Why Is COVID-19 Hitting Men Harder Than Women?

By Tom Ackerman and Diego Perez

Isidro Ruiz Jr. and his wife, Guadalupe Sanchez, are residents of Chicago’s Pilsen neighborhood, one of Chicago’s Latino neighborhoods that has been heavily impacted by COVID-19. Both Ruiz and Sanchez tested positive for COVID-19 earlier this year.

Sanchez, 63, who works at a hair salon near Pilsen, has seen many clients since the reopening of certain small businesses operating with strict health guidelines. One day in August, Sanchez began to feel sick and believed she had a common cold. When her cold would not go away along with the arrival of a fever and headaches, she knew something was different.

“More than anything the headaches were strange because I rarely get any headaches” Sanchez said. “What I considered a common cold lasted more than four days and made me feel terrible. That’s why I thought about taking a test. And that test came back positive.”

Ruiz Jr. and Sanchez are among the 8 million U.S. men and women who have suffered the effects of COVID-19. Data from Chicago, Illinois, the U.S., and other countries suggest that more women contract COVID-19 while more men die from the virus.

As of Oct. 19, out of the 89,920 cases in the City of Chicago, female cases accounted for 50.5% of the total and males accounted for 48.3% of the cases, with 1.2% of the cases “under investigation.” The death comprise 58.7% men while 41.3% of deaths are female.

Those numbers reflect early patterns with the virus as well. April 23 showed a peak of cases reported in the city, according to public data records, with 734 female cases and 533 male cases at that time. Similarly, officials reported on April 24 that 34 men had died while 19 women had died.

CDC data shows more U.S. men have died of COVID-19 than females, but more women have been infected. According to data from Global Health 50/50, countries like Mexico, India and China have all reported more male deaths than females but all three reported more male cases than female, which does not follow the gender pattern trend of the US, Illinois, and Chicago.

Countries like Italy and Brazil, which which ranks third among all nations for having the most confirmed cases, follow the same trend as the US. While some countries do match this trend and others do not, data from Global Health 50/50 is up-to-date, which may skew the numbers and trends.

Dr. Richard Novak, Chief of Infectious Diseases at the University of Illinois at Chicago, and his colleagues are facilitating the clinical trial for the Moderna vaccine that is one of the largest trials, with around 30,000 participants.

Novak said that some people have developed antibodies to alpha interferon, which is an endogenous protein. The protein is an antiviral product that cells make, which has been known for years, he said.

“What’s interesting is there’s a sub-group of people who make antibodies to it and so they’re destroying their own interferons,” he said. “And those people seem to have very serious COVID-19 disease. 90 percent of them are men. For some reason, it’s men that are disproportionately making those antibodies.”

Novak added that UIC’s Moderna trial does not measure gender differences. In the study, there are slightly more men but the study is considered to be fairly balanced among genders. The group recently slowed its trial to recruit more minority participants.

“It’s definitely going much faster than you’d anticipate with other vaccine trials.,” he said. “That’s why they call it ‘operation warp speed’. These are much larger studies and they’re enrolling much faster than a normal study would enroll.”

He estimated that the participants size is at least 10 times that of a typical vaccine trial in which there is less urgency. He that the U.S. is a melting pot, so an emphasis on diverse recruiting in Chicago, for example, offers a reasonable coverage if the particular vaccine were to be distributed in another part of the world.

The Chicago Department of Health did not respond to inquiries on gender patterns with COVID-19, but those impacted by the virus can tell the story all too well.

Ruiz, 61, who regularly goes to the gym, began to feel very sore after a session in August. He noticed his body aches and soreness were more painful than the normal body aches he felt after his workouts. That night, he started to get a headache as well as cold shivers.

“When I got out of the gym, my body ached but I thought it was from the workout,” Ruiz said. “It was a kind of aching more than ever before.”

While Ruiz had minor symptoms that lasted only three days, he describes his time with the virus as “horrible.” Sanchez’s symptoms were much more severe which lasted about a week. Sanchez described her experience with COVID as “painful and fearful.” Both have fully recovered.

