EFFICACY and SAFETY of CHADOX1 NCOV-19/AZD1222 and MRNA-1273 VACCINES: A COMPARATIVE STUDY in PATIENTS with AUTOIMMUNE RHEUMATIC DISEASES

ABSTRACT

Background: Several studies have demonstrated immunogenicity after COVID-19 vaccination in patients with autoimmune rheumatic diseases (AIRD) [1], but the differences between mRNA-based and vector vaccines and the cellular responses to COVID-19 vaccines according to distinct immunogenicity in AIRD patients are still unclear. Objectives: To investigate the differences in efficacy and safety between the vector vaccine ChAdOx1 nCoV-19/AZD1222 (Oxford-AstraZeneca) and mRNA-based vaccine mRNA-1273 (Moderna) in patients with AIRD, and to explore the cell-cell interactions between high and low anti-SARS-CoV-2 IgG levels in patients with rheumatic arthritis (RA) by single-cell RNA sequencing (scRNA-seq). Methods: From September 16 to November 15, 2021, we consecutively enrolled 243 participants aged ≥20 years with AIRD who received COVID-19 vaccination, of whom 113 were immunized with AZD1222 and 130 with mRNA-1273. The level of serum IgG antibodies to the SARS-CoV-2 receptor-binding domain on the spike protein S1 subunit was quantifed by electrochemiluminescence immuno-assay at 4-6 weeks after vaccination. Moreover, peripheral blood mononuclear cells were isolated from two RA patient with high anti-SARS-CoV-2 IgG level and four RA patients with low level for scRNA-seq and cell-cell communication signal was analyzed by CellChat. Results: The anti-SARS-CoV-2 IgG seropositivity rate was 78.8% (89/113) for AZD1222 and 83.1% (108/130) for mRNA-1273. The level of anti-SARS-CoV-2 IgG was higher in patients who received mRNA-1273 than in those who received AZD1222 (β 30.15, 95% CI 11.67-48.63, p=0.002) (Table 1). Prednisolone-equivalent dose >5 mg/day and methotrexate (MTX) use in AIRD patients, and non-anti-tumor necrosis factor (TNF)-α biologics and Janus kinase (JAK) inhibitor use in RA patients were associated with inferior immunogenicity. ScRNA-seq revealed CD16-monocytes were predominant in RA patients with high anti-SARS-CoV2-IgG antibody level, and enriched pathways related to antigen presentation via major histocompatibility complex class II (MHC class II) were found (Figure 1). HLA-DRA and CD4 interaction was vigorous among all identifed MHC-II pathway and was enhanced in high anti-SARS-CoV2-IgG antibody group. Conclusion: mRNA-1273 and AZD1222 vaccines exhibited differential immunogenicity in patients with AIRD. Enriched pathways related to antigen presentation via MHC class II in CD16-monocytes might be associated with higher anti-SARS-CoV2-IgG level in RA patients and further study is warranted.