In Italy, men made up nearly 60 percent of people with confirmed cases of the coronavirus and more than 70 percent of those who died of COVID-19.  In China men and women were infected in roughly equal numbers, but the death rate among men was 2.8 percent, compared with 1.7 percent among women. The same applies to South Korea and numerous other countries.  In New York City, men are dying at nearly twice the rate of women.  As of recently, men made up 59 percent of overall hospitalizations in New York City and 62 percent of fatalities.  In 13 states with sufficient death numbers for analysis, men died more frequently than women.

Men were also disproportionately affected by SARS and MERS, caused by related, but different coronaviruses. For SARS, in Hong Kong in 2003, the case-fatality ratio was 13.2 % for women and 22.3 % for men.  Also, 32% of men with Middle East Respiratory Syndrome (MERS) died, compared with 25.8% of women.

The question is: Why?

At first, risk factors were blamed.  For instance, smoking rates among men exceed those among women in much of the world.  2% of Chinese women smoke, compared with more than 50% of Chinese men.

Chinese men also have higher rates of Type 2 diabetes and high blood pressure than Chinese women, both of which increase the risk of complications following infection with the coronavirus causing COVID-19 (SARS Cov2). Rates of chronic obstructive pulmonary disease are almost twice as high among Chinese men as among women.

Women are more proactive about seeking health care than men. Since the start of the outbreak, public health officials have emphasized the importance of washing hands to prevent infection. But studies have found that men — even health care workers — are less likely to wash their hands or to use soap than women. While these 2 considerations might affect the number of diagnoses made and perhaps the rate of hospitalization, they are unlikely to affect mortality in my view.

Moreover, rates of smoking in the US are quite similar comparing men to women (unlike in China): in 2015, 16.7 percent of adult males and 13.6 percent of adult females smoked cigarettes in US.  Yet the death rate from COVID-19 is clearly much higher among US men compared to US women.

Let’s consider biological differences.  Women have more robust immune systems, some scientists have noted, which helps to fight off infections, although it does make them more prone to autoimmune disorders.

When it comes to mounting an immune response against infections, men are apparently the weaker sex.  “This is a pattern we’ve seen with many viral infections of the respiratory tract — men can have worse outcomes,” says Sabra Klein PhD, a scientist who studies sex differences in viral infections and vaccination responses at the Johns Hopkins Bloomberg School of Public Health.

Says Dr. Klein: “We’ve seen this with other viruses. Women fight them off better. Women also produce stronger immune responses after vaccinations, and have enhanced memory immune responses.”

SARS, influenza, Ebola and HIV viruses all affect men and women differently.

Here are some tantalizing findings:

• A recent research paper from Huazhong University of Science and Technology in Wuhan, using plasma of 331 confirmed coronavirus patients, found that in the most severe cases, women had higher levels of antibodies than men.
• For almost all infectious diseases, women are able to mount a stronger immune response then men. Women with acute HIV infections have 40 percent less viral genetic material in their blood than men. Women are less susceptible to the viruses that cause hepatitis B and C. Men infected with coxsackie virus (which can infect the heart) are twice as likely to die of the disease than women.
• Female birds show higher antibody responses to infection than males, especially during mating season. The immune cells that eat up microbes and cellular debris are less active in male lizards than in their female counterparts.
• Some 60 genes involved in immune function are located on the X chromosome (according to Dr. Sabra Klein). Genetic females have two of these molecules — one from their mother, one from their father — whereas genetic males have only one. When there are two copies of a gene, one copy is often turned off. But as many as a quarter of X-linked genes can escape this inactivation, giving women a “double dosage” of the genetic instructions needed to fight disease.
• One such gene codes for a protein called “toll-like receptor 7,” This receptor recognizes strands of viral RNA (the Coronavirus is an RNA virus)
• Generally, female immune cells respond faster and more powerfully to viral attacks, producing higher amounts of interferons — proteins that stop viruses from replicating — as well as antibodies that neutralize the virus
• Testosterone, has been shown to tamp down inflammation. Estrogen, meanwhile, can bind to immune cells and activate the production of disease-fighting molecules.
• A recent study demonstrates a direct role for estrogen signaling in limiting influenza virus replication in nasal epithelial cells derived from humans
• ACE2 is a receptor for SARS Cov2. It allows the virus to gain access and infect cells. ACE2 is regulated differently in men and in women.
• Experiments published in 2017, in which mice were exposed to the SARS virus (SARS Cov), showed that male mice developed SARS at lower viral exposures, had a lower immune response and were slower to clear the virus from their bodies. They suffered more lung damage and died at higher rates – see the graph below!   When researchers blocked estrogen in the infected female mice or removed their ovaries, they were more likely to die, but blocking testosterone in male mice made no difference, indicating that estrogen may play a protective role.

Solid squares are female mice; open squares are male mice. 12 days after infection, 80% of female mice and only 10% of male mice were still alive. 5000 PFU is the dose of virus used to infect each mouse (PFU = Plaque Forming Unit)

Despite all of this, the coronavirus vaccine trials underway in the U.S. aren’t really considering sex yet, according to Dr. Klein.  If past experience holds up, vaccines will be more effective in women than in men!

Read more here:

https://www.nytimes.com/2020/02/20/health/coronavirus-men-women.html

https://www.nytimes.com/2020/04/03/us/coronavirus-male-female-data-bias.html

https://www.washingtonpost.com/health/2020/04/04/coronavirus-men/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5450662/