Autoantibodies present in long COVID, but not a ‘smoking gun’ for new autoimmune disease
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WASHINGTON — The correlation between autoantibodies and new-onset autoimmune disease in individuals with long COVID symptoms remains “controversial,” according to a speaker at ACR Convergence 2024.
“Disclaimer: This is a controversial topic,” Leonard H. Calabrese, DO, professor of medicine at the Cleveland Clinic Lerner College of Medicine, at Case Western Reserve University, RJ Fasenmyer chair of clinical immunology at the Cleveland Clinic, and chief medical editor of Healio Rheumatology, told attendees. “The post-infectious sequelae have many different names. These sequalae have been marginalized and poorly studied. There is a great need.”
Calabrese acknowledged a host of pathologically documented, non-syndromic complications, including evidence of increased rates of cardiovascular and metabolic disease along with thromboembolic events.
However, there is another part of the story.
“The larger picture is when people have what we call ‘syndromic long COVID,’” Calabrese said.
These patients can experience severe complications such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) or dysautonomia, according to Calabrese.
“They are living a nightmare; they are without answers, they are without treatments,” he said.
Meanwhile, efforts to categorize long COVID symptoms and syndromes are replete with “dozens of definitions” that have “languished or withered under scrutiny for a variety of reasons,” Calabrese added.
One issue is that some groups have defined long COVID as occurring within 30 or 60 days of acute infection, while others define it as occurring 90 or 180 days after.
“The number of symptoms has continuously grown,” Calabrese added. “This has plagued the field of research.”
Enter the National Academy of Sciences, Engineering, and Medicine (NASEM), which recently shouldered the task of defining the broad spectrum of sequelae that can come in the wake of acute COVID-19 infection. The final document suggests that there can be more than 200 long COVID symptoms overall.
Of particular importance for rheumatologists, according to Calabrese, is a component of the NASEM definition of long COVID that suggests autoimmune conditions like lupus, rheumatoid arthritis, Sjögren’s disease and others may arise in the wake of infection. “Rheumatologists are now in the fore,” Calabrese said.
Rheumatology providers are encouraged to use their clinical judgment when assessing these patients.
“It requires data and critical appraisal,” Calabrese said.
However, one of the biggest challenges is that even with observed phenomena in long COVID research, it is difficult to draw conclusions.
“There are incontrovertible data that there is persistent protein of this virus several years after the infection,” Calabrese said. “But what that means is not clear.”
The same is true for autoantibodies.
“It is incontrovertible that there is a broad spectrum of autoantibody reactivity that occurs in the wake of COVID-19,” Calabrese said. “This gives us pause.”
It is similarly incontrovertible that the “breadth and depth” of the autoantibodies correlate with the severity of infection, he added.
“These autoantibodies are functional,” Calabrese said, noting that they bind to cytokines and G-protein coupled receptors.
However, evidence regarding whether these autoantibodies correlate with clinical disease is “varying,” according to Calabrese.
“Autoantibodies are there but it does not mean they are the smoking gun for clinical diseases,” he said.
More research is needed to fully understand all the associations at play between acute COVID infection, long COVID, autoantibody production and autoimmune disease.
“There are inconsistencies and questions of robustness even of the clinical data,” Calabrese said. “At this point in time I think we have a lot of work to do.”
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Calabrese L. Immune Dysregulation and Long COVID: Causation or Association? Presented at: ACR Convergence 2024; Nov. 14-19, 2024; Washington, D.C.
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