We all know this person who, despite the fact that their entire household has contracted Covid-19, has never tested positive for the disease. Now, scientists have found an explanation, showing that a proportion of people experience an “abortive infection” in which the virus enters the body but is cleared by the T cells of the immune system at the earliest stage, which means that PCR and antibody tests show a negative result.
About 15% of healthcare workers who were followed during the first wave of the pandemic in London, England appeared to fit this scenario.
The discovery could pave the way for a new generation of vaccines targeting the T-cell response, which could produce much longer lasting immunity, the scientists said.
Leo Swadling, immunologist at University College London and lead author of the article, said: âEveryone has anecdotal evidence of people exposed but not succumbing to the infection. What we didn’t know was whether these people were really successful in avoiding the virus altogether or whether they naturally cleared the virus before it was detectable by routine testing. “
The latest study intensively monitored healthcare workers for signs of infection and immune responses during the first wave of the pandemic. Despite a high risk of exposure, 58 participants have at no time tested positive for Covid-19. However, blood samples taken from these people showed that they had an increase in T lymphocytes that reacted against Covid-19, compared to samples taken before the pandemic took hold and compared to people who did not. not at all been exposed to the virus. They also had increases in another blood marker of viral infection.
The work suggests that a subset of people already had memory T cells from previous infections of other seasonal cold-causing coronaviruses, which protected them from Covid-19.
These immune cells ‘sniff’ out proteins in the replication machinery – a region of Covid-19 shared with seasonal coronaviruses – and in some people this response was rapid and potent enough that the infection was cleared as soon as possible. âThese pre-existing T cells are ready to recognize SARS-CoV-2,â Swadling said.
The study adds to the known spectrum of possibilities after exposure to Covid-19, ranging from a complete escape from the infection to serious illness.
Alexander Edwards, associate professor of biomedical technology at the University of Reading, said: âThis study identifies [a new] intermediate outcome – enough exposure to the virus to activate part of your immune system, but not enough to feel symptoms, detect significant levels of the virus, or trigger an antibody response.
The finding is particularly significant because the T cell arm of the immune response tends to confer longer lasting immunity, typically years rather than months, compared to antibodies. Almost all of the existing Covid-19 vaccines focus on priming antibodies against the vital spike protein that helps SARS-CoV-2 get into cells. These neutralizing antibodies provide excellent protection against serious illness. 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 does not tend to subside as quickly and the internal replication machinery it targets is highly conserved across coronaviruses, meaning that a vaccine that also targeted this region would protect probably against new strains – and maybe even against entirely new strains. pathogens.
“The information from this study could be critical in designing a different type of vaccine,” said Andrew Freedman, infectious disease reader at Cardiff University School of Medicine. âA vaccine that initiates the immunity of T cells against different viral protein targets that are shared among many different coronaviruses would complement our spike vaccines that induce neutralizing antibodies. Because these are components of the virus, the antibodies are less effective – instead, the T cells come into play. “