TL;DR
Lingering antigen: SARS-CoV-2 RNA can persist in multiple tissues months after mild disease; antigen detection associates with long-term symptoms in cohort data. (Chertow 2022; Zuo 2024, Lancet Infect Dis)
Brain-borders persistence: Spike protein has been observed at the skull–meninges–brain axis in human autopsy tissues. (Rong et al., 2024; Cell Host & Microbe; PMID 39615487)
Post-vaccination syndrome (PVS): A 2025 preprint from the Yale LISTEN group reported elevated circulating spike protein in a subset of PVS participants compared to controls; one case noted up to 709 days post-vaccination; interpretation awaits peer review. (Bhattacharjee 2025, medRxiv)
Viral reactivation: EBV/HSV/CMV reactivation is documented in COVID-19 (and occasionally after vaccination in case series/meta-analyses), with potential symptom impact. (Shafiee 2023; Boers 2024)
Microclots: Spike S1 can induce fibrinolysis-resistant amyloid(oid) fibrin in vitro; microclot/platelet pathology has been reported in Long COVID cohorts. (Grobbelaar 2021; Pretorius 2021/2022)
Brain risk nodes: S1 can engage RAGE on monocytes; APOE4 genotype is linked to BBB leakiness and vulnerability to peripheral inflammation. (Angioni 2023; Montagne 2020; Marottoli 2017)
Holistic support: Nutrient-dense diets, oral-health focus, and Nrf2-activating foods (e.g., broccoli sprouts) are reasonable adjuncts—evidence for outcomes remains preliminary.
If we treated COVID-19 like a two-week respiratory blip, the research now paints a more chronic, multi-system picture. Think "slow burn": antigen persistence, immune perturbations, microvascular changes, and neurovascular stress—especially in vulnerable genotypes. Recent discussions, including endorsements from experts like Jessica Rose, highlight emerging evidence on brain-specific persistence. This article draws heavily from the foundational insights of Dr. Annelise Bocquet, whose detailed analyses on viral persistence and reactivation have been instrumental.
Part 1: Persistence isn't rare
Autopsy mapping detected viral RNA widely up to ~230 days post-infection. (Chertow et al., Nature 2022)
In mild cases, a single-centre cohort found tissue RNA/subgenomic RNA weeks–months after infection, and antigen detection associated with long-COVID symptoms. (Zuo et al., Lancet Infect Dis 2024)
Spike in cells/serum: S1 in non-classical monocytes up to ~15 months after infection (case-control). (Patterson 2022)
Brain-specific persistence: Human autopsy work reported S1 at the skull–meninges–brain interface. (Rong et al., Cell Host & Microbe 2024; PMID 39615487)
PVS preprint: LISTEN reported elevated circulating spike protein in a subset up to 709 days post-vaccination; causality/mechanism unresolved; peer review pending. (medRxiv 2025)
Takeaway: persistence signals exist, but prevalence and clinical meaning differ by cohort and method, and in the context of vaccination, are still being defined in humans. Avoid absolutist language until multi-centre replication matures.
Part 2: Immune drift & latent virus wake-ups
- Regulatory/tolerogenic shifts are described in chronic viral states (e.g., HIV Treg/IDO paradigms) and are hypothesized in post-acute COVID contexts. (Jenabian 2014)
- Herpesviruses: Meta-analyses/case series document EBV/HSV/CMV reactivation with COVID-19; ICU HSV reactivation has been linked to worse outcomes. (Shafiee 2023; Boers 2024)
- Transplant/relapse cases underscore risks under profound immunosuppression. (Cureus 2023; PubMed 372776) // Corrected PMID
Part 3: Microclots & oxygen delivery
- In vitro S1 drives amyloid-like fibrin(ogen) resistant to fibrinolysis. (Grobbelaar 2021)
- Long-COVID studies report fibrin amyloid microclots and platelet hyperactivation, with proteomic cargo that could sustain inflammation and hinder microcirculation. (Pretorius/Kruger 2021–2022, open-access review)
- Clinical significance is under active study; standardization of assays and controlled trials remain key.
