By using population estimates from the INED website (February to June 2020) on daily cumulative deaths by age and sex due to COVID-19 in 10 European countries, we found that the risk of death increased with age, and that men had higher mortality from COVID-19 than women in almost all age groups across the 10 European countries. In most countries, sex differences increased from ages <60 years to 60-69 years but decreased thereafter with the smallest sex difference at ages 80+ years in all countries.
Generally, there is a male disadvantage in mortality rates with women living longer than men in almost all countries of the world . A recent study investigating the survival in seven populations under extreme conditions from famines, epidemics and slavery found that even when mortality is very high, women survived on average better than men . Although the biggest contribution to these differentials came from the large mortality differences among infants, the authors found that for all populations, the extreme age, defined as the age to which 5% of the population survived, was higher for women than for men, supporting the hypothesis of an overall ability of females to withstand higher-mortality crises better than males . The study supports that the survival advantage of women has fundamental biological underpinnings, but also that the female advantage is modulated by a complex interaction of biological, environmental and social factors .
The higher mortality from COVID-19 for men than for women was overall similar to that found in other coronaviruses during the last two decades, such as the severe respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome (MERS-CoV) [14-17]. The reasons for the sex differences in COVID-19 are likely multifactorial and include differences in immune response, biological differences between the sexes, differences in lifestyle such as smoking habits as well as differences in underlying comorbidities [18-20]. Although recent evidence suggests that European women overall have slightly more comorbidities than European men , men are generally reported to have more life-threatening conditions, such as cardiovascular diseases, whereas women tend to have more non-fatal chronic diseases, such as migraine, musculoskeletal and autoimmune diseases as well as physical limitations [22-25]. Thus, the male disadvantage in risk of death from COVID-19 may to some extent be explained by the relatively higher prevalence of underlying comorbidities such as cardiovascular disease, hypertension, diabetes and chronic lung disease for men . According to a recent study, the scale of difference between sexes in COVID-19 mortality is consistent with that found for heart disease, but greater than that seen for death due to diabetes, or combined influenza and pneumonia .
Although we demonstrated a higher mortality from COVID-19 for men than for women in almost all age groups, we found, as hypothesised, a reduction in the relative risk of mortality for men at later ages, consistently with findings elsewhere . A narrowing of the sex gap with increasing age may be consistent with a survival effect, which leaves the healthiest men in the sample . However, if oestrogen protects women from the most serious complications of COVID-19, women may be most protected before the menopause due to the higher serum oestrogen levels .
Evidence from studies investigating sex differences in COVID-19 mortality stresses the importance of addressing the impact of sex differences on disease epidemics, outbreaks, and pandemics in public health policies and efforts. All countries should report data separately by sex, and research studies should, whenever possible, analyse the interactions between age and sex in COVID-19 morbidity and mortality .
The strength of this study was the ability to analyse sex differences in COVID-19 mortality by age groups in 10 European countries showing an overall similar pattern of sex differences, despite the variability in data collection and time coverage among countries. Not all countries have reported data separately by sex, and this study was limited to the European countries providing sex-disaggregated data. Another limitation was that the frequency, recording and reporting of COVID-19 deaths differ from one country to another, but may also differ within countries. The cause of death can be certified by different biological tests, by clinical diagnosis, and by mentioning the infection on the death certificates . Therefore, a cross-national comparison of results should be done with caution.
By using population data on daily cumulative deaths due to COVID-19 from 10 European countries, we confirm a consistently higher mortality from COVID-19 among European men than among European women in almost all age groups. In most countries, sex differences increased from ages <60 years to 60-69 years but decreased thereafter, with the smallest sex difference at ages 80+ years in all countries. This study highlights the importance of addressing the impact of sex on mortality from disease epidemics, but studies using individual-level data are needed to confirm an interaction between age and sex in COVID-19 mortality in order to guide clinical care personal and to address questions of whether men require additional surveillance, prevention, and earlier intervention than women.