COVID-19's deadliness for men is revealing why researchers should have been studying immune system sex differences years ago

  

Category:  News & Politics

Via:  sandy-2021492  •  one month ago  •  44 comments

By:   Adam Moeser (The Conversation)

COVID-19's deadliness for men is revealing why researchers should have been studying immune system sex differences years ago
Why does COVID-19 hit men harder than women? Is the disparity in mortality rates due to male hormones or an underlying difference in the male versus female immune system?

S E E D E D   C O N T E N T



When it comes to surviving critical cases of COVID-19, it appears that men draw the short straw.

Initial reports from China revealed the early evidence of increased male mortality associated with COVID. According to the Global Health 50/50 research initiative, nearly every country is now reporting significantly higher COVID-19-related mortality rates in males than in females as of June 4. Yet, current data suggest similar infection rates for men and women. In other words, while men and women are being infected with COVID-19 at similar rates, a significantly higher proportion of men succumb to the disease than women, across groups of similar age. Why is it then that more men are dying from COVID-19? Or rather, should we be asking why are more women surviving?

I am an immunologist, and I explore how stress and biological sex can impact a person's vulnerability to immune-mediated disease. I study a specific immune cell called the mast cell. Mast cells play a pivotal role in our immune systems as they act as first responders to pathogens and orchestrate immune responses that help clear the invading pathogens.

Our research shows that mast cells from females are able to initiate a more active immune response, which may help females fight off infectious diseases better than men. But the trade-off may be that women are at higher risk for allergic and inflammatory diseases. Recent evidence indicates that mast cells are activated by SARS-CoV-2 which causes COVID-19.

Some clues to why females have higher survival rates may be found in our current understanding of differences in the immune systems of men versus women.

Could sex differences in immune system play a role?


In general, females have a more robust immune response than men which may help females fight off infections better than males. This could be a result of genetic factors or sex hormones such as estrogen and testosterone.

Biological females have two copies of the X chromosome, which contains more immune genes. While the genes on one X chromosome are mostly inactive, some immune genes can escape this inactivation, leading to double the number of immune-related genes and thus double the quantity of certain immune proteins compared with biological men who have only one X chromosome.

Sex hormones such as estrogen and testosterone can also impact the immune response. In one study, researchers showed that activating the estrogen receptor in female mice provided them protection against SARS-CoV. And there is an approved clinical trial that will examine the effects of estrogen patches on the severity of COVID-19 symptoms.

It is, however, interesting that the current data showing that women have better survival rates than men applies to even men and women in the 80-plus age group, when hormone levels in both sexes equalize. This suggests that factors other than adult sex hormone levels are contributing to sex differences in COVID-19 mortality.

Androgens, a group of hormones - including testosterone - that are best known to stimulate the development of male characteristics and can cause hair loss, have also received recent attention as a risk factor for COVID-19 in males. In a study conducted in Italy, prostate cancer diagnosis increased the risk for COVID-19. However, prostate cancer patients who were receiving androgen-deprivation therapy (ADT), a treatment that suppresses the production of androgens which fuels prostate cancer cell growth, had a significantly lower risk for SARS-CoV-2 infection. This suggests that blocking androgens in men was protective against SARS-CoV-2 infection.

It is unknown how ADT works to reduce infection rates in men and whether this has been shown in other countries has yet to be determined. Testosterone, which is an androgen hormone has immune-suppressive effects so one explanation could be that ADT might boost the immune system to combat SARS-CoV-2 infection.

There is also evidence that males and females have different quantities of certain receptors that recognize pathogens or that serve as an invasion point for viruses like SARS-CoV-2. One example is the quantity of angiotensin converting enzyme 2 (ACE2) receptors, which SARS-CoV-2 binds to in order to infect cells. While there is currently no conclusive evidence for a role of ACE2 receptors impacting sex differences and the severity of COVID-19 disease, it remains a potential contributing factor.

Gender, sex and COVID-19 risk


A number of factors can interact with biological sex to increase or decrease one's susceptibility to COVID-19. Another major factor is gender, which refers to social behaviors or cultural norms that society deems appropriate. Males may be at increased risk for severe disease, because in general, they tend to smoke and drink more, wash their hands less frequently and often delay seeking medical attention. All of these gender specific behaviors may put men at higher risk. While there is no current data yet on how gender plays a role in COVID-19, it will be a critically important factor to account for in order to understand sex differences in mortality.

