Safety and Immunogenicity of Coronavac and Chadox1 Vaccines against Sars-Cov-2 in Patients with Rheumatoid Arthritis: Brazilian Multicentric Study

Objectives: To evaluate the safety and immunogenicity of CoronaVac and ChAdOx1 vaccines against SARS-CoV-2 in patients with Rheumatoid Arthritis (RA). Method(s): These data are from the 'SAFER (Safety and Efficacy on COVID-19 Vaccine in Rheumatic Diseases)' study, a Brazilian multicentric longitudinal phase IV study to evaluate COVID-19 vaccine in immunomediated rheumatic diseases (IMRDs). Adverse events (AEs) in patients with RA were assessed after two doses of ChAdOx1 or CoronaVac. Stratification of postvaccination AEs was performed using a diary, filled out daily. The titers of neutralizing antibodies against the receptor-biding domain of SARS-CoV-2 (anti-RBD) were measured by chemilumine scence test after each dose of immunizers. Proportions between groups were compared using the Chi-square and Fisher's exact tests for categorical variables. Clinical Disease Activity Index (CDAI) before and after vaccination was assessed using the McNemar test. Result(s): A total of 188 patients with RA were included in the study, most of them were female. CoronaVac was used in 109 patients and ChAdOx1 in 79. Only mild AEs were observed. The more common AEs after the first dose were pain at injection site (46,7%), headache (39,4%), arthralgia (39,4%) and myalgia (30,5%), and ChAdOx1 had a higher frequency of pain at the injection site (66% vs 32 %, p alpha 0.001) arthralgia (62% vs 22%, p alpha 0.001) and myalgia (45% vs 20%, p alpha 0.001) compared to CoronaVac. The more common AEs after the second dose were pain at the injection site (37%), arthralgia (31%), myalgia (23%) and headache (21%). Arthralgia (41,42 % vs 25 %, p = 0.02) and pain at injection site (51,43% vs 27%, p = 0.001) were more common with ChAdOx1. No patients had a flare after vaccination. The titers of anti-RBDafter two doses of ChAdOx1 were higher compared to two doses of CoronaVac (6,03 BAU/mL vs 4,67 BAU/mL, p alpha 0,001). Conclusion(s): The frequency of local adverse effects, particularly pain at injection site, was high. AEs were more frequent with ChAdOx1, especially after the first dose. The use of the immunizers dis not change the degree of inflammatory activity of the disease. In patients with RA, ChAdOx1 was more immunogenic than CoronaVac. .

Safety and Efficacy of Covid-19 Immunization in Systemic Vasculitides - a Multicentric Cohort

Objectives: Patients with immune-mediated rheumatic diseases (IMRDs) develop more severe outcomes of Coronavirus disease 2019 (COVID-19). Recent studies have contributed to understand the safety and efficacy of COVID-19 vaccines in IMRDs, suggesting that different diseases and therapies may interfere on immunization efficacy. In this study we analyze the immunogenicity of COVID-19 vaccines in patients with Systemic Vasculitides (VASC), the rate of COVID-19 and the frequency of disease relapse following immunization. Method(s): We included patients with VASC (n = 73), a subgroup of the SAFER study (Safety and Efficacy on COVID-19 Vaccine in Rheumatic Disease), a longitudinal, multicenter, Brazilian cohort.We analyzed the geometric means of IgG antibody against receptor-biding domain of protein spike of SARS-CoV-2 (anti-RBD) after two shots of CoronaVac (Inactivated vaccine), ChadOx-1 (AstraZeneca) or BNT162b2 (Pfizer-BioNTech). IgG anti-RBD was measured by chemiluminescence test. We assessed new-onset COVID-19 episodes, adverse events (AE) and disease activity for each VASC. Result(s): The sample included Behcet's disease (BD) (n = 41), Takayasu arteritis (TAK) (n = 15), antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) (n = 14), polyarteritis nodosa (n = 7) and other small vessel VASC(n = 6). The majority of patients were female (69%) without comorbidities (49%) and a median age of 37 years. The most common medication was conventional synthetic disease-modifying anti-rheumatic drugs, followed by biologic drugs. No patient received rituximab at baseline. Most patients received CoronaVac (n = 25) or ChadOx-1 (n = 36), while four received BNT162b2. Baseline IgG-RBD means were 1.34 BAU/mL. They increased to 3.89 and 5.29 BAU/mL after the 1st and 2nd vaccine dose, respectively. ChadOx-1 had higher antibody titers than CoronaVac (p = 0.002). There were no differences between different VASC. There were 3 cases of COVID-19 after immunization with CoronaVac. BD patients had a tendency for more cutaneous-articular activity following ChadOx-1. There were no severe relapses and no serious adverse events. Conclusion(s): Our results show the safety of different SARS-CoV-2 vaccines in VASC population. A progressive increase of IgG-RBD antibodies was observed after each dose. ChadOx-1 led to higher IgG-RBDgeometricmeans compared toCoronaVac. Finally, even though ChadOx-1 presented a tendency of triggering mild disease activity, there were no significant disease activity following vaccination in VASC patients. .

