How long can spike protein persist after SARS-CoV-2 infection versus after vaccination?
Executive summary
Studies show SARS‑CoV‑2 spike protein or spike fragments can persist in blood or tissues for months after infection — multiple reports cite persistence “up to a year or longer” and specific findings up to 15 months post‑infection [1] [2]. After vaccination, most studies report spike detection for only days to weeks in typical cases, but recent reports include exceptional findings of detectable spike in some people more than 700 days after vaccination [3] [4].
1. What researchers mean by “persistence” — antigen vs. antibody vs. tissue reservoirs
Persistence can refer to different things: continued detection of spike protein or spike fragments in blood or tissues, or sustained antibody responses to spike. Multiple studies document persistent spike protein or S1 subunit in tissues and blood months after acute infection — for example, circulation of soluble or extracellular vesicle‑linked spike in individuals with post‑acute sequelae [1] [2]. Separately, antibody responses to spike after infection can last many months (antibodies detected up to ~200 days in some cohorts) and are a different phenomenon from detecting the protein itself [5]. Be careful: persistence of antibodies is not the same as persistence of the spike protein or viral RNA [5].
2. Typical timelines after SARS‑CoV‑2 infection
Multiple peer‑reviewed and preprint reports find spike protein or S1 fragments detectable for many months after infection in a subset of patients. Reviews and studies cite circulation of spike up to a year or longer, and specific work reports S1 persistence in monocyte populations up to 15 months after infection [1] [2]. Tissue imaging studies also show spike accumulation in the skull‑meninges‑brain axis “persisting long after viral clearance,” supporting localized retention [6]. Not every person has detectable spike long term; studies report persistence in subsets of convalescent or post‑COVID cohorts [7] [8].
3. Typical timelines after vaccination
The conventional view across cohorts has been that vaccine‑derived spike protein is detectable for only a few days after mRNA or other spike‑based vaccinations in most people [3]. However, recent investigative work reports rare or exceptional cases: a Yale report describes some participants with “post‑vaccination syndrome” who had detectable spike more than 700 days after their last vaccination [3]. Advocacy or critical sites have highlighted findings of spike on exosomes for at least four months after a second injection in some analyses [4]. These longer detections are not the norm in most immunogenicity studies but are reported in targeted cohorts.
4. How to interpret long persistence reports — method and cohort matter
Detection depends on assay sensitivity, what form of spike is measured (intact protein, S1 fragment, or spike on extracellular vesicles), and the studied group. Several reports link persistent circulating spike to post‑acute sequelae (PASC) or to specialized patient groups [9] [1] [2]. Other studies find persistent spike in only a minority of recovered individuals and do not always correlate persistence with severity or specific symptoms [7] [8]. Methodological differences and selective sampling of people with long COVID or post‑vaccination complaints produce divergent findings.
5. Competing interpretations and open questions
Some researchers interpret persistent spike as evidence of residual viral reservoirs driving chronic inflammation and PASC [9] [1]. Others report persistence without clear linkage to clinical syndromes, finding no association with ME/CFS in certain cohorts [7] [8]. For vaccine‑related persistence, the dominant evidence remains that spike is transient after immunization for most people, yet targeted studies of people with persistent symptoms report rare prolonged detection [3] [4]. Available sources do not mention definitive mechanisms explaining why spike remains in some people but not others.
6. What this means for patients and policy
The evidence supports that infection‑related spike or S1 fragments can linger in tissues or blood for many months in a subset of people, and that rare prolonged vaccine‑related detections have been reported but are not the typical experience [1] [2] [3]. Policymakers and clinicians need better standardized assays, larger longitudinal cohorts, and mechanistic studies to determine whether removing residual spike would change outcomes; investigators have proposed evaluating targeted interventions [3]. Current reporting contains heterogenous cohorts and methods; conclusions about causality between persistence and symptoms remain unsettled [7] [8].
Limitations: this analysis uses only the supplied sources, which include reviews, cohort studies, preprints and advocacy summaries with different levels of peer review; findings vary by method and cohort and do not uniformly establish causation [1] [7] [3].