Age, psychological stress level, coexisting conditions such as obesity, diabetes and cardiovascular disease can also interact with biological sex to increase disease.

While COVID-19 highlights the importance of biological sex in disease risk, sex biases in disease in general is not a new concept. COVID-19 is just another example of a disease that will be added to the growing list of diseases for which males or females are at increased risk.

A history of male-biased research


You might be wondering that if biological sex is so important, then why don't we know what is causing disparities in disease prevalence between the sexes and why are there no sex-specific therapies?

One major reason is when it comes to being included in scientific research, it is mostly males who have been studied.

This disparity between biological sex differences in research has only recently been remedied. It has only been in the last five years that the National Institutes of Health has required sex difference data to be collected for all newly funded preclinical research grants.

While there may be several reasons for choosing one sex over the other in research, the huge disparity that now exists is likely a major reason why we still know relatively little about sex differences in immunity, including the current COVID-19 pandemic.

This has clearly hindered advancement of women's health, but also has negative consequences for men's health. For example, given the biological differences between the sexes, it is very possible that drugs and therapies will have different effects in females than males.

Biological sex is clearly a major factor determining disease outcomes in COVID-19. Precisely how your biological sex makes you more or less resilient to diseases such as COVID-19 remains to be elucidated. Future basic research with animals and clinical trials in people need to consider biological sex as well as interactions with gender as an important variable.

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sandy-2021492
1  seeder  sandy-2021492    one month ago

A possible silver lining - Covid-19 may spur more research into the immunological differences between men and women and how those differences influence our resistance to infectious disease and susceptibility to chronic conditions.

 
 
 
TᵢG
2  TᵢG    one month ago

The coronavirus pandemic has revealed that many (more than I would have imagined) have no appreciation for the complexity of life at this level.   The expectation that scientific research can observe cases of the COVID-19 and immediately articulate the correct precautions (no mistakes, no allowed refinements) is surprising.

Our biggest threat outside of destroying our environment (this has been my opinion for decades) is not from weapons of mass destruction, asteroids, etc. but rather micro-biology.   Countless trillions of near invisible, replicating, harmful forms of life threaten macro life (such as human beings) by virtue of their ability to quickly evolve (to resist counter-measures) and to parasitically use their host to spread their population at a geometric pace.   Our modern abilities of travel provide a super highway for micro-biology to literally span the globe.

The above describes a general scenario and COVID-19 is the most recent example of this scenario in action.

 
 
 
Ender
2.1  Ender  replied to  TᵢG @2    one month ago

I briefly watched a show the other day where they were digging up an extinct animal in permafrost. One man ended up getting an infection on his leg. He ended up with some kind of microbe or virus that had been dormant under the ice for centuries. It was some new kind of bug that we didn't even know existed yet they dug it up and it attack the man.

 
 
 
evilgenius
2.2  evilgenius  replied to  TᵢG @2    one month ago
The coronavirus pandemic has revealed that many (more than I would have imagined) have no appreciation for the complexity of life at this level. 

Most people have no appreciation for complexity in general. If it doesn't fit in a quick social media soundbite post many people get bored. It's sad.

 
 
 
sandy-2021492
2.2.1  seeder  sandy-2021492  replied to  evilgenius @2.2    one month ago

Agreed.  Information that doesn't cater to a short attention span is likely to be ignored.

 
 
 
FLYNAVY1
2.2.2  FLYNAVY1  replied to  sandy-2021492 @2.2.1    one month ago

I find it difficult for people to grasp the concept of "light year"  They can grasp the travel of light from the sun taking 00:08:20 to reach the Earth, but extending that to seeing distant suns going nova millions of years ago and just seeing it now is not something readily grasped.

The same issue may apply to the complexity of life (or non-life in the case of a virus) at the microscopic level for those persons.

 
 
 
FLYNAVY1
2.2.3  FLYNAVY1  replied to  sandy-2021492 @2.2.1    one month ago
short attention span is likely to be ignored.

AKA.... The Sesame Street phenomena.