Safety of the Vaccine against Sars-Cov-2 in Patients with Systemic Lupus Erythematosus: Data from the Safer Study

Objectives: Systemic lupus erythematosus (SLE) is an autoimmune disease which presents infections as one of the most frequent complications, including more severe outcomes of Coronavirus disease 2019 (COVID-19). Immunization of these patients has been strongly recommended, however, data on safety are still scarce. In this study we evaluate the safety after vaccination against SARS-CoV2 in patients with SLE. Method(s): Safety and Efficacy on COVID-19 Vaccine in Rheumatic Disease - the 'SAFER' study, is a longitudinal Brazilian multicenter phase IV study. In this study patients with SLE (according to the 2019 ACR/EULAR criteria), older than 18 years who received vaccination against SARS-CoV-2 CoronaVac (Inactivated SARS-CoV-2 Vaccine), ChadOx-1 (AstraZeneca) and BNT162b2 (Pfizer-BioNTech) were included. The evaluation of adverse events (AEs) was done by telephone contact, symptom diaries and a face-to-face visit on the 28th day after each dose. Patients were followed up also by disease activity, assessed using SLEDAI-2 K score. Result(s): A total of 367 individuals with SLE were included, 207 received CoronaVac, 128 received ChadOx-1 and 32 received BNT162b2. Ninety percent of the subjects were female with a mean age of 37 years. About 50% (182) of patients were using oral glucocorticoids and azathioprine was the most frequent immunosuppressive therapy. Regarding disease activity parameters, 38%(140) of patients had zero SLEDAI-2Kat baseline and 41%(147) had zero SLEDAI-2 K 28 days after the 2nd dose. After the first and second dose the most frequent AEs were pain at injection site (58%/44%), headache (48%/33%) and pruritus (42%/37%). Comparing the three vaccines, after the first dose, local symptoms, myalgia, and fever were less frequent in patients who received CoronaVac (p alpha 0.001) as well as headache, tiredness (p = 0.001) and arthralgia (p = 0.003). After the second dose, only local symptoms such as pain at the application site and thickening of the skin around the application site were less frequent in the CoronaVac group (p alpha 0.05). Headache, tiredness, musculoskeletal symptoms and fever were more common in patients receiving AstraZeneca. No serious adverse events were reported regardless of the vaccination schedule used. Conclusion(s): This study suggests that vaccines against SARS-COV-2 are safe in SLE patients. Neither severe AEs were reported nor worsening of disease activity were reported. Comparing the different vaccines, CoronaVac had fewer adverse events.

Impact of Glucocorticoid on Immunogenicity among Covid-19 Vaccines in Immune-Mediated Diseases

