CoronaVac, an inactivated SARSCoV2 vaccine, has been administered in over 100 countries worldwide, but its immunity wanes quickly over time. In consequence, boosters are being recommended. We evaluated the immunogenicity… Click to show full abstract
CoronaVac, an inactivated SARSCoV2 vaccine, has been administered in over 100 countries worldwide, but its immunity wanes quickly over time. In consequence, boosters are being recommended. We evaluated the immunogenicity of an mRNA vaccine booster (BNT162b2) in inflammatory arthritis (IA) patients with biologic treatments previously vaccinated with CoronaVac. Consenting adults with IA followed at Red Salud UCCHRISTUS (Chile), who were on antiTNF, antiIL6 or antiIL17 biologics, vaccinated with CoronaVac (0, 28), were eligible. Those with a SARSCoV2 infection history were excluded. Humoral response was assessed by measuring IgG SARSCoV2 total antibody (Tab) and neutralising antibody (Nab) within 7 days and 4 weeks after the booster. DMARDs were not discontinued. The primary outcome was the proportion of participants with positive SARSCoV2 Nab 4 weeks after the BTN162b2 booster. A neutralisation of 30% or more at a 1:10 dilution was considered positive. Dichotomous and continuous variables were compared using the McNemar or Wilcoxon signedrank test. Confounding and effect modifiers of covariates were explored using binary regression models. Seventysix individuals were included. Mean age was 51.9 (SD 11.3) and 73.6% were female. Mean years since diagnosis were 6.2 years (SD 7.4), 74% had rheumatoid arthritis (RA), 24% psoriatic arthritis, 1% juvenile idiopathic arthritis and 1% ankylosing spondylitis. Overall, 45% used low dose prednisone, 36% methotrexate, 21% leflunomide and 14% sulfasalazine. The median (IQR) number of days between the second CoronaVac dose and the BNT162b2 booster was 157 (143170). At baseline, 18 participants (24%) had Nab and 40 (53%) had positiveTab. Age was inversely and independently associated with the probability of having detectable Nab at baseline (p value 0.006). In the same model, neither gender, prednisone, methotrexate nor time between CoronaVac vaccination and the booster predicted baseline Nab serostatus. Four weeks after receiving a BNT162b2 booster, 71 (94%) and 73 (96%) individuals had positive Nab and Tab, respectively. The median (IQR) neutralising activity rose from 17% (11%–29%) to 97% (80%–99%) after boosting (figure 1). Five participants (6.8%) remained Nabseronegative; all had RA, received steroids and four of them used methotrexate. Sixtytwo per cent of patients reported adverse events, all mild. Multivariate analysis found no association among age, gender, prednisone, methotrexate and postbooster Nab levels. Response was not correlated to the time elapsed since the second dose of CoronaVac. No COVID19 cases were reported after the booster (followup 1–3 months). After an mRNA vaccine booster, our sample of IA patients using biologics and vaccinated with CoronaVac significantly improved their humoral immune response against SARSCoV2. Little is known about response to vaccine boosters following inactivated vaccines. One study compared BNT162b2 versus CoronaVac in 80 healthy individuals with low antibody response to CoronaVac. Nab seroconversion was observed in 96.8% and 57.7% of participants receiving BNT162b2 or CoronaVac boosters, respectively. A recent study of a homologous booster of CoronaVac in patients with rheumatic disease showed 81.4% of subjects produced Nab. Booster doses have also been explored in rheumatologic patients vaccinated with mRNA vaccines. A small study in RA patients unresponsive to BNT162b2 showed that after a homologous booster plus DMARDS discontinuation, 15 of 17 participants reached adequate Tab titers. Similarly, 16 out of 18 autoimmune disease patients vaccinated with mRNA vaccines and boosted with mRNA or viralvectored vaccines increased Tabs. Our study limitations include the lack of assessment of cellular response and the short postbooster clinical followup. Results should not be generalised to patients receiving other biologics. In conclusion, our study suggests that IA patients on biologic drugs receiving inactivated COVID19 vaccines should receive a booster dose. A mixandmatch approach with mRNA vaccines is well tolerated and highly immunogenic.
               
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