T cells can seek and destroy SARS-CoV-2 (yellow) infected cells.

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Science‘s COVID-19 reporting is supported by the Pulitzer Center.

Immune warriors known as T cells help us fight some viruses, but their importance for battling SARS-CoV-2, the virus that causes COVID-19, has been unclear. Now, two new studies reveal that infected people harbor T cells that target the virus—and may help them recover. Both studies also found that some people never infected with SARS-CoV-2 have these cellular defenses, most likely because they were previously infected with other coronaviruses.

“This is encouraging data,” says virologist Angela Rasmussen of Columbia University.  Although the studies don’t clarify whether people who clear a SARS-CoV-2 infection can ward off the virus in the future, the fact that both identified T cell responses to it “bodes well for the development of long-term protective immunity,” Rasmussen says. The findings could also help researchers create better vaccines.

The more than 100 COVID-19 vaccines in development mainly focus on a different immune response: antibodies. These proteins are made by B cells and ideally latch onto SARS-CoV-2 and prevent it from entering cells. T cells, in contrast, thwart infections in two different ways. Helper T cells spur B cells and other immune defenders into action, whereas killer T cells target and destroy infected cells. The severity of disease can depend on the strength of these T cell responses.

Using bioinformatics tools, a team led by Shane Crotty and Alessandro Sette, immunologists at the La Jolla Institute for Immunology, predicted which viral protein pieces would trigger the most powerful T cell responses. They then exposed immune cells from 10 patients who had recovered from mild cases of COVID-19 to these viral snippets.

All of the patients carried helper T cells that recognized the SARS-CoV-2 spike protein, which enables the virus to barge into our cells. They also harbored helper T cells that react to other SARS-CoV-2 proteins. And the team detected virus-specific killer T cells in 70% of the subjects, they report today in Cell. “The immune system sees this virus and mounts an effective immune response,”  Sette says.

The results jibe with those of a study posted as a preprint on medRxiv on 22 April by immunologist Andreas Thiel of the Charité University Hospital in Berlin and colleagues. They discovered helper T cells targeting the spike protein in 15 out of 18 patients hospitalized with COVID-19.

The teams also asked whether people who haven’t been infected with SARS-CoV-2 had pre-existing immunity to it. Thiel and colleagues analyzed blood from 68 uninfected people and found that 34% hosted helper T cells that recognized SARS-CoV-2. The La Jolla team detected this crossreactivity in about half of stored blood samples collected between 2015 and 2018, well before the current pandemic began. The researchers think these cells were likely triggered by past infection with one of the four human coronaviruses that cause colds; proteins in these viruses resemble those of SARS-CoV-2.

The results suggest “one reason that a large chunk of the population may be able to deal with the virus is that we may have some small residual immunity from our exposure to common cold viruses,” says viral immunologist Steven Varga of the University of Iowa. However, neither of the studies attempted to establish that people with crossreactivity don’t become as ill from COVID-19.

Before these studies, researchers didn’t know whether T cells played a role in eliminating SARS-CoV-2, or even whether they could provoke a dangerous immune system overreaction. “These papers are really helpful because they start to define the T cell component of the immune response,” Rasmussen says. But she and other scientists caution that the results do not mean that people who have recovered from COVID-19 are protected from reinfection.

To spark production of antibodies, vaccines against the virus need to stimulate helper T cells, Crotty notes. “It is encouraging that we are seeing good helper T cell responses against SARS-CoV-2 in COVID-19 cases,” he says. The results have other significant implications for vaccine design, says molecular virologist Rachel Graham of the University of North Carolina, Chapel Hill. Most vaccines under development aim to elicit an immune response against spike, but both studies showed that the T cells they detected reacted to several different viral proteins, suggesting that vaccines that sic the immune system on these proteins as well could be more effective.  “It is important to not just concentrate on one protein,” Graham says.



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