COVID-19 variants carry no increased autoimmune sequelae risk

COVID-19 variants delta and omicron BA.1 or BA.2 do not pose a substantial threat of long-term autoimmune complications, except for a modest elevation in inflammatory bowel disease and bullous skin disorders among hospitalized patients during the omicron predominance in Singapore, as shown in a study.

In a cohort of 1,766,036 adults (mean age 49 years, 51.9 percent female, 73.1 percent Chinese), of which 27.2 had SARS-CoV-2 delta or omicron BA.1 or BA.2 variant infection (case group) and 72.8 percent had a documented negative polymerase chain reaction or rapid antigen test result (control group), there was no notable increase in the incidence of 12 prespecified autoimmune sequelae* after SARS-CoV-2 delta or omicron variant infection.

During the predominance of the Omicron variant, the case group appeared to have a heightened risk of Sjögren syndrome (adjusted hazard ratio [aHR], 1.91, 95 percent confidence interval [CI], 1.01–3.63; p=0.04) and bullous skin disorders (aHR, 1.57, 95 percent CI, 1.06–2.33; p=0.03). However, the significance of the associations disappeared in an analysis that adjusted for multiple comparisons. [JAMA Netw Open 2024;7:e2430983]

Further analysis indicated significantly elevated risks of inflammatory bowel disease (aHR, 2.23, 95 percent CI, 1.45–3.46; p<0.001) and bullous skin disorders (aHR, 4.88, 95 percent CI, 2.47–9.66; p<0.001) in the subgroup of participants with SARS-CoV-2 omicron variant infection who required hospitalization relative to the control group.

Finally, an increased risk of vasculitis (aHR, 5.74, 95 percent CI, 1.48–22.23; p=0.01) was observed among participants with vaccine-breakthrough omicron variant infections than among controls. This risk increase was not seen in the corresponding subgroup of participants who received boosters (aHR, 0.96, 95 percent CI, 0.49–1.88; p=0.90). This finding, according to the investigators, supports the continued enrolment of at-risk individuals for booster vaccinations during COVID-19 endemicity.

Highlighting the benefits of booster vaccination may help increase acceptance in the face of persistent vaccine hesitancy, “particularly as COVID-19 vaccination is likely to be protective against autoimmunity, rather than contributory,” they continued.

In the present cohort, 81.1 percent of participants in the case group had completed a primary vaccination series only and 10.6 percent received boosters during the delta variant period. Meanwhile, 22.2 percent of participants in the case group had completed a primary vaccination series only and 74.6 percent received boosters during the omicron variant period.

Overall, the risk estimates obtained in the study remained consistent even when sensitivity analyses were conducted using inverse propensity weighting instead of overlap weighting. Additionally, subgroup analyses by sex, age, and ethnicity did not show any significant differences in the risk of new-incident autoimmune sequelae.

“[The present study] substantially differ[s] from the majority of studies that have reported increased long-term incidence of a wide range of autoimmune sequelae after SARS-CoV-2 infection, albeit from waves of earlier SARS-CoV-2 variants and without accounting for the potential protection from COVID-19 vaccination, including boosters,” the investigators noted. [EClinicalMedicine 2023;56:101783; BMC Med 2023;21:363; J Clin Rheumatol 2024;30:65-72; Ann Intern Med 2024;177:291-302; JAMA Netw Open 2023;6:e2336120]

“SARS-CoV-2 persistence in tissues has been associated with increased likelihood of developing post–COVID-19 condition symptoms and is hypothesized to play a role in autoimmunity via generation of cross-reactive antibodies targeted against widely distributed SARS-CoV-2 antigens within tissues,” they said. [Lancet Infect Dis 2024;24:845-855; JAMA Netw Open 2023;6:e2336120]

While the burden of new-incident postacute autoimmune sequelae may be less substantial than originally anticipated, the investigators asserted that continued surveillance for autoimmune conditions arising after COVID-19 remains necessary during the Omicron variant era.