In a recent article posted within the Nature Reviews Rheumatology news and views, researchers reviewed data on the incidence of autoimmune diseases within the post-acute coronavirus disease 2019 (COVID-19) period.

Study: High risk of autoimmune diseases after COVID-19. Image Credit: KaterynaKon/Shutterstock.com

Background

COVID-19 has caused unprecedented morbidity and mortality across the globe. The immune protection conferred by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines and prior COVID-19 history, coupled with developing effective therapeutic agents, has reduced COVID-19-associated mortality.

Nonetheless, post-COVID-19 conditions proceed to extend, particularly new-onset autoimmune diseases in COVID-19 convalescents. Autoimmune diseases have been reported following COVID-19 amongst adults; nevertheless, the prevalence and magnitude of the diseases, and the incidence risks amongst individuals infected with SARS-CoV-2, in comparison with uninfected individuals, are usually not well-characterized.

Improving understanding of the impact of COVID-19 on the chance of developing post-acute COVID-19 complications, akin to autoimmune disease, could aid in implementing preventive measures and initiating prompt treatment to forestall COVID-19-associated morbidities.

The findings would even be highly relevant for future pandemics and to investigate the long-term protective effects of COVID-19 vaccines.

Concerning the review

Within the review, researchers presented findings of two large-scale cohort studies, evaluating the incidence of autoimmune diseases following acute SARS-CoV-2 infections using participants’ electronic medical records.

Evidence on post-COVID autoimmune disease obtained before the studies

Studies comprising pediatric COVID-19 patients affected by multisystem inflammatory syndrome amongst children (MIS-C) have indicated that COVID-19 leads to dysregulated immunological responses. The clinical manifestations of MIS-C overlap with hyperinflammatory syndromes, including macrophage activation syndrome, Kawasaki disease, and toxic shock syndrome.

The pathophysiology of COVID-19-associated immunological dysfunction includes molecular mimicry by SARS-CoV-2 proteins, multiorgan involvement resulting from the presence of angiotensin-converting enzyme 2 (ACE2) receptors, essential for SARS-CoV-2 entry into host cells, bystander immune cell activation, autoantigen release following SARS-CoV-2-induced tissue damage, superantigen-regulated lymphocyte activation, and epitope spread.

Moreover, aspects akin to genetic susceptibility, age, and comorbidities may contribute to COVID-19 pathogenesis.

A previous study comparing the immune responses in SARS-CoV-2 infection and autoimmune disease reported that tissue damage in each conditions is especially immune-regulated, demonstrated by the presence of anti-nuclear antibodies, anti-Ro/SSA antibodies, and lupus anticoagulant cold agglutinins in each conditions.

A retrospective evaluation was performed from January 31, 2020, to June 30, 2021, using the Clinical Practice Research Datalink Aurum database, comprising data from 458,147 and 1,818,929 SARS-CoV-2-infected and uninfected adults, respectively, residing in England.

A study preprint reported that the incidence of inflammatory bowel disease, psoriasis, and kind 1 diabetes was significantly related to COVID-19.

Findings of the 2 cohort studies assessed post-COVID autoimmune disease

Chang et al. utilized the TriNetX health research network, comprising six million adults across 48 health organizations globally. The propensity score-matched SARS-CoV-2-infected and uninfected groups comprised 887,455 COVID-19 vaccinees each. Post-COVID-19 autoimmune disease incidence was evaluated between January 1, 2020, and December 31, 2021.

At six months of follow-up, autoimmune disease incidence was significantly greater in SARS-CoV-2-infected individuals, including systemic lupus erythematosus, rheumatoid arthritis, vasculitis, type 1 diabetes, and inflammatory bowel disease, with adjusted hazards ratios (aHR) of two.99,2.98, 1.96, 2.68, and 1.78, respectively. Post-COVID autoimmune disease risk was consistent across ages.

Tesch et al. conducted a study, yet to be peer-reviewed, to guage autoimmune disease risks amongst 640,701 unvaccinated individuals having polymerase chain response (PCR)-confirmed SARS-CoV-2 infections in 2020.

The findings showed that COVID-19 patients were 43.0% more likely to accumulate autoimmune conditions, inside three to fifteen.0 months of infection, in comparison with over a million age- and sex-matched uninfected individuals.

Amongst autoimmune diseases, the incidence rate ratio (IRR) values were the very best for vasculitis. Further, amongst those with prior history of autoimmune diseases, COVID-19 resulted in a 23.0% higher risk of one other autoimmune disease.

Generally, most autoimmune diseases weren’t COVID-19-specific; nevertheless, an important aspect of SARS-CoV-2 infection was a substantial rise within the incidence and spectrum of autoimmune diseases following acute COVID-19.

Conclusions

Based on the review findings, COVID-19 elevates autoimmune disease risks. Because of the retrospective study designs, the 2 cohort studies couldn’t provide a causal association between COVID-19 and autoimmune disease development.

Nonetheless, the temporal relationship with COVID-19 history provides reliable and compelling evidence that COVID-19 is related to elevated autoimmune disease development risks.

Health governments and authorities must conduct future studies on the subject to acquire national data and increase the generalizability of the findings. The definitive mechanisms, including genetic and epigenetic predilection, underlying the association and related pathophysiology are usually not completely understood.

Nonetheless, further research have to be performed using particular gene-deficient experimental animals, bioinformatic evaluation, and biological approaches, e.g., analyzing transcriptomic pandemic data to acquire genomic signatures, and host responses to viral triggers have to be evaluated.

Source:

• Chang, R., Chen, T.Y.T., Wang, S.I., Hung, Y.M., Chen, H.Y. and Wei, C.C.J., 2023. Risk of autoimmune diseases in patients with COVID-19: A retrospective cohort study. EClinicalMedicine, 56, p.101783.

Journal reference: