Why are young people better protected?

Could the immune response that protects us against common coronaviruses (HCoVs) prevent infection by SARS-CoV-2? To answer this question, a team of British researchers at the Francis Crick Institute, London, has developed an efficient test (flow cytometry) which allows the presence of antibodies targeting the spike (S) protein of the virus to be evaluated. This protein governs the entry of the virus into the cell.

The results obtained were systemically validated by more conventional approaches (ELISA), and the capacity of the neutralizing antibodies to block the entry of the virus was evaluated by infection tests in vitro. The results compiled analyses from several small groups of voluntary donors, some having contracted COVID-19 and others not (confirmed by RT-PCR testing). They were then further confirmed by supplementary samples taken prior to the pandemic.

Obviously, the test detected anti-S antibodies in all 156 patients infected by SARS-CoV-2. But unexpectedly, a small fraction (16 out of 302; 5,29%) of non-infected patients reacted positively to the test. Unlike the COVID-19 patients, this antibody response was incomplete (certain categories of antibodies were absent), which suggests the presence of a cross-reactive memory immune response. Although the prevalence was low in adults, levels reached 62% in young people from 6 to 16 years of age, that is, 21 out of 48. Young people in general are particularly sensitive to HCoV infection. Using in vitro  biochemical approaches, researchers discovered that these antibodies were primarily directed against the S2 spike domain, which is relatively stable, that is to say less susceptible to mutations among the various HCoVs strains. The anti-S antibodies of these COVID-19-negative patients are capable of blocking the entry of SARS-CoV-2 into cells, though less effectively than in positive patients.

Several other epidemiological analyses suggest that this cross-reactivity does not last, which explains how we can become reinfected by different strains of coronavirus. On the other hand, infection by an HCoV may reduce transmission as well as symptoms caused by other strains, including SARS-CoV-2. This may explain in part why the severity of COVID-19 is reduced in children exposed to repeated infections by HCoVs, leading to strong immune memory.

This cross-reactive protection needs to be further investigated, but it opens up the possibility of developing a vaccine to target in particular the S2 region of the spike protein in order to enable an almost universal protection against the virus.