One more study has shown that pre-existing T cell memory against four common cold coronaviruses can cross-recognise novel coronavirus (SARS-CoV-2) even when the person has never been infected with SARS-CoV-2 before.

One more study has shown that pre-existing T cell memory against four common cold coronaviruses can cross-recognise novel coronavirus (SARS-CoV-2) even when the person has never been infected with SARS-CoV-2 before. The results were published in the journal Science. This suggests that fighting off a common cold coronavirus can indeed teach the T cell compartment to recognize some parts of SARS-CoV-2 and provides evidence for the hypothesis that four common cold viruses can, in fact, induce cross-reactive T cell memory against SARS-CoV-2.

Based on the results of the study, the authors from La Jolla Institute for Immunology say it is plausible to hypotheses that pre-existing cross-reactive common cold coronavirus CD4 T cells in some people might be a contributing factor to variations in COVID-19 disease outcomes. In other words, previous exposure to common cold coronaviruses might have trained the immune memory against SARS-CoV-2.

This could possible explain why an overwhelming percentage of people only exhibit mild symptoms when infected with novel coronavirus. The authors however insist that variations in COVID-19 disease arising from cross-reactive common cold coronavirus CD4 T cells is currently “highly speculative” and much more data are needed.

Having a strong or better T cell responses might give a person to mount a much quicker and stronger response to the virus when infected. And immune reactivity may be the reason why many people who are infected do not progress to severe forms of the disease.

T cell reactivity to SARS-CoV-2 epitopes from previous exposure to common cold coronavirus seen in people who have not been exposed to novel coronavirus was first reported in the journal Cell. The study by a team led by Alessandro Sette from La Jolla Institute for Immunology, La Jolla, California showed that 40-60% of people never exposed to SARS-CoV-2 had T cells that reacted to the virus. Their immune systems recognized fragments of the virus it had never seen before.

At that time the paper was published in Cell, four other studies, which were posted as preprints, also showed a similar cross-reactivity. One of the preprints was subsequently published in Nature.

How cross-reactivity was confirmed

For the study published in Science, the researchers from La Jolla Institute for Immunology relied on blood samples collected from people between March 2015 and March 2018, well before the emergence of novel coronavirus. These people were conformed to seronegative for SARS-CoV-2.

The researchers were able to define the exact sites of the virus that are responsible for the cross-reactive T cell response. They identified 142 SARS-CoV-2 epitopes — 66 from the spike protein and 76 from the remainder of the genome. The spike protein is the region of the virus that recognizes and binds to human cells. And pre-existing immune memory was also directed to both the spike protein and other SARS-CoV-2 proteins. These findings suggest the hypothesis that inclusion of additional SARS-CoV-2 targets might enhance the potential to take advantage of this cross reactivity and could further enhance vaccine potency.

“The 142 mapped SARS-CoV-2 epitopes may prove useful in future studies as reagents for tracking CD4+ T cells in SARS-CoV-2 infected individuals, and in COVID-19 vaccine trials,” they write.

They found 40 of the 142 epitopes were recognized by two or more donors, thus accounting for 55% of the total response. They however caution that cross-reactive common cold coronavirus T cell are in stark contrast to common cold coronavirus neutralizing antibodies, which are species-specific and did not show cross-reactivity against SARS-CoV-2.