Effects of the second dose of COVID-19 vaccines in patients with autoimmune rheumatic diseases with hybrid immunity.

Abstract

Patients with autoimmune rheumatic diseases with a previous infection by the SARS-CoV-2 virus have exaggerated responses to a single dose of COVID-19 vaccination as compared tofully vaccinated infection naive patients. The second dose is currently recommended at an extended gap after the infection,butthe information available regarding response to the second dose in this subgroupis limited. Patients with AIRDs previously infected with COVID-19, who havereceived at least one dose of AZD1222/ChAdOx1 (n = 200) were included and stratified based on vaccine doses (V), and infection (I) into I + V, I + V + V, V + I, V + V + I. Anti-RBD (receptor binding domain) antibodies were compared across the four groups. In 49 patients of the I + V + V group (AZD12222), paired sera were compared for antibody levels and neutralization after each vaccine dose. Thirty patients with hybrid immunity after BBV152 and 25 with complete vaccination without infection were included as controls. The highest anti-RBD antibody levels were observed in the V + V + I group (18,219 ± 7702IU/ml) with statistically similar titers in the I + V + V (10,392 ± 8514IU/ml) and the I + V (8801 ± 8122IU/ml). This was confirmed in the 49 paired samples that paradoxically showed a lowering of antibody titers after the second dose [9626 (IQR: 4575-18,785)-5781 (2484-11,906); p < 0.001]. Neutralization of the Delta variant was unaffected but Omicron neutralization was significantly reduced after the second dose [45.7 (5.3-86.53)-35% (7.3-70.9); p = 0.028]. Ancillary analyses showed that only the hybrid immune sera could neutralize the Omicron variant and AZD1222 hybrids performed better than BBV152 hybrids. The second dose of AZD1222 did not boost antibody titers in patients with RD who had COVID-19 previously. In the analysis of paired sera, the second dose led to a statistically significant reduction in antibody titers and also reduced neutralization of the Omicron variant.