Why is COVID-19 more severe in men and elders? – 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 isan assistant professor in the department of Laboratory Medicine and Pathology at the University of Washington School of Medicine and head ofthe project. The results of the study appear in the open-access journal PLOS Biology. Here is 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 Cityand University of Texas Medical Branch, Galveston, Texas. These groups havedeveloped techniques to infect cells in cultureto 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 instructionsin 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. Thats because,for the instructions for synthesizing proteins encoded in the DNA of genes tobe read by the cells, the code must first be copied, into RNA. As a result, analyzing the RNA transcriptsin a sample can showwhichgenes are being dialed upin response to the infection and which are being dialed down. This sort of analysis canrevealwhat sort of immune counterattack the cells are mounting against the virus.

The researchers found that the viral load in these patients was high, butalso 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 includeschemical 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 individualsover 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 bodys the most effective antiviral weapons.

The older patients activate a weaker immune response like a singer that just cant hit the high notes anymore, Greninger said.

The researchers also found that men mounted a less vigorous response compared to women. The malesproducedlower levels of transcripts of some anti-viral proteins,and pumped outsome proteins that put a damper onthe immune response.

In men were seeing an up-regulation of signals that turn off the immune system, Lieberman said. Its speculation, but it appears as though some men may throttleback 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 UWSchool of Medicine.

View original post here:
Why is COVID-19 more severe in men and elders? - UW Medicine Newsroom