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In a recent study posted to medRxiv* preprint server, researchers examined the associations between coronavirus disease 2019 (COVID-19) and incident autoimmune diseases.
Some individuals develop long COVID, persistent symptoms following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which are unexplained by alternative diagnoses and linger for more than 12 weeks after acute illness. Much of the research (on long COVID) has been centered on symptoms that wane over time; numerous studies have examined small selective samples of COVID-19 patients, and only a few have included controls or data on chronic conditions.
This evidence is not sufficient to assess the COVID-19 burden. Cardiovascular, neurological, respiratory, and psychological diseases and other symptoms have been studied in the context of long COVID, while less is known about autoimmune disorders. To date, there is limited information on new-onset autoimmune disorders following SARS-CoV-2 infection. Moreover, the similarities between COVID-19 and systemic rheumatic diseases could be challenging for diagnostics.
In the present study, researchers investigated whether the risk of autoimmune diseases increased after SARS-CoV-2 infection. People infected with SARS-CoV-2 in 2020 and controls were followed up for up to 15 months until June 30, 2021. Individuals with a polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infection were included in the COVID-19 cohort. Individuals without a lab-confirmed diagnosis of COVID-19 were excluded.
The team used routine healthcare data from health insurance companies in Germany covering more than 39 million individuals. The data comprised information on diagnoses, medical procedures, outpatient medical services, and medical prescriptions. COVID-19 patients were exact-matched to three non-COVID-19 controls. After matching, subjects were excluded if they died within a quarter of COVID-19 diagnosis.
The authors examined 64 potential outcomes from 41 autoimmune disorders based on clinical experience. Data on pre-existing chronic conditions from 2019 health records were used to adjust for confounders. The incidence rates of autoimmune diseases were estimated, and the differences in the incidence rates between COVID-19 and control cohorts were evaluated by computing incidence rate ratios.
The team matched 670,301 individuals with COVID-19 to controls. After exclusions, 641,407 individuals 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 a pre-existing autoimmune disease before COVID-19.
More than 6400 individuals developed an autoimmune disease during the follow-up period. Of those with pre-existing autoimmunity, 1744 individuals developed an additional autoimmune disorder. Most subjects were females in both cohorts and aged 18 – 64. Around 6.4% of individuals were hospitalized during acute COVID-19, 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 diseases was 1.43. Moreover, incident autoimmune diseases were more frequent in the COVID-19 cohort for individuals with pre-existing autoimmunity.
The most prevalent incident autoimmune diseases in the COVID-19 cohort were Hashimoto thyroiditis, Graves’ disease, psoriasis, rheumatoid arthritis, and Sjögren syndrome. The highest incidence rate ratios were for Wegner’s disease, Behcet’s syndrome, sarcoidosis, and arteritis temporalis.
The incident rate ratios were not significantly different between males and females or across age groups. Nonetheless, the absolute incidence of any first autoimmune disease was higher among older individuals than younger people. It was also higher in females than males and increased according to disease severity during the acute phase.
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 pre-existing autoimmunity were 43% more likely to develop an incident autoimmune disease than controls, while those with pre-existing autoimmunity were 23% more likely to develop another autoimmune disease.
Taken together, COVID-19 was associated with a higher risk of developing an autoimmune disease in the three to 15 months following SARS-CoV-2 infection. Further research is required to ascertain if SARS-CoV-2 triggers autoimmune diseases and identify effective prevention and treatment strategies.
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.