The examine examines the causes of upper COVID mortality in males

Researchers in the United States, Germany, and Uganda have conducted a study that shows that the factors responsible for a higher coronavirus disease 2019 (COVID-19) death rate in men are specific to COVID-19, rather than the one shorter life expectancy of men.

Pascal Geldsetzer of Stanford University in California and colleagues showed that the gender difference in age-standardized COVID-19 mortality was significantly larger than for most other common causes of death.

The gender difference was particularly significant in older age groups, especially those aged 80 and over.

The team says the results support the hypothesis that causal pathways linking male sex to higher COVID-19 mortality are unrelated to those responsible for shorter life expectancy in men or higher death rates in men due to other causes are.

Money setters and colleagues say a combination of biological, behavioral, and social pathways could be responsible. Identifying these causal chains could facilitate the development of therapeutics and preventive measures for COVID-19 and future coronavirus outbreaks.

A pre-print version of the research paper is available on the medRxiv * server while the article is being peer-reviewed.

A higher risk of death in men has been observed since the beginning of the pandemic

Since the COVID-19 outbreak began in Wuhan, China in late 2019, researchers have observed men at higher risk of death from the disease than women.

However, it is not yet clear whether the observed gender-specific difference in COVID-19 mortality is only due to the shorter life expectancy of men or specifically to an infection with the pathogen causing the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is.

Money-setters and colleagues say the gender difference is much larger than expected if it could be explained by the causal pathways linking male sex to shorter life expectancy, suggesting that other pathways might be involved.

Male to female death rate ratio from COVID-19 and all causes.  Caption: The COVID-19 sex differences and all-cause mortality rates were calculated for each country by dividing the age-standardized mortality rate in men by the age-standardized mortality rate in women.

Male to female death rate ratio from COVID-19 and all causes. Caption: The COVID-19 sex differences and all-cause mortality rates were calculated for each country by dividing the age-standardized mortality rate in men by the age-standardized mortality rate in women.

What did the researchers do?

The researchers wanted to find out if the gender difference in COVID-19 mortality was greater than the difference seen in other common causes of death, including other respiratory diseases.

“Our aim is to establish whether the causal pathways for the gender differences in the death rate from COVID-19 are likely to differ from those for other causes of death,” they write.

The team says this information is vital as it could help determine whether the higher COVID-19 death rate in men reflects a survival benefit in women and the pathways responsible for that benefit.

“Understanding these causal pathways could be helpful in developing therapeutics and preventive measures for COVID-19 and future outbreaks of coronavirus disease,” said Geldsetzer and colleagues.

The team extracted the latest available age- and gender-aggregated data on COVID-19 mortality at the country level from the open access database COVerAGEDB, which contains the cumulative counts of confirmed COVID-19 cases and deaths.

Relative difference in male-to-female ratios of COVID-19-specific mortality and all-cause mortality by age group.  The relative difference in rate ratio was calculated by dividing (separately for each age group shown) the male to female ratio for the COVID-19 specific mortality rate by the male to female ratio for the all-cause mortality rate.

Relative difference in male-to-female ratios of COVID-19-specific mortality and all-cause mortality by age group. The relative difference in rate ratio was calculated by dividing (separately for each age group shown) the male to female ratio for COVID-19 specific mortality rate by the male to female ratio for all-cause mortality rating.

All-cause mortality and population size data, disaggregated by age and gender, were also obtained for each of the countries from the United Nations Human Mortality Database and World Population Prospects.

The latest available data on specific causes of death come from the World Health Organization’s mortality database.

The researchers used this data to calculate the age-standardized male to female ratio for COVID-19 mortality, all-cause mortality, and other significant causes of mortality such as cancer, circulatory disease, diabetes, respiratory disease, and neurological disorders.

What did the study find out?

In most countries, the gender difference in age-standardized death rates was significantly larger for COVID-19 than for all-cause mortality and most other common causes of death.

This difference was particularly large in older age groups, especially those aged 80 and over.

The team says their results support the hypothesis that the causal pathways linking males to higher COVID-19 mortality are specific to SARS-CoV-2 and not related to those linking males to shorter life expectancies or higher death rates in other cases link causes of death.

“Ultimately, a combination of biological, behavioral and social pathways may be responsible for the high male disadvantage in COVID-19 mortality,” the researchers write.

“Elucidating these causal chains is important as they can help develop therapeutics and preventive measures for COVID-19 and future coronavirus outbreaks,” they conclude.

* Important NOTE

medRxiv publishes preliminary scientific reports that are not peer-reviewed and therefore should not be considered conclusive, guide clinical practice / health-related behavior, or be treated as established information.

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