Autoimmune and Autoinflammatory Connective Tissue Disorders Following COVID-19

Abstract

ImportanceMultiple cases of autoimmune and autoinflammatory diseases after COVID-19 have been reported. However, their incidences and risks have rarely been quantified.ObjectiveTo investigate the incidences and risks of autoimmune and autoinflammatory connective tissue disorders after COVID-19.Design, Setting, and ParticipantsThis was a retrospective population-based study conducted between October 8, 2020, and December 31, 2021, that used nationwide data from the Korea Disease Control and Prevention Agency COVID-19 National Health Insurance Service cohort and included individuals who received a diagnosis of COVID-19 via polymerase chain reaction testing and a control group with no evidence of COVID-19 identified from National Health Insurance Service of Korea cohort. Data analysis was conducted from September 2022 to August 2023.ExposuresReceipt of diagnosis of COVID-19.Main Outcomes and MeasuresThe primary outcomes were the incidence and risk of autoimmune and autoinflammatory connective tissue disorders following COVID-19. A total of 32 covariates, including demographics, socioeconomic statuses, lifestyle factors, and comorbidity profiles, were balanced through inverse probability weighting. The incidences and risks of autoimmune and autoinflammatory connective tissue disorders were compared between the groups using multivariable Cox proportional hazard analyses.ResultsA total of 354 527 individuals with COVID-19 (mean [SD] age, 52.24 [15.55] years; 179 041 women [50.50%]) and 6 134 940 controls (mean [SD] age, 52.05 [15.63] years; 3 074 573 women [50.12%]) were included. The risks of alopecia areata (adjusted hazard ratio [aHR], 1.12; 95% CI, 1.05-1.19), alopecia totalis (aHR, 1.74; 95% CI, 1.39-2.17), antineutrophil cytoplasmic antibody–associated vasculitis (aHR, 2.76; 95% CI, 1.64-4.65), Crohn disease (aHR, 1.68; 95% CI, 1.31-2.15), and sarcoidosis (aHR, 1.59; 95% CI, 1.00-2.52) were higher in the COVID-19 group. The risks of alopecia totalis, psoriasis, vitiligo, vasculitis, Crohn disease, ulcerative colitis, rheumatoid arthritis, adult-onset Still disease, Sjögren syndrome, ankylosing spondylitis, and sarcoidosis were associated with the severity of COVID-19.Conclusions and RelevanceIn this retrospective cohort study, COVID-19 was associated with a substantial risk for autoimmune and autoinflammatory connective tissue disorders, indicating that long-term management of patients with COVID-19 should include evaluation for such disorders.

New‐onset ANCA‐associated vasculitis presenting with neuropathy after COVID‐19 infection: A case report and literature review

“…57 Recent studies have suggested that COVID-19 infection may trigger or exacerbate autoimmune diseases such as AAV in susceptible individuals. 12,58 In a cohort study by Lim et T A B L E 1 (Continued) significantly higher in the post-group compared to the controls. 58 There are various potential mechanisms which induce autoimmunity after COVID-19 infection.…”

“…12,58 In a cohort study by Lim et T A B L E 1 (Continued) significantly higher in the post-group compared to the controls. 58 There are various potential mechanisms which induce autoimmunity after COVID-19 infection. One of them is molecular mimicry, leading to the immune system falsely attacking its self-tissues when a viral protein is analogous to a protein in the body.…”

COVID‐19 vaccination and autoimmunity: Do we need more evidence?

“…However, there is a substantial body of evidence suggesting that both SARS-CoV-2 natural infection and COVID-19 vaccination (mRNA vaccines, vectored vaccines, and inactivated virus vaccines) are associated with the new onset or exacerbation of existing autoimmune and autoinflammatory conditions. [1][2][3][4][5][6][7][8][9] The question arises whether the current evidence is sufficient to confirm with postvaccination emergence of 31 cases of autoimmune conditions, including systemic lupus erythematosus (SLE), thyroiditis, Graves' disease, IgA vasculitis, inflammatory arthritis, dermatomyositis, ulcerative colitis, autoimmune hepatitis, autoimmune hemolytic anemia, autoimmune pancreatitis, ANCA vasculitis, myasthenia gravis, and Sjögren's syndrome (SS). 2 Similarly, the vectored vaccine Sputnik has also been linked to the emergence of 28 cases of autoimmune conditions in Mexico and Argentina.…”

Increasing autoimmune rheumatic diseases as a consequence of the COVID‐19 pandemic: A hypothesis or fact?

“…Indeed, cohort studies in Taiwan, Germany, the UK, and South Korea, published in 2023, confirmed that SARS-CoV-2 infection was associated with increased ARD morbidity. [5][6][7][8] Notably, in a German cohort of 641 704 patients with COVID-19, matched with controls, there was a 43% higher likelihood of acquiring a new autoimmune disease within 3-15 months after SARS-CoV-2 infection. 6 The COVID-19 global vaccination campaign has raised concerns over the scale of adverse outcomes and the likelihood of associated autoimmunity.…”

“…With time passing and accumulating evidence, similar hypotheses of COVID‐19‐induced RA were tested in large studies with crystallizing a scientific fact of the association. Indeed, cohort studies in Taiwan, Germany, the UK, and South Korea, published in 2023, confirmed that SARS‐CoV‐2 infection was associated with increased ARD morbidity 5–8 . Notably, in a German cohort of 641 704 patients with COVID‐19, matched with controls, there was a 43% higher likelihood of acquiring a new autoimmune disease within 3–15 months after SARS‐CoV‐2 infection 6 …”