Objectives: The use of glucocorticoids (GC) has been associated with increased risk of hospitalization for coronavirus infection and reduced immunogenicity of SARS-CoV-2 vaccines in immune-mediated diseases (IMD) patients. However, there is still controversy of which dose of GC is correlated with impaired vaccine response on each of the diverse COVID-19 vaccines available, as well as the possible influence of other concurrent immunosuppressants. This study aimed at evaluating the effect of GC on serological response after two doses of BNT162b2 (Pfizer/BioNTech), CoronaVac (inactivated SARS-CoV-2 Vaccine) and ChadOx1 (AstraZeneca) and after the booster dose in patients with IMD. Method(s): The data were extracted from a multicenter longitudinal observational Brazilian cohort (SAFER: Safety and Efficacy on COVID19 Vaccine in Rheumatic Disease). Patients >18 years of age with IMD were evaluated after 2 doses of the same vaccine against COVID-19 and after a booster vaccine, applied according to Brazilian National Immunization Program. All patients underwent clinical examination and collected blood samples for immunogenicity tests. Serological response was evaluated by Anti-RBD titers (IgG) at baseline and 4 weeks after each vaccine dose. Result(s): Among the 1009 patients evaluated, 301 were using GC (196/401 SLE, 52/199 RA and 27/74 vasculitis). Patients using GC were younger (38.2 vs 40,8 years, p = 0,002), had higherBMI (27,6 vs 26,4 p = 0,008), higher prevalence of kidney disease (3,3% vs 0,5%, p = 0,001) and of thrombosis (11,6% vs 5,9%, p = 0,002) than non-users. Regarding the type of vaccine, most of the GC users received CoronaVac (61.7%), while only 31.9%of non-users received this vaccine (p alpha 0.001). Although there were similar rates of pre-vaccination infections among them, patients with GC tended to have a higher incidence of confirmed COVID-19 infection after the 2nd dose of the vaccine compared to non-users (4.5% vs 2.0% p = 0.054). The antibody titers after the 1st dose of COVID-19 vaccines were similar between groups, but there was a worse response in the GC group after the 2nd dose (p = 0.039). However, this difference was not statistically significant after the 3rd dose (Figure). Conclusion(s): GC use may compromise vaccine-induced immunogenicity after a 2-dose regimen;however, this effect does not remain significant after the booster dose. Multivariate analysis is still pending to assess the potential difference in the impact of GC on the immune response depending on GC dose, type of vaccine and associated drugs.

Evaluation of Homologous and Heterologous Vaccine against Sars-Cov-2 in Systemic Lupus Erythematosus Patients: Data from Safer Study

Objectives: To evaluate the immunogenicity of ChAdOx1, Coronavac and BNT162B2 vaccines in SLE patients, including homologous and heterologous immunizations. Method(s): The 'Safety and efficacy on COVID-19 Vaccine in Rheumatic Disease-SAFER study' is a Brazilian multicentric longitudinal phase IV study to evaluate COVID-19 Vaccine in immune-mediated rheumatic diseases (IMRD) in real life, started on May 2021. SLE patients (according to the 2012 SLICC classification criteria), older than 18 years of age were recruited after 2 or 3 doses of vaccine against COVID-19 (ChAdOx1, BNT162b2 and CoronaVac) and were evaluated at baseline and on the 28th day after each dose. Homologous immunization was considered if they received three doses of the same vaccine and heterologous if a different one was applied. IgG antibody against SARS-CoV-2 spike receptor-binding domain were measured by chemiluminescence (SARS-CoV-2-IgG-II Quant assay, Abbott-Laboratories) at baseline and 28 days after the first, 2nd and 3rd doses (Seropositivity IgGSpike>= 7.1BAU/mL). Statistical analysis: ANOVA and pairwise comparisons tests Results: 316 SLE patients were included (255 heterologous and 61 homologous immunization), 89.2% were female and the mean age was 37.6 +/- 11.2 years. The two groups were homogeneous regarding demographical data, disease activity and immunosuppressive treatment. 49.7% used corticosteroids (alpha 5 mg/day in 52.3%), 83.5% antimalarials, 22.8% azathioprine and 20.3% mycophenolate mofetil. 207 patients received the first two doses with CoronaVac, 128 ChadOx-1 and 32 BNT162b2. Regarding the first two doses of the same vaccine, there was no difference in IgG titers over time between CoronaVac or ChadOx-1 (p = 0.313). IgG titers increased in all vaccine groups, with difference only after 2nd dose: 4.96 +/- 1.71BAU/mL CoronaVac vs. 6.00 +/- 1.99BAU/mL ChadOx-1 vs. 7.31 +/- 1.49BAU/mL BNT162b2 (p alpha 0.001). There was no difference in IgG titers over time between homologous or heterologous vaccine schedule (p = 0.872). IgG titers also increased in all groups, with difference only after 2nd dose: 5.49 +/- 1.96BAU/mL heterologous vs. 6.30 +/- 2.10BAU/mL homologous (p = 0.009). Conclusion(s): Induction of immunogenicity occurred in different vaccine regimens in SLE patients. Future research to explore different heterologous schemes in IMRD must be performed.