 
 
 
It Is ME
2.2.4  It Is ME  replied to  FLYNAVY1 @2.2.2    one month ago
I find it difficult for people to grasp the concept of "light year"  They can grasp the travel of light from the sun taking 00:08:20 to reach the Earth, but extending that to seeing distant suns going nova millions of years ago and just seeing it now is not something readily grasped.

I thought "Light Year" was a measure of "Length/Measure/Distance" …. not time ?

 
 
 
sandy-2021492
2.2.5  seeder  sandy-2021492  replied to  FLYNAVY1 @2.2.2    one month ago
They can grasp the travel of light from the sun taking 00:08:20 to reach the Earth, but extending that to seeing distant suns going nova millions of years ago and just seeing it now is not something readily grasped.

True.  I think it's the distance they have trouble grasping.  The idea that the closest star other than our own sun is so far away that it takes light 4-ish years to reach us is hard to wrap your brain around.  And that's the closest one.  If we ever make it to Mars (or further) with manned missions, I imagine many people will be surprised at the lag in communications due to distance.  They shouldn't be, but they will.

 
 
 
sandy-2021492
2.2.6  seeder  sandy-2021492  replied to  It Is ME @2.2.4    one month ago

It is.  FLYNAVY was addressing the distance those stars are from Earth, that is so vast that it takes light thousands or millions of years to reach us.

 
 
 
sandy-2021492
2.2.7  seeder  sandy-2021492  replied to  FLYNAVY1 @2.2.3    one month ago
The Sesame Street phenomena.

Or the result of social media.  Sesame Street, being aimed at children, had to tailor itself to their naturally short attention spans.  Adults should strive for better, but often don't.

 
 
 
It Is ME
2.2.8  It Is ME  replied to  sandy-2021492 @2.2.6    one month ago

But:

I find it difficult for people to grasp the concept of "light year"  They can grasp the travel of light from the sun taking 00:08:20 to reach the Earth, but extending that to seeing distant suns going nova millions of years ago and just seeing it now is not something readily grasped.

I just don't see what you're seeing.

 
 
 
Ender
2.2.9  Ender  replied to  sandy-2021492 @2.2.5    one month ago

The Ansible will come into play. jrSmiley_100_smiley_image.jpg

 
 
 
sandy-2021492
2.2.10  seeder  sandy-2021492  replied to  It Is ME @2.2.8    one month ago

Vast distances take more time for light to travel, yes? 

 
 
 
sandy-2021492
2.2.11  seeder  sandy-2021492  replied to  Ender @2.2.9    one month ago
Ansible

I had to look that up.

TBH, I think sci fi may have some blame here.  We see Picard contacting Starfleet from anywhere in the Alpha Quadrant, and holding a conversation in real time.  Yeah, yeah, they used subspace communications, but it downplays the distance in our imaginations.

 
 
 
It Is ME
2.2.12  It Is ME  replied to  sandy-2021492 @2.2.10    one month ago
Vast distances take more time for light to travel, yes? 

When it comes to "Light traveling", I think they call that a ….. wave phenomenon. It's still a bit of a mystery though !

 
 
 
FLYNAVY1
2.2.13  FLYNAVY1  replied to  It Is ME @2.2.4    one month ago

Are you making a point or just poking?

Light-year is a unit of measure for distance, based upon the known constant velocity of the speed of light per unit of time.  By knowing any one of the variables of distance, or time duration, one can solve for the other using the speed of light constant.

Time dilatation due the impact of gravity is another fun topic to poke at.  

 
 
 
FLYNAVY1
2.2.14  FLYNAVY1  replied to  sandy-2021492 @2.2.5    one month ago

Time-distance I think is closer to the point.

The fact that telescopes are actually seeing into the past is what they are challenged by as time travel would seem to be an impossibility given our understanding of physics.

 
 
 
1stwarrior
2.2.15  1stwarrior  replied to  sandy-2021492 @2.2.6    one month ago

The speed of light in a vacuum is 186,282 miles per second (299,792 kilometers per second), and in theory nothing can travel faster than light. In miles per hour, light speed is, well, a lot: about 670,616,629 mph. If you could travel at the speed of light, you could go around the Earth 7.5 times in one second.  But Alpha Centauri A is only 4.32 light years and B is only 4.22 light years, so, with one light year being 6,000,000,000,000 (yes, trillion) miles, then the two closest stars are ONLY a tad over 24,000,000,000,000 miles away.

