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expert reaction to study looking at cross reactivity of T cells from common colds and protection against SARS-CoV-2 infection

A study published in Nature Communications looks at cross-reactive memory T cells associated with protection against SARS-CoV-2 infection.


Prof Mala Maini, Professor of Viral Immunology, UCL, said:

“This study from Kundu et al from Imperial constitutes another important piece in the puzzle, corroborating a number of others pointing to a protective role for cross-reactive T cells in Covid. We have all come across households where one member repeatedly tests negative for COVID whilst others around them become positive. These days that’s most likely due to differences in the efficiency with which they’ve maintained immunity following variable exposure to COVID itself, in the form of vaccines and infections during previous waves. This study recruited community infections soon after the start of symptoms during the second wave, before vaccines were available, and showed that those who tested PCR negative on 3 occasions and remained antibody negative had more cross-reactive T cells than those who became PCR positive. Their cross-reactive T cells could have resulted from previous seasonal coronavirus infection or perhaps an abortive COVID infection in the first wave. In our study in Nature we were additionally able to access blood samples from well before the start of the pandemic to show that cross-reactive responses were already present before household contacts could possibly have seen COVID and then preferentially expanded in those without PCR or antibody confirmation of infection.

“T cells recognise viral fragments once they have got into cells, rather than blocking infection as antibodies can, so it is likely that the household members testing negative in this study had a transient abortive infection that didn’t get picked up by PCR tests as described in rather than completely resisting infection. As in our study, Kundu et al highlight the non-structural proteins within the virus (as opposed to spike on the surface) as important targets for future T cell based pan-coronavirus vaccines. Just because somebody didn’t get infected once doesn’t mean their cross-reactive T cells can protect them against more infectious variants so future vaccines that boost more robust and flexible immune responses are the key going forward.”


Dr Simon Clarke, Associate Professor in Cellular Microbiology, University of Reading, said:

“The current crop of Covid-19 vaccines target the spike protein, but it seems likely that other components of the virus are involved in post-infection immunity.  This study found that people who remined negative for Covid-19, despite being exposed to the infection, had a higher number of T-cells that reacted to such other bits of the virus and it is presumed that these were generated in response to prior infection with other coronaviruses, such as those that cause the common cold.  These T-cells did not attack the virus directly or kill cells which it had invaded, but produced molecules that stimulate the activity of other types of white blood cells which would tackle the infection. 

“Although this is a relatively small study, it adds to our understanding of how our immune system fights the virus and shows that future vaccines might benefit from targeting components in addition to the spike protein.

“These data should not be overinterpreted.  It seems unlikely that everyone who has died or had a more serious infection, has never had a cold caused by a coronavirus.  It could be a grave mistake to think that anyone who has recently had a cold is protected against Covid-19, as coronaviruses only account for 10-15% of colds1.   Similarly, there is no measurement of how much protection the reported effect gives people and a link is only hinted at, it has not been proven conclusively. It should be noted that the authors of the study do not make any claims that a coronavirus cold will protect against Covid-19.”



Dr Peter English, Retired Consultant in Communicable Disease Control, Former Editor of Vaccines in Practice, past Chair of the BMA Public Health Medicine Committee, said::

“The adaptive immune system – the parts of the immune system that kick in when the system has previous experience of a pathogen, or of antigens from it – can broadly be divided into circulating antibodies, and the cellular response.

“Antibodies are very important in the immediate recognition and neutralisation of an invader.

“The cellular response is far more complicated, and includes the “killer T-cells” that attack and destroy cells that have been taken over by a virus.

“The cellular immune system is often both longer-lasting and less specific than the antibody response. Antibodies may provide some “cross-protection” against closely related pathogens – for example, where the 2, 4, and 9-valent human papillomavirus vaccines actually provide a considerable degree of protection against other human papillomavirus “types”; but in general antibody responses are fairly specific to the precise antigen they remember.

“The degree of cross-protection provided by T-cells seems to be much broader, and able to respond to a wider range of related pathogens.

“With coronaviruses, this is partly because there are structures that are common to all coronaviruses, whereas the spike proteins in the SARS-CoV-2 virus that causes Covid-19 occur only in SARS-CoV-2 viruses. Some of the other proteins making up the structure of the virus are likely to be highly conserved between SARS-CoV-2 and other coronaviruses.

“It is this concept that lies behind the initial trials on a multivariant coronavirus vaccine that we commented on recently.1

“The common cold can be caused by quite a number of viruses, including four or five coronaviruses. It is not at all surprising that some of their proteins may also occur in SARS-CoV-2; and that immunity to these common cold coronaviruses might provide some degree of protection against SARS-CoV-2.

“That said, we should remember that nearly everybody has been infected with a wide range of common cold viruses, and this does not appear to have provided much protection during the pandemic; although – as this study shows – it might partly explain some of the differences in the way people have responded.

“New variants of the coronavirus have – and will continue – to arise. Most will be more infectious (or they won’t become a problem). Some may differ in their pathogenicity: any reassurance we are getting that the omicron variant might cause less serious disease (and we don’t yet know what effects it will have on Long Covid and other longer term sequelae) should not lead us to believe that other yet-to-arise variants will be cause less severe illness; they could be worse.

“New vaccines may be better able to provide protection against a wider range of not-yet-known variants, as well as the lasting protection against infection (not just against severe illness) that might help us, through vaccination, to reduce spread.

“This highly technical and quite detailed research will likely be very useful to researchers working on what the authors refer to as “second generation” vaccines.”

  1. Bangham C, English PMB. Expert reaction to press release discussing early data from a phase 1 study (CORAL-BOOST) of a T cell-enhanced self-amplifying mRNA (samRNA) COVID-19 vaccine candidate (after two doses of AstraZeneca). Science Media Centre 2021; Updated 04 Jan 2022; Accessed: 2022 (04 Jan): (



‘Cross-reactive memory T cells associate with protection against SARS-CoV-2 infection in COVID-19 contact’ by Rhia Kundu et al. was published in Nature Communications at 10:00 UK time on Monday 10 January.




Declared interests

Prof Mala Maini: “My only conflict is our paper with overlapping findings quoted above.”

Dr Peter English: “Dr English is on the editorial board of Vaccines Today: an unpaid, voluntary, position.  While he is also a member of the BMA’s Public Health Medicine Committee (and its chair until Oct 2020), this comment is made in a personal capacity.  Dr English sometimes receives honoraria for acting as a consultant to various vaccine manufacturers, most recently to Seqirus.”

None others received.

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