Project description:ObjectiveAntibody responses to coronavirus disease 2019 (COVID-19) vaccines are reduced among immunocompromised patients but are not well quantified among people with rare disease. We conducted an observational study to evaluate the antibody responses to the booster SARS-CoV-2 vaccine in people with rare autoimmune rheumatic diseases (RAIRD).MethodsBlood samples were collected after second, before third, after third and after fourth vaccine doses. Anti-spike and anti-nucleocapsid antibody levels were measured using an in-house ELISA. Logistic regression models were built to determine the predictors for non-response. Results were compared with age- and sex-matched healthy controls.ResultsForty-three people with RAIRD were included, with a median age of 56 years. Anti-spike seropositivity increased from 42.9% after second dose to 51.2% after third dose and 65.6% after fourth dose. Median anti-spike antibody levels increased from 33.6 (interquartile range 7.8-724.5) binding antibody units after second dose to 239.4 (interquartile range 35.8-1051.1) binding antibody units after the booster dose (third dose, or fourth dose if eligible). Of the participants who had sufficient antibody levels post-second dose, 22.2% had insufficient levels after the booster, and 34.9% of participants had lower antibodies after the booster than the lowest healthy control had after the second dose. Rituximab in the 6 months prior to booster (P = 0.02) and non-White ethnicity (P = 0.04) were associated with non-response. There was a dose-response relationship between the timing of rituximab and generation of sufficient antibodies (P = 0.03).ConclusionAlthough the booster dose increased anti-spike IgG and seropositivity rates, some people with RAIRD, particularly those on rituximab, had insufficient antibody levels despite three or four doses.
Project description:BackgroundLittle is known about the safety of SARS-CoV-2 vaccination in patients with rheumatic musculoskeletal disease (RMD). We evaluated the occurrence of adverse events following immunization (AEFI) in RMD patients and heathy subjects who received anti-SARS-CoV-2 mRNA vaccine.MethodsWe performed a telephone interview collecting any adverse event (AE) following immunization (AEFI) that occurred in RMD patients and healthy controls after the two doses of mRNA vaccine including common local reactogenicity and systemic events (for example, fever, fatigue/malaise, joint and muscle pain). We also investigated the onset of new signs or symptoms of the RMD after the vaccination.ResultsWe evaluated 126 patients with RMDs [105 females and 19 males, median age 51(IQR 17)] and 85 controls [62 females and 23 males, (median age 49 (20)]. Seventy patients (55.6%) were taking immunosuppressants, conventional synthetic (n=31, 43.3%) and/or biological [TNF inhibitors (n=49, 68.6%)], and 30 (23.8%) were taking hydroxychloroquine; treatment remained unchanged in 77% of patients. Eleven out of 126 patients and none of the 85 controls previously contracted COVID-19. The median follow-up from the completion of vaccination was 15 (3) weeks both in patients and controls. We reviewed 5 suspected cases confirming mild articular flares in 3 women (2.8) with inflammatory arthritis (2 psoriatic arthritis and 1 rheumatoid arthritis) while no disease reactivation was recorded in patients with connective tissue diseases; the incidence rate of RMD reactivation was 0.007 person/month. Multivariable logistic regression analysis showed similar frequencies of local and systemic AEFI in patients and controls with no effect of therapies or previous COVID-19. Local reaction-pain in the injection site-was the most frequently reported AEFI both in RMD and controls (71% and 75% of all the AEFI, respectively) after the first dose. Overall, up to 66% of patients experienced at least one AEFI at the second dose and up to 62% in the control group. Most of AEFI occurred within 2 days of vaccine administration. Two RMD patients developed pauci-symptomatic COVID-19 after the first dose of vaccine.ConclusionThe low incidence rate of disease reactivation and the similar AEFI occurrence compared to controls should reassure on mRNA vaccine safety in RMD patients.
Project description:Using a rapid response web-based survey, we identified gaps in public understanding of the Centers for Disease Control and Prevention's messaging about the pause in use of the Johnson & Johnson-Janssen COVID-19 vaccine and estimated changes in vaccine hesitancy using counterfactual questions.
