Studies have reported that the new SARS-CoV-2 vaccines are safe and effective in the general population. However, limited information is available on the safety and effectiveness of vaccines in susceptible populations, such as those with systemic autoimmune and inflammatory diseases (SAIDs), those taking immunosuppressive medications, and pregnant women [14]. We aimed to determine whether the efficacy and safety of the inactivated vaccine in patients with RMDs are comparable to those in HCs.

According to one of our previous studies, the safety and efficacy of the SARS-CoV-2 inactivated vaccine in patients with RA and SLE were comparable to those in HCs [8]. In this study, no notable differences were observed between the RMD and HC groups in the rate of seroconversion. A previous study found that the effectiveness of SARS-CoV-2 vaccines was lower in immunosuppressed individuals than in the general population [15]. However, the immunosuppressed study participants were not limited to patients with RMDs taking immunosuppressive drugs, and this could account for the observed discrepancies. However, the previous studies suggest that immunosuppressed populations require additional protection against COVID-19 and related diseases and therefore should be prioritized when implementing additional and/or future SARS-CoV-2 vaccine dosing recommendations.

In this study, the frequency of vaccination-related adverse events was 23.4% and 18.7% in the RMD and HC groups, respectively, with fever and myalgia being the most frequently reported side effects. Concerns about vaccination-related adverse events were also one of the most common reasons for many patients with RMDs refusing vaccination. Another cross-sectional study found that patients with SAIDs were more likely to experience certain mild side effects. However, the absolute risk was very modest [16]. Overall, the adverse events were significantly higher in patients with SAIDs than in HCs. However, among vaccinated individuals the incidence of adverse events and hospitalization rates did not differ significantly between groups [16]. Another clinical investigation found a higher incidence of rash in individuals with idiopathic inflammatory myopathies [14]. Adjuvants and immune activators in vaccines can also cause immunological thrombosis, demyelinating events, and episodes of autoimmune disease. However, no similar unfavorable outcomes were noted in this study. In vaccine studies, fever (46%), weariness (44%), headache (39%), and muscle pain (17%) are the most frequently reported systemic adverse effects [17]. Active measures should be taken to ensure that patients with RMDs are vaccinated, as adverse vaccination events are easily manageable and the risk of hospitalization as a result of vaccination is minimal.

Among the participants of this study with previous Omicron variant infection, the occurrence of mild disease in many patients in the RMD group may be a consequence of chronic administration of immunosuppressive drugs, resulting in their immune systems not responding promptly and dramatically to the viral infection. SARS-CoV-2 vaccines are effective in preventing hospitalization and death [18, 19], severe COVID-19, and COVID-19 pneumonia, with no statistically significant difference between the vaccine types [20]. In patients infected with the Omicron variant, upper airway symptoms and nonspecific symptoms are the predominant clinical characteristics. The most frequent symptom is fever, which is followed by a light, dry cough [21]. According to a Korean study, fever (20%) and sore throat (25%) are the most typical signs and symptoms. In that study, patients infected with the Omicron variant had a 91.33% vaccination rate, indicating no correlation between infection with the Omicron variant and the COVID-19 vaccine. The numerous mutations in the Omicron variant cause immunological escape from the vaccine [22]. However, in another serum neutralization trial, the escape was incomplete, with relatively high neutralizing antibody titers against the Omicron variant being detected in vaccinated patients [23].

The antibody titers produced by patients with RMDs infected with the Omicron variant were lower than those produced by HCs. Many immunosuppressive agents used to treat RMDs impair the immunogenicity of the vaccine. The degree of reduction in antibody titers varies according to the immunosuppressant being used. For example, the immunogenicity of the mRNA COVID-19 vaccination may be reduced in patients treated with certain drugs, including methotrexate [24], MMF, and abatacept [25]. When used alone or in conjunction with methotrexate, rituximab significantly lowered the humoral response to vaccination [26]. The degree of B-cell recovery after vaccination coincides with the degree of humoral response to vaccination, and seroprotective effects can, therefore, still be acquired following vaccination [25]. Patients with insufficient humoral responses may still be protected by T-cell-mediated immunity because defense against SARS-CoV-2 depends on both humoral and cellular immunity. Patients with RMDs infected with the Omicron variant produce lower antibody titers than do HCs, but these are still sufficient to provide protection from the virus.

Patients with RMDs who received two or more doses of the inactivated vaccine had significantly greater serum concentrations of neutralizing antibody IgG against SARS-CoV-2 than did those who received one or no dose of the vaccine. Clinical studies of inactivated vaccines and changes in serum antibody concentrations resulting from mRNA vaccination [27] have shown the value of increasing the number of doses of vaccine to improve SARS-CoV-2 neutralizing antibody responses [28, 29]. Patients with RMDs should be encouraged to receive a second, third, or even fourth dose of the vaccine.

This study has certain limitations. First, antibody titers may not reflect the total efficacy of the vaccine, but only a portion of the overall response. The antibody levels required for vaccination to be effective remain unclear. Further studies are required to clarify the relationship between antibody titers and vaccine efficacy. Second, the relatively small sample size of the study population, of which only 111 participants were fully vaccinated with the inactivated SARS-CoV-2 vaccine and only 111 were infected with the Omicron variant, may undermine the robustness of the study. Finally, there is a risk of selection bias. Most of the patients with RMDs who had available data in the outpatient and inpatient departments were in the group with relatively high adherence to medication, and most of the data on those who did not have regular follow-up visits is lacking.