Common Cold Coronaviruses Might Prime the Immune System to Recognize SARS-CoV-2

A group of scientists think they’re closer to understanding why some people’s immune systems seem to recognize the coronavirus that causes covid-19, despite the person never having been infected by it. The team’s new research released Monday suggests that past infections with much milder but related coronaviruses that cause the common cold can produce T cells in people that also react to the novel coronavirus—cells that possibly could provide some protection against covid-19.

T cells are a key aspect of our immunity to infectious diseases. Similar to antibodies, which are proteins released by B immune cells, some types of T cells can be produced that specifically recognize a part of a virus or other pathogen that tries to reinfect you; once that happens, the body’s immune response tends to kick into high gear and either prevents or weakens the new infection. Both antibodies and T cells can cross-react, where they respond to a new foreign invader with some familiarity, as if they had encountered it before. Oftentimes, this happens because the germ in question is related genetically to the germ that the original antibodies or T cells were created in response to.

Several studies in recent months have noticed a peculiar pattern: people who have T cells that respond to the novel coronavirus, SARS-CoV-2, without any other signs of infection, such as recent illness or virus-specific antibodies. In some cases, this could be explained by an asymptomatic person simply not having produced antibodies despite infection, a rare but not unprecedented thing to happen with other germs. But other studies have shown this T cell response happening in blood samples taken from people long before the covid-19 pandemic began last late year, meaning it should be impossible for them to have gotten infected.

Because there are at least four other coronaviruses that routinely infect people and cause mild-to-moderate colds, the leading theory has been that these cross-reactive T cells belong to the immune response our bodies made to fend off those viruses. But this study, published in Science, is one of the first to provide some experimental evidence for that theory.

The researchers took blood samples collected between 2015 and 2018, grew the immune cells from these samples in the lab, and isolated T cells that seemed to cross-react to specific pieces of the 29 proteins that make up the novel coronavirus. These bits of a virus or any antigen that our immune system responds to are also called epitopes.

In total, they found 142 different epitopes that prodded a cross-reactive T cell response across the samples. Roughly half of these epitopes were found in the spike protein of the virus, the part that it uses to invade cells so it can take over their machinery and create new copies of itself. The vast majority of these cross-reactive T cells (over 90%) were also CD4+ cells, also known as T helper cells. As their nickname implies, these cells help regulate the rest of the immune system and its response to infection.

The team also performed the same basic experiment with the common cold coronaviruses. And when they did, they noticed a lot of similarities between how the T cells responded to those viruses and how they responded to the novel coronavirus. In many cases, they concluded, the T cells were responding to genetic pieces shared by SARS-CoV-2 and the common cold viruses.

The results, they wrote, are in stark contrast to other studies that haven’t seen a similar effect when it comes to antibodies. In other words, scientists haven’t found that antibodies to past common cold coronaviruses are reacting to the infection caused by the novel coronavirus. But the findings do provide plausibility to the theory that T cell cross reactivity to the novel coronavirus is the result of past infections from these common cold viruses.

If verified by other research, the discovery is likely to be a crucial piece of the puzzle that is covid-19, according to the authors.

“We have now proven that, in some people, pre-existing T cell memory against common cold coronaviruses can cross-recognize SARS-CoV-2, down to the exact molecular structures,” said co-author Daniela Weiskopf, a researcher at the La Jolla Institute for Immunology, in a statement released by the research organization. “This could help explain why some people show milder symptoms of disease while others get severely sick.”

Unfortunately, immunity is not a simple thing to pin down, even when we’re not in the middle of a pandemic. It’s possible, for instance, that having a preemptive immune response to an unfamiliar agent like SARS-CoV-2 can actually make the illness it causes even more severe—a phenomenon known as “original antigenic sin.” When this happens, the immune system relies too much on the existing weapons it has against the new infection and doesn’t build up a new specific response as effectively as it would normally. In this study, however, the researchers didn’t find evidence for that happening with covid-19. Still, as many researchers studying this issue admit (including some of this study’s authors), it’s unclear how these cross-reactive T cells will affect a person’s real-world response to SARS-CoV-2 infection, both in the symptoms it may cause or their ability to transmit it to others, or even whether these interactions will be the same for everyone who has cross-reactive T cells.

By creating a map of how preexisting T cells can react to the novel coronavirus, though, we’re one step closer to answering these important questions.