ABSTRACT
Background: Vaccination for COVID-19 is an essential tool to fght the pandemic. Evidence suggests that patients with immune mediated infammatory diseases (IMIDs) have less response. The application of a booster shot is a strategy that has been implemented in this population, however there is scarce information about its efficacy. Objectives: To assess the humoral and cellular immune response after a third dose of SARS-CoV-2 vaccine in patients with rheumatoid arthritis (RA) with undetectable antibodies titles after primary regimen of two doses. Methods: Observational study. Patients with RA (ACR/EULAR 2010 criteria) from two rheumatology centers, ≥18 years old, with no seroconversion after two doses of SARS-CoV-2 vaccine, who received a third dose of either mRNA or vector-based vaccines (BNT162b2 or ChAdOx1 nCoV-19) were included. Anti-SARS-CoV-2 IgG antibodies, neutralising activity and T cell responses were assessed between 21 and 40 days after the third dose. Sociodemographic data, comorbid-ities, treatment, vaccine applied and the presence of adverse events (AE) were recorded. Statistical analysis: descriptive analysis. Chi2 or Fischer test and T test. Results: A total of 21 non-responder patients were included, all of them females with a mean age of 63.7 years (SD 11,6) and mean disease duration of 15.8 years (SD 8). Most of them (81%) reported comorbidities, being the most frequent arterial hypertension, obesity and dyslipidemia. At vaccination time, 6 (28.6%) were receiving glucocorticoids, 3 of them ≥10 mg/day, 17 c-DMARDs (methotrexate 57.1%) and 18 (85.1%) b-DMARDs, 6 abatacept (ABT) and 4 rituximab (RTX). Regarding the primary vaccination regimen, 13 (61.9%) received two doses of BBIBP-CorV, 3 (14.3%) Gam-COVID-Vac, 3 (14.3%) ChAdOx1 nCoV-19 and 2 (9.5%) a mix regimen of Gam-COVID-Vac/mRNA-1273. The majority (95.2%) received BNT162b2 vaccine and only one of them ChAdOx1 nCoV-19, with a mean time between the second and third dose of 151,4 days (SD 46,4). After the third dose, 90.5% of the patients presented detectable anti-SARS-CoV-2 IgG and 76.2% presented neutralizing activity. The median of neutralizing antibodies titers was 1/12 (IQR 1/7-1/48). Both patients who did not present detectable antibodies were obese, recieved BBIBP-CorV during the primary regimen and BNT162b2 as the third dose, one of them was taking methotrexate and ABT and the other one RTX. Compared to other treatments, ABT and RTX was associated with no neutralizing activity in 4 (80%) patients and lower titers of neutralizing antibodies [median 1/3 (IQR 0-1/20) vs median 1/8 (IQR 1/4-1/128), p=0.197]. A T-cell response was present in 41.2% of all patients after the second dose, increasing to 75% after the third dose. The use of ABT was associated with a lower frequency of T-cell response (80% vs 20%, p=0.014). Sixteen (76.1%) patients reported at least one AE, 66.7% injection site reaction and 25% fu-like syndrome. Conclusion: In this RA cohort who failed to seroconvert after two doses of SARS-CoV-2 vaccine, 90.5% presented detectable anti-SARS-CoV-2 IgG and 75% T-cell responce after a third dose. The use of ABT was associated with a lower frequency of T-cell response. This data highlights the importance of a third vaccine in this group of patients.
ABSTRACT
Background: Patients with rheumatic diseases (RD) have been excluded from SARS-CoV-2 vaccine trials. Though data appear to show safety and efficacy, mostly evidence remains in mRNA vaccines. However in our country, adenovirus and inactivated vaccines, as well as heterologous schemes are frequently used. Objectives: To describe clinical characteristics and outcomes of SARS-CoV-2 infection after vaccination in patients with RD from de the SAR-CoVAC registry and to compare them with patients who got infected before vaccination. Additionally, factors associated with COVID-19 unfavorable outcome were assessed. Methods: Adult patients with RD who have been vaccinated for SARS-CoV-2 were consecutively included between June 1st and December 21st, 2021. Con-frmed SARS-CoV-2 infection (RT-PCR o serology) was reported by the treated physician. Infection after an incomplete scheme was defned when the event was diagnosed at least 14 days after frst dose;and after a complete scheme when it occurred > 14 days after second dose. Homologous scheme is defned by two same doses of vaccine and heterologous by two different doses. Patients with previous SARS-CoV-2 infection were excluded. To compare SARS-CoV-2 infection characteristics in not vaccinated patients, subjects from the SAR-COVID registry, which includes patients with RD and SARS-CoV-2 infection, were matched 2:1 by gender, age and RD. WHO-Ordinal Scale ≥5 was used to defne unfavorable infection outcome. Descriptive statics, Chi2 test, Fischer test, T test and ANOVA were used. Results: A total of 1350 patients from the SAR COVAC registry were included, 67 (5%) presented SARS-CoV-2 infection after vaccination. The later were mostly (72%) females with a mean age of 57 (SD 15) years old. The most frequent RD were rheumatoid arthritis (41%), psoriatic arthritis (12%) and systemic lupus erythematosus (10%). At vaccination, most of them (75%) had low disease activity or remission, 19% were taking steroids, 39% methotrex-ate, 27% bDMARDs and 6% JAK inhibitors. A total of 11 (16%) patients had SARS-CoV-2 infection <14 days after the frst vaccine dose, 39 (58%) after an incomplete scheme and 17 (25 %) following a complete one. In the incomplete scheme group, 59% received Gam-COVID-Vac, 31% ChAdOx1 nCov-19 and 10% BBIBP-CorV;and in patients with complete scheme 47%, 24% and 29%, respectively. No event was reported after a complete heterologous scheme. No signifcant differences regarding sociodemoghraphic characteristics, RD, disease treatment, type of vaccine and regimen was found between in those with infection and those without it. After vaccination only 8 (12%) of the patients who got infected had an unfavorable course, 88% of them following an incomplete scheme (5 received Gam-COVID-Vac, 1 ChAdOx1 nCov-19 and 1 BBIBP-CorV) and one subject after a complete homologous Gam-COVID-Vac scheme. Having an unfavorable outcome of SARS-CoV-2 infection was associated to: male gender [63% vs 24%, p=0.036], older age [mean 70 years (SD 7) vs 55 years (SD 15), p=0.005], being Caucasian [100% vs 54%, p=0.018], higher education [mean 17 years (SD 4) vs 12 years (SD 4), p=0.010], the presence of comorbid-ities [100% vs 39%, p=0.001, having pulmonary disease [37% vs 5%, p=0.019], dyslipidemia [63% vs 17%, p=0.011] and arterial hypertension [63% vs 24%, p=0.036], RD, treatments, disease activity and types of vaccines received were comparable between groups. When comparing patients with and without vaccination prior SARS-CoV-2 infection, those who received at least one dose of vaccine had less frequently severe COVID-19 (12% vs 24%, p=0.067) and presented lower mortality due to COVID-19 (3% vs 6%, p=0.498). However these differences did not reach statistical signifcance. Conclusion: In the SAR-CoVAC registry 5% of the patients had SARS-CoV-2 infection after vaccination, most of them mild and 25% after a complete scheme. Any vaccine was associated with severe COVID-19. When comparing with non-vaccinated patients, those with at least one dose, had less frequently severe disease and died due COVID-19.