Does COVID change the body’s response to other threats? It depends on the gender

Does COVID change the body’s response to other threats? It depends on gender.


The long-term effects of infections on the immune system have long intrigued Yale immunobiologist, John Tsang. After the body has dealt with a pathogen, does the immune system go back to baseline? Or does a single infection change it in a way that alters its response not only to an already known virus but also to the next new viral or bacterial threat it will face? Tsang, a professor of immunobiology and biomedical engineering at Yale, has long believed that the immune system reverts to its previous baseline after a viral infection. The emergence of the COVID-19 pandemic in 2020 allowed him and his colleagues to test this theory. According to a study published on Jan. 4 in the journal Nature, the answer depends on the gender of the individual.


For the study, a team led by Tsang, who was then working at the National Institute of Allergy and Infectious Diseases (NIAID), and colleagues, including lead author Rachel Sparks, also of NIAID, systematically analyzed the immune responses of healthy people who had received the flu vaccine. Using this data, they then compared the responses of those who had never been infected with SARS-CoV-2, the virus that causes COVID-19, and those who had had mild cases but recovered. Much to their surprise, they discovered that the immune systems of men, who had recovered from mild cases of COVID-19, responded more strongly to flu shots than women who had had mild cases or men and women who had never been infected.


“It was a real surprise,” Tsang said. “Women usually have a stronger overall immune response to pathogens and vaccines, but they are also more likely to suffer from autoimmune diseases.” The findings may also be linked to an observation made early in the pandemic: Men were much more likely to die from an uncontrolled immune response than women after contracting the COVID-19 virus. Even mild cases of COVID-19, the new findings suggest, could trigger stronger inflammatory responses in males than females, resulting in more pronounced functional changes to the male immune system, even long after recovery.


Unbiased analysis of the state of the immune system down to the single cell level has revealed several differences between males and females with COVID, both before and after influenza vaccination. For example, previously infected males produced more influenza antibodies and increased interferon levels, which are produced by cells in response to infections or vaccines. Understanding the lingering effects of COVID-19 on the immune system is critical, say the authors, since more than 600 million people have been infected worldwide to date, and the appearance of “long-lasting” symptoms in some people continues to be a major health concern. “Our results point to the possibility that any infection or immune challenge could change immune status to establish new set points,” Sparks said. “An individual’s immune status is likely shaped by a multitude of prior exposures and perturbations.” Tsang believes these findings could help scientists create better vaccines against different threats, for example by mimicking the way mild COVID-19 changes male immunity.


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