To Örebro University

Background: Although many studies have been conducted on COVID-19 in recent years, there are still unanswered questions regarding breakthrough infections (BTIs), particularly in patients with systemic lupus erythematosus (SLE).

Objectives: This study aimed to determine the occurrence of breakthrough COVID-19 infections in patients with SLE versus other autoimmune rheumatic diseases (AIRDs), non-rheumatic autoimmune diseases (nrAIDs), and healthy controls (HCs).

Methods: The study was based on data from the COVAD questionnaire which amassed a total of 10,783 complete responses from patients with SLE, AIRD, or nrAIRD, and HCs. After exclusion of individuals who were unvaccinated, those who received one vaccine dose only, and those with uncertain responses regarding the vaccine doses, a total of 9,595 patients formed the study population of the present investigation. If a COVID-19 infection occurred after the initial two vaccine doses and at least one booster dose (at least three doses in total, herein termed full vaccination), it was considered a BTI. Data were analysed using multivariable regression models. Statistically significant results were denoted by p values <0.05.

Results: A total of 7,016/9,595 (73.1%) individuals were fully vaccinated. Among those, 1,002 (14.2%) reported at least one BTI, and 166 (2.3%) reported at least two BTIs. Among SLE patients, 867/1,218 (71.2%) were fully vaccinated. Among fully vaccinated SLE patients, 137 (15.8%) reported at least one BTI while 28 (3.2%) reported at least two BTIs. BTI frequencies in fully vaccinated SLE patients were comparable to those of other AIRDs (OR: 1.0; 95% CI: 0.8–1.3; p=0.447) and nrAIDS (OR: 0.9; 95% CI: 0.6–1.3; p=0.856) but higher compared with HCs (OR: 1.2; 95% CI: 1.0–1.6; p=0.022).

For SLE patients with three vaccine doses, 113/137 (82.5%) reported at least one BTI while the corresponding number for four vaccine doses was 24/137 (17.5%). Compared with HCs (OR: 10.6; 95% CI: 1.2–93.0; p=0.032) and other AIRDs (OR: 3.5; 95% CI: 1.08–11.5; p=0.036), SLE patients showed higher frequencies of hospitalisation.

AID multimorbidity was associated with a 15-fold increased risk for a need of advanced treatment for COVID-19 (OR: 15.3; 95% CI: 2.6–88.2; p=0.002).

Conclusion: COVID-19 BTIs occurred in nearly 1 every 6th fully vaccinated patient with SLE, and 20% more frequently in this patient population compared with fully vaccinated HCs. Moreover, BTIs in SLE patients were more severe compared with BTIs in HCs or patients with AIRDs other than SLE, resulting in a greater need for hospitalisation. AID multimorbidity contributed to a more severe COVID-19 BTI requiring advanced management. These insights call for greater attention to vaccination in the vulnerable group of SLE patients, with appropriate risk stratification towards optimised vaccination strategies.