Nature: Whether previous infection with SARS-CoV-2 alters the body's immune response to other threats depends on the sex of the body

The long-term effects of infection on the immune system have long fascinated Yale immunobiologist John Tsang
.
After the body is confronted with a pathogen, does the immune system return to its previous baseline? Or does one infection change its ways, making it respond not only to familiar viruses, but also to new viral or bacterial threats the next time?

Tsang has long believed that the immune system returns to its previous stable 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 new study, they found that the answer depends on the gender
of the individual.
The results of the study were published online on January 4, 2023 in the journal Nature under the title "Influenza vaccination reveals sex dimorphic imprints of prior mild COVID-19.
"

In the new study, Tsang and his colleagues systematically analyzed the immune response
in healthy people who had been vaccinated against the flu.
Based on these data, they then compared the immune response
between those who had never been infected with SARS-CoV-2, the coronavirus that causes COVID-19, and those who had developed mild symptoms after contracting the virus but had recovered.

To their surprise, they found that men who recovered from mild cases of COVID-19 had stronger immune systems that responded to the flu vaccine than women who had mild cases or had never been infected
.
They noted that in essence, the baseline immune status of men previously infected with SARS-CoV-2 changed, altering the response
to exposure different from SARS-CoV-2.

Tsang said, "It was completely unexpected
.
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 SARS-CoV-2.
These 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 performed an unbiased analysis of immune system status, down to the individual cell level, and the results showed several differences
between men who recovered from COVID-19 and healthy controls and women who recovered from COVID-19 before and after receiving influenza vaccination.
For example, men previously infected with SARS-CoV-2 produced more influenza antibodies and produced more interferons, which are produced
by cells in response to infection or vaccines.
In general, healthy women have a stronger
interferon response than men.

Image from Nature, 2023, doi:10.
1038/s41586-022-05670-5
.

Understanding the lingering effects of SARS-CoV-2 on the immune system is critical, the authors say, as more than 600 million people worldwide have been infected to date, and "long COVID" (long COVID) in some remains a major health problem
.

Co-first author Rachel Sparks of the National Institute of Allergy and Infectivity said, "Our findings suggest that any infection or immune challenge has the potential to alter immune status and establish new setpoints
.
A person's immune status is likely to have been formed
by multiple previous exposures and perturbations.
”

Tsang thinks the findings could also help scientists develop better vaccines to deal with different threats, such as simulating how mild COVID-19 can alter men's immune baselines
.
(Biovalley Bioon.
com)

Resources:

Rachel Sparks et al.
 Influenza vaccination reveals sex dimorphic imprints of prior mild COVID-19.
Nature, 2023, doi:10.
1038/s41586-022-05670-5.