Common cold coronaviruses hinder antibody immune response to SARS-CoV-2 infection

Immunologist Maureen McGargill and graduate student Chun-Yang Lin stand outside the Inspiration4 Advanced Research Center

Maureen McGargill, Ph.D., Department of Immunology, and graduate student Chun-Yang Lin.

Prior infection with coronaviruses that cause the common cold impedes the antibody immune response against SARS-CoV-2, the coronavirus responsible for COVID-19. The results from St. Jude Children’s Research Hospital appeared in print today in the journal Cell Host and Microbe.

“The findings highlight an additional factor that contributes to the range of COVID-19 symptoms and their severity,” said corresponding author Maureen McGargill, Ph.D., of the St. Jude Department of Immunology.

“The results also support COVID-19 vaccination, which seems to override the downside of prior immunity to common cold coronaviruses,” she said.

Similar viruses, different antibodies

The viruses that cause COVID-19 and the common cold belong to the same large family of coronaviruses. By early in life, most people in the world have been infected with all four common cold coronaviruses, including two coronaviruses with features and structures with pronounced similarities to SARS-CoV-2.

“Prior to this study there were conflicting reports of how pre-existing immunity to common cold coronaviruses affected susceptibility to SARS-CoV-2 infection,” McGargill said.

To account for individual differences in antibody levels to common cold coronaviruses, researchers measured antibody levels from the same person before and after SARS-CoV-2 infection and vaccination.

The results showed the viruses were similar enough that SARS-CoV-2 infection boosted levels of common cold coronaviruses antibodies, but those antibodies did not neutralize or block SARS-CoV-2 infection.

Investigators showed that high levels of pre-existing antibodies to common cold coronaviruses correlated with higher levels of SARS-CoV-2 antibodies after infection, an indicator of greater disease severity.

Additional findings

  • Levels of pre-existing antibodies to common cold coronaviruses varied dramatically from person to person. The same was true following SARS-CoV-2 infection or vaccination.
  • Higher baseline levels of betacoronavirus antibodies, or a greater increase of those antibodies following SARS-CoV-2 infection, were associated with increased antibodies to SARS-CoV-2. Elevated antibodies to the pandemic virus were linked to more severe disease as measured by antibody levels.
  • Researchers did not find a similar association between baseline common cold coronavirus antibodies and SARS-CoV2 antibodies following COVID-19 vaccination. That suggests vaccines may induce an immune response strong enough to override the antibody production advantage of common cold coronaviruses.
  • Investigators reported that production of SARS-CoV-2 neutralizing antibodies were inhibited in SARS-CoV-2-immunized mice that were previously immunized against common cold coronaviruses.

St. Jude employee volunteers

The research relied on about 1,500 St. Jude employee volunteers who enrolled in the St. Jude Tracking of Viral and Host Factors Associated with COVID-19 study (SJTRC). The study began in 2020 to better understand the immune response to the pandemic virus and use the findings to improve COVID-19 prevention and treatment.

Blood samples were collected at different times in the study, including before and after confirmed SARS-CoV-2 infections and vaccination. The samples allowed researchers to track the evolving immune response. The St. Jude cohort appears to be the largest assembled with blood samples from the same person before and after COVID-19 infection.

Authors and funding

Chun-Yang Lin and Joshua Wolf, Ph.D., M.B.B.S., of St. Jude, are the first authors. The other authors are David Brice, Yilun Sun, Sean Cherry, Ashley Castellaw, Marie Wehenkel, Jeremy Chase Crawford, Kim Allison, E. Kaitlynn Allen, Scott Brown, Alexandra Mandarano, Jeremie Estepp, the SJTRC Study team, Stacey Schultz-Cherry, Li Tang and Paul Thomas, of St. Jude; Macauley Locke, Daniel Duque and Charles Taylor, University of Leeds, United Kingdom; Veronika Zarnitsyna, Emory University School of Medicine; and Carmen Molina-Paris, University of Leeds and Los Alamos National Laboratory.

The SJTRC Study team includes Aditya Gaur, James Hoffman, Tomi Mori, Elaine Tuomanen, Richard Webby, Hana Hakim, Randall Hayden, Diego Hijano, Walid Awad, Resha Bajracharya, Brandi Clark, Valerie Cortez, Ronald Dallas, Thomas Fabrizio, Pamela Freiden, Ashleigh Gowen, Jason Hodges, Allison Kirk, Ericka Kirkpatrick Roubidoux, Robert Mettelman, Jamie Russell-Bell, Aisha Souquette, James Sparks, Lee-Ann Van de Velde, Ana Vazquez-Pagan, Kendall Whitt, Taylor Wilson, David Wittman, Nicholas Wohlgemuth and Gang Wu of St. Jude.

The research was funded in part by National Institutes of Allergy and Infectious Diseases contracts (HHSN272201400006C, 75N93021C00016, 75N93019C00052) and a grant (3U01AI144616-02S1); a National Cancer Institute grant (CA021765-42) and ALSAC, the St. Jude fundraising and awareness organization.

Read the full text of the Cell Host & Microbe article:

Pre-existing humoral immunity to human common cold coronaviruses negatively impacts the protective SARS-CoV-2 antibody response

Cell Host & Microbe, published online January 12, 2022

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