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

This study examined the association between SARS-CoV-2 infection and autoimmune disease. Reviewers found this study to be reliable and present robust evidence demonstrating an association between SARS-CoV-2 infection and increased risk of incident autoimmune disease.

Published onMar 20, 2023
Review 2: "Incident autoimmune diseases in association with a SARS-CoV-2 infection: A matched cohort study"
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key-enterThis Pub is a Review of
Incident autoimmune diseases in association with a SARS-CoV-2 infection: A matched cohort study

AbstractObjectivesTo investigate whether the risk of developing an incident autoimmune disease is increased in patients with previous COVID-19 disease compared to people without COVID-19.MethodA cohort was selected from German routine health care data covering 38.9 million individuals. 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.ResultsIn 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 disease of the vasculitis group. Patients with a more severe course of COVID-19 were at a greater risk for incident autoimmune diseases.ConclusionsSARS-CoV-2 infection is associated with an increased risk of developing new-onset autoimmune diseases after the acute phase of infection.

RR:C19 Evidence Scale rating by reviewer:

  • Reliable. The main study claims are generally justified by its methods and data. The results and conclusions are likely to be similar to the hypothetical ideal study. There are some minor caveats or limitations, but they would/do not change the major claims of the study. The study provides sufficient strength of evidence on its own that its main claims should be considered actionable, with some room for future revision.



We have had the privilege to review the manuscript titled “Incident autoimmune diseases in association with a SARS-CoV-2 infection: A matched cohort study” from Falko Tesch et al.

In this matched cohort study the authors aimed to investigate the association of COVID-19 and a set of incident autoimmune diseases in a large cohort of patients enrolled in German statutory health insurances. Infected patients with SARS-CoV-2 during 2020 were compared to matched controls (1:3) and were followed for 3-15 months. The index date was defined as the date of COVID-19 onset. Only individuals with polymerase chain reaction (PCR)-confirmed COVID-19 diagnosis were included in the COVID-19 group. The authors included only patients from 2020 to ensure that the effect was not influenced by vaccination status. The study concludes that patients with previous COVID-19 had an increased risk of being newly diagnosed with an autoimmune disease after the acute phase showing the strongest association for the autoimmune diseases of the vasculitis group.

The results of the study are based on a very large and representative data set of more than 600,000 confirmed COVID -19 patients with a follow-up period of at least 3 and up to 15 months, which is a longer follow-up period than previously published studies on the topic. To reduce bias due to the observational nature of the study, the authors performed a propensity score matching and subgroup analyses to characterize subpopulations at high risk for future autoimmune disease. The results were generally well presented and discussed.

An important limitation of the study acknowledged by the authors is the inability to determine causal interpretation of the results because of the possibility of unmeasured confounding variables; they did not have access to the vaccination status of the included patients, nor could they exclude the possibility of asymptomatic patients or undocumented SARS-COV-2 infected patients in the control cohort.

Another limitation noted in the study is the lack of information on other variables that might contribute to the development of autoimmune disease, such as occupational exposure to risk factors, lifestyle-related variables including tobacco use, obesity, and genetic predisposition to autoimmunity. Additional information on these variables might contribute to a better understanding of the relationship between COVID- 19 and autoimmunity.

Finally, the study group included only patients enrolled in the German statutory health insurance, compromising the external validity of the results.

For further studies, it would be interesting to measure the amounts and types of autoantibodies produced during COVID -19 newly diagnosed autoimmune disease and to specify the specific variant of SARS-CoV-2 associated with subsequent autoimmune disease.

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