We’ve all met someone who, despite their entire family contracting Covid-19, has never tested positive.
Scientists have now discovered an explanation, suggesting that certain people suffer from “abortive infection,” in which the virus enters the body but is removed by the immune system’s T-cells at the earliest stage, resulting in a negative PCR and antibody test result.
This scenario looked to fit about 15% of healthcare workers tracked during the first wave of the epidemic in London, England.
According to scientists, the discovery could pave the way for a new class of vaccine that target the T-cell response, which could result in considerably longer-lasting protection.
The paper’s lead author, Leo Swadling, an immunologist at University College London, said:
“Everyone has anecdotal evidence of people being exposed but not succumbing to infection. What we didn’t know is whether these individuals really did manage to completely avoid the virus or whether they naturally cleared the virus before it was detectable by routine tests.”
During the initial wave of the pandemic, the latest study closely observed healthcare professionals for symptoms of infection and immunological responses. Despite the significant risk of exposure, none of the 58 individuals tested positive for Covid-19 at any stage during the study.
Blood tests collected from these individuals, however, revealed that they had a higher number of T-cells that reacted to Covid-19 than those taken before the pandemic and people who had not been exposed to the virus at all. They also had an increase in another viral infection blood marker.
According to the findings, some participants had memory T-cells from earlier infections with other seasonal coronaviruses that cause common colds, which protected them from Covid-19.
These immune cells “sniff out” proteins in the replication machinery – a part of Covid-19 that is shared with seasonal coronaviruses – and in some patients, this response was fast and effective enough to eliminate the infection at an early stage.
“These pre-existing T-cells are poised ready to recognise SARS-CoV-2,” said the study author.
The findings extend to the recognized spectrum of outcomes following Covid-19 exposure, which range from complete aversion to severe sickness.
According to the associate professor Alexander Edwards from the University of Reading: “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 mount an antibody response.”
The discovery is particularly relevant since, in comparison to antibodies, the T-cell arm of the immune response tends to impart longer-lasting immunity, generally years rather than months. Almost every Covid-19 vaccine now on the market focuses on priming antibodies against the critical spike protein that allows SARS-CoV-2 to enter cells. Antibodies that neutralize pathogens provide good protection against serious illness. However, immunity fades with time, and spike-based vaccines may be vulnerable because this area of the virus is known to change.
The T-cell response, on the other hand, does not fade as fast, and the internal replication machinery that it targets is highly conserved across coronaviruses, implying that a vaccination that also targeted this region would likely protect against new strains, if not wholly different diseases.
“Insights from this study could be critical in design of a different type of vaccine,” said the professor.
“A vaccine that primes T-cell immunity against different viral protein targets that are shared between many different coronaviruses would complement our spike vaccines that induce neutralising antibodies. Because these are components within the virus, antibodies are less effective – instead, T-cells come into play.”
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