Question: I’ve heard that men are more likely than women to die from COVID-19. Is this true, and what accounts for the difference?
Answer: We have known for some time that older folks and those with pre-existing medical conditions – such as heart disease, diabetes and obesity – face an elevated risk of suffering a severe and potentially fatal reaction if they become infected with the novel coronavirus that causes COVID-19.
But a growing body of evidence from COVID-19 hot spots around the world suggests that a person’s sex is also a significant factor in determining their chance of survival.
In China, 64 per cent of the recorded deaths were among men, compared with only 36 per cent among women. A similar pattern has emerged in other countries. In Italy, for instance, men accounted for 71 per cent of deaths, while in Germany they represented 66 per cent.
Officially known as SARS-CoV-2, this cornonavirus is so new that researchers cannot say with any certainty why infected men are at a greater risk of death than women.
“This is all very speculative,” says Dr. Cara Tannenbaum, scientific director of the Institute of Gender and Health at the Canadian Institutes of Health Research in Montreal.
Some experts believe that the reason for the stark divergence in mortality rates might be found in the fact that the immune systems of men and women are not identical.
Previous research has clearly identified sex-based immune-system differences, says Dr. Juan Carlos Zuniga-Pflucker, a senior scientist at Sunnybrook Health Sciences Centre and chair of the Department of Immunology at the University of Toronto.
One key reason for sex-based differences is pregnancy – a time when a woman essentially has a foreign entity growing inside her body. Without the ability to modify or dampen its response, the immune system would reject the developing fetus, he says.
Over all, “women tend to have a more distinctly regulated version of the immune system,” he says. This tendency can sometimes increase a woman’s chances of getting certain diseases, such as lupus and multiple sclerosis. “But it may be beneficial in responding to a virus like this one,” he adds.
Indeed, an overactive or overaggressive immune response appears to be contributing to many COVID-19 deaths – and that may account for a higher number of fatalities among men. It might also explain why some relatively young and apparently healthy individuals are brought down by the illness.
At this point, it’s worth reviewing what we do know about COVID-19.
The infection usually starts when the virus enters the upper airway. It invades a cell and then takes over the cellular machinery to start churning out copies of itself. In some patients, there may be limited viral replication in the upper airway, but in others, replication may include the lungs and be associated with more severe disease.
The lungs are extremely vulnerable. The virus can damage the air sacs called alveoli, where blood normally picks up oxygen to be distributed to the rest of the body.
As the infection gains steam, the immune system starts marshalling its resources for a counterattack.
The immune system is made up of numerous specialized cells. Many of them produce cytokines, which are chemical messengers that help direct a co-ordinated assault on the microbial invader. But for reasons that are not fully understood, the immune system sometimes produces too many, leading to what is called a “cytokine storm.”
As more and more immune cells converge on the lungs, they generate additional cytokines that then call for reinforcements. They create a “feedback loop” that intensifies the immune response, Zuniga-Pflucker says.
“Under these circumstances, the cytokines end up causing collateral damage and normal cells end up being harmed,” says Dr. Samira Mubareka, an infectious-diseases physician and virologist at Sunnybrook.
At the same time, cytokines cause vascular leakage from surrounding tissues and fluid begins filling the lungs.
“It becomes harder and harder for patients to get enough air into their lungs,” Mubareka says. Some of these people will develop a life-threatening condition called acute respiratory distress syndrome (ARDS).
But the lungs are not the only parts of the body harmed by the virus. Many patients experience heart, kidney and liver problems, as well as gastrointestinal and central nervous system abnormalities. Whether the virus is directly invading these other tissues isn’t yet clear. They might be compromised simply because oxygen levels in the blood are plummeting. Whatever the cause, patients can develop another potentially life-threatening condition: multiorgan system failure.
Although men, in general, are more likely than women to succumb to COVID-19, there is still a lot of individual variability. After all, some infected men die, some don’t. So, that suggests the infected person’s genetics may play a role.
“We won’t know which [genetic] variants are important until we do large-scale population-wide genome studies, where we compare a lot people who had serious outcomes to those with mild disease,” Mubareka says.
Plans are already under way to do such studies. But it will take some time before we have a full understanding of why this illness is not an equal-opportunity killer.
Sign up for the Coronavirus Update newsletter to read the day’s essential coronavirus news, features and explainers written by Globe reporters and editors.