ABSTRACT
We found a higher incidence of myocarditis in young males who had received Pfizer-BioNTech BNT162b2 vaccinations as compared with historical controls and unvaccinated individuals. The analyses focused on risk following the first and second vaccine in adults and adolescents, as well as risk in adults following the third (booster) vaccine. Males, mainly aged 12-30 years, were found to be at higher risk. However, the question remains what causes lead one specific young male, but not another, to develop post-vaccination myocarditis. The HLA molecule is known to play an important role in infectious and auto-inflammatory diseases. We hypothesized that differences in HLA alleles could lead to either protection or susceptibility to vaccination-induced myocarditis. On this basis, HLA typing was performed using next-generation sequencing technology for the HLA-A, -B, -C, -DRB1, -DQB1 and -DPB1 loci, in 21 wellcharacterized patients who developed myocarditis after the second Pfizer BNT162b2 vaccination. The HLA genotypes were compared with high-resolution HLA data of 272 healthy controls from the Hadassah Bone Marrow registry samples, who are representative of HLA frequencies in the Israeli population. Our findings demonstrated that in HLA class II, DRB1*14:01 (19.04% vs. 5.3%, Pcorr = 0.028, OR = 4.17), HLA-DQB1*05:03 (19.04% vs. 6.06%, Pcorr = 0.034, OR = 3.64) and DRB1*15:03 (7.14% vs. 0.0%, Pcorr = 0.003, OR = 41.76) were significantly associated with disease susceptibility. We further discovered susceptibility motifs in the HLA-DR peptidebinding grooves: His60 (Pcorr0.01, OR = 3.52) and Arg70 (Pcorr = 0.0047, OR = 3.43). Our findings suggest that immunogenetic fingerprints in HLA peptide-binding grooves may have changed the binding affinity of different peptides derived from the Pfizer-BioNTech BNT162b2 vaccination, and induced myocarditis.
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.