Researchers have identified sex-specific differences in a type of immune cell and in the production of antibodies, as part of the response to COVID-19, which may explain why men are at higher risk from the disease.

Men show a higher risk of COVID-19 infection but the underlying cellular basis for this difference is not fully understood.

The researchers at Osaka University in Japan have now uncovered sex-specific differences in a type of immune cell called regulatory T cells, or "Treg cells," and in the production of proteins called antibodies.

The immune system is responsible for clearing viral infections, as well as producing many of the acute symptoms of COVID-19, so it is critical to understand the changes that occur to the immune system of infected patients.

The "humeral response," the production of antibodies, is dysregulated in COVID-19. Treg cells were suspected to be responsible for this, as their role in the immune system is to regulate other immune cells and suppress their activities to control the strength of the immune response.

The T-follicular regulatory cells (Tfr cells), a subset of the Treg cell population are responsible for the control of antibody production.

The study, published in the journal Proceedings of the National Academy of Sciences, observed that male patients lose circulating Tfr cells at a faster rate than female patients.

The researchers also identified sex-specific differences in a whole network of different cell types that are associated with the production of antibodies. Many COVID patients begin to produce "autoantibodies" as part of their response to the virus.

These antibodies are aimed at proteins produced by the human body instead of targeting the virus and can neutralise protective host factors, and the production of these may play a critical role in how the infection progresses.

The team used an approach known as single-cell proteomics by mass spectrometry, allowing individual immune cells to be identified and analysed.

This showed that patients with COVID-19 have changes in the ratio between circulating Tfr cells and a network of other cells associated with the production of antibodies, which in turn is strongly correlated with the antibody levels.

A sex bias was seen in this response, with females having more circulating Tfr cells while males had higher antibody levels, according to the researchers.

"This provides significant cellular evidence of dysregulated antibody responses in COVID-19 patients," said senior study author James Badger Wing.

"The reduction of cTfr observed in all COVID-19 patients, but particularly in males, may underlie this dysregulated antibody production," Wing said.

The identification of this cellular basis for the known sex-specific differences will be key in protecting everyone, especially those most at risk, from COVID-19 infection, the researchers added.