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Cross-reactive T cells offer protection against COVID-19 infection

12th January 2022

Cross-reactive T cells developed in response to coronaviruses before the pandemic appear to provide immunity against infection with COVID-19

Cross-reactive T cells that have developed in response to earlier infections with a coronavirus appear to offer protection against infection with COVID-19. This was the conclusion of a small study by a team led by researchers from the NIHR HPRU in Respiratory Infections, Imperial College London, UK.

Although the current COVID-19 pandemic has, as of January 9th 2022, resulted in nearly 5.5 million worldwide deaths, studies suggest that 20 to 50% of people who had not been exposed to COVID-19 had significant T cell reactivity directed against COVID-19 peptides.

However, no studies have considered the possible association between cross-reactive T cells with the outcomes after exposure to COVID-19. For the present study, the UK team speculated that infection with pre-existing and circulating human coronaviruses, such as the common cold, might help explain why some individuals do not become infected with COVID-19 after contact with someone already infected.

The team created a specific COVID-19 peptide pool and used peripheral blood mononuclear cell (PBMC) samples obtained from 52 patients with a median age of 33 years, with confirmed exposed contacts from the INSTINCT study, between 1 and 6 days after onset of COVID-19 symptoms.

The PNMC samples were assayed for interferon-gamma (IFN-G) and interleukin-2 (IL-2) secreting T cells responses to proteins in the peptide pool. The results showed that 26 PCR positive and PCR negative samples reacted to peptides in the pool and that there was no statistical difference (p = 0.42) in the response from either IFN-G or IL-2 secreting T cells from PCR positive and negative samples.

Interestingly, the team observed that among those who were PCR negative, following exposure to COVID-19, there was a decrease in cross-reactive T cells secretion of IL-2 which they felt implied an active response to the temporary COVID-19 exposure. A further observation was how PCR negative samples, had a higher prevalence of seropositivity to other coronavirus viral strains, which supported the notion that these pre-existing T cells were induced by prior exposure.

Discussing their findings, the authors suggested that the presence of IL-2 secreting cross-reactive T cells was associated with protection from infection among COVID-19 contacts. They believed that this protection was most likely to have developed through priming of these T cells after exposure to other coronaviruses in the past.

Although based on a small number of patients, the authors concluded that their results are consistent with the notion of pre-existing non-spike cross-reactive memory T cells which protected COVID-19 naive patients.


Kundu R et al. Cross-reactive memory T cells associate with protection against SARS-CoV-2 infection in COVID-19 contacts. Nat Commun 2022.