T cells—one of the main cells in the immune system—are the first line of defense against bacteria or viruses. T cells have thousands of arms that are in contact with each other, communicating with other cells to defend against a person’s immune system.

More than half of all patients who experience a partial or full COVID-19 hospitalization develop whole blood clots, called acute bacterial skin infections, and many of them die. These are the symptoms, but the underlying cause is not well understood. Several studies have shown that biomarkers for skin-infection-associated T cell infiltration increase in the blood after infection, but developments have not been entirely clear.

The discovery from a team led by scientists at Massachusetts General Hospital (MGH) may improve understanding of this issue. Their study, which will be published Nov. 24 in the journal Nature Immunology, showed that bacteria that were thought to be immune markers in the blood have instead been found as interactions between T cells and the bacteria. This result is consistent with other studies that show the role of T cells as a type of immune cell in the body with respect to spreading the virus.

“Bacteria seem to signal the T cells to get involved providing them lots of food. Although that’s good for the bacteria—and it looks like a good reason to go the extra mile in the immune system—getting the T cells involved helps control the infection as well as prevent the severity of the cough,” said lead author Brian Almeida, a research physician at the Gordon and Virginia MacDonald Research Institute (GRi); senior author of the study.

It has been suspected by other groups but never demonstrated definitively that bacteria in the blood lead to acute skin infections, said first author Margaret Lair, MD, who holds the Michael W. and Lillian Baughman Distinguished Chair in Physiology at the University of Houston.

In fact, some studies have shown that T cells are more active following a penicillin-like-ine viral infection than following a methicillin-like-ue bacterium (MLM). No studies have shown that T cells are involved in spreading COVID-19 among patients.

“The findings suggest that both types of bacteria are bothblocked by T cell antibody. It may be that T cell antibody T cell availability, and T cell involvement, are low (!) both contributing to the same thing,” she said.

The change in T cell activity was observed in both a mouse model of infection with COVID-19 as well as in a human patient in whom metabolic stress was greatly increased. The roles of T cells and their power to record chemical signals were equally or even more important, the researchers said.

“It’s an interesting observation that T cells appear to be playing different roles in COVID-19 than in other diseases,” Lair said. “COVID is not uncommon. We see it in cold-related infections, meningitis, cytomegalovirus infection—airway infections—anemia, and we see it in people being treated for blood clots, which might be common in people who have cardiovascular disease as well as in COVID-19.”

After analyzing thousands of samples of both blood as well as plasma from patients, the researchers found 73 T cells that actively helped the skin fight infections by targeting the bacteria. That number is up from 47 the previous study. The highest number of T cells in the blood in any site was around 80 percent while the lowest was around 30 percent.

In addition, the control group had up to 45 percent T cell activation, versus 35 percent in the MGH group.

The discovery that these T cell signatures varied in the blood, and not just whether T cells are present, may help explain why the infection prevalence of COVID-19 varies as dramatically as it does” says Dr. Lionel Jameson, Ph.D., director of Clinical Viral Laboratory research at MGH, the senior author of the paper.

Although triggering both bacteria and T cells have the same goal of shutting down infection, and also does not allow for an unlimited supply of T cells, T cells cannot attack the infection—so it would be more challenging to stimulate both to trigger allergic status, he explains.

“It’s more complicated than having T cells and knowing either they can kill the infection or not,” he said. “T cells cannot attack the infection. It further raises the difficulty in promoting an antibody response.”