ABSTRACT
Background: Adolescents with juvenile-onset autoimmune infammatory rheumatic diseases (AIIRD) could be at risk for disease fare secondary to SARS-CoV-2 infection or to withholding anti-infammatory therapy. While vaccination can protect against COVID-19, safety and immunogenicity data regarding anti-SARS-CoV-2 vaccines among adolescents with AIIRD are limited. Objectives: This international, prospective, multicentre study evaluated the safety and immunogenicity of the BNT162b2 anti-SARS-CoV-2 vaccine among adolescents and young adults with juvenile-onset AIIRD, 80% of whom are on chronic immunomodulatory therapy. Methods: Vaccine side effects, disease activity, and short-term efficacy were evaluated after 3 months in 91 patients. Anti-spike S1/S2 IgG antibody levels were evaluated in 37 patients and 22 controls, 2-9 weeks after the second dose. Results: Ninety-one patients and 40 healthy controls were included. Safety pro-file was good, with 96.7% (n=88) of patients reporting mild or no side-effects, and no change in disease activity. However, 3 patients had transient acute symptoms: 2 following the frst vaccination (renal failure and pulmonary haemorrhage) and 1 following the second dose (mild lupus fare vs. viral infection). Seropositivity rate was 97.3% in the AIIRD group compared with 100% among controls. However, anti-S1/S2 antibody titres were signifcantly lower in the AIIRD group compared with controls (242±136.4 vs. 387.8±57.3 BAU/ml, respectively;p<0.0001). No cases of COVID-19 were documented during the 3-month follow-up. Conclusion: Vaccination of juvenile-onset AIIRD patients demonstrated good short-term safety and efficacy, high seropositivity rate, but lower anti-S1/S2 antibody titres compared to healthy controls. These results should encourage vaccination of adolescents with juvenile-onset AIIRD, even while on immunomodulation.
ABSTRACT
Introduction: : The safety, efficacy, and immunogenicity data of the vaccine against COVID-19 for adolescents with Juvenile-onset Autoimmune Inflammatory Rheumatic diseases (AIIRD) is currently limited. Vaccinating the immunocompromised adolescents for COVID-19 is particularly valuable to protect this vulnerable population. Objectives: To evaluate the safety and immunogenicity of the BNT162b2 mRNA vaccine in adolescents with AIRD treated with immunosuppressive medications compared with healthy adolescents. Methods: This prospective multicenter study examined the safety and immunogenicity of the two-dose regimen BNT162b2 mRNA vaccine in adolescents aged 12-18 years diagnosed with juvenile-onset AIIRD including Juvenile Idiopathic Arthritis (JIA), connective tissues diseases (CTD) including systemic lupus erythematosus (SLE), systemic vasculitides and uveitis. Patients were evaluated 2-10 weeks after the second dose of the vaccine. Safety and post-vaccination COVID-19 infection were evaluated, as well as disease activity prior and following the vaccine. Post vaccination serum IgG antibody levels against SARS-CoV-2 spike S1/S2 proteins were measured. Seropositivity was defined as IgG ≥15 binding antibody units (AU/ml). Anti-Nuclear (N) IgG antibodies were measured for evidence of past COVID-19 infection (level above 1.4RLU was considered positive). Results: 71 adolescents with AIIRD patients and 28 controls from 2 countries, 4 centers, participated in the study. The most common diagnosis in the AIIRD cohort was JIA (N=27), followed by SLE (N=14). The mean disease duration was 5.1±4.48 years (N=70). A total 84.5% (N=60) of the patients were treated with immunomodulatory medications. Post vaccination disease activity remained stable in 96.88% of the adolescents with AIIRD, and post vaccination treatment change was made in the minority of the patients (N=3, 4.84%). Both patients and controls have tolerated the vaccine well, with minimal side effects. There were no severe adverse events in both groups. No post vaccination infection with COVID-19 was documented in both groups. Seropositivity rate was 90.32% in adolescents with AIIRD and 100% in the healthy controls (N=28/31 vs. N=14/14;p=0.54). The level of the S1/S2 antibodies was significantly reduced in adolescents with AIIRD compared to controls (mean± SD 218.97±150.9 vs 380.78± 71.89, P<0.0001). The N Index was negative in both adolescents with AIIRD (0.09±0.09, [N=15]) and healthy controls (0.054±0.036 [N=11]), indicating that none of these participants suffered from past COVID- 19 infection. Conclusion: In our cohort, the BNTb262 mRNA COVID-19 vaccine was shown to have excellent safety profile in immunocompromised adolescents with Juvenile-onset AIIRD, with mild post vaccination side effects, similar to the safety profile of the healthy controls. No post vaccination COVID-19 illness was documented. Post vaccination disease activity was mostly kept stable. Immunogenicity was very good in both groups, with significantly higher S antibody titers in the healthy controls.
