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BackgroundSystemic lupus erythematosus (SLE) is an autoimmune disease, which presents an immune disorder that leads to the production of autoantibodies with potential involvement of multiple organs. Infections are one of the most frequent causes of hospitalization and death in lupus patients, and SARS-CoV-2 infection has been a global threat since March 2020. Immunization of these patients has been strongly recommended, although vaccine evaluation studies have not included this profile of patients.ObjectivesTo evaluate the immunogenicity and safety after 2 doses of the vaccine against SARS-CoV2 in patients with SLE.MethodsSubgroup of SLE patients from the prospective multicenter cohort of patients with immune-mediated diseases "SAFER” – Safety and Efficacy on COVID-19 Vaccine in Rheumatic Disease, a phase IV study. Vaccination against SARS-CoV-2 took place with vaccines approved by Brazilian regulatory bodies CoronaVac (Inactivated SARS-CoV-2 Vaccine), ChadOx-1 (AstraZeneca) and BNT162b2 (Pfizer-BioNTech) and this project followed in line with the guidelines of the National Immunization Plan in Brazil. Patients aged 18 years or older with a previous diagnosis of SLE (according to the 2019 ACR/EULAR criteria) were included. Patients were evaluated by telephone contact and in a face-to-face visit on the 28th day after each dose. Patients were followed up by means of blood collection for measurement of IgG antibody against SARS-COV-2 by chemiluminescence and disease activity assessed using SLEDAI-2K score.ResultsA total of 367 individuals with SLE were included, of whom 207 received 2 doses of CoronaVac, 128 received 2 doses of ChadOx-1 and 32 received 2 doses of BNT162b2. 90% of the subjects were female with a mean age of 37 years. About 42% (154) of the individuals included did not have any other associated comorbidity. 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-2K at baseline and 41% (147) had zero SLEDAI-2K 28 days after the 2nd dose. Anti-DNA positivity was 30.7% (16/52) at inclusion and 32.6% (17/52) 28 days after the 2nd dose. Complement consumption was present in 18% (10/55) at inclusion and in 14.5% (8/55) 28 days after the 2nd vaccine dose. The geometric mean titers of IgG antibodies against SARS-COV-2 increased in the different vaccine groups, log 2.27 BAU/mL at inclusion and log 5.58 BAU/mL 28 days after the 2nd dose. Antibody titers after second dose varied between different vaccines, 4.96 BAU/mL CoronaVac, 6.00 BAU/mL ChadOx-1 and 7.31 BAU/mL BNT162b2 vaccine, p < 0.001. Only 3.54% (13/367) patients had covid-19 infection after the 15th day of the second dose of immunization, 9 of them having received 2 doses of CoronaVac, 4 of them of ChadOx-1 and none of them receiving BNT162b2, with p-value of 0.63.ConclusionThis study suggests that vaccines against SARS-COV-2 are safe in SLE patients. Induction of immunogenicity occurred in different vaccine regimens. Only 3.5% of individuals had COVID-19 infection with no difference between the types of vaccines evaluated. Future analyzes to explore the association of the effect of immunosuppressive medication, as well as the impact of booster doses and longer follow-up on clinical outcome will be performed.References[1]Mason A, et al. Lupus, vaccinations and COVID-19: What we know now. Lupus. 2021;30(10):1541-1552.[2]Furer V, Eviatar T, Zisman D, et al. Immunogenicity and safety of the BNT162b2 mRNA COVID-19 vaccine in adult patients with autoimmune inflammatory rheumatic diseases and in the general population: A multicentre study. Ann Rheum Dis. 2021;80(10):1330-1338.[3]Izmirly PM, Kim MY, Samanovic M, et al. Evaluation of Immune Response and Disease Status in SLE Patients Following SARS-CoV-2 Vaccination. Arthritis Rheumatol. Published online 2021.Acknowledgements:NIL.Disclosure of InterestsNone Declared.