Experts say that this pattern of males dying more than females as well as more females contracting the virus than males may be related to women having a more robust auto immune system that helps fight infections but also makes them more susceptible to autoimmune disorders.

Yale doctors Akiko Iwasaki and Aaron Ring are working to uncover sex-specific differences in immune response to SARS-CoV-2, the virus which causes COVID-19.

According to their research, women have a more robust immune response to bacteria and disease-causing viruses that could be due to having two X chromosomes which improve the expression of key immune functions. The study also says that women consistently produce at least twice as many antibodies in response to receiving seasonal flu vaccines. COVID-19 and Influenza (flu) can easily be mistaken as they share common symptoms.

Investigating the differences between how the virus initially affects both men and women could be the key to understanding the underlying mechanisms of the virus. Since the virus has a long incubation period, most people who begin to show symptoms have been infected for an average of 5 to 6 days.

Understanding how both men and women’s immune systems immediately respond could be a crucial component of developing a vaccine, according to Iwasaki, a leading expert in immune responses to viral infections.

In their research, Iwasaki noted that it is important to study the body’s first response against the virus, “In those cases, we have missed that period of the initial immune response,” Iwasaki said. “The sex difference we are seeking could very well be on day one or day two, and it will be important to see if we can catch this as it is happening.”

Since the science behind COVID-19 is still relatively new and currently being studied, researchers are working constantly to provide a solution. Both Iwasaki and Ring say they are confident that science will produce solutions that the world needs.

“If we can understand why men are more susceptible to this virus, that will tell us the fundamental mechanism of this disease,” Iwasaki said. “If we understand that, we can have better therapeutics and preventative measures to save lives, protect people, and stitch the world back together again.”

In Illinois, patterns throughout the state are similar to that of Chicago.

The Illinois Department of Public Health (IDPH) reports that out of the 310,700 confirmed cases in Illinois, females account for 51.3% and males account for 47.1% with 1.65% considered unknown/left blank. Of those cases, 53.7% of deaths are males and 46.3% are females.

According to the CDC demographic trends in the US, females have contracted COVID-19 more than males: females accounting for 51.7% and males accounting for 48.3%. However, of those cases, males account for 54% of the deaths while females account for 46%. This data includes cases from all age groups

A 2010 news article in the Johns Hopkins Public Health Magazine offers a doctor’s perspective about vaccines and their undervalued potential according to gender differences.

“A lot of vaccine trials aren’t designed to answer that [gender] question,” said [Sabra Klein, assistant professor in the W. Harry Feinstone Department of Molecular Microbiology and Immunology MMI]. Because of that, they perpetuate the blind spot. A trial may not have an equal proportion of males and females, for example, making it difficult to analyze differences adequately, which was reported under A Clearer View of Vaccines for Women and Men.

Klein explored how hormones affect immune response to viruses and vaccines, noting that most clinical studies ignore gender related biology.

As of Oct. 19, the United States has hit over 8 million confirmed cases. The state of Illinois houses over 347,000 confirmed cases of COVID-19 with thousands of tests being conducted daily across the state. Chicago is close to having over 90,000 confirmed cases in the city and could potentially revert back to restrictions on some businesses as city officials fear a second surge of COVID-19 cases.

Data show that males are more heavily affected by the virus than females. While each person has different experiences dealing with COVID-19, Ruiz describes his short period with the virus as hurtful.

“ You feel like your whole body aches,” Ruiz said. “ It felt like I was at the gym for a whole day and my body just kept hurting.”

Sanchez’s experience with COVID-19 does not follow the trend that appears in the data presented by the CDC, the state of Illinois, and the city of Chicago. She had a much more difficult time with COVID-19 than her husband. Her entire experience from the initial symptoms to taking a test and now dealing with what she calls “secondary effects” is an entirely new feeling that is not normal.

“I have nightmares,” Sanchez said. “I will still get headaches and body aches every couple of days. Obviously every person is different but I do think there is something that stays with you that will still affect you, whatever it is.”