Scientists explain why men are at higher risk from COVID-19

By Angela Betsaida B. Laguipo, BSNSep 9 2020

Some populations are at a higher risk of developing severe coronavirus disease (COVID-19). The elderly, those who are immunocompromised, and those with underlying health conditions may experience severe symptoms at a heightened risk of death. As the pandemic evolved, more people are deemed at higher risk, including men and obese people.

Men and women have similar odds of contracting COVID-19, but men are at a higher risk of death. A new study suggests that varying immune responses to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), due to age and sex, may depend on viral load and the time-course infection.

This means that among older adults and in men, certain factors may lead to a weaker immune system, making it hard for the body to fight SARS-CoV-2 infection, the virus that causes COVID-19. The researchers explained why there is a high rate of intensive care unit admission and death among these patients.

Study: In vivo antiviral host transcriptional response to SARS-CoV-2 by viral load, sex, and age. Image Credit: zstock / Shutterstock

Weaker immune systems

To arrive at the study findings, the researchers studied the genetic material (RNA) collected from the nasal swabs of 430 people, who tested positive for COVID-19, and 54 people who tested negative.

Published in the journal PLOS Biology, the study aimed to provide a better understanding of the mechanisms that drive the varying responses of the infected individuals among different patient demographics, including sex and age.

The team analyzed the antiviral and immune responses across infection status, age, sex, and viral load. They found that immune cell responses were not activated until three days after the infection onset. Further, the strength and makeup of the immune cell response depended on the amount of viral load, and they also differed by age and sex.

The immune cell composition and function varied with viral loads, showing a dysfunctional antiviral response in males and the elderly. The study findings are significant in the development of treatments for COVID-19, and the team suggests additional research since the swabs were taken from the nasopharynx, which is not a sensitive anatomic location to precisely examine markers of systemic inflammation.

"Collectively, our data demonstrate that host responses to SARS-CoV-2 are dependent on viral load and infection time with observed differences due to age and sex that may contribute to disease severity," the researchers said.

Interferon-responsive genes

Interferons are proteins that cells make in response to the presence of some viruses. A virus-related cell will release interferons, leading to the activation of antiviral defenses. The scientists believe that the timing of the interferon response may help influence the course of the disease. With the novel coronavirus, there can be weak activation of interferons at the start of an infection and too much late in the disease, which then leads to severe COVID-19.

In the study, the team found that interferon-responsive genes tend to appear in the samples of men and older patients. Also, the team determined patterns of gene expression manifested by older people and men that appear to throw off the process. For instance, men had lower levels of B-cell specific antiviral responses.

"The bias toward the expression of B cell transcripts in females in our study is consistent with higher levels of B cells in females regardless of age. Females also tend to have increased inflammation in response to viral infections," the researchers wrote in the paper.

"The observed increased expression of inhibitors of nuclear factor kappa-B (NF-κB) in males with SARS-CoV-2 may represent either inappropriate throttling of the antiviral immune response or an adaptive mechanism to reduce deleterious inflammation, a hallmark of COVID-19 pathogenesis," they added.

Meanwhile, older patients had reduced expression of the Th1 chemokines CXCL9/19/11, their cognate receptor CXCR3, and as well as CD8A and granzyme B. These are all crucial genes to examine, since lower levels may mean dysfunction of cytotoxic T-cells and natural killer cells.

"Collectively, we demonstrate the induction of an antiviral response characterized by type I and II interferon induction, which wanes with time and is correlated with viral load. We also find evidence of transcriptional repression by SARS-CoV-2," the team concluded.

Lastly, we show that differences in immune responses may underlie disparities in outcomes for two higher-risk groups, males and the elderly," they added.