Some people had non-neutralizing antibodies against SARS-CoV-2 prior to COVID-19

Some people had non-neutralizing antibodies against SARS-CoV-2 prior to COVID-19

By Susha Cheriyedath, M.Sc.Nov 12 2020

Study: Seasonal human coronavirus antibodies are boosted upon SARS-CoV-2 infection but not associated with protection

Coronaviruses frequently infect humans. The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent behind the ongoing coronavirus disease (COVID-19) pandemic. It rapidly spread in humans, many of whom have been exposed to antigenically distinct seasonal human coronaviruses in the past.

Does previous exposure to seasonal human coronaviruses affect SARS-CoV-2 infections or their severity?

Seasonal coronaviruses that commonly infect humans include the alphacoronaviruses 229E and NL636-9 and the betacoronaviruses HKU1 and OC43. SARS-CoV-2 is a betacoronavirus and is more closely related to HKU1 and OC43 than the alphacoronaviruses 229E and NL6310.

A recent study examined several medical records and found that while past human coronavirus exposures are not linked to decreased SARS-CoV-2 infections, they are associated with reduced COVID-19 severity. It is not clear if prior exposure to human coronaviruses produces antibodies that influence the clinical outcomes of SARS-CoV-2 infections. Moreover, it is not known if individuals of different ages may have different human coronavirus immune histories that could impact SARS-CoV-2 susceptibility.

To address this issue, a team of researchers from various departments of the University of Pennsylvania, Children’s Hospital of Philadelphia, and Thomas Jefferson University, Philadelphia, USA, completed a serological survey using serum samples taken from individuals of different ages before the COVID-19 pandemic. Their study is published on the preprint server medRxiv*.


Researchers quantified SARS-CoV-2 and human coronavirus antibodies in pre-pandemic serum samples

The team measured the levels of antibodies that are reactive to human coronavirus viral proteins and tested if these antibodies offered SARS-CoV-2 protection. They quantified levels of antibodies reactive to SARS-CoV-2 and antibodies reactive to human coronaviruses in serum samples collected prior to the COVID-19 pandemic.

They also measured pre-pandemic antibody levels in serum collected from a separate group of individuals who became infected with SARS-CoV-2, which was confirmed by PCR tests. Finally, the team longitudinally measured serum human coronavirus and SARS-CoV-2 antibodies in COVID-19 patients who were hospitalized.

23% of the participants possessed non-neutralizing antibodies to SARS-CoV-2 S and N proteins

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The results of their analyses indicate that many people had antibodies for human coronaviruses prior to the COVID-19 pandemic. The research team found that about 23% of the study participants had non-neutralizing antibodies that reacted with the spike and nucleocapsid proteins of the SARS-CoV-2 virus. While these antibodies were not associated with protection against SARS CoV-2 infections, or the severity of these infections, the levels of human coronavirus reactive antibodies increased upon SARS-CoV-2 infection.

“We show that pre-pandemic SARS-CoV-2 cross-reactive antibodies are non-neutralizing and are not associated with reducing SARS-CoV-2 infections and hospitalizations.”

Prior exposure to human betacoronaviruses elicit non-protective antibodies reactive to SARS-CoV-2 proteins

This study used serum samples collected in 2017 and found that 23% of the samples had antibodies against the SARS-CoV-2 S & N proteins. The amount of antibodies against the N protein (18.6% seropositive) were more prevalent than those directed against the S protein (5.4% seropositive).

They also evaluated the need for respiratory support and ICU admission as indications of COVID-19 severity. However, this study cohort was small and larger cohorts, including individuals with varying clinically defined disease severities, will be needed to assess if pre-pandemic antibodies levels play any role in reducing the severity of COVID-19 in some patients.

Although their data suggest that prior exposure to seasonal human betacoronaviruses such as OC43 elicit antibodies reactive to SARS-CoV-2 proteins, it is unknown why only some OC43 seropositive individuals had antibodies reactive to SARS-CoV-2 pre-pandemic.

“Although our data suggest that prior infections with seasonal human betacoronaviruses (such as OC43) likely elicit antibodies that cross-react with SARS-CoV-2 proteins, it is unclear why only a subset of OC43 seropositive individuals possessed antibodies reactive to SARS-CoV-2 before the pandemic.”

According to the team, further studies are required to determine the relationship between seasonal human betacoronavirus infections and the production of SARS-CoV-2 antibodies and if these antibodies have a role in resolving or worsening the severity of SARS-CoV-2 infections.

“Additional studies need to be completed to determine if neutralizing antibodies elicited by SARS-CoV-2 infections protect against subsequent reinfections with SARS-CoV-2.”

*Important Notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.


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