Study of COVID-19 provides 'unparalleled' chance to advance autoimmunity knowledge
Studies examining the immunopathogenesis of COVID-19 and its link to immune system dysregulation are providing an “unparalleled opportunity” to learn more about autoimmunity, according to a review published in Pathogens and Immunity.
“This is a very recent review and like all things in COVID it is already dated,” Leonard H. Calabrese, DO, RJ Fasenmyer chair of clinical immunology at the Cleveland Clinic, and one of the authors of the review, told Healio Rheumatology. “Over the past several months, there has been a surge in publications regarding the COVID-19–autoimmune axis. A series of papers have clearly identified a host of autoantibodies present in acute COVID, yet at this time we don’t know the function or implications. Unknown at present is whether these autoantibodies are drivers or mere passengers in both acute and post COVID manifestations.”
In the review, Calabrese, who is also chief medical editor for Healio Rheumatology, joined Nicole Eve Winchester, BS, of the Cleveland Clinic Lerner College of Medicine, and Cassandra Calabrese, DO, of the Cleveland Clinic department of rheumatic and immunologic diseases, in posing critical questions regarding the intersections of COVID-19 and autoimmunity. They then aimed to address those questions with a critical synthesis of selected articles and research.
Critical questions included: What do we know about the clinical course of patients with immune mediated inflammatory diseases (IMIDs) who develop COVID-19? What lessons may be learned from examining the clinical outcomes of patients on immuno-modulatory therapy at baseline? Does COVID-19 induce autoantibodies and autoimmune disease?
Also: What is the relationship between autoimmunity and the newly defined post COVID-19 syndromes such as multisystem inflammatory syndrome in children (MIS-C) and adults (MIS-A)? Do we understand the mechanisms of autoimmunity in COVID-19? What do we know about immunizing patients with IMIDs for COVID-19? Does autoimmunity contribute to the syndrome of long COVID-19?
According to the authors, several critical questions remain unanswered regarding those with pre-existing IMIDs and COVID-19, whether they have an increased risk for infection, and whether they may demonstrate more severe disease once infected. Regarding patients receiving baseline immunomodulatory therapy, the authors noted “one consistent finding” that daily moderate- to high-dose glucocorticoids were associated with a significant risk for severe outcomes.
“Even more potentially informative is the examination of the clinical outcomes of COVID-19 in patients with IMIDs who acquire the infection while already on biologic disease-modifying antirheumatic drugs, in particular anti-cytokine agents, as well as targeted synthetic DMARDs (i.e., JAK inhibitors and others),” they wrote. “In these settings the effects of select immune inhibition early in the course of infection may provide unique opportunities for insights not possible when such agents are not started until the disease progresses.”
The authors also noted that more than 1,200 cases of MIS-C have been reported since April 2020. The current understanding of the immunopathogenic mechanisms underlying MIS-C is rapidly evolving, they wrote. According to Calabrese and colleagues, some data “implicate” aberrant innate immunity in MIS-C, with reports of increased complement activation and activated neutrophils, as well as monocytes and elevated pro-inflammatory cytokines and markers of inflammation.
Finally, the authors wrote that the “next frontier” of the disease will be “long COVID-19,” or the various long-term signs and symptoms demonstrated by patients who have recovered from the acute phase of infection. So far, these have most commonly included fatigue, dyspnea, brain fog, arthralgia, autonomic symptoms and others. According to the researchers, there is currently little data on any role for autoimmunity in long COVID-19, and studies to better understand its pathogenesis are sorely needed.
“The study of COVID-19 in terms of its immunopathogenesis and its relationship to dysregulation diseases of the immune system is providing an unparalleled opportunity for progress in the study of the human immune system,” the authors wrote in the review. “The massive output of this biomedical research effort will likely yield important insights into the immunopathogenesis, treatment, and possibly prevention of diseases of the immune system, including inborn errors of immunity, autoimmune and auto-inflammatory, and immunothrombotic diseases, among others.”
In addition, the authors pointed out the “unprecedented” pace of research and other output on these topics, with nearly 100,000 articles and studies published as of Dec. 30, 2020 — less than a year since the pandemic began.
“It should be noted that some of the things we are seeing post COVID like postural orthostatic tachycardia syndrome, or POTS, are associated with autoantibodies, yet we await robust studies,” Calabrese told Healio Rheumatology. “Also happening as we speak: The early reporting of a variety of post COVID vaccine anecdotes of inflammatory origin that clearly incriminate acute inflammation and possible immune dysregulation. What is clear is that the COVID–autoimmune intersection will be busy as we move ahead, and rheumatologists will have a lot to offer.”