Incident autoimmune diseases in association with SARS-CoV-2 infection: a matched cohort study

Abstract

Objectives To investigate whether the risk of developing an incident autoimmune disease is increased in patients with prior COVID-19 disease compared to those without COVID-19, a large cohort study was conducted. Method A cohort was selected from German routine health care data. Based on documented diagnoses, we identified individuals with polymerase chain reaction (PCR)-confirmed COVID-19 through December 31, 2020. Patients were matched 1:3 to control patients without COVID-19. Both groups were followed up until June 30, 2021. We used the four quarters preceding the index date until the end of follow-up to analyze the onset of autoimmune diseases during the post-acute period. Incidence rates (IR) per 1000 person-years were calculated for each outcome and patient group. Poisson models were deployed to estimate the incidence rate ratios (IRRs) of developing an autoimmune disease conditional on a preceding diagnosis of COVID-19. Results In total, 641,704 patients with COVID-19 were included. Comparing the incidence rates in the COVID-19 (IR=15.05, 95% CI: 14.69–15.42) and matched control groups (IR=10.55, 95% CI: 10.25–10.86), we found a 42.63% higher likelihood of acquiring autoimmunity for patients who had suffered from COVID-19. This estimate was similar for common autoimmune diseases, such as Hashimoto thyroiditis, rheumatoid arthritis, or Sjögren syndrome. The highest IRR was observed for autoimmune diseases of the vasculitis group. Patients with a more severe course of COVID-19 were at a greater risk for incident autoimmune disease. Conclusions SARS-CoV-2 infection is associated with an increased risk of developing new-onset autoimmune diseases after the acute phase of infection. Key Points• In the 3 to 15 months after acute infection, patients who had suffered from COVID-19 had a 43% (95% CI: 37–48%) higher likelihood of developing a first-onset autoimmune disease, meaning an absolute increase in incidence of 4.50 per 1000 person-years over the control group.• COVID-19 showed the strongest association with vascular autoimmune diseases.

Persistent Risk of Developing Autoimmune Diseases Associated With COVID-19

“…These findings are almost consistent with those of previous studies. 20,21 Remarkably, we observed a persistent risk for many autoimmune diseases. For certain diseases, such as IgG4RD and SSc, the risk was observed to be even higher in the later period (day 391-∞) compared with the earlier period.…”

“…A recent study demonstrated that the outpatient setting was associated with a higher risk of developing autoimmune diseases than the inpatient setting, 20 whereas another study showed that hospitalization and intensive care were associated with a higher risk of autoimmune diseases associated with COVID-19. 21 They investigated the effect of COVID-19 compared with non-COVID-19 patients using subgroup analysis, such as inpatients or outpatients. In the non-COVID-19 group, the reasons for hospitalization were likely to be variable and may be associated with symptoms resulting from the preclinical stages of autoimmune diseases.…”

Autoimmune and Autoinflammatory Connective Tissue Disorders Following COVID-19

“…Subgroup analyses stratified by race indicated that White patients generally exhibited a higher risk than Asian patients, except for SLE . Another study assessing the incidence of autoimmune diseases after COVID-19 in the German population also observed an elevated risk within the COVID-19 cohort (first onset of autoimmune disease incidence rate ratio, 1.43; 95% CI, 1.37-1.48). Given that our study primarily included Asian participants, we hypothesize that their estimated risks were lower, or may appear to be lower, as a result of delayed disease development or progression, compared with those observed in other ethnic groups.…”

“…In this cohort study, we comprehensively examined and compared the risks of autoimmune and autoinflammatory connective tissue disorders in COVID-19 and control cohorts. Several previous reports have evaluated the incidence of autoimmune diseases following COVID-19 . One large cohort study using a global COVID-19 data set found that the COVID-19 group had a higher risk of various autoimmune diseases compared with a control group.…”

Systemic lupus erythematosus after SARS‐CoV‐2 infection: A causal or temporal relationship?

“…Furthermore, Chang et al 28 analyzed data from an extensive global COVID‐19 database and found an increased risk of SLE (adjusted hazard ratio [HR] 2.98; 95% CI 2.78–3.20) among 887 455 individuals with COVID‐19 compared to non‐COVID‐19 individuals during a 6‐month follow‐up period. However, another study by Tesch et al 29 examined a cohort of 640 701 non‐vaccinated individuals with polymerase chain reaction‐confirmed COVID‐19 in 2020 and reported an incidence rate ratio of 1.35 (95% CI 0.92–1.95) for developing SLE between 3 and 15 months after SARS‐CoV‐2 infection. Therefore, most SLE cases emerge during or shortly after the acute phase of SARS‐CoV‐2 infection, suggesting the involvement of specific pathogenic mechanisms.…”