Common coronavirus may prime immune system to develop long COVID

COVID-19
Woman blowing nose

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Previous infection with an endemic coronavirus that causes the common cold may predispose COVID-19 patients with rheumatic disease to persistent symptoms, a Brigham and Women's Hospital-led study suggests.

Published yesterday in Science Translational Medicine, the study involved serologic testing for antibodies against SARS-CoV-2, a panel of endemic pathogens, and a panel of routine vaccine antigens in two groups of patients with pre-existing systemic autoimmune rheumatic disease (SARD) who either did or didn't develop long COVID, or post-acute sequelae of COVID-19 (PASC).

The team first analyzed a discovery cohort recruited before December 13, 2021, to identify potential antibody profiles tied to long COVID, then replicated the results in a validation cohort recruited from December 14, 2021, to September 16, 2022. 

SARD patients, who have illnesses such as rheumatoid arthritis or other inflammatory autoimmune diseases, are at increased risk for severe COVID-19.

Partial COVID immunity, control, clearance

Up to 45% of SARD patients experienced long COVID 28 days after infection. The researchers observed that long-COVID patients had weaker Fcγ receptor (FcγR)-binding anti–SARS-CoV-2 antibodies and stronger Fcγ receptor (FcγR)-binding pro-inflammatory antibody responses against the endemic coronavirus OC43 linked to cross-reactivity against SARS-CoV-2 and common coronaviruses.

"Rather than identifying an autoimmune marker of PASC, these results from two independent cohorts point to immunological imprinting by human endemic coronaviruses in patients with SARDs and PASC that may result in the generation of incomplete SARS-CoV-2 immunity, control, and clearance," the study authors wrote.

We know that, in the setting of influenza, previous exposure to a viral strain can influence a person's immune response to subsequent strains.

Galit Alter, PhD

In a Mass General Brigham news release, co-corresponding author Zachary Wallace, MD, of Massachusetts General Hospital, said, "Our study offers evidence and explanation for why some of our patients may be experiencing the persistent and wide-ranging symptoms of long COVID. Identifying a biomarker that helps us better understand current and previous infections could shed light on an inappropriate immune response that leads to some cases of long COVID."

Co-corresponding author Galit Alter, PhD, of Moderna Therapeutics, said that a first exposure to a virus can shape lifelong immunity. "We know that, in the setting of influenza, previous exposure to a viral strain can influence a person's immune response to subsequent strains," she said. "This concept—which we call 'original antigenic sin,' may be at play for coronaviruses, too, and may influence risk of long COVID, especially among individuals with rheumatic disease."

The authors called for further research into whether the results could be applied to long-COVID patients who don't have pre-existing autoimmune disease. "By starting with patients with rheumatic diseases, we may be able to develop biomarkers that help us understand who is at high risk for developing long COVID and strategically enroll individuals into clinical trials to either prevent long COVID or develop therapies to treat it," Wallace said.

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