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BackgroundPatients with immune-mediated rheumatic diseases (IMRDs) have been prioritized for COVID-19 vaccination to mitigate the infection severity risks. Patients with rheumatoid arthritis (RA) are at a high risk of severe COVID-19 outcomes, especially those under immunosuppression or with comorbidities associated. However, few studies in the literature assessed the safety and immunogenicity of the COVID-19 heterologous vaccine schedules in patients with RA.ObjectivesEvaluate the safety and immunogenicity of two heterologous vaccine schedules against SARS-CoV-2 in patients with RA.MethodsThese data are from the study "SAFER - Safety and Efficacy on COVID-19 Vaccine in Rheumatic Diseases,” a Brazilian multicentric prospective phase IV study to evaluate COVID-19 vaccine in IMRDs in Brazil. Immunogenicity and adverse events (AEs) in patients with RA of all centers were assessed after two doses of ChAdOx1 plus additional dose of BNT162b2 or after two doses of inactivated SARS-CoV-2 vaccine CoronaVac plus additional dose of BNT162b2. The titers of neutralizing antibodies against the receptor-biding domain of protein spike (S) of SARS-CoV-2 (anti-RBD) were measured by chemiluminescence 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.ResultsA total of 107 patients with RA were include in the study, most of them female, with a mean age of 46 years. Biological disease modifying anti-rheumatic drugs (DMARDs) were used by 50 % of the patients and conventional synthetics DMARDs in 48 %. Two doses of CoronaVac plus additional dose of BNT162b2 was used in 66 patients and two doses of ChAdOx1 plus additional dose of BNT162b2 in 41. Only mild AEs were observed, mainly after the first dose. The most common AEs after all doses, regardless of the immunizer type, were pain at the injection, headache, arthralgia and myalgia. ChAdOx1 had a higher frequency of pain at the injection (66% vs 32 %, p < 0,001) and arthralgia (68% vs 15%, p < 0,001) compared to CoronaVac. No patients had flare after the vaccination. The titers of anti-RBD after two doses of ChAdOx1 were higher compared to two doses of CoronaVac (6,03 BAU/mL vs 4,67 BAU/mL, p < 0,001). However, after the additional dose of BNT162b2, the anti-RBD titers were similar in both groups (7.28 BAU/mL vs 7.06 BAU/mL, p = 0.56). Only two cases of COVID 19, with mild symptoms, were reported, one in each group.Figure 1.ConclusionChAdOx1, CoronaVac, and BNT162b2 vaccines are safe in RA patients. The frequency of local adverse effects, particularly pain at the injection site, is high. AEs are more frequent with ChAdOx1, especially after the first dose. The use of the immunizers does not change the degree of inflammatory activity of the disease. The immunogenicity of the two heterologous regimens analyzed was similar.References[1]Marques C, Kakehasi AM, Gomides APM, Paiva EDS, Dos Reis Neto ET, Pileggi GCS, et al. A Brazilian Cohort of Patients With Immuno-Mediated Chronic Inflammatory Diseases Infected by SARS-CoV-2 (ReumaCoV-Brasil Registry): Protocol for a Prospective, Observational Study. JMIR Res Protoc.[2]Medeiros-Ribeiro AC, Aikawa NE, Saad CGS, Yuki EFN, Pedrosa T, Fusco SRG, et al. Immunogenicity and safety of the CoronaVac inactivated vaccine in patients with autoimmune rheumatic diseases: a phase 4 trial. Nat Med. 2021;27(10):1744-1751.[3]Machado PM, Lawson-Tovey S, Strangfeld A, Mateus EF, Hyrich KL, Gossec L, et al. Safety of vaccination against SARS-CoV-2 in people with rheumatic and musculoskeletal diseases: results from the EULAR Coronavirus Vaccine (COVAX) physician-reported registry. Ann Rheum Dis. 2022;81(5):695-709.[4]Tavares ACFMG, Melo AKG, Cruz VA, Souza VA, Carvalho JS, Machado KLLL, et al. Guidelines on COVID-19 vaccination in patients with immunemediated rheumatic diseases: a Brazilian Society of Rheumatology task force. Adv Rheumatol. 2022;62:3.Acknowledg ments:NIL.Disclosure of InterestsNone Declared.
