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How long does spike protein persist in the body after SARS-CoV-2 infection versus after mRNA or vector vaccination (2020-2024 studies)?
Executive Summary
Multiple peer-reviewed and preprint studies from 2023–2025 report that SARS‑CoV‑2 spike protein can be detected months to over a year after acute infection, while a smaller and more heterogeneous set of studies reports detectable spike or S1 fragments in some vaccinated individuals for periods ranging from weeks to many months. The strongest evidence for long persistence comes from studies of people with post‑acute sequelae of COVID‑19 (PASC), which repeatedly identify circulating spike or tissue‑localized spike antigens; evidence for comparable persistence after mRNA or adenoviral vector vaccination exists but is less consistent, limited by small samples, retracted reports, and varying assay techniques [1] [2] [3] [4] [5].
1. Why the persistence claim gained traction — repeated detections months later
Multiple research teams have reported detectable spike antigen months after infection, linking persistence with ongoing symptoms in subsets of patients. A study identified circulating glycoprotein S in some individuals up to a year or longer after infection and implicated persistent viral components in endothelial and immune dysfunction associated with long COVID [1]. Other cohorts specifically detecting spike in the majority of long‑haul patients bolster the hypothesis that viral reservoirs or trapped antigens can persist and drive PASC biology [2]. These infection‑based findings are supported by methods ranging from immunoassays to mass spectrometry, and they consistently show that persistence after infection is biologically plausible and measurable, although prevalence estimates vary by cohort and detection method [5].
2. What the vaccination literature actually shows — mixed and limited signals
Studies examining spike persistence after mRNA or adenoviral vaccination report variable results. Some investigations find transient circulating spike or S1 fragments shortly after vaccination, which is expected given antigen expression, while a few small studies report S1 detection in CD16+ monocytes up to ~245 days post‑vaccination and isolated reports of much longer detection in select individuals [3] [4]. However, the vaccination literature includes retracted case reports and small, sometimes non‑peer‑reviewed studies, and larger immunogenicity trials focus on antibody and cellular responses rather than direct antigen persistence [6] [7]. The data therefore show that vaccination can produce brief antigen presence and occasional longer detections in limited samples, but population‑level evidence for routine long‑term spike persistence after vaccination is weak and inconsistent [8] [7].
3. Direct comparisons are rare — methods, reservoirs, and interpretation differ
There are few rigorous head‑to‑head studies that directly compare post‑infection versus post‑vaccine spike persistence using the same assays and sampling schedules. Infection studies typically sample patients with ongoing symptoms and search multiple tissues or plasma for antigen, producing higher detection rates; vaccination studies often sample healthy vaccinated cohorts and emphasize antibody kinetics, producing lower detection rates of antigen [1] [5] [7]. Analytical differences — assay sensitivity, targeted spike fragment (full S vs S1), cell types analyzed (monocytes vs plasma), and selection of symptomatic vs asymptomatic subjects — drive much of the apparent discrepancy. Therefore, apparent longer persistence after infection may reflect biological reservoirs plus study design, not just intrinsic differences in antigen clearance [2] [3].
4. Strengths, weaknesses, and retractions — why certainty is limited
The body of work contains robust assays and reproducible signals in some infection cohorts, but also small sample sizes, reliance on preprints, and at least one high‑profile retraction related to “post spike syndrome” that undermines some claims about vaccine‑induced persistence and proposed treatments [6]. Several 2024–2025 studies are preprints or focused on selected symptomatic groups, limiting generalizability, while others provide mass spectrometry confirmation of spike fragments in cells or plasma, strengthening biological plausibility [3] [4] [5]. Policymakers and clinicians must weigh confirmed detection with cohort bias and variable assay specificity, and avoid extrapolating single case reports to broad population risk [1] [5].
5. Bottom line and what remains to be settled
The best available evidence through 2024 indicates that spike protein persistence after SARS‑CoV‑2 infection is documented and often associated with PASC, while detectable persistence after vaccination occurs in isolated cases and small cohorts but lacks consistent population‑level support. Resolving this question requires standardized assays, larger longitudinal cohorts that sample both symptomatic and asymptomatic people, and direct comparisons using identical methods; until then, claims of routine long‑term spike persistence after vaccination remain unproven and contested, whereas persistence after infection is a reproducible finding in multiple independent studies [1] [2] [3].