For decades, immunobiologists have pondered what are the long-term effects of infections on people’s immune systems. For instance, after the organism fights off a pathogen, does the immune system return to a previous baseline, or could a single infection change it in ways that alter how it will respond not only to an already familiar virus or bacteria but also to a new pathogenic threat?
Now, a team of researchers led by Yale University and the National Institute of Allergy and Infectious Diseases (NIAID) has systematically analyzed immune responses of healthy people who had received the flu vaccine, and compared the responses between those who had never been infected with SARS-CoV-2 and those who experienced mild cases but recovered.
The analysis revealed that the immune systems of men previously infected with the new coronavirus responded more robustly to flu vaccines than previously-infected women or people who had never been infected with SARS-CoV-2. These findings suggest that the immune statuses of men previously infected with SARS-CoV-2 was altered in ways that changed their response to a different type of future exposure.
“This was a total surprise,” said study senior author John Tsang, an immunobiologist at Yale. “Women usually mount a stronger overall immune response to pathogens and vaccines, but are also more likely to suffer from autoimmune diseases.”
According to the scientists, this discovery could also be linked to an intriguing aspect noticed already early in the Covid-19 pandemic: men appeared much more likely to die from a runaway immune response than women after contracting Covid. The new study shows that even mild cases of Covid-19 may trigger stronger inflammatory responses in males than females, resulting in stronger functional changes to the male immune system, even a long time after recovery.
When analyzing the participants’ response to flu vaccinations, the experts found that males previously infected with SARS-CoV-2 produced more antibodies to influenza and increased levels of interferons (proteins produced by cells in response to infections or vaccines). This was surprising since, in general, healthy females have stronger interferon responses than males.
Since hundreds of millions – if not, according to some estimates, several billions – of people worldwide have been infected with the new coronavirus so far, and the emergence of long-Covid symptoms in some people is currently a major health concern, understanding the lingering effects of Covid on the immune system is crucial.
“Our findings point to the possibility that any infection or immune challenge may change the immune status to establish new set points. The immune status of an individual is likely shaped by a multitude of prior exposures and perturbations,” Sparks concluded.
The study is published in the journal Nature.
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