Scientists claimed to have found the first definitive evidence of a protective role for cross-reactive T cells from the common cold against SARS-CoV-2 infection. Such protection has been suspected before, but not previously associated with outcome after SARS-CoV-2 exposure.

The researchers said their findings may help in formulating a second-generation, universal COVID-19 vaccine to combat new variants of the virus.

The small study, published in the journal Nature Communications , built on previous investigations that demonstrated that T cells induced by other coronaviruses might be able to recognise SARS-CoV-2.

It examined how the presence of these non-spike cross-reactive memory T cells at a time of SARS-CoV-2 exposure influenced whether someone became infected or not.

Dr Rhia Kundu, first author of the study, from the National Heart & Lung Institute at Imperial College London (ICL), said: “Being exposed to the SARS-CoV-2 virus doesn’t always result in infection, and we’ve been keen to understand why.

“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.”

Small Study

The study began in September 2020 when most people in the UK had neither been infected nor vaccinated against SARS-CoV-2.

The researchers assessed 52 household contacts of people with PCR-confirmed COVID-19 to capture immune responses at the earliest time points after SARS-CoV-2 exposure. Participants took PCR tests at the outset and at 4 and 7 days later, to determine if they developed infection.

Blood samples from the participants were also taken within 1 to 6 days of them being exposed to the virus. This enabled the researchers to analyse the levels of pre-existing T cells induced by previous common cold coronavirus infections that were cross-reactive to proteins of the SARS-CoV-2 virus. They compared the frequency of these cross-reactive T cells in SARS-CoV-2 PCR-positive and PCR-negative COVID-19 contacts.

The researchers found significantly higher levels of cross-reactive and nucleocapsid-specific IL-2-secreting memory T cells in the 26 household contacts who remained PCR-negative despite exposure, compared with the 26 people who converted to being PCR-positive.

These T cells targeted internal proteins within the SARS-CoV-2 virus, not the spike protein on the surface of the virus. No significant difference in the frequency of responses to the spike protein were observed, they said, “hinting at a limited protective function of spike-cross-reactive T cells”.

The results were thus “consistent with pre-existing non-spike cross-reactive memory T cells protecting SARS-CoV-2-naïve contacts from infection, thereby supporting the inclusion of non-spike antigens in second-generation vaccines”.

‘Clear Evidence’ of T Cell Protective Role

Prof Ajit Lalvani, senior author of the study, and director of the NIHR Health Protection Research Unit in Respiratory Infections at ICL, said: “Our study provides the clearest evidence to date that T cells induced by common cold coronaviruses play a protective role against SARS-CoV-2 infection.

“These T cells provide protection by attacking proteins within the virus, rather than the spike protein on its surface.

“The spike protein is under intense immune pressure from vaccine-induced antibody, which drives evolution of vaccine escape mutants. In contrast, the internal proteins targeted by the protective T cells we identified mutate much less. Consequently, they are highly conserved between the various SARS-CoV-2 variants, including Omicron.”

However, Dr Kundu advised: “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.”

Limitations to the study included the small sample rate, and the large percentage of participants from White European backgrounds.

The investigation was funded by the NIHR Health Protection Research Unit in Respiratory Infections, and the Medical Research Council.

Kundu, R., Narean, J.S., Wang, L. et al. Cross-reactive memory T cells associate with protection against SARS-CoV-2 infection in COVID-19 contacts. Nat Commun 13, 80 (2022). https://doi.org/10.1038/s41467-021-27674-x