Disease Flare and Reactogenicity in Patients With Rheumatic and Musculoskeletal Diseases Following Two‐Dose SARS–CoV‐2 Messenger RNA Vaccination

Abstract

To evaluate disease flare and postvaccination reactions (reactogenicity) in patients with rheumatic and musculoskeletal diseases (RMDs) following 2-dose SARS-CoV-2 messenger RNA (mRNA) vaccination.Methods. RMD patients (n = 1,377) who received 2-dose SARS-CoV-2 mRNA vaccination between December 16, 2020 and April 15, 2021 completed questionnaires detailing local and systemic reactions experienced within 7 days of each vaccine dose (dose 1 and dose 2), and 1 month after dose 2, detailing any flares of RMD. Associations between demographic/clinical characteristics and flares requiring treatment were evaluated using modified Poisson regression.Results. Among the patients, 11% reported flares requiring treatment; there were no reports of severe flares. Flares were associated with prior SARS-CoV-2 infection (incidence rate ratio [IRR] 2.09, P = 0.02), flares in the 6 months preceding vaccination (IRR 2.36, P < 0.001), and the use of combination immunomodulatory therapy (IRR 1.95, P < 0.001). The most frequently reported local and systemic reactions included injection site pain (87% after dose 1, 86% after dose 2) and fatigue (60% after dose 1, 80% after dose 2). Reactogenicity increased after dose 2, particularly for systemic reactions. No allergic reactions or SARS-CoV-2 diagnoses were reported.Conclusion. Flares of underlying RMD following SARS-CoV-2 vaccination were uncommon. There were no reports of severe flares. Local and systemic reactions typically did not interfere with daily activity. These early safety data can help address vaccine hesitancy in RMD patients.The analyses described here are the responsibility of the authors alone and do not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government.

Flares of mixed cryoglobulinaemia vasculitis after vaccination against SARS-CoV-2

“…The overall rate of postvaccination flare observed in patients with MC is similar to that reported in other autoimmune rheumatic diseases [1][2][3] ; importantly, flares did not endanger patients and subsided spontaneously. This reassures the safety of SARS-CoV-2 vaccination in patients with MC.…”

“…Studies on the safety and immunogenicity of SARS-CoV-2 vaccination in patients with inflammatory rheumatic diseases have so far not included mixed cryoglobulinaemia (MC) vasculitis. [1][2][3] We report a prospective observational multicentre study on this disorder.…”

COVID‐19 vaccination can occasionally trigger autoimmune phenomena, probably via inducing age‐associated B cells

“…At first glance, the results of that study seem to oppose our hypothesis. However, we want to make it clear that we do not call into question the safety of COVID‐19 vaccines (besides, the data derived from participants in observational studies 14 , 15 clearly suggest that rheumatic disease flares and new‐onset disease following COVID‐19 vaccination are uncommon, mild to moderate in severity, and in most cases are treated with oral corticosteroids) and we propose an ABC‐induction only in the rare cases that autoimmune phenomena occur after the vaccination, as ABCs are indissolubly associated with autoimmunity. 2 , 3 , 7 , 8 , 11 , 12 , 13 Furthermore, it is wise to keep in mind that ABC‐induction and as a result the estimation of ABC percentages are affected by various parameters, such as the age of the individual, 1 , 26 the ethnicity (as these cells are more marked in African‐American people), 13 , 27 and of course the interval between vaccination and cell counting.…”

“…Autoimmune disease flares and new‐onset disease following coronavirus disease 2019 (COVID‐19) vaccination have recently been reported. 14 , 15 In general, all these cases appeared rare and most of them were moderate in severity and had an excellent resolution of inflammatory features, with the use of corticosteroids alone 14 , 15 (indicating that COVID‐19 vaccines are actually safe). The use of TLR7/8 and TLR9 agonists, as adjuvants of the available mRNA and DNA severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) vaccines, may be the trigger of these post‐vaccination autoimmune/inflammatory phenomena, 14 as it is well known that both TLR7 and TLR9 are involved in the generation and amplification of autoreactive immune responses.…”

Better outcomes of COVID-19 in vaccinated compared to unvaccinated patients with systemic rheumatic diseases

“…Vaccination against the SARS-CoV-2 virus has managed to curb the pandemic with an excellent safety profile. [1][2][3][4][5] On the other hand, breakthrough infections (COVID-19 after vaccination) have been observed in the general population of healthcare workers, 6 7 whereas few data are available for patients with SRD. 8 9 Moreover, a handful of studies suggest that immunogenicity is impaired in these patients, especially in those treated with rituximab or mycophenolate mofetil.…”