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Betacoronaviruses are a subfamily of the coronaviruses – a group of related viruses that cause illness in birds and mammals, including humans. Members of this subfamily include SARS-CoV-1 (which causes severe acute respiratory syndrome, or SARS), MERS-CoV (which causes Middle East respiratory syndrome, or MERS), SARS-CoV-2 (which causes COVID-19), and HCoV-OC43 (which causes the common cold). A 2013 study found that betacoronaviruses generate cross-reactive antibodies against SARS-CoV in serological testing.

Serological tests detect antibodies present in the blood following a response to a specific infection, such as SARS or COVID-19. Previous studies have found that SARS-CoV-1 can generate antibodies against HCoV-OC43 (which could offer cross-immunity). Similarly, HCoV-OC43 can generate cross-reactive antibodies against SARS-CoV-1 (which could generate false positives on serological antibody tests).

The seroprevalence study involved 94 game-food animal handlers, 28 SARS patients, and 152 healthy blood donors in Southern China. The authors of the study used indirect immunofluorescence and neutralizing antibody tests to screen for antibodies.

They found that two of the animal handlers had antibodies against HCoV-EMC and SARS-CoV-1, with low levels of neutralizing antibodies. However, 17 of the SARS patients had neutralizing antibodies against HCoV-OC43. None of the healthy blood donors had any antibodies against either virus.

These findings suggest that betacoronaviruses can induce immune responses against one another, generating neutralizing antibodies and/or cross-reactive antibodies against each other. This could confound serological surveillance studies investigating the prevalence of SARS-CoV-2 infection, while also raising the possibility for cross-immunity. No data currently exist demonstrating that betacoronaviruses generate cross-reactive and/or neutralizing antibodies against SARS-CoV-2. Both scenarios are probable.

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