In labs all over the world lately, scientists working on COVID-19 have stumbled on an intriguing sort of finding again and again. They’ve found that blood samples from healthy people who were never exposed to the SARS-CoV-2 coronavirus contain reactive immune cells and targeted antibodies that could, perhaps, help stave off COVID-19.
These people may—it is still just a hypothesis—possess some degree of pre-existing immunity. If correct, it’s even possible that this immunity has saved thousands from the worst manifestations of this terrible disease.
Some of the first hints of pre-existing immunity came via T cells, the white blood cells that destroy infected cells in the body or help other parts of the immune system target an invading pathogen. In one study originally published as a preprint on medRxiv April 22, a group of scientists in Germany reported an intriguing result.
Out of 68 healthy donors who had been tested for prior exposure to SARS-CoV-2 and who were found to be negative, 24 of them had a small number of T cells in their blood that reacted when exposed to the SARS-CoV-2 spike (S) protein—a complex structure protruding from the virus’s exterior surface. The study, which was later published in Nature July 29, explains that the cells in question produced proteins on their surfaces, an indication of an immune response.
If that is indeed what’s going on here, one possible explanation would be that the healthy donors had been infected by another coronavirus relatively recently, perhaps one that causes a common cold, says coauthor Andreas Thiel, an immunologist at the Charité hospital, part of Universitätsmedizin Berlin. Besides more serious diseases such as COVID-19 and SARS, human coronaviruses have been known for decades to cause what are usually much milder infections. The specific viruses that cause these illnesses are found all around the world.
Immunity to common cold viruses is not thought to be very long-lasting for people, regardless of age, so it is debatable how durable a protective effect would be.
“Although these viruses are not very similar [to SARS-CoV-2], the low degree of similarity is of course sufficient that the immune system, at least partly, is cross-reacting, which is a very normal thing,” he says.
An earlier study in Nature on July 15 from Singapore reported that 23 patients who had caught the original SARS virus 17 years ago and a further 37 individuals who had never been found to have had SARS or COVID-19 possessed CD4+ helper T cells and CD8+ killer T cells that reacted to the SARS-CoV-2 nucleocapsid (N) protein.
Lead author Nina Le Bert, an immunologist at Duke-NUS Medical School in Singapore, says that her paper chimes with Thiel’s work and a few other studies that have also found SARS-CoV-2 reactive T cells in blood from people who never had COVID-19, or who were sampled before the pandemic.
A study in Science today (August 4) also found SARS-CoV-2 reactive T cells in pre-pandemic blood samples from 25 healthy individuals. In this case, the authors also mapped 142 specific points on the SARS-CoV-2 virus called epitopes associated with this activity.
This allowed them to show, in subsequent experiments, that the T cells also reacted when exposed to epitopes on common cold coronaviruses that were similar to SARS-CoV-2 epitopes, supporting the idea that previous exposure to these common viruses might leave our immune systems primed to respond to the novel coronavirus.
Determining whether the T cell activity really is protective against COVID-19 is tricky, Le Bert says. “You would need to study people before and after getting infected.”
Le Bert adds that having some degree of immunity also does not mean that people definitely won’t get infected in the first place. They may still experience mild symptoms, for example, as their immune system fends off the virus.
Thiel points out that reactive T cells could even produce the opposite result—a detrimental immune response that ultimately harms the patient, for example, when someone experiences excessive inflammation or an inability to clear the virus. “Maybe particularly in the old people, having such cross-reactive T cells could be bad,” he suggests.
Pre-existing immunity might not be limited to T cells. A preprint published on medRxiv July 23 reports that SARS-CoV-2–reactive antibodies were found in blood samples taken from people in the UK between 2018 and early 2020, before COVID-19 became widespread in the country.
Not only did the authors find that 15 out of 262 people who never had COVID-19 have IgG antibodies reactive with certain SARS-CoV-2 proteins, but further tests showed that these antibodies had a neutralizing effect on the SARS-CoV-2 spike protein, which suggests that they might be able to restrict infection by the virus.
One of the most striking findings was that these antibodies were far more prevalent in children between the ages of 1 and 16 years old. In fact, 60 percent of children had neutralizing IgG antibodies—an order of magnitude greater than the proportion of adults who were found to have the same antibodies. Coauthor Rupert Beale, an immunologist at the Francis Crick Institute in London, remarked on Twitter that this particular result was completely unexpected—“a kind of bombshell,” as he put it.
In their preprint, the authors write that kids are generally more frequently exposed to other coronaviruses, such as those that cause common colds. This could explain the prevalence of those IgG antibodies in their blood.
It is notable that, while Beale’s team detected IgG neutralizing antibodies in some of their subjects, none of the healthy donors in the study by Thiel and his colleagues were found to have reactive IgG antibodies, though they did have reactive T cells.
The presence of neutralizing antibodies does not guarantee that these children are immune to COVID-19 but it does offer one possible explanation as to why children, generally speaking, experience milder symptoms when they catch the disease.
The findings are “really interesting,” says Sheena Cruickshank, an immunologist at the University of Manchester in the UK, via email. She notes that, in the study, a different type of antibody that is protective against SARS-CoV-2, IgA, was not detected in the healthy individuals unexposed to the new coronavirus. That might mean any pre-existing immunity is limited. The other big caveat is that immunity to common cold viruses is not thought to be very long-lasting for people, regardless of age, so it is debatable how durable a protective effect would be, she adds.
In Le Bert’s study, patients appeared to have retained reactive T cells for nearly two decades. She and her colleagues write in their report that this has potentially significant implications: that immunity acquired through, say, a vaccine could last for many months or years.