112 ] and, in the case of influenza A and B viruses, RSV, SARS-CoV, and other sources of community-acquired pneumonia, more severe disease compared to females [ 113 , 114 ]. Similarly, with SARS-CoV-2 infection, males are hospitalized [ 8 , 115 ], are admitted to intensive care unit (ICU) [ 8 , 116 ] and die [ 117 , 118 ] more often, although infection rates appear to be similar to those of women [ 119 ]. Sex-disaggregated estimates of the infection fatality ratio show consistently higher fatality rates among males in every age category [ 8 , 9 ].…”

Sex differences in cardiovascular complications and mortality in hospital patients with covid-19: registry based observational study

“… 9 In patients with covid-19 who required admission to the intensive care unit and vital organ support, female participants were still 37% less likely than male participants to die in the intensive care unit, independent of age, severity of the acute critical illness, lifestyle factors, and comorbidities. 26 In our study, female participants had a 35% lower odds of death than male participants while in hospital. Whether this difference between the sexes is the same or greater than would be expected in the general population, where male individuals have a shorter life expectancy, is unclear.…”

“…This result is in line with previous findings showing persistent sex differences even after adjusting for the Acute Physiology and Chronic Health Evaluation II (APACHE II) score, indicating the severity of acute illness. 26 Previous research, however, has shown that the association between peak levels of C reactive protein and adverse outcomes in covid-19 is stronger in male individuals. 47 The higher risk of severe disease in male individuals among patients admitted to hospital for covid-19 might also be explained by their later presentation to hospital than female individuals.…”

Gender differences in comorbidities of patients with COVID-19: An Italian local register-based analysis

“…However, their review highlighted a lack of gender-sensitive awareness in the translation of clinical research findings into gender-specific treatment regimens, guidelines, and preventive strategies, as well as in the development of gender-oriented health policies. Similarly to other diseases, COVID-19 exhibits a high degree of heterogeneity in its clinical course and disease severity [ 50 , 51 ]. Many factors can trigger the differences between individuals, including their clinical condition, access to healthcare services and preventive programs, and the local epidemiological context [ 14 , 23 , 25 , 27 , 48 ].…”