She and her colleagues on the front lines of the pandemic had little time to think about why covid-19 seems more lethal to men than to women – a phenomenon she never remembered happened. with other illnesses, like the flu. “I don’t think there is anything very clear that shows me the ideology of why there have been more men,” she said.
Coronavirus data reported by more than a dozen states and the nation’s largest city supports Jackson’s experience. In most states, slightly more women are infected than men. But of the more than 3,600 deaths in 13 states and New York that report deaths by sex, the majority of the victims are men.
The disproportionate toll of the virus appears to have deep biological roots. An emerging body of research has revealed that women’s bodies are more effective at fighting infections, thanks to the hormones in their systems and the genes in their two X chromosomes.
Scientists say these differences may partly explain why men were the hardest hit by the Covid-19 pandemic. And they can provide an essential clue in the search for a cure.
The Washington Post has identified 37 states that provide a breakdown of the number of men and women who tested positive for covid-19. In 30 of these states, including the large outbreaks in Massachusetts, Michigan and Washington, women reported higher numbers of cases, but not always to a large extent. In several large states, including California and Florida, and in the vast New York epidemic, the data shifts the other way to male cases, leaving an overall ambiguous picture.
Fewer states provide an analysis of the different numbers of deaths among men and women. But at least 13 people with a significant number of deaths reported these data. (The Post did not analyze some states, such as Alaska, where the number of deaths remains low.) In each of these states, men died more frequently, and this was the case even if they had fewer total cases of the disease at baseline. .
This is also true in the city with the largest epidemic in the country. On Friday, men accounted for 59% of all New York hospitalizations and accounted for 62% of more than 1,800 deaths.
“I have seen more men who need immediate breathing assistance – to be intubated or for additional oxygen,” said Jackson. “This is the major difference. They come sicker. ”
In New York, men die at a disproportionate rate, even taking into account the fact that there are more male cases at the start. Men represent 55% of the cases but represent 62% of the deaths.
A difference in genes
Often the virus doesn’t start to feel deadly, said Katrina Hawkins, an intensive care doctor at the George Washington University Hospital in the district. Many patients experience mild symptoms for about a week and then recover.
But in a small fraction of the cases, the disease takes a sudden and dramatic turn. A dry cough and shortness of breath will give way to acute breathing problems and dangerously low levels of oxygen in the blood. The body’s immune system sets off a storm of protective cells and other molecules that can overwhelm vital organs, sometimes causing more damage than the virus itself.
This progression suggests that the worst form of the disease is triggered in part by the patient’s own immune system, said Hawkins. “There is probably something written in their DNA that we do not yet know or understand yet,” she said.
For Robyn Klein, director of the Center for Neuroimmunology and Neuroinfectious Diseases at Washington University in St. Louis, the combination of unbalanced statistics and divergent immune responses is an indicator that gender differences may be at play.
For almost all infectious diseases, women are able to develop a stronger immune response than men, she said. Women with acute HIV infection have 40% less viral genetic material in their blood than men. They are less susceptible to the viruses that cause hepatitis B and C. Men infected with coxsackie viruses – which in severe cases can cause inflammation of the heart tissue – are twice as likely to die from the disease.
This is true even in other animals. Female birds exhibit higher antibody responses to infection than males, especially during the mating season. The immune cells that absorb microbes and cell debris are less active in male lizards than in their female counterparts.
“With regard to viral infection, it is very well established that women have much stronger immune responses than men,” said Klein. “Not just as a result of exposure or behavior. But there are real differences in the response of immune cells. “
About 60 genes involved in immune function are found on the X chromosome, said Sabra Klein, microbiologist at Johns Hopkins University, who has no connection to Robyn Klein.
Genetic females have two of these molecules – one from their mother, one from their father – while genetically male people have only one. When there are two copies of this genetic molecule, the gene on one copy is usually disabled. But up to a quarter of X-linked genes can escape this inactivation, giving people with two copies of the chromosome a “double dose” of the genetic instructions to fight the disease.
One of these genes codes for a protein called “toll receptor 7”, which takes its name from a German word for “large”. These receptors recognize strands of viral RNA and alert the body to the presence of an invader.
“What we have seen in my lab is that you get a greater expression of this gene in women’s immune cells,” said Sabra Klein, “which means you will get all kinds of downstream effects . “
Generally, female immune cells respond faster and more powerfully to viral attacks, producing higher amounts of interferons – proteins that prevent viruses from replicating – as well as antibodies that neutralize invaders.
