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Cross-reactive T cells protect against COVID-19 infection

Cross-reactive T cells produced after an earlier coronavirus infection appear to offer protection against infection with COVID-19

Cross-reactive T cells developed in response to an earlier infection with a coronavirus prior to the current pandemic, 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 as of January 9th 2022, the COVID-19 pandemic has led to nearly 5.5 million deaths worldwide, preliminary analyses suggested that 20 to 50% of people who had not been exposed to COVID-19, had significant T cell reactivity directed against COVID-19 peptides.

To date however, studies have not explored the possible association between cross-reactive T cells with the outcomes after exposure to COVID-19. Thus in 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 who is 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. 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 naïve 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

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