Fourth COVID-19 vaccine dose significantly benefits autoimmune rheumatic disease patients

The increased risk of COVID-19 in patients with systemic autoimmune rheumatic diseases (SLE) is accentuated by the DMARD use, comorbidity burden, disease activity, and impaired immune responses. To address this concern, the U.S. Centers for Disease Control and Prevention recommends administering a fourth dose of the mRNA vaccine and the standard three-dose primary series for patients on DMARDs to enhance protection against COVID-19. A recent study, published in the Lancet Rheumatology by researchers from Mass General Brigham, has concluded on the potential of the fourth dose in reducing the risk of SARS-CoV-2 infection as well as the severity of COVID-19 in SLE patients using DMARDs. 

Hanberg and colleagues conducted the emulated target trial utilizing observational data from the Mass General Brigham healthcare system to compare rheumatic patients taking DMARDs who received a fourth dose of the mRNA vaccine to those who did not. The study encompassed data from 4,305 patients, with 3,126 receiving a fourth vaccine dose and 1,179 who did not partake in the additional dose. The median follow-up time for those who received a fourth dose was 135 days, while for those who did not, it was 65 days. Following overlap weighting in both groups, the demographic distribution revealed that 72.7% of the participants were women, 27.3% were men, and 87.5% identified as White ethnicity. Among the total participants, 54.3% had rheumatoid arthritis, with the prevailing treatments being conventional synthetic DMARDs (58.1%) or biological DMARDs (39.3%). These insights provide a comprehensive overview of the patient cohorts studied, laying the foundation for a nuanced understanding of the impact of the fourth vaccine dose on individuals with rheumatic conditions and DMARD use. 

 The researchers noted a lower risk of SARS-CoV-2 infection in patients who received a fourth dose compared to those who did not, with a hazard ratio (HR) of 0.59 (95% CI 0.47–0.74). Furthermore, the administration of the fourth dose significantly decreased the risk of hospital admission or death within –3 to +14 days of SARS-CoV-2 infection, with an HR of 0.35 (0.14–0.85). Supporting these findings, other studies highlight the positive impact of COVID-19 mRNA vaccines on reducing mortality rates in individuals with autoimmune rheumatic diseases. A recent two-year study by Papagoras et al. identified anti-SARS-CoV-2 vaccination as a pivotal factor contributing to the reduction of mortality in patients with systemic autoimmune rheumatic diseases. These insights underscore the potential benefits of additional vaccine doses in mitigating both infection risk and severe outcomes, offering valuable considerations for the ongoing management of individuals with autoimmune conditions. 

The recent findings underscore the potential of vaccination strategies in improving the overall health outcomes for this vulnerable population. In conclusion, advocating for the administration of at least four doses of mRNA vaccines stands as a key public health measure to safeguard individuals with systemic autoimmune rheumatic diseases against the COVID-19 and to reduce the associated severity. 


  1. Hanberg JS, Fu X, Wang X, Patel NJ, Kawano Y, Schiff A, et al. Effectiveness of a fourth dose of COVID-19 mRNA vaccine in patients with systemic autoimmune rheumatic diseases using disease-modifying antirheumatic drugs: an emulated target trial. The Lancet Rheumatology; 2023. 
  2. Papagoras C, Zioga N, Papadopoulos V, Gerolymatou N, Kalavri E, Bounos C, et al. Omicron variant dominance and anti-SARS-CoV-2 vaccination are key determinants for a milder course of COVID-19 in patients with systemic autoimmune rheumatic diseases. Clin Rheumatol. 2023;42(12):3375–85.