Nature: After contracting the new coronavirus, has the body's response to other threats changed? It depends on the gender

The long-term effects of infection on the immune system have long piqued the interest
of Yale immunobiologist John Tsang.
After the body defeats the pathogen, does the immune system return to its previous baseline level? Or does one infection change it, changing not only its response to familiar viruses, but also its response to the next new viral or bacterial threat it faces?

Tsang, a professor of immunobiology and biomedical engineering at Yale University, has long believed that after a viral infection, the immune system returns to its previous stable baseline
.

The emergence of the COVID-19 pandemic in 2020 allowed him and his colleagues to test this theory
.
According to a study published Jan.
4 in the journal Nature, they found that the answer depends on the sex
of the individual.

In the study, a team led by Tsang, who at the time at the National Institute of Allergy and Infectious Diseases (NIAID), and his colleagues, including lead author Rachel Sparks, also from NIAID, systematically analyzed the immune response
in healthy people who received the flu vaccine.
Based on these data, they compared the response
between people who had never been infected with SARS-CoV-2, the virus that causes COVID-19, and those who had experienced mild cases but had recovered.

To their surprise, they found that men who recovered from mild COVID-19 cases had immune systems that responded more strongly
to the flu vaccine than women with mild cases or men and women who had never been infected.

Essentially, the baseline immune status of men previously infected with SARS-CoV-2 was altered, altering the response
to different exposures than SARS-CoV-2, the authors said.

"It was completely unexpected," Tsang said
.
"Women generally have a stronger overall immune response to pathogens and vaccines, but are also more likely to develop autoimmune diseases
.
"

The findings may also be related to an observation early in the pandemic: that men were more likely than women to die from an uncontrolled immune response
after contracting the COVID-19 virus.
The new findings suggest that even mild cases of COVID-19 may trigger a stronger inflammatory response in men than in women, leading to more pronounced functional changes in the male immune system, even long after recovery
.

They conducted an unbiased analysis of the state of the immune system, down to the individual cell level, and the results showed several differences
between men who recovered from the new coronavirus before and after the flu vaccination and healthy controls and women who recovered from the new coronavirus.
For example, previously infected men produced more flu antibodies and produced higher levels of interferons, which are produced
by cells that respond to infections or vaccines.
In general, healthy women have a stronger interferon response
than men.

Understanding the ongoing impact of COVID-19 on the immune system is critical because, to date, more than 600 million people worldwide have been infected and some people experiencing symptoms of "Long Covid" remain a major health problem
, the authors said.

"Our findings suggest that any infection or immune challenge can alter immune status, establishing new set points
," Sparks said.
A person's immune status may be determined by a large number of prior exposures
and perturbations.
”

Tsang believes the findings could also help scientists develop better vaccines to deal with different threats, for example, by simulating how mild COVID-19 can alter the baseline
of immunity in men.

Other researchers include William Lau, a computational biologist at the National Institutes of Health, and Can Liu, a graduate student in systems immunology at the University of Maryland, who is also affiliated with NIAID
.