 
 
 
It Is ME
2.2.16  It Is ME  replied to  FLYNAVY1 @2.2.13    one month ago

light year
[ˈlīt ˈˌyi(ə)r]

NOUN
astronomy
a unit of astronomical distance equivalent to the distance that light travels in one year, which is 9.4607 × 1012 km (nearly 6 trillion miles).

Actual Clock Time....doesn't come into it !

  Because it includes the word "year", the term light-year may be misinterpreted as a unit of time.

 
 
 
sandy-2021492
2.2.17  seeder  sandy-2021492  replied to  1stwarrior @2.2.15    one month ago

Yup, I get it.  I was trying to explain why  FLYNAVY's reference to the time it takes light to travel from distant stars is speaking to the vast distances between us and those stars - and that yes, the lightyear is a measure of distance (and it's a really long distance, that takes a really long time to cover).

 
 
 
sandy-2021492
2.2.18  seeder  sandy-2021492  replied to  It Is ME @2.2.16    one month ago

Of course time comes into it.  The light year is the amount of distance time travels in a year.

Speed is measured in distance and time.  When we talk about the speed of light, and light years, and distances measured in light years, there is no way to omit time from the discussion.

Simple physical science.

 
 
 
It Is ME
2.2.19  It Is ME  replied to  sandy-2021492 @2.2.18    one month ago

 Because it includes the word "year", the term light-year may be misinterpreted as a unit of time. 

 
 
 
sandy-2021492
2.2.20  seeder  sandy-2021492  replied to  It Is ME @2.2.19    one month ago

And nobody here is misinterpreting it.  It's unfortunate that you're having trouble following the discussion.

 
 
 
It Is ME
2.2.21  It Is ME  replied to  sandy-2021492 @2.2.20    one month ago
And nobody here is misinterpreting it. 

I don't think so !

" It's unfortunate that you're having trouble following the discussion."

Maybe it's You having trouble ?

Maybe, Explain your position to me better ?

 
 
 
sandy-2021492
2.2.22  seeder  sandy-2021492  replied to  It Is ME @2.2.21    one month ago

I'm not having trouble.  I learned years ago that speed by definition takes into consideration both distance and time.  I've explained my position.  Perhaps a remedial course in basic physics would be helpful, if you're still having trouble understanding the relationship of speed, distance, and time.

 
 
 
It Is ME
2.2.23  It Is ME  replied to  sandy-2021492 @2.2.22    one month ago
I learned years ago that speed by definition takes into consideration both distance and time.

We aren't talking about "Speed" (Rate), we're talking about "Light Years" (Distance) !

 
 
 
sandy-2021492
2.2.24  seeder  sandy-2021492  replied to  It Is ME @2.2.23    one month ago
we're talking about "Light Years" (Distance)

And the time it takes to travel those distances, which is dependent on both speed and distance.  It's understandable that you've become lost in the conversation.  As a refresher, this was the comment to which you replied.

I find it difficult for people to grasp the concept of "light year"  They can grasp the travel of light from the sun taking 00:08:20 to reach the Earth, but extending that to seeing distant suns going nova millions of years ago and just seeing it now is not something readily grasped.

You do understand that when conversations address distances travelled and the time it takes to travel them, that speed (distance/time) has therefore been implicitly introduced to the conversation, yes?  By virtue of the definition of speed that most of us learned in childhood.  Or does that need to be spelled out?  Am I expecting too much here?

 
 
 
It Is ME
2.2.25  It Is ME  replied to  sandy-2021492 @2.2.24    one month ago
And the time it takes to travel those distances

You're trying it again !

It's a "Unit of Length/Distance".... Not "Time" !

I'm done !

 
 
 
FLYNAVY1
2.2.26  FLYNAVY1  replied to  It Is ME @2.2.16    one month ago
Velocity = distance/time.  Speed = distance/time.
Speed is the rate of change of motion......  distance moved by an object in a specified time irrespective of direction.
Velocity is speed with respect to direction.
In my 2.3.13, I should have correctly use "velocity of light, whereas the common vernacular "speed of light" which is just as wrong in this exchange as there is the component of direction implied.
And for the last time.  Light-Year is a unit of measurement of DISTANCE measured at the standard constant velocity of light.