Project description:ObjectivesTo evaluate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine acceptance among patients with rheumatic diseases (RMD).MethodsAll rheumatology patients attending a large suburban health network were invited to participate in an anonymized online survey. The primary outcome of interest was SARS-COV-2 vaccine acceptance.ResultsThe mean (SD) age of respondents (n = 641) was 52.7 (15.1) years and 74.4% (n = 474) were female. Sixty-five percent were willing to have a SARS-COV-2 vaccine, while 34.4% were vaccine-hesitant (unwilling or undecided). On multivariate analysis, vaccine acceptance was associated with smoking (OR: 2.25 [95% CI: 1.22-4.15; p = .009]), history of malignancy (OR: 2.51 [95% CI: 1.19-5.26; p = .015]), influenza or pneumococcal vaccination in the preceding year (OR: 2.69 [95% CI: 1.78-4.05; p < .001]) and number of COVID-Safe measures practiced (OR: 1.54 [95% CI: 1.05-2.26; p = .027]). Vaccine acceptance correlated with positive beliefs regarding vaccine efficacy (r = 0.40; p < .001) and safety (r = 0.36; p < .001). Vaccine acceptance correlated negatively with concerns regarding side-effects (r = -0.30; p < .001) and vaccine-associated RMD flare (r = -0.21; p < .001). In vaccine-hesitant respondents, 39.2% were more likely to accept vaccination if given a choice of which vaccine they receive and 54.5% if their rheumatologist recommended it. Twenty-seven percent of patients on immunomodulators were willing to withhold medications while 42.1% were willing if advised by their rheumatologist.ConclusionSARS-COV-2 vaccine hesitancy is prevalent amongst RMD patients and associated with concerns regarding vaccine safety, efficacy, side effects and RMD flare. Clinician recommendation, vaccine choice and communications targeting patient concerns could facilitate vaccine acceptance.Significance and Innovations Vaccine hesitancy is prevalent in RMD patientsVaccine acceptance is associated with beliefs regarding vaccine safety and efficacy and concerns regarding RMD flare and vaccine-associated side effectsVaccine choice and clinician recommendation have the potential to improve vaccine acceptance in patients who are hesitant.
Project description:ObjectivesImmunogenicity to the SARS-CoV-2 mRNA vaccines in adolescents and young adults (AYA) with childhood-onset rheumatic diseases (cRD) is unknown. We aimed to evaluate the humoral immunogenicity and safety of the vaccines in our AYA with cRD.MethodsA monocentric observational study with 159 AYA (50.3% female and 70.4% Chinese). Humoral immunogenicity was assessed at 2-3 and 4-6 weeks following first and second vaccination by cPass™ SARS-CoV-2 Neutralization Antibody Assay. Inhibition signal of ≥30% defined the cut-off for positive detection of the SARS-CoV-2 neutralizing antibodies. Vaccine safety and disease activity were assessed within 6 weeks after second vaccination.ResultsA total of 64.9% and 99.1% of 159 patients (median age: 16.9, IQR: 14.7-19.5) mounted positive SARS-CoV-2 neutralizing responses after first and second vaccination, respectively. Most patients (89.8%) had ≥90% inhibition signal after second vaccination. Methotrexate and mycophenolate mofetil increased the risk associated with negative cPass neutralization responses following the first vaccination. Holding both medications after each vaccination did not affect immunogenicity. There was no symptomatic COVID-19 infection. Local reaction remained the most common (23.3-25.2%) adverse event, without serious complication. Two and seven patients flared following the first and second vaccination, respectively. Subgroup analyses of the 12-18-year-old cohort did not show any differences in vaccine efficacy, predictors of poor response and general safety, but higher proportion of disease flares.ConclusionsSARS-CoV-2 mRNA vaccines were efficacious after the two-dose regimen in almost all AYA with cRD without serious adverse event. The rate of disease flare observed is 4.4% after the second mRNA vaccine dose.
Project description:COVID-19 has proven to be particularly serious and life-threatening for patients presenting with pre-existing pathologies. Patients affected by rheumatic musculoskeletal disease (RMD) are likely to have impaired immune responses against SARS-CoV-2 infection due to their compromised immune system and the prolonged use of disease-modifying anti-rheumatic drugs (DMARDs), which include conventional synthetic (cs) DMARDs or biologic and targeted synthetic (b/ts) DMARDs. To provide an integrated analysis of the immune response following SARS-CoV-2 infection in RMD patients treated with different classes of DMARDs we carried out an immunological analysis of the antibody responses toward SARS-CoV-2 nucleocapsid and RBD proteins and an extensive immunophenotypic analysis of the major immune cell populations. We showed that RMD individuals under most DMARD treatments mount a sustained antibody response to the virus, with neutralizing activity. In addition, they displayed a sizable percentage of effector T and B lymphocytes. Among b-DMARDs, we found that anti-TNFα treatments are more favorable drugs to elicit humoral and cellular immune responses as compared to CTLA4-Ig and anti-IL6R inhibitors. This study provides a whole picture of the humoral and cellular immune responses in RMD patients by reassuring the use of DMARD treatments during COVID-19. The study points to TNF-α inhibitors as those DMARDs permitting elicitation of functional antibodies to SARS-CoV-2 and adaptive effector populations available to counteract possible re-infections.