Sex hormones also play a role in the body’s response to infection. Testosterone, which is produced in abundance by male testicles, has been shown to reduce inflammation. Estrogen, on the other hand, can bind to immune cells and activate the production of disease-fighting molecules.
“It seems that everything is designed for women to have a more robust immune response,” said Robyn Klein.
Yet this powerful immune response can be a double-edged sword. It explains why women have autoimmune diseases at a higher rate than men. This may also explain why women are more likely to die from the common flu. Studies of influenza viruses in mice have shown that females have a “hyper-sensitive” immune response to the pathogen – their lungs fill up with chemicals that damage tissue and fight germs.
The best immune system is one that is well regulated, said Sabra Klein; disease-fighting cells must be controlled, lest they become armies of marauders. Women’s bodies tend to give a little more freedom to their immune systems, while men’s systems are more often restrained.
These trends can be harmful or hurtful, depending on the disease in question. Faced with Covid-19, it is more and more evident that the male system is doing worse.
Strong evidence from states – and beyond
The 50 states and the District of Columbia have very different practices for reporting epidemics within their borders. Some provide downloadable spreadsheets of all deaths with ages and genders listed. Some give a daily update containing the same information. Others simply provide a percentage for the distribution of cases by sex, but not for deaths. The Post searched each coronavirus state’s website or page for gender-based information, but journalists may not have identified everything that is available.
In the United States, women initially make up a slightly higher percentage of the population, which may explain why in many states, they contract slightly more cases of the disease.
But men regularly die more often. This is true in Michigan, where men account for 61% of the state’s 479 deaths to date. Of the 284 people killed by coronavirus in Washington State, 57% are men.
In Florida on Friday, men accounted for more than 61% of the 163 fatal cases. There, 53% of the cases concern men.
This trend continues in at least 10 other states (and New York) that report sex-specific mortality data. And this corresponds to a model now recognized by epidemiologists around the world. From China to Italy, France and South Korea, men die more frequently than women.
Efforts to explain the disparity initially focused on social differences, such as the higher rate of risky behavior among men. In China, where the death rate for men is almost twice that of women, almost half of men over the age of 15 smoke, compared to only 2% of women.
A recent poll by Reuters found that men are more likely to minimize the risk of the coronavirus, which can lead them to behave in a way that puts them at risk. And at least one study of more than 3,000 people has found that half of men don’t wash their hands with soap after using the toilet.
“Women are generally more likely to seek care than men,” added Tara Smith, an epidemiologist at Kent State University in Ohio. “So it could just be bias in this aspect: as a gender, we’re just more likely to go to a doctor when we’re sick, so we’re more likely to have a test done in the first place. “
Men are also more likely to have underlying conditions that make them vulnerable. According to the World Health Organization, American men live on average five years less than their female counterparts and have a higher probability of dying from heart disease, cancer, diabetes and respiratory illnesses.
Behavioral factors are important, said Sabra Klein. But she noted that men and women fell ill in roughly equal numbers in most countries affected by the coronavirus. It is only after the disease has worsened, causing serious breathing problems, that gender differences appear.
“That it seems to happen to a significantly higher degree in men than in women, it speaks to biology,” said Sabra Klein.
The disease is so new and scientists still have so little data on it that no one can identify the source of these biological differences. But the differences are important to consider.
Robyn Klein pointed out that female immune systems working quickly can be more effective in clearing the virus from the body in the first week after infection, making women less likely to reach the later stage of precipitous decline.
“The way the inflammatory response develops in the presence of this virus needs to be studied in different genders,” she said. “Because the more you understand how a process can differ, the more you can develop treatments that will work. “
Sabra Klein also hypothesized that the disease could suppress testosterone in men, exacerbating their intense inflammatory response. Testosterone levels decrease with age, she noted, which may explain why older men are more vulnerable to the disease.
These are just theories, the scientists noted. Until governments provide detailed disease and death reports, and researchers are able to probe potential gender differences in the laboratory, no one will be sure if the disparity in death is biological or why.
At present, the majority of states do not appear to disaggregate deaths by sex, nor does it appear the Centers for Disease Control.
And many researchers are still not analyzing their results by gender or even experimenting with male and female models, said Sabra Klein. This disparity has been attributed to the fact that women have lower rates of survival from heart attacks and more adverse drug reactions than men.
“We are really in our infancy” in the study of gender differences, she said. “Maybe the coronavirus will be this call to really take this very seriously. “