Post-COVID-19 Vaccine Hyperproduction of Anti-Spike Antibodies and Rheumatological Manifestations

Vaccines are the most widely used public health measure to control the global COVID-19 pandemic. Most vaccines used in Europe and North America are mRNA-based. A mass vaccination campaign was carried out between 2021 and 2024. Some adverse events have been reported based on analogies with previous virus-attenuated vaccines.

Given the new mechanism inducing specific antibodies, we questioned the role of mRNA Spike vaccines and the significance of hyperproduction of anti-Spike antibodies in the emergence of early and late onset rheumatological manifestations observed after one or more injections.

A prospective observational study involving two cohorts was initiated. The first cohort was observed from 13 September 2021 to 30 September 2022, and the second cohort from 1 October 2022 to 30 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 compared both cohorts and ankle arthritis case series to analyze the differences between early and late-onset adverse events.

In both cohorts and case series, the majority of patients were women. The most common symptoms included diffuse muscle pain, which mimics polymyalgia rheumatica, and ankle arthritis. Very high levels of anti-Spike antibodies (>2080 BAU/mL) were generally detected. The Pearson correlation coefficient between both cohorts and case series was very high, confirming the reproducibility of post-vaccine clinical and biological features.

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.