 
 
 
FLYNAVY1
2.2.27  FLYNAVY1  replied to  It Is ME @2.2.25    one month ago

Length/Distance

In this case you are saying length OR distance.....   

 
 
 
sandy-2021492
2.3  seeder  sandy-2021492  replied to  TᵢG @2    one month ago
The coronavirus pandemic has revealed that many (more than I would have imagined) have no appreciation for the complexity of life at this level.   The expectation that scientific research can observe cases of the COVID-19 and immediately articulate the correct precautions (no mistakes, no allowed refinements) is surprising.

Unfortunately true.  And even when a precaution has consistently been correct (think social distancing - there has never really been a question that it works), they have little patience for complying with it.  Some really seem to have no thought for the harm they could be doing to themselves or others, if preventing that harm inconveniences them.

 
 
 
TᵢG
2.3.1  TᵢG  replied to  sandy-2021492 @2.3    one month ago
Some really seem to have no thought for the harm they could be doing to themselves or others, if preventing that harm inconveniences them.

I think it is a combination of not actually thinking things through and an element of narcissism.

 
 
 
Perrie Halpern R.A.
2.3.2  Perrie Halpern R.A.  replied to  TᵢG @2.3.1    one month ago
I think it is a combination of not actually thinking things through and an element of narcissism.

There seems to be a lot of that going around these days. Also false equivalencies. 

 
 
 
Kavika
3  Kavika     one month ago

A very interesting article. IMO, micro biology can be the biggest threat to the human population. Far more than I believe we have ever imagined.

 
 
 
Ender
4  Ender    one month ago

Interesting. I didn't know drug therapies would/could have different impacts.

 
 
 
Perrie Halpern R.A.
5  Perrie Halpern R.A.    one month ago

So this article explains a lot to me that now makes sense. 

Women are predisposed to autoimmune diseases (overactive immune diseases). That double XX is also a double edge sword.

The stronger sex physically, is also the one with the weaker immune system. How odd is nature?

 
 
 
sandy-2021492
5.1  seeder  sandy-2021492  replied to  Perrie Halpern R.A. @5    one month ago

It's even more odd, since women carry fetuses which could potentially trigger an immune response, causing miscarriage, or harm to the mother.  But such immune responses rarely happen, despite our more robust immune systems, which would ordinarily be expected to react to something "other" as it might to a foreign object or parasite.  Pregnancy could easily be similar to rejection of a transplanted organ, but it's not.

 
 
 
Perrie Halpern R.A.
5.1.1  Perrie Halpern R.A.  replied to  sandy-2021492 @5.1    one month ago

That is because pregnancy hormones actually set in motion an effect to shut down the mother's immune system (with the exception of when a baby has a different blood factor from the mother). 

 
 
 
sandy-2021492
5.1.2  seeder  sandy-2021492  replied to  Perrie Halpern R.A. @5.1.1    one month ago

Yup.  Women who have autoimmune disorders often see a decrease in symptoms during pregnancy.

 
 
 
Kathleen
6  Kathleen    one month ago

Having a over-reacting immune system is what I have been reading about lately.  I have also been reading about Vitamin D.  Vitamin D helps to regulate your immune system as well as other things for your body. Nothing is set in stone yet, but slowly we are understanding more about this virus. 

Good informative article.

 
 
 
sandy-2021492
6.1  seeder  sandy-2021492  replied to  Kathleen @6    one month ago
Having a over-reacting immune system is what I have been reading about lately.

Yes, sometimes the virus causes an overreaction of the immune system called a cytokine storm, that leads to extensive blood clots.  That's why we sometimes hear of Covid patients dying of strokes or heart attacks.  It would be interesting to see if there is a breakdown on whether cytokine storm occurs more frequently in male or female patients.  Cytokine storm was one reason the Spanish flu was so deadly, and more in young, healthy people than in the very young or very old, like most flus.  Their own immune systems were their demise.

 
 
 
Kathleen
6.1.1  Kathleen  replied to  sandy-2021492 @6.1    one month ago

Yep, the cykotine storm.  It’s when your immune systems goes haywire and starts attacking the healthy tissues.  This virus centers around the immune system. It’s not really the virus itself that makes a bad outcome in some patients, it’s the reaction from their immune system from it.

 
 
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