The Age Pattern of the Male- to- Female Ratio in Mortality from COVID-19 Mirrors that of Cardiovascular Disease but not Cancer in the General Population
Authors: Nimgaonkar Ila , Valeri Linda , Susser Ezra , Hussain Sabiha , Sunderram Jag , Aviv Abraham 
Published: July 2020

AbstractBackgroundMales are at a higher risk of dying from COVID-19. Older age and cardiovascular disease are also associated with COVID-19 mortality. We compared the male-to-female (sex) ratios in mortality by age for COVID-19 with cardiovascular mortality and cancer mortality in the general population.MethodsWe obtained data from official government sources in the US and five European countries: Italy, Spain, France, Germany, and the Netherlands. We analyzed COVID-19 deaths by sex and age in these countries and similarly analyzed their deaths from cardiovascular disease (coronary heart disease or stroke) and cancer, the two leading age-related causes of death in middle-to-high income countries.FindingsIn both the US and European countries, the sex ratio of deaths from COVID-19 exceeded one throughout adult life. The sex ratio increased up to a peak in midlife, and then declined markedly in later life. This pattern was also observed for the sex ratio of deaths from cardiovascular disease, but not cancer, in the general populations of the US and European countries.InterpretationThe sex ratios of deaths from COVID-19 and from cardiovascular disease exhibit similar patterns across the adult life course. The underlying mechanisms are poorly understood, but could stem partially from sex-related biological differences that underlie the similar pattern for cardiovascular disease. These include, we propose, comparatively longer telomeres in females, ovarian hormones, and X chromosome mosaicism.FundingThe authors received no specific funding for this work.Research in ContextEvidence before this studyMortality from COVID-19 is higher in males and older persons. We searched PubMed.gov in June 2020, with no date restrictions, for articles published in English using the search terms “COVID-19”, “deaths”, “mortality”, “sex”, “male”, “female”, “age”, “disaggregated”, “ratio”, and “stratified”. We identified studies in several countries that stratified COVID-19 mortality data by age or by sex, but no study examined male-to-female (sex) ratios by age at a multi-national level.Added value of this studyTo our knowledge, this is the first study to aggregate data on COVID-19 deaths at a multi-national level, and analyze how the sex ratio in deaths varies by age, taking into account the population at risk in each sex/age stratum. We found a distinctive pattern in sex ratio of deaths by age, illuminating the nature of the sex effect on death from COVID-19. Moreover, we found a similar pattern in sex ratio of deaths by age for cardiovascular disease, which is strongly associated with increased risk of dying from COVID-19. We did not find a similar age pattern for the sex ratio in deaths by cancer.Implications of all the available evidenceThe sex ratio in deaths from COVID-19 peaks in middle age and decreases at older ages, a pattern mirrored in deaths from cardiovascular disease. This intriguing similarity warrants research about whether sex-based differences in mortality from COVID-19 and from cardiovascular disease in general are partly due to common biological causes.