ABSTRACT
Background: The Pfizer/BioNTech BNT162b2 vaccine, employing mRNA technology, has been recently approved by both the FDA and EMA for the prevention of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, demonstrating a 94.6% protection rate in a phase 3 study. While this vaccine is recommended by the FDA, EBMT and ASH-ASTCT for immunosuppressed patients, data regarding protection efficacy and safety in patients undergoing immunologic cell therapy are scarce. Aims: We aimed to evaluate efficacy and toxicity of the BNT162b2 vaccine in patients that underwent hematopoietic cell transplantation and CAR-T therapy. Methods: All patients under active treatment at the long-term follow-up HCT clinic (n=124) at the Tel Aviv Sourasky Medical Center, were evaluated for immunologic recovery (CD19+, CD4+, and CD8+ cell blood levels) pre-vaccination and were recommended to receive the commercial vaccination based on the EBMT recommendations. Patients were prospectively followed for vaccination-safety profile (laboratory tests, GVHD monitoring, and symptom-based questionnaire). We evaluated the humoral immune response to vaccine, 7-14 days after the second vaccine dose, by in vitro quantitative determination of anti-SARSCoV- 2S antibodies using Elecsys. assay and cellular immune response by ELISpot, estimating IL-2 and IFN-gamma secretion in response to a pool of lyophilized SARS-COV-2 S and M peptides (PepTivator;Miltenyi). The trial was approved by the local Ethics Committee and was registered by the clinical trials network (NCT04724642). Results: From 23-Dec-2020 all sequential patients (allogeneic, n=101 and CAR-T, n=23) were assessed for eligibility based on the EBMT recommendations (Version 5.0, Feb 21, 2021). Of those, 100 patients were eligible and 79 patients (allogeneic, n=65 and CAR-T, n=14) were vaccinated per-protocol. Characteristics of patients are depicted in Table 1. Overall, the 2 vaccine doses were well tolerated. Adverse events were reported in 39% of allogeneic HCT recipients (4.6% grade ≥3) and 32% of CART recipients (7% grade ≥3). All events resolved within few days, with the exception of 1 secondary graft rejection which is still under investigation. Among the CAR-T group, 5 patients (36%) had humoral antibody response. Patients with CD19+ lymphocytes >0 had a higher likelihood to develop antibodies compared to those with B cell aplasia (67% vs. 12.5%, p=.036). Among the allogeneic HCT group - 47 patients (81%) had a humoral antibody response. Incidence of positive serology was lower in patients with concomitant high intensity immunosuppressive therapy (IST) compared to those with low intensity IST (69% vs. 94%, p=.016). Linear regressions identified that male sex (beta=-.380, p=.012) and high intensity IST (beta=-.497, p=.014) were associated with lower antibody titer, while age, months from HCT, intensity of conditioning, low CD19 cell count, and active GVHD did not predict response. Analysis of peptide induced cytokine release by ELISpot is ongoing and will be presented at the EHA meeting. Summary/Conclusion: Humoral response to the BNT162b2 mRNA COVID-19 vaccine in CAR-T patients with B cell aplasia is significantly impaired, while overall response in patients after allogeneic HCT is encouraging. Patients on concomitant high intensity IST had impaired humoral response to BNT162b2. Longer follow-up is mandatory to test persistence of antibodies, and general preventive practices should be continued until more data are available.
