Why Are So Many More Men Dying from Coronavirus?

By Sharon Moalem

The disproportionate toll this virus is taking on males isn’t an anomaly. When it comes to survival, men are the weaker sex.

As coronavirus continues its spread across borders, oceans and continents, there is a perplexing piece of data that has so far evaded a proper explanation: It’s still early, but in almost every country that we have numbers for, more men than women are dying from the virus.

Most attempts to explain this discrepancy have focused primarily on behavior, some of which are almost certainly valid. Higher rates of tobacco consumption, a reluctance to seek proper and timely medical care and even lower rates of hand-washing absolutely do play a role in who will be hit hardest.

But what is being overlooked in these explanations is that the disproportionate toll coronavirus is taking on men isn’t an anomaly. Rather, it may be a timely and high-profile demonstration of what up until recently has been an underappreciated scientific fact: When it comes to survival, men are the weaker sex.

This isn’t just the case during once-in-a-lifetime pandemics. This innate biological advantage is apparent at every age and stage of human life: Baby girls are consistently more likely to make it to their first birthday; 80 percent of all centenarians today are women; an incredible 95 percent of those who reach the formidable age of 110 years old are women. While on average genetic males have more muscle mass and greater height, overall size, and physical strength, when it comes to surviving the physical hardships encountered from birth to late-in-life, genetic females almost always outlast genetic males.

We have long assumed that the only reason behind the earlier and disproportionate demise of men was behavioral. But in fact, the female survival advantage between the sexes still holds, regardless of education, economic factors, and alcohol, drug, or tobacco consumption.

I came to understand the female biological advantage in a very personal and painful way a few years ago. It was a beautiful summer’s day. The sun was finally out after a very long winter and a wet spring. I promised my wife, Emma, some quiet time, just the two of us: just her, an XX female, and me, an XY male. The last thing I remember was reaching over and holding her hand as we were driving westbound on a mostly empty street.

Witnesses later told us that we were hit dead-on broadside by someone who ran a red light and barreled toward us at more than 45 miles per hour. Our car rolled twice. The impact was severe, the roof of our car caved in, and none of the airbags deployed. Because of the extent of damage to our car, the first responders were preparing themselves for horrific traumatic injuries. We were lucky to be alive.

Given what we had just experienced, our injuries turned out to be relatively minor and pretty similar — but Emma’s were a bit more serious. So, while I was strapped to a spine board in the back of an ambulance hurtling toward the hospital one of the things I was thinking about — in addition to wondering why all seven airbags failed to deploy — was how grateful I was that Emma was a genetic female — because I knew that even if my wife’s injuries were the same as mine, given the odds, she was more likely to make a better and faster recovery.

What lies behind this female genetic superiority? It starts at the chromosomal level.

To review the typical basic chromosomal differences between the sexes: The cells of genetic females have two X chromosomes — one from their mothers, and one from their fathers — while those of genetic males have only the one X chromosome, from their mothers, and one Y chromosome.This is crucial, because X chromosomes come in handy for vital functions like building and maintaining the human brain and the immune system. And biologists have long understood that XX chromosomes give females an advantage in some arenas: Having the use of a spare X in case the other is somehow defective is why females are less susceptible to disorders like color blindness, for instance.But we’re only just now beginning to understand the full advantage that this extra X chromosome confers: It’s not just that women have a spare X chromosome to swap in. Rather, the more than 2,000 genes that, combined, make up two X chromosomes, are used by cells that actually interact and cooperate within a woman’s body. Each cell predominantly uses one X chromosome over the other — so if one X chromosome has genes that are better at recognizing invading viruses like Covid-19, for instance, immune cells using that X can focus on that task, while immune cells using the other X chromosome focus on, say, killing cells infected with Covid-19 instead, making the fight against the virus more efficient.

Typical males, by contrast, are forced to get by in life with just the one X chromosome. What if a male’s particular genes aren’t able to competently recognize or kill off cells infected with a coronavirus? In that case, his ability to fight the infection will be limited; his solitary X is the only one he’s got.

The bottom line is when it comes to dealing with the trauma and stressors of life — whether it’s avoiding a serious congenital malformation, a developmental disability, or fighting off an infection — females have genetic options. And genetic males don’t.

My wife doesn’t win only when it comes to overall longevity. Her risk for developing cancers in organs we both have, for example, is lower than mine. And if she does develop cancer, she has better odds of surviving, as research shows that women respond better than men to treatments.

And our sex chromosomes by and large determine our sex hormones — which also give her an advantage: Higher levels of testosterone appear to suppress the immune system; conversely, estrogens have been found to stimulate a more vigorous immunological response. As our recoveries from the accident took two very distinct trajectories — my injuries and subsequent infections took many weeks longer to heal — the reality of her genetic superiority truly sunk in. No matter what life throws our way, Emma is likely to outlive me.

The cost women seem to pay for having a more aggressive immune system, one that’s better at battling both malignant cells and invading microbes, is being more prone to autoimmune diseases. The immune systems of genetic females are much more likely to attack themselves, which is what occurs in conditions like rheumatoid arthritis, multiple sclerosis, autoimmune thyroiditis, Sjögren’s syndrome, and lupus. The only thing that I, as an XY male, have going for me is a lower chance of developing one of these conditions.

Progress in understanding and addressing these biological differences between the sexes in the practice of clinical medicine has been sluggish. For the most part, this is because the medical establishment has largely overlooked the profound chromosomal, hormonal and anatomical uniqueness of genetic females. The current practice of medicine was built using research that was done primarily on male cells, male tissues, male organs, male animals and male test subjects. As a result, we tend to know more about men when it comes to the determinants of health and well-being. With a few exceptions, such as gynecological and obstetric issues, we tend to clinically treat women just like we treat men. As a result, our comprehension of the staggering medical impact stemming from the differences between the sexes is only in its infancy.But the understanding of these differences has the potential to fill in the gaps of knowledge that have kept us from making medical breakthroughs. Our male-centric, one-size-fits-all model of health care and the research culture that stems from it need to change. Nowhere is this urgency more apparent than the current global pandemic, as the alarming numbers of male deaths worldwide continues to climb daily.

Almost 20 years ago the Institute of Medicine of the National Academy of Sciences published a report that claimed the following: “Being male or female is an important fundamental variable that should be considered.” And yet, two decades later there has been little tangible progress that’s made its way into how we practice medicine. We must now push beyond mere consideration of this variable to apprehending the real biological strength that each genetic female inherently possesses and how men differ in this regard. The future of medicine depends upon it.

https://www.nytimes.com/2020/04/02/opinion/coronavirus-men-women.html