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.