Friday, April 24, 2020

'Men are at a huge disadvantage' — who is getting hit hardest by COVID-19 and why

As COVID-19 case numbers rise around the world, a striking pattern is appearing in all of the hardest hit places -- more men are dying than women.

The pattern started emerging in China, where 70 per cent of fatalities have been men. Numbers from Italy are similar. In New York City, a study of over 4000 COVID patients showed that men and women caught the disease in about equal numbers, but of the patients hospitalized, 62 per cent were male. This pattern is echoed in places like France, Iran, the UK, South Korea, and Germany.

And while not every Canadian province has released sex-based data, Ontario has. This week, University of Toronto epidemiologist Dr. David Fisman crunched the COVID numbers to find that here, too, men are at a higher risk.

"In all age groups, overall, men are twice as likely to die as women in Ontario right now," Fisman told Quirks & Quarks host Bob McDonald. "There's something about being male for this disease, and for some other diseases, where being male is a real disadvantage in terms of survival."
Women may be more likely to be infected, but men get sicker

Canadian government data suggests that women represent 55 per cent of confirmed cases of COVID-19, but men represent 56 per cent of COVID-related hospitalizations, and 64 per cent of ICU admissions.

"I think that is driven at least in part by the fact that we have a lot of testing of health care workers, and especially nurses are more likely to be female than male," said Fisman. "Under age 50 you have a big majority of female cases over male cases. Once you get over age 50 men predominate, and I think that represents people showing up in the data because they're sick enough that they get tested." 


Initially, the findings were attributed to the fact that men have more comorbidities than women, associated with risk factors like smoking. But another study looking patients in China shows that only 12.5 per cent of severely ill patients were smokers.

Men were also more susceptible during the SARS and MERS epidemics, which were caused by different coronaviruses.

"It's almost more obvious here [with COVID-19] because with both SARS and MERS there were fewer cases and there it was a little harder to identify the male predominance," researcher Stanley Perlman told Bob McDonald. "But in this infection there's so many cases that we can get a really good feeling for how men are more susceptible than females."


Perlman, a professor of microbiology and immunology at the University of Iowa, studied how male and female mice reacted differently to SARS and MERS.

"Mouse studies are only partly relevant for what goes on in humans. But in my studies where our mice don't smoke and don't have any other risk factors, we know that the male mice do much worse than female mice," said Perlman. "We find that [male] mice get sicker at lower doses of virus and succumb much more quickly. So male mice in general are much more sensitive to coronaviruses."

He experimented with estrogen and testosterone, and found that blocking estrogen in the female mice made them as susceptible as the males. "Suggesting that at least in mice, the hormone estrogen, which has huge numbers of effects downstream, actually protected mice from the severe disease," said Perlman. Testosterone had no effect.

His research was published in the Journal of Immunology.


The effects of age on COVID susceptibility

Perlman's study also found that older mice fared much poorer than the younger mice.

"Age was a risk factor there," said Perlman. "And the same thing was true: aged male mice were more sensitive than aged female mice."

And age is proving to be a major risk factor for COVID-19 as well, with people over the age of 60 making up 94 per cent of COVID-related deaths.

The fact that COVID-19 is infecting older people more than younger people is not what epidemiologists expect from an easily transmissible disease, because younger people tend to have contact with more individuals on a daily basis.

"You expect to see the most infections in kids and young adults," said Fisman. "You see the opposite… If you look at risk of confirmed infection in Ontario by age, it more or less goes up and up and up through the lifespan."


While some of this can be blamed by biological factors, such as our immune systems weakening with age, there are also sociological factors that make older people more at risk, which are being seen in the devastating outbreaks in nursing homes.

"I think with many communicable diseases you see that some of it's biology. Some of that's how we connect and interact in societies, and what that does to risk of infection. And then some of it is health disparities," said Fisman. "Socioeconomic status is a big driver of communicable disease mortality. So economics plays a role too."

There is still much more to learn about why COVID-19 is so much more deadly to certain groups, but scientists like Fisman and Perlman are working to collect as much data as possible to help answer these questions, so that we can prepare for whatever is to come.

"I always want more data because I think we can use data to get to knowledge, and knowledge to get to understanding, and when we understand things that's when we're actually able to predict and control" said Fisman.

"We think Canada is at peak right now and we're headed down the other side of this first wave. And I think there probably will be other waves. But we're trying to share that with public health partners so folks can plan ahead in terms of where this epidemic is going." 


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