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The SARS-CoV-2 vaccination is one of the major strategies against the COVID-19 pandemic. The novel platforms of vaccines were developed to replace the time-consuming traditional vaccine manufacturing process, but this worldwide campaign raises new safety issues. A new panel of adverse events was recently reported at nation-wide registry levels.1 However, the information is very limited in patients with rheumatic diseases, who potentially have increased risks of adverse events due to immune dysregulation or concomitant therapies.
We retrospectively collected the diseases, immunomodulators, types of vaccines and adverse events from patients receiving at least one dose of primary SARS-CoV-2 vaccine at rheumatology clinics of a tertiary referral centre in Taiwan. The data were analysed using the Fisher’s exact test for dichotomous variables and Wilcoxon rank sum test for continuous variables. Between July 2021 and September 2021, 265 patients were enrolled, including patients with Sjogren’s syndrome (n=49), rheumatoid arthritis (n=34), systemic lupus erythematosus (n=33), spondyloarthritis (n=21) and other rheumatic diseases (online supplemental table S1). Eighty-nine (33.7%) patients received ChAdOx1 nCoV-19 (AZD1222) vaccine (AstraZeneca/Oxford) and 176 (66.3%) received mRNA-1273 (Moderna) vaccines. The median (IQR) ages were 50 years (39, 60) in AZD1222 and 58 years (45, 67) in mRNA-1273 groups (p value<0.001). The overall adverse events were comparable in AZD1222 (18%) and mRNA-1273 groups (19%). The AZD1222 was associated with prolonged constitutional symptoms (6.7% vs 1.1%, p value=0.019), but the flare rates of rheumatic diseases (5.6% vs 6.2%) were similar in both groups. In addition, the rate of thromboembolic events (suggested by initial tender lesions evolving to ecchymoses and subsequent cerebral infarction occurred in one patient) was more in mRNA-1273 group than AZD1222 (5.7% vs 3.4%, p value=0.6), which is not reported as the major concerns in mRNA-1273.
Notably, herpes zoster reactivation occurred in 10 patients among mRNA-1273 group versus none in AZD1222 group (6.2% vs 0%, p value=0.019) (table 1). The median time from vaccination to herpes zoster attack was 10 days. Significantly, nine patients experienced the first herpes zoster event in their lives and multidermatome involvement was seen in five patients. Moreover, two patients were complicated with pemphigus-like oral mucositis and one patient developed toxic epidermal necrolysis (TEN). Most patients were successfully treated with valaciclovir except the three complicated patients who also received moderate-dose glucocorticoids.
Herpes zoster reactivates in cases of compromised cell-mediated immunity or viral arousal. Only one patient received rituximab 4 months ago with potential immunosuppression. The other patients received only conventional disease-modifying antirheumatic drugs or low-dose glucocorticoids. Based on the characteristics in those herpes zoster attacks, the pathogenesis might involve overactivating varicella zoster virus (VZV) by the mRNA-1273 vaccines.2 Similar findings were reported in other studies3 and herpes zoster was more common in patients receiving mRNA vaccines.4 The possible hypothesis proposes that COVID-19 mRNA or vaccine adjuvants enhance strong T-cell responses5 while compromising VZV-specific CD8+ T-cell immunity. In addition, vaccine mRNA or nanoparticle envelope may enhance the cytokines such as the type 1 interferons via Toll-like receptors signalling.6 The severe mucositis and TEN might imply a fulminant activating VZV, which is one of the precipitating factors for erythema multiforme or TEN.
In this study, we reported the incidence of various adverse events, including the constitutional symptoms, disease flares, thromboembolic events and herpes zoster reactivation in different types of SARS-CoV-2 vaccines. The study is limited by the retrospective, single-centre design and the patients receiving AZD1222 were younger than the mRNA-1273 group. Nonetheless, our report discloses the potential risk of thromboembolism and herpes zoster reactivation by mRNA-1273 in patients with rheumatic diseases. More efforts are needed to clarify the safety and the possible pathogenesis of mRNA SARS-CoV-2 vaccines in autoimmune diseases.
Data availability statement
The full dataset and statistical codes are available from the corresponding author (email@example.com). Participant consent for data sharing was not obtained but the presented data are anonymized, and the risk of identification is low.
Patient consent for publication
This study involves human participants and was approved by the National Taiwan University Hospital Research Ethics Committee Office (NTUH RECO), with the reference number 201912045RINC.The study is a retrospective analysis of the medical records. The participants are anonymised and the waiver from informed consent was approved by the NTUH RECO.
The authors would like to thank the Clinical Immunology and Transplantation Research Center at the Department of Medical Research, National Taiwan University Hospital.
Handling editor Josef S Smolen
Contributors All authors were involved in collecting patients' data and executing the study. S-CH and T-JL drafted the manuscript. T-JL performed the statistical analysis. C-HL gave critical inputs.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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