CEIRR Researchers Find Immunity from Prior Common Cold Coronavirus Infections Inhibits the SARS-CoV-2 Antibody Response

Publication CommentaryDecember 22, 2022

Investigators suggest that pre-existing antibodies from the common cold may worsen COVID-19 clinical outcomes

Researchers, including Dr. Stacey Schultz-Cherry, Dr. Paul Thomas, and Dr. Maureen McGargill, from the St. Jude Children’s Research Hospital Centers of Excellence for Influenza Research and Response (SJCEIRR) addressed the important question of whether prior infection with coronaviruses, like the ones that cause common colds in humans, affects the level of disease caused by SARS-CoV-2. It is now well-established that SARS-CoV-2 infection causes diverse disease outcomes ranging from no symptoms to severe respiratory complications that can result in hospitalization and/or death. Although certain health conditions are known to increase risk of severe disease, the complete array of COVID-19 associated risk factors remains unknown. 

On left, blue SARS-CoV-2 virus with spike proteins (orange) protruding from surface. Behind & to right, scanning electron micrograph of cells (green) that are infected by Omicron strain (blue). Image not to scale & artificially colored.
Scanning electron micrograph of cells (green) that are infected by SARS-CoV-2 Omicron strain (blue). Image not to scale and artificially colored. Image credit: NIAID Flickr.

As of December 2022, more than 99 million COVID-19 cases and over one million deaths have been reported in the United States. To better understand the disease dynamics and susceptibility of the general population to SARS-CoV-2, it is vital to understand what variables contribute to disease severity. Currently, there are four common cold (non-SARS-CoV-2) coronaviruses in wide circulation across the globe that cause mild respiratory symptoms in humans. Dr. McGargill led a research team that investigated whether pre-existing immunity to common cold coronaviruses positively or negatively impacts SARS-CoV-2 immunity or COVID-19 clinical outcomes. 

Researchers collected a baseline blood sample from a cohort of St. Jude employees, who then underwent weekly nasal swabs to screen for SARS-CoV-2. Those who became infected with SARS-CoV-2 during the study provided post-infection blood samples, while those who did not test positive provided post-vaccination blood samples. Samples were assessed for antibodies against SARS-CoV-2 and the four common cold coronaviruses. The researchers found that nearly all participants had antibodies specific for the common cold coronaviruses. Interestingly, SARS-CoV-2 infection was associated with increased antibodies to the common cold viruses but did not provide protection against SARS-CoV-2. Rather, cross-reactive antibody levels correlated with higher SARS-CoV-2 specific antibodies, an indicator of more severe disease. The authors also speculate that pre-existing common cold antibodies may even delay production of SARS-CoV-2 specific antibodies. These findings suggest pre-existing common cold coronavirus antibodies that cross-react with SARS-CoV-2 may negatively impact COVID-19 clinical outcomes. The study provides important insight into the complex and difficult to characterize immune response to a novel virus when pre-existing immunity to a similar but distinct endemic virus is present. 

Lin, CY et al. (2022) Pre-existing humoral immunity to human common cold coronaviruses negatively impacts the protective SARS-CoV-2 antibody response. Cell Host and Microbe. 30(1): 83-96.e4