Correlates of breakthrough Omicron (B.1.1.529) infections in a prospective cohort of vaccinated patients with rheumatic diseases

Abstract

Background Data on the effectiveness of SARS-CoV-2 vaccines and the durability of protection against the prevalent Omicron variant are scarce, especially in patients with autoimmune rheumatic diseases (AIRDs). Hence, we prospectively studied Omicron breakthrough infections in patients with AIRDs and attempted to isolate associated risk factors. Methods Patients with AIRDs who had completed primary vaccination with either AZD1222 or BBV152 vaccines were included and prospectively followed up from January 2022 onwards for the development of breakthrough Omicron infections. The time interval from the last event [2nd dose of vaccination (V) or past COVID-19 infection (I) whichever was later] to Omicron infection was recorded. Patients were divided based on the events and their order of occurrence into V + V, V + I, I + V, V + I + V, and V + V + I groups. The incidence of breakthrough infections and their predictors were studied with a focus on the vaccine type and hybrid (H) immunity (vaccinated individuals with a history of COVID-19 infection). Results We included 907 patients with AIRDs (53.5 ± 11.7 years and a male-to-female ratio of 1:5.1), and the majority of patients had received AZD1222 (755, 83.2%). Breakthrough infections were observed in 158 of 907(17.4%) of which 97 (10.4%) were confirmed by RT-PCR. Breakthrough infections were significantly greater in the V versus the H group (15.7% and 3.5%, log-rank test, p = < 0.01). Among the hybrid group, the order of infection and vaccination had no bearing on the risk of breakthrough infections. On multivariate analysis, breakthrough infections were significantly lesser in the H versus the V group [HR: 0.2(0.1–0.4); p = 0.01]. Conclusion The risk of breakthrough Omicron infections in fully vaccinated patients with AIRDs was 17.4% with a significantly lower risk in patients with hybrid immunity.

Breakthrough COVID-19 After Tixagevimab/Cilgavimab Among Patients With Systemic Autoimmune Rheumatic Diseases

“…Several other studies have described early experiences with tixagevimab/cilgavimab in patients with SARDs and observed a low proportion of patients with breakthrough COVID-19 (2-14%) as well as overall mild infections. [16][17][18] We observed a slightly higher proportion (18.7%) with breakthrough 20,21 In our study, approximately 10% of the patients with symptomatic COVID-19 required hospitalization; although this is lower than in prior studies in patients with SARDs, [22][23][24] it is still substantially higher than the values reported for the general population during a similar period, 25 thus highlighting the ongoing need for additional strategies to protect this group. The similar risk of infection observed in CD20 inhibitor users and those using csDMARDs highlights the importance of the PrEP strategy, especially for our most vulnerable patients with SARDs.…”

“…Finally, the majority of patients also received outpatient treatment with COVID-19 specific treatments such as nirmatrelvir/ritonavir. Thus, the relatively mild infections observed in our cohort could be attributed to the outpatient treatments 20 in addition to the effects of PrEP with tixagevimab/cilgavimab.…”