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Background: Vaccination represents a cornerstone in mastering the COVID-19 pandemic. Data on immunogenicity, efficacy, and safety of the novel BNT162b2 mRNA vaccine in patients with autoimmune inflammatory rheumatic diseases (AIIRD) are limited. Objectives: To investigate the immunogenicity, efficacy, and safety of the BNT162b2 mRNA vaccine in patients with AIIRD compared to the general population. Methods: A prospective multicenter study investigated immunogenicity, efficacy, and safety of the two-dose regimen BNT162b2 mRNA vaccine in adult patients with AIIRD including rheumatoid arthritis (RA), psoriatic arthritis (PsA), axial spondyloarthropathy (axSpA), systemic lupus erythematosus (SLE), connective tissues diseases (CTD), systemic vasculitides, and idiopathic inflammatory myositis (IIM), compared to control subjects without rheumatic diseases or immunosuppressive therapies. Serum IgG antibody levels against SARS-CoV-2 spike S1/S2 proteins were measured 2 -6 weeks after the second vaccine dose. Seropositivity was defined as IgG ≥15 binding antibody units (BAU)/ml. Post-vaccination efficacy defined as post-vaccination COVID-19 infection and safety were assessed. Preand post-vaccination disease activity indices were assessed as appropriate for each disease. Results: A total of 686 AIIRD patients and 121 controls participated into the study. AIIRD patients were significantly older than controls, mean age±SD 56.76±14.88 vs 50.76±14.68, respectively, p<0.0001. A total of 95.2% (n=653) AIIRD patients were treated with immunomodulatory medications. The seropositivity rate was 86% (n=590) in patients with AIIRD compared to 100% in controls (p <0.0001) The level of the S1/S2 antibodies was significantly reduced in AIIRD patients compared to controls (mean± SD 132.9±91.7 vs 218.6±82.06, P<0.0001). In patients with PsA, AxSpA, SLE, and LVV, the seropositive rate was above 90%. In RA, the seropositive rate was 82.1% and the lowest seropositive rate (<40%) was observed in patients with AAV and IIM. Anti-CD20 significantly impaired the vaccine's immunogenicity, with the lowest seropositivity rate of 39%. The use of GC, mycophenolate mofetil (MMF), and abatacept was associated with a significantly lower rate of seropositivity (Figure 1). MTX significantly reduced the seropositivity in patients treated with MTX monotherapy and in combinations with other treatments (92% and 84%, respectively), although at a lesser magnitude than anti-CD20, MMF, and abatacept. More than 97% of patients treated with anti-cytokine therapies including TNFi, interleukin-17 and interleukin-6 inhibitors had an appropriate immunogenic response when used as monotherapy. The combination of TNFi with MTX significantly reduced the rate of seropositivity to 93%, p=0.04. Age over 65 years, a diagnosis of RA, IIM, ANCA-associated vascilitis, and treatment with GC, MMF, anti-CD20, and abatacept were associated with a reduced likelihood of seropositivity. There were no post-vaccination symptomatic cases of COVID-19 among AIIRD patients and one mild case in the control group. Major adverse events in AIIRD patients included death (n=2) several weeks after the second vaccine dose, non-disseminated herpes zoster (n=6), uveitis (n=2), and pericarditis (n=1). Post-vaccination disease activity remained stable in the majority of patients. Conclusion: Vaccination with the BNTb262 vaccine resulted in an adequate immunogenic response with an acceptable safety profile in the majority of patients with AIIRD. Treatment with GC, rituximab, MMF, and abatacept may impair BNT162b2-induced immunogenicity. Postponing administration of rituximab, when clinically feasible, seems to be reasonable to improve vaccine-induced immunogenicity. Holding treatment with abatacept and MMF may be considered on an individual basis.
ABSTRACT
Patients diagnosed with B-cell non-Hodgkin lymphoma (B-NHL), particularly if recently treated with anti-CD20 antibodies, are at risk of severe COVID-19 disease. Because studies evaluating humoral response to COVID-19 vaccine in these patients are lacking, recommendations regarding vaccination strategy remain unclear. The humoral immune response to BNT162b2 messenger RNA (mRNA) COVID-19 vaccine was evaluated in patients with B-NHL who received 2 vaccine doses 21 days apart and compared with the response in healthy controls. Antibody titer, measured by the Elecsys Anti-SARS-CoV-2S assay, was evaluated 2 to 3 weeks after the second vaccine dose. Patients with B-NHL (n = 149), aggressive B-NHL (a-B-NHL; 47%), or indolent B-NHL (i-B-NHL; 53%) were evaluated. Twenty-eight (19%) were treatment naïve, 37% were actively treated with a rituximab/obinutuzumab (R/Obi)-based induction regimen or R/Obi maintenance, and 44% had last been treated with R/Obi >6 months before vaccination. A seropositive response was achieved in 89%, 7.3%, and 66.7%, respectively, with response rates of 49% in patients with B-NHL vs 98.5% in 65 healthy controls (P < .001). Multivariate analysis revealed that longer time since exposure to R/Obi and absolute lymphocyte count ≥0.9 × 103/µL predicted a positive serological response. Median time to achieve positive serology among anti-CD20 antibody-treated patients was longer in i-B-NHL vs a-B-NHL. The humoral response to BNT162b2 mRNA COVID-19 vaccine is impaired in patients with B-NHL who are undergoing R/Obi treatment. Longer time since exposure to R/Obi is associated with improved response rates to the COVID-19 vaccine. This study is registered at www.clinicaltrials.gov as #NCT04746092.