Résumé
BackgroundThe 3rd booster of mRNA vaccines against SARS COV2 was highly efficient against delta variant but data regarding the efficacy of the 3rd and 4th boosters against the omicron variants, among AIRD pts are scarce.ObjectivesWe aimed to assess the effect of the 3rd and 4th booster mRNA vaccines against SARS CoV2, in preventing severe COVID-19, in AIRD patients (pts) treated with immunomodulating drugs.Methods212 pts (mean age(SD) 57(13), disease duration 11.2(7.4), who received the 3rd booster (Pfizer) were included in the study. We performed serology tests 24 weeks after the second dose of vaccine and 4-8 weeks after the 3rd booster. IgG Antibodies (Ab) against SARS COV2 virus were detected using the SARS-Cov-2 IgG II Quant (Abbott) assay. The test was considered positive above 50 AU/ml. Data regarding COVID-19 infection during the 5th outbreak (omicron) were collected from the medical files. The length of observation period was defined as the time from the 3rd booster to the last hospital visit or COVID 19 diagnosis, whichever occurred first.ResultsThe 3rd booster administration (Pfizer) significantly augmented the humoral response (from mean(SD) 1121(4723) AU/ml to 12153(13687)). 58 patients received the 4th booster and 18 the 5th booster. COVID-19 was diagnosed in 103 pts (49%) within mean(SD) 224.8(106.5) days after the 3rd booster vaccination. 109 pts remained free of disease during mean(SD) follow-up 230.6(133.9). Following the 4th booster, 26 (45%) out of 58pts contracted COVID-19 within mean(SD) 97.6(78.7) days after the vaccination. One 70 year old patient (vaccinated 3 times) died and 2 other pts (rituximab treated) had severe COVID-19. The IgG Ab titer after the 3rd booster was lower in pts who contracted COVID 19 compared to those uninfected (mean(SD), median 8777.9(11716.4),3475 AU/ml vs 15348.1(14649.1),10801, p=0.004).There were no statistically significant differences between the pts with COVID-19 and those without, regarding age, type of disease, treatment and humoral response 24 weeks after the 2nd vaccination.ConclusionDespite an enhanced humoral response obtained after the 3rd booster, 49% of AIRD pts vaccinated with 3 doses and 45% of pts vaccinated with 4 doses had COVID-19 during the omicron outbreaks. Higher humoral response to the 3rd booster was associated with a lower rate of COVID19. The booster vaccines conferred 99% protection against severe COVID-19.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.
Résumé
Background: Previous studies proved that mRNA vaccinations against SARS CoV2 induced signifcant humoral responses in AIRD patients (pts). However, the humoral response was blunted in pts treated with CD20 depleting antibodies. There are limited data regarding the long-term outcome of the humoral response and the contribution of the booster vaccine, in immunosuppressed AIRD pts. Objectives: To assess the long-term outcome of the humoral response to mRNA vaccine against SARS CoV2, in AIRD pts treated with immunomodulating drugs, and the contribution of the booster vaccination. Methods: Consecutive pts treated at the Rheumatology Institute at Rambam Hospital who received their frst SARS-CoV-2 (Pfzer) vaccine were recruited to the study, at their routine visit. The visit included AIRD activity assessment and questioning regarding vaccine side effects. We performed serology test 4-6 weeks and 24 weeks after receiving the second dose of vaccine. Pts who received the booster (3rd vaccine) were invited for serology tests 4-8 weeks afterwards. The immunomodulating treatment was not modifed, either before or after the vaccination. IgG Antibodies (Ab) against SARS COV2 virus were detected using the SARS-Cov-2 IgG II Quant (Abbott) assay based on a chemi-luminescent microparticle immunoassay (CMIA) on the ARCHITECT ci8200s-ystem from Abbott. This assay is measuring IgG antibodies against the spike receptor-binding domain (S-RBD) of the virus. The test was considered positive above 50 AU/ml. Results: 262 pts (mean age(SD) 57(13), disease duration 11.2(7.4), were recruited. The cohort included 152 pts with infammatory joint disease, 26 pts with systemic lupus erythematosus, 62 pts with other connective tissue disease and 22 pts with vasculitis;27 % received csDMARDs only, 35%-b/tsDMARDs only, 30%-combined therapy (csDMARDs+b/tsDMARDs) and 26% received steroids. 225 pts (86%) were seropositive for IgG Ab against SARS CoV2 virus (median 2832.5 AU/ml, IQR 58-29499). 37 (14%) pts had negative tests, 23 (62.2%) of them were rituximab treated. The IgG levels correlated with the medication used to treat the AIRD, the patients' age but not with the type of the AIRD (Figure 1). 24 weeks afterwards, the median IgG level dropped to 282 AU/ml and 15% of the pts with previous seropositive tests became negative. The booster administration (Pfzer) signif-cantly augmented the humoral response (median 8328 AU/ml, IQR 375-40000). De novo serologic response was observed in 10 out of 37 pts (4/23 rituximab treated pts). The reported side effects of the vaccine were minor (muscle sore, headache, low grade fever). The AIRD remained stable in all pts following all three vaccinations. Conclusion: Although the vast majority of AIRD pts developed a substantial humoral response following the administration of the second dose of the Pfzer mRNA vaccine against SARS CoV2 virus, the humoral response signifcantly declined 24 weeks afterwards. An enhanced response was obtained after the third booster vaccination. Only minor side effects were reported and no apparent impact on AIRD activity was noted. Notably, 62% of the non-responders were treated with B cell depleting agents.