Association Between COVID-19 Vaccination and Polymyalgia Rheumatica: A Review and Case Series Report

Introduction: COVID-19 mRNA vaccines are associated with the development of a wide range of autoimmune diseases. Rare autoimmune conditions, such as polymyalgia rheumatica (PMR), have received limited attention in medical literature. The purpose of this study is to review PMR, examine reports of PMR in the government database monitoring vaccine safety, and evaluate the potential association between PMR, COVID-19 vaccination, and spike protein antibody levels.Methods: Data were obtained from the U.S. Centers for Disease Control and Prevention (CDC) and the U.S. Food and Drug Administration (FDA). The CDC/FDA Vaccine Adverse Event Reporting System (VAERS) was queried for reports of polymyalgia rheumatica (PMR) from January 1, 1990, through January 30, 2026. This period encompasses 433 months for all vaccines; however, COVID-19 vaccines were available to the public for only 61 of those 433 months (January 1, 2021, through January 30, 2026). Odds ratios over time (ORt) were calculated by comparing the occurrence of PMR following the administration of specific vaccinations to including COVID-19, influenza, and all other vaccines combined. The CDC/FDA defines a safety signal as a disproportionality measure of ≥ 2. Data are presented as odds ratios over time ORt with corresponding 95% confidence intervals, p-values, and Z statistics. Three cases of PMR from the authors’ recent clinical practices were reviewed. A literature review on PMR was conducted using PubMed, MEDLINE, and Google Scholar.Results: Significant safety signals were observed when comparing reports of PMR following COVID-19 vaccination with those following influenza vaccination. This association persisted when PMR following COVID-19 vaccination was compared with PMR following all other vaccines combined. There were 2,227 reported cases of PMR following COVID-19 vaccination during the 61 months after vaccine rollout. In comparison, 233 cases were reported following influenza vaccination, and 526 cases were reported following all other vaccines combined over a 433-month period. The ORt for COVID-19 vaccination compared with influenza vaccination was 69.4, 95% CI 51.4 - 93.6, p < 0.0001, Z statistic 27.7. When comparing PMR following COVID-19 vaccination with PMR following all other vaccines combined including influenza, a significant safety signal persisted: 30.7, 95% CI 23.1 - 40.8, p < 0.0001, 23.6. Three exemplary cases and a review of the literature are also presented. Conclusions: Strong safety signals were detected when comparing polymyalgia rheumatica (PMR) following COVID-19 vaccination with PMR following influenza vaccination and, when compared to all other vaccines combined. The strength of the signal, its statistical robustness, and its consistency with observed clinical cases and biologically plausible immunoinflammatory mechanisms suggest the need for heightened clinical awareness of PMR occurring temporally following COVID-19 vaccination. These findings corroborate other research documenting the occurrence of PMR after COVID-19 vaccination and the pathophysiological pathway for spike protein-induced autoimmunity. Future research should prioritize validation of direct assays for spike protein detection rather than relying solely on surrogate antibody measurements. Additional investigation is also warranted to clarify the role of COVID-19 vaccinations and spike protein in musculoskeletal pathology and to evaluate preventive and therapeutic strategies.