Penn Research: COVID-19 Survivors at Risk for Autoimmunity


E. John Wherry, PhD, was a co-author of the report.
An international investigation led by researchers at the Perelman School of Medicine, among others, warns that a significant subset of patients with COVID-19 could be at risk for progression to symptomatic, classifiable autoimmunity in the future.

As the present pandemic evolved, clinicians and researchers sensed an equation between the sequelae of SARS-CoV-2 infection in COVID survivors—including fatigue, arthralgia, myalgia, and thrombosis—and those of autoimmune disease. Over time, observational studies arriving from Asia, Europe and the Middle East seemed to bear this out with the finding of serum autoantibodies in hospitalized patients with COVID-19. A hallmark of most autoimmune diseases, autoantibodies are a self-directed aberration of the normal immune response to pathogens and cell destruction.

Having discovered autoantibodies in patients with COVID-19, researchers then began a search for candidate target autoantigens, which could be employed for diagnostic and therapeutic ends. Achieving this goal, however, meant identifying autoantibody molecular targets in persons with COVID-19, as well as the association of these targets with anti-viral immune responses, particularly with regard to the timing of autoantibody appearance in SARS-CoV-2 infection.

New-Onset IgG Autoantibodies in Hospitalized Patients with COVID-19

To address the latter, investigators at the Perelman School of Medicine, Stanford University and the Philipps Universität Marburg, Marburg, Germany, conducted a multi-center study that employed a multiplexed, bead-based platform and protein assays in 147 COVID-19 patients to measure hallmark IgG autoantibodies associated with connective tissue diseases (CTDs), as well as anti-cytokine antibodies (ACA) and anti-viral antibody responses.

Among the findings of the study: autoantibodies were identified in about half of hospitalized COVID-19 patients, but in fewer than 15% of healthy controls. For the most part, when present, these autoantibodies targeted autoantigens associated with rare immune disorders such as myositis and systemic sclerosis.

Importantly, a subset of autoantibodies and anti-cytokine antibodies developed de novo following SARS-CoV-2 infection, potentially placing some patients at risk for progression to autoimmunity in the future. 

In a recent interview, study co-author E. John Wherry, PhD, commented, "It seems to give the virus a powerful advantage. Now your immune system, instead of having a tiny little hill to climb, is staring at Mount Everest." He continued, "That really is devious. I'm not aware of another viral infection where that happens." 

Dr. Wherry directs the Institute for Immunology, and is Chair, Department of Systems Pharmacology and Translational Therapeutics at the University of Pennsylvania.

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