Study of mechanisms of immunity against SARS-Cov-2 through infection with cold coronaviruses

A high percentage of 85 to 90 percent of people infected with SARS-Cov-2 remain with no or mild symptoms. Most of them don’t even notice the infection. It has long been suspected that there is immunity here. Researchers from the USA and Australia have now presented the results of their studies on the mechanisms of immunity from previous infections with the common cold coronaviruses.

There are many unknowns about human immune responses to the SARS-CoV-2 virus. SARS-CoV-2 reactive T cells have already been found in non-exposed people in several studies, which indicates an already existing cross-reactive T cell memory in humans. Further results have now been found in Sciencemag published as preprint.

The type and function of the T cells that provide immunity has so far been speculative. In human blood samples taken before the SARS-CoV-2 virus was discovered in 2019, a number of existing CD4 + T storage cells showed cross-reactivity to SARS-CoV-2 and the common cold coronaviruses HCoV-OC43, HCoV -229E, HCoV-NL63 or HCoV-HKU1. Therefore, T-cell memory for coronaviruses that cause colds may account for at least part of the overall immunity seen in SARS-Cov-2 infections.

Previous study results

Studies examining the human immune response to SARS-CoV-2 have begun to characterize SARS-CoV-2-specific T cell responses, and several studies have shown marked activation of T cell subsets in acute COVID-19 Patients.

For example, T-cell studies conducted in five different countries reported that 20-50% of people not exposed to SARS-CoV-2 showed significant T-cell reactivity to SARS viruses. The studies came from the USA, the Netherlands, Germany, Singapore and the UK. The general pattern observed was that the T cell reactivity found in non-exposed persons was predominantly mediated by CD4 + T cells (T helper cells). It was believed that this phenomenon was due to pre-existing detection of human cold coronaviruses such as HCoV-OC43, HCoV-HKU1, HCoV-NL63 or HCoV-229E. These HCoVs have a similar structure and components as SARS-CoV-2, are widespread in the general population and are usually responsible for mild symptoms.

This cross-reactive T-cell immunity to SARS-CoV-2 has far-reaching implications as it could explain aspects of the diverse clinical outcomes of COVID-19, influence epidemiological models of herd immunity, and affect the performance of COVID-19 vaccine candidates.

The study results

The study used samples from non-exposed volunteers, which were collected between March 2015 and March 2018, long before SARS-CoV-2 spread around the world. The non-exposed subjects were confirmed as negative for SARS-CoV-2.

SARS-CoV-2 reactive T cells were tested for their reactions to the various “spikes” and their components. In 82 of 88 cases (93.2%) the cells that reacted to the SARS-CoV-2 were clearly CD4 + T cells (T helper cells). In four cases (4.5%) the responding cells were CD8 + T cells (the suppressor or killer cells) and in two cases (2.3%) the responses were detected by both CD4 + and CD8 + T cells .

The investigation was also able to clarify which parts (epitopes) of SARS-Cov-2 were recognized by the existing T cells. These virus parts are the same for cold viruses and SARS and can therefore be recognized by T cells that originated in your of the two types of virus and thus also combated.

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