Abstract Background Early assumptions about COVID-19 vaccine components suggested that modified messenger RNA and spike protein would be rapidly cleared from the body, consistent with the known degradation pathways of natural RNA. However, multiple studies have identified these vaccine-derived components in human tissues and bodily fluids for unexpectedly prolonged periods after vaccination. This persistence challenges initial expectations and raises important questions about the mechanisms enabling such long-term presence. Main body This review systematically examines the evidence for enduring COVID-19 vaccine components, including modified messenger RNA, spike protein, and lipid nanoparticles, in the human body long after administration. We evaluate the techniques used to detect these substances, highlighting the sensitivity and specificity of various assays, and summarize the specific tissues and fluids where these components have been found. Special attention is given to methodological considerations that may influence detection and interpretation. Furthermore, this review explores potential biological explanations for the prolonged presence of vaccine-derived material. Possible mechanisms include altered RNA stability due to chemical modifications, slow clearance of lipid nanoparticles, and the formation of stable complexes or reservoirs within tissues. The evidence for each hypothesis is discussed, with an emphasis on distinguishing between true persistence and assay artifacts. Conclusion The reported persistence of COVID-19 vaccine components in the body is a phenomenon that warrants deeper investigation. While methodological factors must be carefully considered, the available data suggest that certain vaccine derivatives may remain detectable for extended periods. Understanding the underlying mechanisms is important for assessing vaccine safety and optimizing future mRNA-based therapeutics. Graphic abstract Figure adapted Halma MTJ, Rose J, Lawrie T (2023) The Novelty of mRNA Viral Vaccines and Potential Harms: A Scoping Review. J 6:220–235. https://doi.org/10.3390/j6020017 under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Selem et al. (Tue,) studied this question.