SARS-CoV-2 Linked to Immune-Mediated Inflammatory Diseases

Shamil Haroon, MBChB, PhD, MPH

Credit: University of Birmingham

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is associated with an increased incidence of type 1 diabetes mellitus (T1DM), inflammatory bowel disease (IBD), and psoriasis, according to findings from a retrospective matched cohort study. Exposure to SARS-CoV-2 infection was associated with a 22% relative increase in the incidence of 11 immune-mediated inflammatory diseases compared to patients in an unexposed cohort.¹

“Long COVID is emerging as one of the major public health challenges of the modern era. Despite this, the pathogenesis behind the condition remains unclear.” wrote investigators.¹

Some people who have been infected with SARS-CoV-2 can experience long-term effects from their infection, known as long COVID. Individuals with long COVID may experience a wide range of new, returning, or ongoing health problems. More severe cases might face multiorgan effects or autoimmune conditions with symptoms lasting weeks, months, or even years after illness.²

To assess the association between SARS-CoV-2 infection and the incidence of immune-mediated inflammatory diseases, senior investigator Shamil Haroon, MBChB, PhD, MPH, and a team of investigators used primary care electronic health record data from the Clinical Practice Research Datalink Aurum database to match patients with confirmed SARS-CoV-2 infection with up to 4 patients without SARS-CoV-2 based on age, sex, and registered general practice. Investigators examined the incidence of autoimmune thyroiditis, coeliac disease, IBD, myasthenia gravis, pernicious anemia, psoriasis, rheumatoid arthritis (RA), Sjogren’s syndrome, systemic lupus erythematosus (SLE), type 1 diabetes mellitus (T1DM), and vitiligo in both groups.¹

Patients were eligible for inclusion in the study if they were aged ≥18 years, had no prior history of the immune-mediated inflammatory diseases included in the primary outcome, had an acceptable patient flag indicating provision of good quality data, and if they were registered with an eligible general practice for ≥12 months to allow sufficient time for recording baseline information.¹

In total, investigators identified 458,147 patients with confirmed SARS-CoV-2 infection, defined by a SNOMED-CT coded diagnosis of either a positive reverse transcriptase polymerase chain reaction or lateral flow antigen test for SARS-CoV-2, and matched them to 1,818,929 patients who lacked a confirmed or suspected diagnosis of COVID-19. The mean age was 43.6 years (standard deviation [SD], 17.1) in the exposed cohort and 42.8 years (SD, 18.0) in the unexposed cohort. Both groups had slightly more females than males (54.7% and 45.3%, respectively).¹

The primary outcome was a composite of any of the 11 immune-mediated inflammatory diseases, while secondary outcomes examined the individual diseases included in the primary outcome to discern which, if any, had the strongest association with SARS-CoV-2 infection. Participants were followed up from the index date until a coded diagnosis of an immune-mediated inflammatory disease, date of death, study end date (June 30, 2021), date of practice de-registration, or date of the last practice contribution to the CPRD Aurum database.¹

Upon analysis, SARS-CoV-2 was associated with an increased incidence of immune-mediated inflammatory diseases. In total, 696 (.15%) patients in the exposed cohort developed the primary outcome compared to 2230 (.12%) in the unexposed cohort. The crude incidence rate per 1000 person-years was higher for the exposed cohort (4.59) than the unexposed cohort (3.65) and yielded a crude hazard ratio of 1.26 (95% confidence interval [CI], 1.16–1.37) for the composite primary outcome. When adjusted for covariates, the hazard ratio slightly reduced to 1.22 (95% CI, 1.12–1.33).¹

Investigators noted SARS-CoV-2 infection was significantly associated with an increased incidence of T1DM, IBD, and psoriasis:

• T1DM was 56% more likely to occur in the exposed cohort compared to the unexposed cohort (adjusted hazard ratio [aHR], 1.56; 95% CI, 1.09-2.23).
• IBD was 36% more likely to occur in the exposed cohort compared to the unexposed cohort (aHR, 1.36; 95% CI, 1.18-1.56) and was the most commonly diagnosed immune-mediated inflammatory disease during the study period, accounting for 39.6% of diagnoses in the exposed cohort and 36.6% in the unexposed cohort.
• Psoriasis was 23% more likely to occur in the exposed cohort compared to the unexposed cohort (aHR, 1.23; 1.05-1.42) and was the second most diagnosed immune-mediated inflammatory disease, representing more than 30% of all new diagnoses in both cohorts.

“Our findings provide epidemiological evidence that SARS-CoV-2 infection is associated with an increased risk of a range of IMIDs, including T1DM, IBD, and psoriasis,” investigators concluded.¹ “This provides evidence that autoimmunity may be a potential mechanism that accounts for some of the longer-term symptoms and health impacts of a subgroup of those with long COVID.” 

References:

1. Syed U, Subramanian A, Wraith DC et al. Incidence of immune-mediated inflammatory diseases following COVID-19: a matched cohort study in UK primary care. BMC Med. https://doi.org/10.1186/s12916-023-03049-5
2. Centers for Disease Control and Prevention. Long COVID or Post-COVID Conditions. COVID-19. July 20, 2023. Accessed September 28, 2023.https://www.cdc.gov/coronavirus/2019-ncov/long-term-effects/index.html