Since the very beginning of the pandemic, a key feature of the spread of COVID has been its apparently random nature.
Why are some people readily infected after an exposure, while others remain untouched?
A new study, published in Nature Communications and led by Imperial College London (ICL) researchers, provides insight into the underpinnings of the COVID infection lottery, and suggests that the common cold could be key.
"Being exposed to the SARS-CoV-2 virus doesn't always result in infection, and we've been keen to understand why," says Dr Rhia Kundu, from ICL's National Heart & Lung Institute and first author of the study.
"We found that high levels of pre-existing T-cells, created by the body when infected with other human coronaviruses like the common cold, can protect against COVID-19 infection."
While previous studies have shown that T-cells induced by other coronaviruses can recognise SARS-CoV-2, the new study examines for the first time how the presence of these T-cells at the time of SARS-CoV-2 exposure influences whether someone becomes infected.
The study began in September 2020 when most people in the UK had neither been infected nor vaccinated against SARS-CoV-2.
The researchers looked at healthy, uninfected individuals who were living with someone with a PCR-confirmed active COVID infection. They tested participants on days four and seven, to determine if they subsequently developed an infection.
Using blood samples taken within the first week of exposure to COVID, the researchers then cross-referenced these infection rates with levels of pre-existing T-cells induced by previous common cold coronavirus infections, that also recognise proteins of the SARS-CoV-2 virus.
The findings were stark: half of all participants developed a COVID infection after exposure while the other half did not, and those who remained impervious showed significantly higher levels of these cross-reactive T-cells than their infected counterparts.
What makes these T-cells such a formidable defence, and how can we put them to work in our efforts to reign in the global scourge? Should we all be trying to pick up a case of the sniffles?
Aside from that being very unwise, we might struggle to find someone from whom to catch a cold in any case. Global rates of infections with common respiratory illnesses have plummeted during the pandemic, potentially even driving one strain of flu to extinction, in response to improved personal hygiene practices, mask-wearing and social distancing.
Luckily, there are other avenues available to exploit this T cell defence. The researchers believe they understand what makes these T-cells so effective in guarding against COVID, and say their findings provide a blueprint for a second-generation, universal vaccine that could prevent infection from current and future SARS-CoV-2 variants, including Omicron.
Current vaccines act by targeting the spike protein on the surface of the virus - something that is proving troublesome for long-term vaccine effectiveness.
"The spike protein is under intense immune pressure from vaccine-induced antibodies," says Professor Ajit Lalvani, senior author of the study and director of the NIHR Respiratory Infections Health Protection Research Unit at ICL.
It's this pressure that drives the evolution of vaccine escape mutants. The study found that T-cells attack the virus through an entirely separate mechanism, targeting internal proteins within the SARS-CoV-2 virus - something that current vaccines can't do.
"The internal proteins targeted by the protective T-cells we identified mutate much less," says Lalvani. "Consequently, they are highly conserved between the various SARS-CoV-2 variants, including Omicron. New vaccines that include these conserved, internal proteins would therefore induce broadly protective T cell responses that should protect against current and future SARS-CoV-2 variants."
The researchers say that - alongside our existing effective spike protein-targeting vaccines - future vaccines that use T-cells to target internal proteins could also provide significantly longer-lasting protection because T-cell responses persist longer than antibody responses, which wane within a few months of vaccination.
Although this fresh insight into our immune response to COVID could prove pivotal, Kundu emphasises that our best strategy is one that incorporates as many defences as possible.
"While this is an important discovery, it is only one form of protection, and I would stress that no one should rely on this alone. Instead, the best way to protect yourself against COVID-19 is to be fully vaccinated, including getting your booster dose."
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