COVID-19 vaccine data provide reassurance.

Abstract

The efficacy of COVID-19 vaccines is now incontrovertible. Recent studies report more than 96% protection against severe COVID-19 and COVID-19-related hospitalisation or death. Such studies—along with increasing data from patients with rheumatic diseases—have helped to quell fear and uncertainty among these patients and also to inform patient–physician communications, counter vaccine hesitance, and maximise vaccine uptake. Among patients with rheumatic diseases, there have been questions about COVID-19 vaccine safety and efficacy, with concerns about adverse events and the possibility of disease flares reported as the top reasons for vaccine hesitancy in recent surveys. As with overall vaccine efficacy, the emerging data are reassuring. The American College of Rheumatology guidance on COVID-19 vaccination continues to acknowledge a theoretical risk of disease flare after vaccination, but studies published thus far have indicated that adverse events in patients with autoimmune and rheumatic diseases are comparable to the general population, independent of the type of vaccine. In an international survey of patients with systemic lupus erythematosus, only 3% reported a disease flare after vaccination; 83% of other vaccine-related side-effects were of mild or moderate intensity. Low disease flare rates (5%) were also reported in patients with inflammatory rheumatic diseases in early data from the EULAR COVID-19 Vaccination Registry. Global surveillance of vaccine-related adverse events will be crucial to further clarify and quantify the risk of disease flare in these patients. Another potential concern among patients and rheumatologists is the effect of ongoing treatment with immunosuppressive therapies. Again, the available data are mostly reassuring. Although immunogenicity to COVID-19 vaccines appears to be reduced in patients with rheumatic diseases compared to controls, the majority of patients generate an antibody response after vaccination. This seems to be true regardless of vaccine type, with one study of patients with autoimmune diseases in the Netherlands reporting similar seroconversion rates and IgG titres after first vaccination with the ChAdOx1 nCoV-19 (AstraZeneca) and BNT162b2 (BioNTech-Pfizer) vaccines. In an ongoing study in Brazil, 70% of patients with autoimmune rheumatic diseases seroconverted after the second dose of the CoronaVac inactivated vaccine versus 96% of controls. Correlates of protection after COVID-19 vaccination remain unclear, and seroconversion alone might not adequately reflect vaccine immunogenicity. The contribution of T cells was studied in a recent Article, which showed that neutralising antibody responses after a single dose of the BNT162b2 vaccine were impaired in patients taking methotrexate, but not in those taking biologics, whereas T-cell responses were preserved. Likewise, while B-cell depleting therapies substantially impair antibody production—only around 40% of the patients on rituximab seroconverted after two vaccine doses in a recent report—T-cell responses appeared to be robust, even in the absence of circulating B cells. For patients with rheumatic diseases and the general population alike, questions remain around vaccine-induced protection against the highly transmissible Delta variant and whether additional booster immunisations might bolster immunity, perhaps particularly relevant in patients taking methotrexate or B-cell depleting agents. Likewise, the COVID-19 Global Rheumatology Alliance registry has pivoted to focus on understanding so-called breakthrough infections after vaccination. As mandatory pandemic mitigation measures are lifted in the UK and elsewhere, continued vigilance and data collection will be essential. Questions remain surrounding immune correlates of protection, and it is as yet too early to assess the full consequences of relaxing public health measures. Even when more data accrue, disentangling the relative causative effects of the many viral and societal factors that contribute to virus transmission will probably be impossible. As such, rheumatology societies continue to recommend that vaccinated patients follow current public health guidelines and discuss with their rheumatologist whether continued preventive measures, such as physical distancing, might be appropriate. The effectiveness of COVID-19 vaccines in patients with rheumatic diseases with regard to severe infection, hospitalisation, and death awaits further study, and pharmacovigilance studies will be crucial to unpick how immunological findings relate to clinical effectiveness. We have no doubt that the collaborative rheumatology community will continue to address and answer these outstanding questions.