Patients with IMIDs take long-term immunosuppressive drugs, such as glucocorticoids, biological agents, and immunosuppressants, which makes them predisposed to COVID-19. The American College of Rheumatology [3] recommends priority vaccination for Rheumatic and Musculoskeletal Diseases patients because they have a higher risk of COVID-19 and a worse outcome after infection than healthy controls. Studies also have shown that patients with rheumatic disease possess higher rates of hospitalization and severe illness after contracting COVID-19 [4, 5]. After the systemic rheumatic disease patients were vaccinated, their prognosis was better than that of unvaccinated patients, and the hospitalization rate and mortality were significantly reduced [6]. In some studies, it has been shown that SLE, pSS, and vasculitis patients may have more severe courses of COVID-19, and the use of prednisone at doses of ≥ 10 mg/day, mycophenolate mofetil, and rituximab has been associated with poorer outcomes [5, 7,8,9,10,11]. Therefore, vaccination may be more necessary for such patients to reduce the risk of contracting COVID-19 and to avoid serious adverse outcomes.

Vaccine efficacy, safety, immunogenicity must be carefully studied. Safety, which is mainly represented by vaccine-related side effects and the risk of IMID disease activity, is a possible factor for the hesitancy of patients with systemic autoimmune rheumatic disease to receive vaccination [12]. There are some reports of adverse events from COVID-19 vaccines. On March 18, 2021, the European Medicines Agency announced the discovery of thrombosis with thrombocytopenia syndrome following the administration of the ChAdOx1 nCoV-19 vaccine (Vaxzevria, Oxford/AstraZeneca), which uses a recombinant replication-defective chimpanzee adenovirus vector [13]. After six cases of cerebral venous sinus thrombosis with thrombocytopenia were reported among Janssen vaccine recipients between April 13 and 23, 2021, the US Centers for Disease Control and Federal Drug Administration recommended suspending the use of the Janssen vaccine [14], but there were no IMID patients in those case reports. According to previous experiences of vaccination in IMID patients, including vaccines against influenza, hepatitis B and hepatitis A, no serious adverse events like herpes rash, pneumonia, human papillomavirus, and tickborne encephalitis have been observed [15]. Similarly, COVID-19 vaccines, whether in inactivated or mRNA forms, have been shown to be safe for IMID patients in studies with a relatively large sample size [16, 17]. Although two patients died several weeks after vaccination in a multicenter study of mRNA vaccination of patients with autoimmune rheumatic diseases, the deaths were both irrelevant to the vaccines themselves [16].

However, mRNA vaccination seems to result in an increased incidence of herpes zoster virus among patients with IMIDs. For example, Furer et al. [18] have reported that the incidence of herpes zoster after BNT162b2 mRNA COVID-19 vaccination among IMID patients (n = 491) was 1.2%, while that in the control group (n = 99) was 0%. No herpes zoster virus infection was observed in our study, whether the participants were inoculated with inactivated vaccine or the recombinant subunit vaccine. In addition, Machado et al. have reported that adverse events were observed in 37% of cases, with serious events in 0.5%, and SARS-CoV-2 vaccines were safe for rheumatic and musculoskeletal disease (RMD) patients [19]. Likewise, in our study, the prevalence of adverse events in the IMID group was 18.4%, and no serious adverse events occurred. Interestingly, the incidence of adverse events in the IMID group was less than that in the control group, which may be due to the use of nonsteroidal anti-inflammatory drugs and glucocorticoids. Overall, IMID patients who received COVID-19 vaccines rarely experience vaccine-related side effects.

Do COVID-19 vaccines induce autoimmune diseases? Do they cause stable autoimmune diseases to flare? Theoretically, vaccination may induce an autoimmune disease flare, which is probably caused by molecular mimicry of the vaccine components, overstimulation of the immune system, and pathogenic effects of adjuvants. According to previous studies, there have been sporadic cases showing SLE disease flares after vaccination. For instance, Li et al. [20] have reported two cases of women presenting with SLE after measles vaccination. Moreover, Soybilgic et al. [21] have demonstrated that the disease recurrence rate among SLE patients after human papillomavirus (HPV) vaccination reached 30%, while no increase in the risk of disease activity in RMD patients was detected. Furthermore, Milanovic et al. [22] observed that no significant worsening of underlying disease occurred after influenza vaccination in 47 patients with SLE, RA, or pSS compared with 52 controls. Additionally, a large cohort study by Miranda et al. [23] showed that there was no difference in the probability of SLE between individuals who received the HPV vaccine and those who were not vaccinated. In a study with a large sample size, there were also no cases of disease activity in IMID patients who received mRNA COVID-19 vaccines [16]; however, no data on the disease activity related to CoronaVac have been reported [17]. In another study [19], there were rare reports of an inflammatory/autoimmune rheumatic and musculoskeletal disease (I-RMD) flare after vaccination (Pfizer/BioNTech vaccine, AstraZeneca/Oxford, and Moderna vaccine). A flare following vaccination was reported in 4.4% of I-RMD cases, with 29 cases (0.6%) of severe flares, implying that a higher disease activity may be associated with a higher flare rate.

In our study, none of the patients showed significant IMID activity. Noticeably, there was one SLE patient who developed new-onset proteinuria after vaccination. This patient had a SLEDAI score of 4 and had repeated proteinuria before vaccination, which means that her kidney disease was not in complete remission, and there were no other changes in her disease at the end of the follow-up. Therefore, this case was considered as no disease activity. All patients in our study ensured disease stability for at least three months before vaccination, and our results suggest that the likelihood of disease activity occurrence after vaccination is extremely low. In sum, although there is a theoretical risk of disease activity after receiving a COVID-19 vaccine, the benefits of vaccination overweigh the risks of disease activity and side effects.

Due to the long-term use of glucocorticoids and immunosuppressive drugs, IMID patients are immunosuppressed, which may lead to a decreased vaccine efficacy. Our data showed that there were no cases of COVID-19 in the two groups, which supports the protective effects of vaccination against COVID-19, no matter which vaccine is utilized. In a phase IV trial of CoronaVac [17], the seroconversion(SC) and the positive rate of neutralizing antibody in the autoimmune rheumatic diseases group were less than those in the control group (70.4% vs. 95.5% and 56.3% vs. 79.3%, respectively), and the rate of seropositivity of the mRNA vaccine among autoimmune rheumatic disease patients also was less than that of the healthy controls (86% vs. 100%) [16], which suggests the low immunogenicity of the COVID-19 vaccine in autoimmune rheumatic disease patients. Additionally, a phase IV clinical study of CoronaVac revealed that patients with autoimmune rheumatic diseases receiving biologics, rituximab, or abatacept had the greatest negative impact on immunogenicity [17], which was attributed to drug-induced immunogenicity. Among the immunosuppressive drugs, methotrexate and mycophenolate mofetil had the greatest negative impact on immunogenicity.

Our study had some limitations that must be addressed. On the one hand, only the COVID-19 rate after vaccination was utilized to evaluate the efficacy of the vaccine, while the levels of neutralizing antibodies and anti-SARS-CoV-2 IgG were not tested due to the restricted conditions in our center. In addition, the sample size of this study was insufficient, and a study with a much larger sample size will be conducted in the future.