Sex differences in the case-fatality rates for COVID-19—A comparison of the age-related differences and consistency over seven countries

Abstract

Background Early in the COVID-19 pandemic, it was noted that males seemed to have higher case-fatality rates than females. We examined the magnitude and consistency of the sex differences in age-specific case-fatality rates (CFRs) in seven countries. Methods Data on the cases and deaths from COVID-19, by sex and age group, were extracted from the national official agencies from Denmark, England, Israel, Italy, Spain, Canada and Mexico. Age-specific CFRs were computed for males and females separately. The ratio of the male to female CFRs were computed and meta-analytic methods were used to obtained pooled estimates of the male to female ratio of the CFRs over the seven countries, for all age-groups. Meta-regression and sensitivity analysis were conducted to evaluate the age and country contribution to differences. Results The CFRs were consistently higher in males at all ages. The pooled M:F CFR ratios were 1.71, 1.88, 2.11, 2.11, 1.84, 1.78 and 1.49, for ages 20–29, 30–39, 40–49, 50–59, 60–69, 70–79, 80+ respectively. In meta-regression, age group and country were associated with the heterogeneity in the CFR ratios. Conclusions The sex differences in the age-specific CFRs are intriguing. Sex differences in the incidence and mortality have been found in many infectious diseases. For COVID-19, factors such as sex differences in the prevalence of underlying diseases may play a part in the CFR differences. However, the consistently greater case-fatality rates in males at all ages suggests that sex-related factors impact on the natural history of the disease. This could provide important clues as to the mechanisms underlying the severity of COVID-19 in some patients.

Was Alpha deadlier than wild-type COVID? Analysis in rural England

“…Our higher CFR probably reflects that these were Pillar 1 cases: most were individuals known to require medical attention at point of diagnosis. Male sex was an expected risk factor for raised mortality, roughly doubling likelihood of death following COVID-19 diagnosis, in line with other observations [ 19 ]. Persons living in relatively more deprived areas (IMD quintiles 1–3 were over-represented (relative to the total NWCCG population in these deciles) among both the first wave cases and deaths (Table 1 ).…”

Gender Differences in Adverse Events Following the Pfizer-BioNTech COVID-19 Vaccine

“…The mechanisms underlying the higher risk of adverse events in females are not fully understood. The lower COVID-19 case-fatality rates in women compared with men [24] may reflect an enhanced immune response in women. This could be part of the explanation of the higher frequency of adverse events in females due a stronger immediate response to the antigen, modulated through the innate immune system.…”

Study of Post-COVID-19 Syndrome in Saudi Arabia

“…People who are in close contact with infected persons and those with impaired immunity and chronic medical conditions are more susceptible to the disease and its complications [1]. Mortality is higher among males in all age groups [7]. Complications of COVID-19 include acute respiratory failure, pneumonia, acute respiratory distress syndrome, acute liver injury, acute cardiac injury, secondary infection, acute kidney injury, septic shock as well as post-COVID-19 syndrome and death [8].…”