Why is COVID-19 more severe in men and elders? | UW Medicine

Why is COVID-19 more severe in men and elders? | UW Medicine

SARS-CoV-2 usually triggers a strong immune response, but less so in men and people over 60

By UW Medicine | Newsroom

The immune system usually mounts a strong immune response to infection by SARS-CoV-2, the virus that causes COVID-19. That defensive response, however, appears to be weaker in men and people over the age of 60, a study led by researchers at the University of Washington School of Medicine in Seattle has found.

“There were some early studies that suggested that there was a fairly weak antiviral response shortly after infection, but we found a very robust immune response in patients at the time of symptom onset,” said lead author Nicole Lieberman. “But differences in the immune response in older individuals and men may contribute to the greater severity and higher mortality we see in these groups.”

Lieberman is a research scientist in the laboratory of Alex Greninger. He is an assistant professor in the department of Laboratory Medicine and Pathology at the University of Washington School of Medicine and head of the project. The results of the study appear in the open-access journal PLOS Biology. Click here for the paper.

In the study, the researchers compared samples swabbed from the noses and throats of 430 people who were infected with SARS-CoV-2 and 54 people who were not. They also worked with colleagues at Columbia University Medical Center in New York City and University of Texas Medical Branch, Galveston, Texas. These groups have developed techniques to infect cells in culture to track changes in the immune response over time.

To assess immune responses the researchers analyzed the RNA in the samples. Because the SARS-CoV-2 stores its genetic instructions in RNA, levels of viral RNA in the samples revealed the amount of virus, or “viral load,” an indicator of the severity of infection. In human cells. On the other hand, RNA reveals which proteins the cells are producing in response to the infection. That’s because, for the instructions for synthesizing proteins encoded in the DNA of genes to be “read” by the cells, the code must first be copied, into RNA. As a result, analyzing the RNA transcriptsin a sample can show which genes are being dialed up in response to the infection and which are being dialed down. This sort of analysis can reveal what sort of immune counterattack the cells are mounting against the virus.

The researchers found that the viral load in these patients was high, but also that SARS-CoV-2 triggers a strong antiviral response. This includes up-regulation of genes for a number of antiviral factors that activate the cells’ defenses against viral invaders. It also includes chemical signals that summon immune cells to fight the infection, such as interferons and chemokines.

“The viral load with SARS-CoV-2 infection is one of the highest seen,” Greninger said. “But the immune response is very strong, and the higher the viral load, the stronger the response.”

However, in older individuals over age 60, infection did not activate genes to summon virus-fighting cells called cytotoxic T cells and natural killer cells that are some of the body’s the most effective antiviral weapons.

“The older patients activate a weaker immune response – like a singer that just can’t hit the high notes anymore,” Greninger said.

The researchers also found that men mounted a less vigorous response compared to women. The males produced lower levels of transcripts of some anti-viral proteins, and pumped out some proteins that put a damper on the immune response.

“In men we’re seeing an up-regulation of signals that turn off the immune system,” Lieberman said. “It’s speculation, but it appears as though some men may throttle back their immune system too soon before mounting an effective response to infection.”

This work was supported by National Institutes of Health (AI146980, AI121349, and NS091263) and the Department of Laboratory Medicine and Pathology at the UW School of Medicine.


In consideration of how we voice our opinions in the modern world, we’ve closed comments on our websites. We value the opinions of our readers and we encourage you to keep the conversation going.

Please feel free to share your story tips by emailing editor@kirklandreporter.com.

To share your opinion for publication, submit a letter through our website https://www.kirklandreporter.com/submit-letter/. Include your name, address and daytime phone number. (We’ll only publish your name and hometown.) We reserve the right to edit letters, but if you keep yours to 300 words or less, we won’t ask you to shorten it.

More in Northwest

Whole Foods grocery store entrance (Shutterstock)
King County could pass grocery store worker hazard pay next week

The King County Metropolitan Council will vote during its next meeting on… Continue reading

FILE - This Dec. 2, 2020, file photo provided by Johnson & Johnson shows vials of the COVID-19 vaccine in the United States. The U.S. is getting a third vaccine to prevent COVID-19, as the Food and Drug Administration on Saturday, Feb. 27, 2021 cleared a Johnson & Johnson shot that works with just one dose instead of two  (Johnson & Johnson)
Inslee OKs use of single-shot Johnson & Johnson vaccine

The governor acted after receiving the recommendation of a scientific panel enlisted by Western states.

Freshwater variety of kokanee salmon from Lake Sammamish. File photo
Encouraging numbers for kokanee salmon spawn count

Lake Sammamish kokanee aren’t out of the woods by any stretch, but… Continue reading

In this file photo, Tayshon Cottrell dons his graduation cap and gown, along with a face mask reading: “Wear it! Save America” at Todd Beamer High School’s virtual graduation walk recording on May 20, 2020, in Federal Way. Olivia Sullivan/Sound Publishing
Law gives Washington high school seniors leeway to graduate

Gov. Jay Inslee signed a bill that can waive some requirements for students who were on track before the pandemic.

File photo
Study shows Washingtonians exceeded ‘heavy drinking’ threshold in 2020

The survey suggests Washingtonians drank more than 17 alcoholic beverages a week on average.

Mercer Island School District first-graders returned to in-person classes on Jan. 19, 2021. Here, Northwood Elementary School students head into the building. Photo courtesy of the Mercer Island School District
Governor: Educators are now eligible for coronavirus vaccine

“This should give educators more confidence,” Jay Inslee said. Other frontline workers could soon be next.

Malden, after a wildfire burned down 80% of the town’s buildings in Eastern Washington. Courtesy photo
DNR commissioner seeks $125 million to fight wildfires

In Washington state last September, some 600,000 acres burned within 72 hours.

Stock photo
First-time home buyers increasingly priced out of Washington housing market

Building Industry Association of Washington says state’s median home price is $522,023

t
King County Elections seeks better voter turnout in historically excluded communities

$950,000 in grants to be distributed over next two years to groups

Most Read