Background: Patients with autoimmune and immune-mediated diseases (AI-IMD) are at greater risk of COVID-19 infection; therefore, they should be prioritized in vaccination programs. However, there are concerns regarding the safety of COVID-19 vaccines in terms of disease relapse, flare, or exacerbation. In this study, we aimed to provide a more precise and reliable vision using systematic review and meta-analysis.

Methods: PubMed-MEDLINE, Embase, and Web of Science were searched for original articles reporting the relapse/flare in adult patients with AI-IMD between June 1, 2020 and September 25, 2022. Subgroup analysis and sensitivity analysis were conducted to investigate the sources of heterogeneity. Statistical analysis was performed using R software.

Results: A total of 134 observations of various AI-IMDs across 74 studies assessed the rate of relapse, flare, or exacerbation in AI-IMD patients. Accordingly, the crude overall prevalence of relapse, flare, or exacerbation was 6.28% (95% CI [4.78%; 7.95%], I² = 97.6%), changing from 6.28% (I² = 97.6%) to 6.24% (I² = 65.1%) after removing the outliers. AI-IMD patients administering mRNA, vector-based, and inactive vaccines showed 8.13% ([5.6%; 11.03%], I² = 98.1%), 0.32% ([0.0%; 4.03%], I² = 93.5%), and 3.07% ([1.09%; 5.9%], I² = 96.2%) relapse, flare, or exacerbation, respectively (p-value = 0.0086). In terms of disease category, nephrologic (26.66%) and hematologic (14.12%) disorders had the highest and dermatologic (4.81%) and neurologic (2.62%) disorders exhibited to have the lowest crude prevalence of relapse, flare, or exacerbation (p-value < 0.0001).

Conclusion: The risk of flare/relapse/exacerbation in AI-IMD patients is found to be minimal, especially with vector-based vaccines. Vaccination against COVID-19 is recommended in this population.