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

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

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.

Journal reference:
  • Seasonal human coronavirus antibodies are boosted upon SARS-CoV-2 infection but not associated with protection Elizabeth M. Anderson, Eileen C. Goodwin, Anurag Verma, Claudia P. Arevalo, Marcus J. Bolton, Madison E. Weirick, Sigrid Gouma, Christopher M. McAllister, Shannon R. Christensen, JoEllen Weaver, Phillip Hicks, Tomaz B. Manzoni, Oluwatosin Oniyide, Holly Ramage, Divij Mathew, Amy E. Baxter, Derek A. Oldridge, Allison R. Greenplate, Jennifer E. Wu, Cécile Alanio, Kurt D’Andrea, Oliva Kuthuru, Jeanette Dougherty, Ajinkya Pattekar, Justin Kim, Nicholas Han, Sokratis A. Apostolidis, Alex C. Huang, Laura A. Vella, The UPenn COVID Processing Unit, E. John Wherry, Nuala J. Meyer, Sara Cherry, Paul Bates, Daniel J. Rader, Scott E. Hensley medRxiv 2020.11.06.20227215; doi:,
Susha Cheriyedath

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Susha Cheriyedath

Susha has a Bachelor of Science (B.Sc.) degree in Chemistry and Master of Science (M.Sc) degree in Biochemistry from the University of Calicut, India. She always had a keen interest in medical and health science. As part of her masters degree, she specialized in Biochemistry, with an emphasis on Microbiology, Physiology, Biotechnology, and Nutrition. In her spare time, she loves to cook up a storm in the kitchen with her super-messy baking experiments.


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