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Uninfected People especially children have pre-existing SARS-CoV-2 antibodies

Although there is a lot of emphasis on SARS-CoV-2, the coronavirus at the heart of the global pandemic, there are many coronaviruses that infect humans. Sometimes, these seasonal coronavirus infections occur and usually lead to a mild, widespread cold-like disease. The presence of these coronavirus infections in the population has led to the hypothesis that, among these associated viruses, immune cross-reactivity may occur and that SARS-CoV-2 may provide some protection. Now, in a limited proportion of people who were uninfected at the time of sampling, a group of scientists have established pre-existing antibody-driven immunity against SARS-CoV-2.

This paper is published in the journal Science. "Preexisting and de novo humoral immunity to SARS-CoV-2 in humans". 229E (alpha coronavirus), NL63 (alpha coronavirus), OC43 (beta coronavirus), and HKU1 (beta coronavirus) are the four coronaviruses that cause a widespread cold-like infection when infecting humans. Much more severe infections are caused by the other three coronaviruses known to infect humans. These are MERS-CoV (beta-coronavirus that causes respiratory syndrome in the Middle East, or MERS), SARS-CoV (beta-coronavirus that causes SARS), and SARS-CoV-2, the novel coronavirus that causes COVID-19. People around the world are typically infected with 229E, NL63, OC43, and HKU1 human coronaviruses.

The London-based research group found that 16 out of 302 adults (5.3%) harboured IgG antibodies that were possibly produced during previous seasonal 'common cold' coronavirus infections and cross-reacted with the SARS-CoV-2 spike protein complex subunit S2.

Notably, in an additional cohort of SARS-CoV-2 uninfected children and adolescents (aged 1 to 16 years), the presence of these cross-reactive IgG antibodies was even more prevalent: at least 21 of these 48 subjects (43.8%) had detectable levels of SARS-CoV-2 S-reactive IgG antibodies.

Using flow cytometry, Kevin Ng, a graduate student at the Francis Crick Institute, and colleagues, discovered that uninfected individuals' SARS-CoV-2-reactive antibodies were primarily from the IgG class, rather than IgM or IgA antibodies, which targeted the viral S2 protein, responsible for cell entry and thought to be more organized across distinct coronaviruses than subunit S1.

The authors wrote, on the other hand, that "SARS-CoV-2 infection induced higher SARS-CoV-2 S-reactive IgG antibody titers, targeting both the S1 and S2 subunits, and concomitant IgM and IgA antibodies, lasting throughout the observation period." In particular, "SARS-CoV-2-uninfected donor sera exhibited specific neutralizing activity against pseudotypes of SARS-CoV-2 and SARS-CoV-2 S."

Sera from both older and younger uninfected individuals with cross-reactive antibodies demonstrated the ability to neutralise SARS-CoV-2 and SARS-CoV-2 S pseudotypes in cell culture experiments, while serum from uninfected patients without cross-reactive antibodies showed no such neutralising activity. The authors said that further exploring possible S2 targets that are preserved across multiple coronaviruses may hold the promise of a universal coronavirus vaccine.

Together, these results may help to explain the higher vulnerability of COVID-19 in the elderly and provide insight into whether pre-established immunity to seasonal coronaviruses provides SARS-CoV-2 defence.

Although previous studies indicate that cross-reactive immunity is neither sterilizing nor long-lasting, the presence of cross-reactivity is an important area of research and can minimize viral transmission and relieve symptoms. The authors noted that for our understanding of susceptibility to and the natural course of SARS-CoV-2 infection, separating preexisting and de novo immunity' would be important.

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