Postvaccination anti-S IgG levels predict anti-SARS-CoV-2 neutralising activity over 24 weeks in patients with RA

Abstract

ObjectivesTo correlate immune responses following a two-dose regimen of mRNA anti-SARS-CoV-2 vaccines in patients with rheumatoid arthritis (RA) to the development of a potent neutralising antiviral activity.MethodsThe RECOVER study was a prospective, monocentric study including patients with RA and healthy controls (HCs). Assessments were performed before, and 3, 6, 12 and 24 weeks, after the first vaccine dose, respectively, and included IgG, IgA and IgM responses (against receptor binding domain, S1, S2, N), IFN-γ ELISpots as well as neutralisation assays.ResultsIn patients with RA, IgG responses developed slower with lower peak titres compared with HC. Potent neutralising activity assessed by a SARS-CoV-2 pseudovirus neutralisation assay after 12 weeks was observed in all 21 HCs, and in 60.3% of 73 patients with RA. A significant correlation between peak anti-S IgG levels 2 weeks after the second vaccine dose and potent neutralising activity against SARS-CoV-2 was observed at weeks 12 and 24. The analysis of IgG, IgA and IgM isotype responses to different viral proteins demonstrated a delay in IgG but not in IgA and IgM responses. T cell responses were comparable in HC and patients with RA but declined earlier in patients with RA.ConclusionIn patients with RA, vaccine-induced IgG antibody levels were diminished, while IgA and IgM responses persisted, indicating a delayed isotype switch. Anti-S IgG levels 2 weeks after the second vaccine dose correlate with the development of a potent neutralising activity after 12 and 24 weeks and may allow to identify patients who might benefit from additional vaccine doses or prophylactic regimen.

Should we stop methotrexate or not for vaccination?

“…Schmiedeberg et al reported an equivalent T cell response in a treated RA population compared with healthy controls after the COVID-19 vaccine. 16 They observed also in this study that only anti-COVID-19 IgG were lowered and IgA and IgM levels were maintained. Interestingly, Kapetanovic et al demonstrated that despite a decreased total immunoglobulin level following pneumococcal vaccination, the numbers of circulating total and vaccine-specific IgG or IgA producing plasmablasts did not differ between patients with RA with or without MTX.…”

COVID-19 Vaccination and Immunosuppressive Therapy in Immune-Mediated Inflammatory Diseases

“…Regarding the cellular response, data are scarcer than for humoral immunogenicity. Schmiedeberg et al found a similar T cell response in a treated RA population and healthy controls after the COVID-19 vaccine, although it declined earlier in patients with RA [ 17 ]. The preservation of the cellular response reaffirms the positive role of the COVID-19 vaccine even in patients in whom the humoral response may foreseeably be more affected due to the disease or its treatments, although it would be of great interest to know if temporary DMARD rest strategies also enhance cellular immunity in these patients.…”