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Objectives: To evaluate the humoral immune response to the third dose (booster) of vaccine against SARS-CoV-2 in patients with autoimmune rheumatic diseases who were seronegative after a two-dose regimen. Method(s): Observational study. Patients with autoimmune rheumatic diseases who had not achieved seroconversion after a two-dose vaccine schedule against SARS-CoV-2 were included. To assess the humoral immune response, anti-RBD IgG (S protein receptor binding domain) neutralizing antibody titers were determined by ELISA (cutoff titer 200). The determination was made between 30 to 45 days after the third dose. Result(s): From 66 patients who received SARS-CoV-2 vaccination, 18 patients (29.5%) were seronegative after a two-dose schedule. 61% had SLE, 77% had comorbidities (61% with hypertension, p = 0.03). Patients were on treatment: 10 with prednisone (8 with doses greater than 10 mg/d, p = 0.01), 10 with hydroxychloroquine, one with methotrexate, one with leflunomide, four with azathioprine, five with my cophenolatemofetil and five with rituximab (they are the total number of non-responders on biological treatment, p = 0.03). Regarding the primary vaccination regimen, 11 received BBIBP-CorV (p = 0.01), 5 AZD1222, 1 Gam-COVID-Vac and 1 mRNA1273/Gam-COVID-Vac heterologous scheme. Of these 18 non-responders, 14 received a third dose;nine patients (62%) presented anti-RBD IgG detectable. Of the five patients who did not respond to the booster vaccination, three had received BBIBP-CorV as the initial schedule and the vaccines applied as a third dose were Ad5-nCoV (1), BNT162b2 (1), AZD 1222 (2) and Gam-COVID-Vac (1). They were being treated with: rituximab (2), azathioprine (2) and mycophenolate mofetil (1). Treatment with higher doses of prednisone was the only factor associated with non-seroconversion to the third dose (8 +/- 4.5;p 0.02). Conclusion(s): The third dose of SARS-CoV-2 vaccine allowed to improve the serological response to vaccination, achieving a seroconversion of 62% in this group of patients.
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Background: Several trials have reported lower seroconversion rates in patients with autoimmune rheumatic diseases than in healthy patients. In Argentina, the vaccines that were available during the development of this study were: Sputnik V (Gam-COVID-Vac), AstraZeneca (ChAdOx1 nCov-19), Sinopharm (BBIBP-CorV) and Moderna (mRNA-1273). Limited information is available about vaccines against SARS-CoV2 with inactivated virus or viral vector in autoimmune patients. Objectives: To evaluate the humoral immune response to vaccines against SARS-CoV2 in patients with autoimmune rheumatic diseases;to compare the humoral response among patients with Systemic Lupus Erythematosus (SLE) and other autoimmune diseases and to analyse the variables associated. Methods: We included patients with autoimmune rheumatic diseases (Rheumatology Unit of Padilla Hospital, Tucumán, Argentina), who received vaccination against SARS-CoV2 from June 2021. Sociodemographic, comorbidities, related to rheumatic disease, vaccination and SARS-CoV2 infection were the variables recorded. To evaluate the humoral immune response, the neutralizing anti-S-RBD IgG antibody titres were determined by ELISA 'In House' test with a cut-off titre of 200 (IMMCA). The times established for the serological determinations were: T0 or baseline: 1st vaccine dose, T1: 14 ± 2 days after the 1st dose, T2: 2nd dose, T3: 21-45 days after the 2nd dose, T4: 30 days after the 3rd dose, T5: 6 months and T6: 12 months after the 3rd dose. Results: 66 patients were included, 91% women and 92.4% Amerindians. The mean age was 40.7 ± 11.4 years;53% with SLE, 15.2% Rheumatoid Arthritis, 7.6% Systemic Sclerosis, 7.6% Juvenile Idiopathic Arthritis, 7.6% Systemic Vasculitis and 9% other diagnoses;mean disease duration was 12.05 ± 7. 5 years;63.6% had at least one comorbidity (57% HBP, 31% overweight or obesity). At baseline, the treatments received were: corticoster-oids (37.9%, prednisone mean dose 4.12 ± 8 mg/day), cDMARDs (75.7%), bDMARDs (18.2%): Rituximab (58.3%) and anti TNF (25%). Sixteen patients (24.2%) had previous COVID19 (75% mild symptoms). The vaccines applied were: AstraZeneca 38.2%, Sinopharm 31.7%, Sputnik V 19%, and combined schedule Sputnik V/Moderna in 11%. At baseline, 28.8% had detectable anti-S-RBD IgG antibodies. This frequency increased to 48.4% at 1st dose and 70.2% at 2nd dose. The variables that were associated with lower sero-conversion rates and lower antibody titre were vaccination with Sinopharm (p 0.028) and treatment with bDMARDs (p 0.02), none of the 5 patients with Rituximab showed seroconversion. There were no significant differences in the levels of anti-S-RBD IgG antibodies between patients with SLE and the other rheumatic diseases. Patients who had SARS-CoV2 infection prior to vaccination had higher antibody titres in both T1 (p 0.006) and T2 (p 0.002) but after the two doses this difference was not significant (p 0.67). In the regression analysis, the variables that were independently associated with seroconversion were the type of vaccine applied at the 1st dose and the hypertensive disease. The chance of responding to vaccination was 13 and 9 times higher for those who received Sputnik V (OR 12.78;95% CI 1.46-315.9) or AstraZeneca (OR 8.61;95% CI 1.63-72.5) respectively, than Sinopharm in the 1st dose. The chance of being a responder was 88% lower for hypertensive patients (OR 0.12;95% CI 0.02-0.58). Conclusion: In this preliminary analysis, a seroconversion rate of 70.2% was associated with two-dose vaccination for SARS-CoV2 in patients with autoimmune rheumatic diseases. There were no differences in the serological response between patients with SLE and other rheumatic diseases. The humoral immune response was lower in patients with bDMARDs and null in those who received Rituximab. Seroconversion and antibody titres levels were associated with the type of vaccine applied, being Sinopharm who presented the lowest response. The follow-up will provide more knowledge about the behaviour of the humoral response in our patients.
