Sex Differences in COVID-19 Mortality Fades After Vaccine Rollout

A new analysis published in eClinicalMedicine found that the male mortality disadvantage widely reported during COVID-19 was largely a feature of the pandemic's early, prevaccine phase and depended heavily on how researchers measured it.¹

The study investigators examined all-cause excess mortality data from 34 high-income countries between February 2020 and July 2023, comparing absolute death-rate differences between men and women against relative, baseline-adjusted P-scores. They found that although men experienced substantially higher absolute excess mortality during the deadliest months of the pandemic, that disadvantage largely evaporated—or in some cases reversed—once differences in men's higher baseline mortality were accounted for.¹

“A significant male disadvantage was seen in more than half of the age group–country combinations (60%, 81 out of 136) during the pre-vaccine period for excess mortality death rates,” the study authors wrote.¹ “By the endemic period, the male disadvantage remained significant in about only one-fifth of age group–country combinations (23%, 31 out of 136); where the remaining combinations showed either no significant sex difference or a significant female disadvantage.”

Absolute Versus Relative Measures Tell Different Stories

The study used the Short-Term Mortality Fluctuations dataset, drawing on weekly death records from 34 countries, and modeled expected mortality using a generalized additive model fitted separately by country, sex, and age group. Researchers then compared observed to expected deaths across 3 pandemic phases: prevaccine (February 2020 to April 2021), postvaccine Delta/Omicron (May 2021 to April 2022), and endemic (May 2022 to July 2023).¹

In absolute terms, men experienced significantly higher excess mortality death rates than women in 60% (81 of 136) of age group-country combinations during the prevaccine phase, decreasing to 51% (70 of 136) postvaccine and 23% (31 of 136) in the endemic period.¹

When the same data were expressed as P-scores—the percentage difference between observed and expected deaths, which accounts for each sex's underlying mortality risk—the male disadvantage was far less common, appearing in only 28% (38 of 136) of combinations prevaccine and 14% (19 of 136) postvaccine. In several age group–country combinations, including 65 to 74 and 75 to 84 year-olds in the United States, women actually showed higher relative mortality increases than men during parts of the pandemic.¹

Country and Age Patterns Varied Widely

The pattern was far from uniform across the 34 countries studied. Bulgaria and the United States saw sizable male disadvantages in both the prevaccine and postvaccine phases that narrowed considerably by the endemic period.¹

England, Wales, and Italy recorded large excess-mortality peaks early in the pandemic with a clear male disadvantage during those peak months, and Germany's sex gaps were concentrated mainly in adults younger than 75 years. In Denmark, Finland, Iceland, New Zealand, and Northern Ireland, prediction intervals for male and female excess mortality overlapped across all 3 pandemic phases, showing little evidence of a sex gap at any point.¹

Age also mattered. Absolute sex differences in excess mortality tended to grow with age during the prevaccine phase, increasing monotonically from the 15 to 64 years group through the 85 years and older group in just over half (56%, 19 of 34) of countries, though this pattern weakened in later phases.¹

Overall, sex ratios in observed mortality narrowed during the endemic phase compared with prevaccine levels in 31 of 34 countries, with Estonia, Latvia, and Iceland as exceptions.¹

Possible Drivers Behind the Pattern

The authors pointed to several plausible, though not definitively proven, mechanisms. Occupational and behavioral differences may have shaped exposure risk. Female-dominated sectors such as education and administrative work shifted more readily to remote work, and male-dominated industries including agriculture, construction, and manufacturing saw larger mortality increases during the pandemic.¹

Survey data cited in the study also showed men were less likely to adhere to protective measures such as mask-wearing and social distancing. Biologically, women tend to mount stronger and longer-lasting immune responses, partly attributed to estrogen and X-linked genetic factors, which the authors suggest may have offered a survival advantage, particularly early in the pandemic when populations were largely immune-naive.¹

The researchers also noted that surveys in Europe and the United States found higher vaccine hesitancy among women, which could help explain the faster decline in male mortality and the narrowing sex gap in later phases.¹

The authors were careful to frame these explanations as hypotheses rather than proven drivers, noting the excess-mortality framework used in the study cannot distinguish direct COVID-19 deaths from indirect consequences of the pandemic, such as delayed care or economic disruption.¹

What This Means for Pharmacists

The findings carry direct relevance for pharmacists involved in vaccination outreach and counseling. With survey evidence in the study pointing to higher COVID-19 vaccine hesitancy among women in several countries, pharmacists—among the most accessible vaccinators for the public—are well positioned to address sex-specific gaps in uptake through targeted counseling at the point of care.¹

The study's finding that indirect effects of the pandemic, including disrupted preventive care and delayed treatment, may have disproportionately affected women's health outcomes also underscores the pharmacist's role in re-engaging patients who deferred routine care, screenings, or medication management during and after acute waves of illness.¹

Supplemental data reinforce that COVID-19 mortality risk has continued to shift over time. The CDC data on age-adjusted COVID-19 death rates by state show a steep decline in the years following the initial pandemic waves, with rates now representing a small fraction of their 2020-2021 peak.²

As of mid-2026, the World Health Organization's COVID-19 dashboard reported more than 7.1 million cumulative deaths from COVID-19 reported globally, with the United States and Brazil accounting for the largest national totals.³

Even as the disease has moved into a more endemic phase, these figures suggest pharmacists should continue to view COVID-19 vaccination and counseling as an ongoing, rather than emergency-driven, part of preventive care—one where understanding sex-specific patterns in risk perception and uptake can help close persistent gaps.

REFERENCES

1. Doniec K, Schöley J, Kühn M, Dowd JB. Sex differences in excess mortality during the COVID-19 pandemic: a longitudinal ecological analysis of 34 high-income countries. EClinicalMedicine. 2026;98:104072. Published 2026 Jul 23. doi:10.1016/j.eclinm.2026.104072

2. Centers for Disease Control and Prevention, National Center for Health Statistics. COVID-19 Mortality. Stats of the States. Updated March 1, 2026. Accessed August 4, 2026. https://www.cdc.gov/nchs/state-stats/deaths/covid19.html

3. World Health Organization. COVID-19 deaths. WHO COVID-19 Dashboard. Updated July 18, 2026. Accessed August 4, 2026. https://data.who.int/dashboards/covid19/deaths