We all know that person who, despite their entire household contracting Covid-19, has never tested positive for the disease. Now scientists have found a statement showing that a subset of people experience an “abortive infection” where the virus enters the body but is removed at the earliest stage by the immune system’s T cells, meaning PCR and antibody tests produce a negative result.
About 15% of the health professionals monitored during the first wave of the pandemic in London, England, seemed to fit this scenario.
The discovery could pave the way for a new generation of vaccines that target the T-cell response, which could provide much longer-lasting immunity, scientists say.
Leo Swadling, an immunologist at University College London and lead author of the paper, said: “Everyone has anecdotal evidence that people are exposed but do not succumb to infection. What we didn’t know is whether these individuals actually managed to transmit the virus.” completely or that they cleared the virus naturally before it could be detected by routine testing.”
The latest study closely monitored health professionals for signs of infection and immune responses during the first wave of the pandemic. Despite a high exposure risk, 58 participants did not test positive for Covid-19 at any time. However, blood samples from these people showed that they had an increase in T cells that responded to Covid-19, compared to samples taken before the pandemic broke out and compared to people who had not been exposed to the virus at all. They also had elevations in another blood marker of viral infection.
The work suggests that a subset of people already had memory T cells from previous infections from other seasonal coronaviruses that caused the common cold and protected them from Covid-19.
These immune cells “sniff up” proteins in the replication machinery — a region of Covid-19 shared with seasonal coronaviruses — and in some people, this response was fast and powerful enough to clear the infection in its earliest stages. “These preexisting T cells are ready to recognize SARS-CoV-2,” Swadling said.
The study adds to the well-known spectrum of possibilities after exposure to Covid-19, ranging from complete escape from infection to serious illness.
Alexander Edwards, associate professor of biomedical engineering at the University of Reading, said: “This study identifies [a new] intermediate outcome – enough virus exposure to activate part of your immune system, but not enough to experience symptoms, detect significant levels of virus, or elicit an antibody response.”
The finding is particularly important because the T-cell arm of the immune response tends to confer longer-lasting immunity, usually lasting years rather than months, compared to antibodies. Nearly all existing Covid-19 vaccines aim to prepare antibodies to the vital spike protein that helps SARS-CoV-2 enter cells. These neutralizing antibodies provide excellent protection against serious diseases. However, immunity wanes over time and a potential weakness of spike-based vaccines is that this region of the virus is known to mutate.
In contrast, the T-cell response doesn’t tend to fade as quickly, and the internal replication machinery it targets is highly conserved across coronaviruses, meaning a vaccine targeting this region as well would likely protect against new strains — and possibly even against entirely new pathogens.
“Insights from this study could be critical in designing a different type of vaccine,” said Andrew Freedman, reader in infectious diseases at Cardiff University School of Medicine. “A vaccine that boosts T-cell immunity against several viral protein targets shared by many different coronaviruses would complement our spike vaccines that induce neutralizing antibodies. Because these are components in the virus, antibodies are less effective — T cells come into play instead.”