Autoimmune Sequelae After Delta or Omicron Variant SARS-CoV-2 Infection in a Highly Vaccinated Cohort.

Importance: Studies have reported increased risk of autoimmune sequelae after SARS-CoV-2 infection. However, risk may potentially be attenuated by milder Omicron (B.1.1.529) variant infection and availability of booster vaccination.

Objective: To estimate the 300-day risk of new-incident autoimmune sequelae after SARS-CoV-2 Delta or Omicron BA.1 or BA.2 variant infection in adults who received COVID-19 vaccines and boosters, compared with a contemporary control group without infection.

Design, Setting, And Participants: This cohort study in Singapore enrolled adults from September 1, 2021, to March 7, 2022, and followed up for 300 days. Participants were adults aged 18 years or older with SARS-CoV-2 infection during the predominance of the Delta and Omicron BA.1 or BA.2 variants and were still alive at 30 days after COVID-19 diagnosis.

Exposure: The national SARS-CoV-2 testing registry was used to construct cohorts of adults with SARS-CoV-2 Delta or Omicron BA.1 or BA.2 variant infection (hereafter, cases) and a contemporaneous group with negative polymerase chain reaction or rapid antigen test results (hereafter, controls).

Main Outcomes And Measures: New-incident autoimmune diagnoses after SARS-CoV-2 infection. This information was recorded in the MediClaims national health care claims database and identified 31 to 300 days after index date of infection. Risks and excess burdens were estimated using Cox proportional hazards regression model with overlap weights applied.

Results: In total, 1 766 036 adults (915 096 females [51.9%]; mean [SD] age, 49 [18] years) were included in the study population, with 480 082 (27.2%) categorized as cases and 1 285 954 (72.8%) as controls. Of these adults, 73.1% had Chinese, 13.7% Malay, and 9.9% Indian ethnicity. There were 104 179 cases and 666 575 controls included during the Delta variant-predominance transmission, while 375 903 cases and 619 379 controls were included during the Omicron variant-predominance transmission. During the Delta variant period, 81.1% of cases had completed primary vaccination; during the Omicron variant period, 74.6% of cases received boosters. No significantly elevated risk of 12 prespecified autoimmune sequelae was recorded across the Omicron and Delta variant cohorts. Elevated risks of inflammatory bowel disease (adjusted hazard ratio [AHR], 2.23; 95% CI, 1.45-3.46; P < .001) and bullous skin disorders (AHR, 4.88; 95% CI, 2.47-9.66; P < .001) were observed only in the subset of COVID-19 cases requiring hospitalization during the predominance of the Omicron variant. While elevated risk of vasculitis (AHR, 5.74; 95% CI, 1.48-22.23; P = .01) was observed in vaccine-breakthrough Omicron variant infections, no increased risk of vasculitis was observed in the corresponding subgroup who received boosters.

Conclusions And Relevance: This cohort study observed no significantly elevated long-term risk of autoimmune sequelae after SARS-CoV-2 Delta and Omicron BA.1 or BA.2 variant infection, except for a modestly increased risk of inflammatory bowel disease and bullous skin disorders in the hospitalized subgroup during the predominance of the Omicron variant. Booster vaccination appeared to mitigate the risk of long-term autoimmune sequelae.