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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.
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Background: Currently there is little information on the efficacy and safety of SARS-CoV-2 vaccination in patients with immune-mediated diseases and/or under immunosuppressive treatment in our country, where different types of vaccines and mix regimens are used. For this reason, the Argentine Society of Rheumatology (SAR) with the Argentine Society of Psoriasis (SOARPSO) set out to develop a national register of patients with rheumatic and immune-mediated infammatory diseases (IMIDs) who have received a SARS-CoV-2 vaccine in order to assess their efficacy and safety in this population. Objectives: To assess SARS-CoV-2 vaccine efficacy and safety in patients with rheumatic and IMIDs. Methods: SAR-CoVAC is a national, multicenter and observational registry. Adult patients with a diagnosis of rheumatic or IMIDs who have been vaccinated for SARS-CoV-2 were consecutively included between June 1st and September 17th, 2021. Sociodemographic data, comorbidities, underlying rheumatic or IMIDs, treatments received and their modifcation prior to vaccination and history of SARS-CoV-2 infection were recorded. In addition, the date and place of vaccination, type of vaccine applied, scheme and indication will be registered. Finally, adverse events (AE), as well as SARS-CoV-2 infection after the application of the vaccine were documented Results: A total of 1234 patients were included, 79% were female, with a mean age of 57.8 (SD 14.1) years. The most frequent diseases were rheumatoid arthritis (41.2%), osteoarthritis (14.5%), psoriasis (12.7%) and spondy-loarthritis (12.3%). Most of them were in remission (28.5%) and low disease activity (41.4%). At the time of vaccination, 21% were receiving glucocorti-coid treatment, 35.7% methotrexate, 29.7% biological (b) Disease Modifying Anti-Rheumatic Drugs (DMARDs) and 5.4% JAK inhibitors. Before vaccine application 16.9% had had a SARS-CoV-2 infection. Regarding the frst dose of the vaccine, the most of the patients (51.1%) received Gam-COV-ID-Vac, followed by ChAdOx1 nCoV-19 (32.8%) and BBIBP-CorV (14.5%). In a lesser proportion, BNT162b2 (0.6%), Ad26.COV2.S (0.2%) and Coro-naVac (0.2%) vaccines were used. Almost half of them (48.8%) completed the scheme, 12.5% were mix regimenes, the most frequent being Gam-COVID-Vac/mRNA-1273. The median time between doses was 51days (IQR 53). More than a quarter (25.9%) of the patients reported at least one AE after the frst dose and 15.9% after the second. The fu-like syndrome and local hypersensitivity were the most frequent manifestations. There was one case of mild anaphylaxis. No patient was hospitalized. Altogether, the incidence of AE was 246.5 events/1000 doses. BBIBP-CorV presented signifcantly lower incidence of AE in comparison with the other types of vaccines. (118.5 events/1000 doses, p<0.002 in all cases) Regarding efficacy, 63 events of SARS-CoV-2 infection were reported after vaccination, 19% occurred before 14 days post-vaccination, 57.1% after the frst dose (>14 days) and 23.8% after the second. In most cases (85.9%) the infection was asymptomatic or had an outpatient course and 2 died due to COVID-19. Conclusion: In this national cohort of patients with rheumatic and IMIDs vaccinated for SARS-CoV-2, the most widely used vaccines were Gam-COVID-Vac and ChAdOx1 nCoV-19, approximately half completed the schedule and in most cases homologously. A quarter of the patients presented some AE, while 5.1% presented SARS-CoV-2 infection after vaccination, in most cases mild.