Temporal trends of sex differences for COVID-19 infection, hospitalisation, severe disease, intensive care unit (ICU) admission and death: a meta-analysis of 229 studies covering over 10M patients

Abstract

Background: This review aims to investigate the association of sex with the risk of multiple COVID-19 health outcomes, ranging from infection to death. Methods: Pubmed and Embase were searched through September 2020. We considered studies reporting sex and coronavirus disease 2019 (COVID-19) outcomes. Qualitative and quantitative data were extracted using standardised electronic data extraction forms with the assessment of Newcastle Ottawa Scale for risk of bias. Pooled trends in infection, hospitalization, severity, intensive care unit (ICU) admission and death rate were calculated separately for men and women and subsequently random-effects meta-analyses on relative risks (RR) for sex was performed. Results: Of 10,160 titles, 229 studies comprising 10,417,452 patients were included in the analyses. Methodological quality of the included studies was high (6.9 out of 9). Men had a higher risk for infection with COVID-19 than women (RR = 1.14, 95%CI: 1.07 to 1.21). When infected, they also had a higher risk for hospitalization (RR = 1.33, 95%CI: 1.27 to 1.41), higher risk for severe COVID-19 (RR = 1.22, 95%CI: 1.17 to 1.27), higher need for Intensive Care (RR = 1.41, 95%CI: 1.28 to 1.55), and higher risk of death (RR = 1.35, 95%CI: 1.28 to 1.43). Within the period studied, the RR for infection and severity increased for men compared to women, while the RR for mortality decreased for men compared to women. Conclusions: Meta-analyses on 229 studies comprising over 10 million patients showed that men have a higher risk for COVID-19 infection, hospitalization, disease severity, ICU admission and death. The relative risks of infection, disease severity and death for men versus women showed temporal trends with lower relative risks for infection and severity of disease and higher relative risk for death at the beginning of the pandemic compared to the end of our inclusion period. PROSPERO registration: CRD42020180085 (20/04/2020)

The Long-Term Effect of COVID-19 Disease Severity on Risk of Diabetes Incidence and the Near 1-Year Follow-Up Outcomes among Postdischarge Patients in Wuhan

“…We observed a sex difference in the relationship between critical illness and subsequent risk of diabetes incidence among postdischarge COVID-19 patients. Current evidence suggests that men have a higher risk of COVID-19 infection, hospitalization, disease severity, ICU admission, and death than women [ 31 ], which may partly support our result about sex differences. Though the mechanism was unclear, genetic/epigenetic factors, sex differences in the immune response [ 32 , 33 ], androgens-mediated ACE2 expression [ 34 , 35 ], and gut microbiome-mediated immune modulation [ 36 ] may be reasons for sex-based differences.…”

Genomic surveillance of SARS-CoV-2 in patients presenting neurological manifestations

“…On the other hand, the sampled population is heterogeneous in terms, for instance, of age and sex. Indeed, despite the limited number of patients, we found an association between neurological and severe respiratory symptoms and between symptom severity in general, and age and sex, as reported in the literature [ 42 , 60 ]. Thus, the reported results are worth of attention and deserve further validation in larger cohorts of patients.…”

Risk of severe COVID-19 outcomes associated with rheumatoid arthritis and phenotypic subgroups: a retrospective, comparative, multicentre cohort study

“…This difference might be the result of factors (eg, smoking status, obesity, and comorbidities) more common in male comparators that also increased the risk of severe disease; alternatively, the proportion of men in our cohort was smaller, so our study might have lacked power to detect differences. 21 , 23 Indeed, a study by England and colleagues 7 using the US Veterans Affairs rheumatoid arthritis cohort, which is enriched for men, also examined the risk of COVID-19 hospitalisation or death among patients with rheumatoid arthritis versus patients without rheumatoid arthritis from the Veterans Affairs system. They found that rheumatoid arthritis was associated with a 35% higher risk, especially among those patients with rheumatoid arthritis using DMARDs or glucocorticoids.…”