Why men are at higher risk from COVID-19

During acute COVID-19, there was a sex-specific disruption between T-follicular regulatory cells (Tfr), T-peripheral helper cells (Tph), antibody-producing B-cells, and plasmablasts. Credit: Developed by Dr. Wing using Biorender

Since its initial outbreak in 2019, COVID-19 has had a significant worldwide impact. Men and women react to this illness differently, with men being more susceptible to infection. A research team from Osaka University has discovered sex-specific differences in regulatory T cells, also known as "Treg cells," and in the production of proteins known as antibodies as part of the response to COVID-19 infection. The underlying cellular basis for this difference is still not fully understood.

Understanding the alterations to the immune system that take place in infected people is crucial because the immune system is responsible for eradicating viral infections as well as creating many of the acute symptoms of COVID-19. COVID-19 has a dysregulated "humeral response," or the generation of antibodies. Treg cells were suspected of being in charge of this because one of their functions in the immune system is to control the activity of other immune cells by regulating them.

 

T-follicular regulatory cells ("Tfr cells"), a subgroup of the Treg cell population in charge of regulating antibody production, are particularly important. The team discovered sex-specific changes in a vast network of several cell types that are connected to the generation of antibodies and found that male patients lose circulating Tfr cells at a faster rate than female patients.

 

As part of their defense against the virus, a large number of COVID patients start to develop "autoantibodies." Instead of focusing on the virus, these antibodies can destroy protective host factors made by the body, and the creation of these factors may be crucial to how the infection develops.

According to the study's first author, Jonas N. N. Sndergaard, "Regulation of the immune system by Treg cells may therefore be crucial in understanding susceptibility to and recovery from COVID-19." The findings were reported in Proceedings of the National Academy of Sciences.

Individual immune cells could be recognized and studied thanks to the team's employment of a technique called single-cell proteomics by mass spectrometry. This demonstrated that COVID-19 patients had altered ratios of circulating Tfr cells to a network of other cells linked to antibody synthesis, which is closely correlated with antibody levels. This response exhibited a gender bias, with males having higher antibody levels and females having more circulating Tfr cells.

According to senior author James Badger Wing, "This gives important biological evidence of dysregulated antibody responses in COVID-19 patients." "This dysregulated antibody production may be caused by the decrease of cTfr found in all COVID-19 patients, but particularly in men."

To prevent everyone from contracting COVID-19 infection, especially the people who are most vulnerable, it will be essential to identify the cellular basis for the known sex-specific differences.