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Introduction: Vaccine is the most widely used public health measure to control the global COVID-19 pandemic. Most of the vaccines used in Europe and North America are mRNA-based vaccine A mass vaccination campaign was carried out between 2021 and 2024. Some adverse events have been reported. We question the role of vaccines in the pathogenesis of rheumatological manifestations observed following one or more injections. Material and methods: A prospective observational study involving two cohorts was initiated, with the first cohort observed from 13th September 2021 to 30th September 2022, and the second cohort from 1st October 2022 to 30th September 2023. The study also focused on the interval between the last vaccine injection and the onset of rheumatic symptoms. None of the patients had a history of rheumatic or inflammatory diseases. We compare both cohorts and ankle arthritis case series to analyze the differences between early and late onset adverse events patients. Results: In both cohorts and case series, the majority of patients are women. The most common symptoms include diffuse muscle pain, which mimics polymyalgia rheumatica and ankle arthritis. Very high levels of anti-Spike antibodies (> 2080 BAU/ml) were generally detected. Pearson correlation coefficient between both cohorts and case series is very high, confirming the reproducibility of post-vaccine clinical and biological features. Conclusion: These rheumatological manifestations might be triggered by inappropriate individual immune responses to the vaccine's Spike protein and/or the overproduction of Spike protein, which can mediate a pro-inflammatory reaction explaining early and late-onset effects.