COVID-19 could increase the risk of autoimmune diseases

In a recent study published on medRxiv*preprint server, researchers examined associations between coronavirus disease 2019 (COVID-19) and incident autoimmune diseases.

Background

Some people develop long, persistent COVID symptoms after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which are unexplained by alternative diagnoses and persist for more than 12 weeks after acute illness. Much of the research (on the long COVID) has focused on symptoms fading over time; many studies have looked at small, selective samples of patients with COVID-19, and only a few have included controls or chronic disease data.

This evidence is not sufficient to assess the burden of COVID-19. Cardiovascular, neurological, respiratory and psychological diseases and other symptoms have been studied in the context of the long COVID, while autoimmune diseases are less well known. To date, there is little information on recent-onset autoimmune disorders following SARS-CoV-2 infection. Additionally, the similarities between COVID-19 and systemic rheumatic diseases could be difficult for diagnosis.

About the study

In the current study, researchers investigated whether the risk of autoimmune diseases increases after infection with SARS-CoV-2. Individuals infected with SARS-CoV-2 in 2020 and controls were followed for up to 15 months through June 30, 2021. Individuals with chain reaction-confirmed SARS-CoV-2 infection polymerase (PCR) tests were included in the COVID-19 cohort. People without a laboratory-confirmed COVID-19 diagnosis were excluded.

The team used routine health data from health insurance companies in Germany covering more than 39 million people. The data included information on diagnoses, medical procedures, outpatient medical services and medical prescriptions. The COVID-19 patients were exactly matched to three non-COVID-19 controls. After matching, subjects were excluded if they died within a quarter of being diagnosed with COVID-19.

The authors reviewed 64 potential outcomes of 41 autoimmune diseases based on clinical experience. Pre-existing chronic disease data from health records from 2019 was used to adjust for confounders. Autoimmune disease incidence rates were estimated, and differences in incidence rates between COVID-19 and control cohorts were assessed by calculating incidence rate ratios.

Results

The team matched 670,301 people with COVID-19 to controls. After exclusions, 641,407 people with COVID-19 were matched to more than 1.56 million controls. Most individuals had three matched controls, while some patients had two or one. In the COVID-19 cohort, 11.9% of individuals had pre-existing autoimmune disease prior to COVID-19.

More than 6400 people developed an autoimmune disease during the follow-up period. Of those with pre-existing autoimmunity, 1744 people developed additional autoimmune disease. Most subjects were female in both cohorts and aged between 18 and 64 years. About 6.4% of people were hospitalized during an acute COVID-19 attack and 1.6% required intensive care or mechanical ventilation.

The incidence rate of any autoimmune disease was 15.05 and 10.55 per 1000 person-years in the COVID-19 and control cohorts, respectively. This meant that the excess risk due to COVID-19 was 4.5 per 1000 person-years. The incidence rate ratio for incident autoimmune disease was 1.43. Additionally, incident autoimmune diseases were more common in the COVID-19 cohort for those with pre-existing autoimmunity.

The most prevalent incident autoimmune diseases in the COVID-19 cohort were Hashimoto’s thyroiditis, Graves’ disease, psoriasis, rheumatoid arthritis and Sjögren’s syndrome. The highest incidence rate ratios were for Wegner’s disease, Behcet’s syndrome, sarcoidosis, and temporal arteritis.

Incident rate ratios were not significantly different between males and females or between age groups. Nevertheless, the absolute incidence of any first autoimmune disease was higher in the elderly than in the young. It was also higher in women than in men and increased with disease severity during the acute phase.

conclusion

In summary, the excess risk of developing autoimmunity due to COVID-19 was 4.5 per 1000 person-years in the study. The highest incidence rate ratios were for rare autoimmune diseases involving vasculitis. Individuals without preexisting autoimmunity were 43% more likely to develop incident autoimmune disease than controls, while those with preexisting autoimmunity were 23% more likely to develop another autoimmune disease.

Taken together, COVID-19 was associated with a higher risk of developing autoimmune disease within three to 15 months of SARS-CoV-2 infection. Further research is needed to determine whether SARS-CoV-2 triggers autoimmune diseases and to identify effective prevention and treatment strategies.

*Important Notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be considered conclusive, guide clinical practice/health-related behaviors, or treated as established information.