Men are three times more likely to die from the coronavirus disease (Covid-19) than women, according to a yet-to-be peer reviewed meta-analysis of 32 studies published in MedRxiv, a pre-print server for health sciences.

The study found that deaths related to Covid-19 were higher than reported in studies in China, with the pooled death rate of hospitalised patients being 6.6%. The study was the first, systematic review of Covid-19 clinical characteristics, and sex-specific risk of death.

Men hospitalised with Covid-19 had a significantly higher death rate (9.2%) compared to women (3.4%), showed the analysis of data from 4,789 hospitalised patients, who had a mean age of 49 years. “These findings could indicate the need for more aggressive treatment of Covid-19 in males,” said study authors, from Iran and the United States.

Covid-19 has consistently shown a bias against men, with data from China first revealing that men accounted for close to two-thirds (64%) of deaths.

A similar gender gap in mortality rates has emerged from Italy, Spain, South Korea, France and Germany, with men accounting for 71% of the Covid-19 deaths in Italy.

 

There were also disproportionately high deaths in men in other coronavirus outbreaks caused by Middle East Respiratory Syndrome (Mers) and Severe Acute Respiratory Syndrome (Sars), with data from Hong Kong showing deaths in men were 50% higher even though more women got infected.

“We still don’t know for sure why it is happening but smoking and higher coronary artery disease rates in men play a role. The lungs of smokers are already damaged, which makes them more susceptible to collapse,” said Dr K Srinath Reddy, president, Public Health Foundation of India (PHFI).

Virus behaviour also plays a role. The cellular receptor used by the Sars-CoV-2 to enter human cells is angiotensin-converting enzyme-2 (ACE-2), which is a protein found on the cell surface that plays a role in heart and immune function. Sars-CoV-2 infection begins with the crown-like spike protein of the virus, which gives the virus its name (‘corona’ means ‘crown’ in Latin) binding to ACE-2. Sars-CoV-2 mainly invades alveolar epithelial cells in the lungs, leading to respiratory distress. These symptoms are more severe in patients with cardiovascular disease, which may lead to increased secretion of ACE-2 in people with heart disease compared to healthy people.

Since ACE-2 is a functional receptor for Sars-CoV-2, people having ACE-inhibitors to control high blood pressure need to be carefully treated.

“Higher comorbidities such as hypertension and cardiovascular diseases could be related to the pathogenesis of the virus through ACE-2 receptor, which open doors for future studies to evaluate the role of ACE inhibitor drugs in the high-risk group. There are still a lot of unknown features of Covid-19 for the broad scientific community to investigate in an effort to slow the progression and mortality of Covid-19 and finally defeat this pandemic,” said the study.

The jury is still out on whether patients with Covid-19 and hypertension, who are taking an ACE inhibitor or angiotensin-receptor blocker, should switch to another antihypertensive drug, but further evidence is required.

The study also found that progressive fever, cough and fatigue were the most common symptoms, with than half of hospitalised patients showing leukopenia (low white blood cells count) or a high C-reactive protein, which are indicators of inflammation and infection.