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Objectives: Few studies evaluate the immunogenicity and safety of different COVID-19 vaccine platforms in patients with primary Sjogren's Syndrome (pSS). The present study aims to assess the immunogenicity through anti-spike IgG antibodies after the COVID-19 vaccine dose in heterologous groups compared to homologous regimen in patients with pSS. Method(s): These data are from the SAFER study: 'Safety and efficacy of the COVID-19 vaccine in rheumatic disease', a real-life phase IV multicenter longitudinal study, evaluating patients since before the first dose. Pregnant women, those with a history of serious adverse events prior to any vaccine, and those with other causes of immunosuppression were excluded. Patients with pSS > 18 years, classified according to ACR/EULAR 2016 classification criteria were included. Antibodies against the Receptor Binding Domain - RBD portion of the Spike protein of SARS-CoV-2 (IgG-S) were measured by chemiluminescence (Architect SARS-CoV-2 Quanti II, Abbott), before the first dose and 28 days after the 2nd and 3rd dose. Seropositivity was defined as IgG-Spike titers >=7.1 BAU/mL. Patients received adenoviral vector (ChAdOx1, Astrazeneca), mRNA (Pfizer) or inactivated SARS-COV-2 (Coronavac). Non-parametric methods were used. The alpha level of significance was set at 5%. Result(s): 56 participants received 3 doses, 46 +/- 11 years old, disease duration 7.62 years, 92.9% female, 41.1% White and 55.4% Mixed. The homologous third-booster dose group (n = 15, all ChAdOx1) and heterologous group (n = 41) were homogeneous for age, sex, ethnicity, comorbidities, medication and baseline IgG-S median [IQR] titers. After primary vaccination (2 doses) IgG-S median and titers [IQR] were similar in homologous and heterologous groups (373.03 [179.58, 843.92] vs. 473.36 [119.05, 1059.60], p = 0.705). Third-booster dose induced higher IgG-S median [IQR] titers compared to only 2 doses (1229.54 [333.55, 4365.47] vs 464.95 [140.42, 1015.25], p alpha 0.001). Heterologous 3rd-booster induced higher IgG-S median [IQR] titers than homologous scheme with ChAdOx1 (1779.52 [335.83, 4523.89] vs 730.76 [303.37, 1858.98], p = 0.150), Fig 1 and 2, although not statistically significant. Conclusion(s): Third booster dose induced higher humoral immune response compared to two doses whichmay improve protection against COVID-19 in patients with pSS. Although not statistically significant, the response to the heterologous scheme tended to be better than the response to the homologous booster vaccination, which heterologous booster scheme tended to respond better than homologous booster vaccination, which is relevant in this immunosuppressed population. Increasing the sample size will help clarify this issue. .
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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. .
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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.
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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.
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Background: Reddit is an anonymous, international, social media platform with 430 million active users;most are age 18-40 and a majority are male. Its discussion-based format is well-suited to healthcare, allowing patients, loved ones, and healthcare providers (HCPs) to interact, and numerous medical-focused 'subreddit' (SR) communities exist. Previous work has analyzed SR topics including breast cancer, radiation therapy, COVID-19, and depression. To date, no comprehensive list of cancer-related SRs has been compiled or analyzed. Methods: Between 1/7/21 and 2/10/21, a list of cancer-related keywords were queried on reddit.com, SRs were identified, and information was coded from their homepages;final membership numbers were updated on 2/10/21. Tumor subtypes included those listed on the SEER website (seer.cancer.gov/statfacts) where data on prevalence, annual incidence, death, and 5-year survival were pulled. Historical SR membership data was determined using subredditstats.com. Descriptive stats, Pearson's correlation, and regression were performed using R software and Excel. Results:36 cancer-related SRs were identified: 31 (86.1%) active in last 6 months, 17 (47.2%) with daily activity, 24 (66.7%) focused on tumor subtypes, 9 (25.0%) for general support and discussion, and 3 (8.3%) focused on treatment modalities. Median time since inception of SRs was 6 years (range 1 - 12), median number of members was 739 (range 42 - 36519), and median number of moderators was 2 (range 1 - 8). 16 (44.4%) had formal rules for members. Only 1 (2.7%) prohibited those without cancer from posting. Among the groups with > 500 members (25, 69.4%), median growth since 1/1/20 was 66% (range 10 - 370%). 16 (59.3%) of the 27 SEER tumor sub-types were represented by a SR, 5 (18.5%) of which had more than one SR, and 14 (51.8%) had > 500 members. Correlation and R Square via regression between tumor subtype prevalence, annual incidence, deaths, and 5-year survival and associated SR members was 0.61 and 0.368 (p = 0.02), 0.45 and 0.199 (p = 0.11), -0.07 and 0.005 (p = 0.82), 0.33 and 0.107 (p = 0.26), respectively. Based on the prevalence regression line, over-represented tumor subtypes include brain, testicular, and lymphoma. Underrepresented sub-types include cervical, ovarian, colon/rectal, prostate, and lung. Conclusions: SRs represent rapidly growing online communities for those with cancer to seek information and support. Many tumor subtypes are represented;however, some common cancers are either not represented (renal, liver, stomach, endometrial) or underrepresented (colon, prostate, lung). The demographic makeup of Reddit users may explain the over-representation of brain, testicular, and lymphoma, as they can arise in younger patients, particularly men. Future work should assess the content of specific SRs and investigate the role of anonymous HCP input.