Part 4: Neurovascular nodes — APOE4, RAGE, BBB
- RAGE axis: Multi-omics + cell work indicates S1–RAGE engagement on monocytes; separately, N protein can interact with RAGE. (Angioni 2023; complementary literature on RAGE)
- APOE4 & BBB: APOE4 carriers show hippocampal BBB breakdown independent of Aβ/tau, predicting cognitive decline. (Montagne 2020)
- Peripheral inflammation × APOE4: LPS challenges can exacerbate cerebrovascular leak and cognition in E4/Aβ-prone mice. (Marottoli 2017)
- Oral–immune link: Prevotella intermedia proteases cleave CD14/LBP, altering LPS handling; sCD14 can amplify LPS signaling in oral cells—plausible inputs to systemic inflammation and barrier stress. (Deschner 2003; Andrukhov 2016)
Takeaway: Together, these pathways sketch a model of a brain made vulnerable by genetics, with its defenses weakened by persistent spike and systemic inflammation.
Terrain-centric support (adjunctive, not curative)
- Diet quality & polyphenols: Reasonable bet for inflammation/oxidative-stress modulation, but causality in PASC/PVS is unproven. (Review 2024)
- Oral health & biofilms: Target periodontitis; consider clinician-guided antimicrobials where indicated (herbal agents like oregano oil have in-vitro biofilm effects but limited RCT evidence).
- Nrf2 activators: Foods rich in sulforaphane (broccoli sprouts) are mechanistically plausible adjuncts; clinical endpoints for PASC need trials.
- Barrier support: Sleep, stress control, exercise within tolerance; GI care; and, where appropriate, medical evaluation for coagulopathy or reactivation.
Disclaimer: Informational only; not medical advice. Management decisions belong with qualified clinicians.
Evidence roundup (curated)
- Tissue persistence & long-COVID association: Zuo et al., 2024 (Lancet Infect Dis, PMID 38663423).
- Autopsy mapping to 230 days: Chertow et al., 2022 (Nature, PMID 36517603).
- S1 in monocytes: Patterson et al., 2022 (Front Immunol, PMID 35082777).
- Skull–meninges–brain spike persistence: Rong et al., 2024 (Cell Host & Microbe, PMID 39615487).
- PVS spike up to 709 days (preprint): Bhattacharjee et al., 2025 (medRxiv).
- Herpesvirus reactivation (COVID & post-vax reports): Shafiee et al., 2023 (PMID 37559096); Boers et al., 2024 (PMID 39017695).
- S1-induced amyloid fibrin in vitro: Grobbelaar et al., 2021 (PMID 34328172).
- Long-COVID microclots & proteomics: Pretorius/Kruger 2021–2022 (PMID 34425843).
- RAGE pathway & spike S1: Angioni et al., 2023 (Cell Rep Med, PMID 37944530).
- APOE4 → BBB leak & decline: Montagne et al., 2020 (Nature, PMID 32376954).
- LPS worsens E4/Aβ model cognition & BBB: Marottoli et al., 2017 (PMID 28707482).
- P. intermedia proteases cleave CD14/LBP; sCD14 boosts LPS signaling: Deschner 2003 (PMID 12728301); Andrukhov 2016 (PMID 27135432). // Added PMID
Acknowledgments: A Special Thanks to Open-Source Pioneers
In the spirit of collaborative science and open discourse, this article owes a profound debt to the tireless work of Dr. Annelise Bocquet and Dr. Jessica Rose. Both have generously shared their expertise through public platforms, demystifying complex topics like viral persistence, immune dysregulation, and post-vaccination effects for a global audience.
Dr. Bocquet, a Doctor in Health Biology and educator in hematology/immunology, has provided invaluable threads and analyses on X, challenging assumptions and fostering discussion with her mantra: "In science, we can affirm nothing, but we can discuss everything." Her insights into SARS-CoV-2 latency, spike persistence, and reactivation have been foundational to this piece.
Similarly, Dr. Jessica Rose, through her X posts and Substack "Unacceptable Jessica," has amplified critical data on vaccine safety, persistence, and long-term health impacts, often with a blend of rigor and accessibility that empowers readers to engage deeply.
By open-sourcing their hard work—via threads, articles, and public commentary—they've advanced public understanding and encouraged evidence-based dialogue. Thank you both for your courage, dedication, and commitment to transparency. Your contributions remind us that science thrives in the open.
Key Resources
- Nature - Tissue Persistence
- Frontiers - Monocyte Spike
- Lancet - Mild COVID Persistence
- Cell Host Microbe - Brain Spike Persistence
- PNAS Nexus - APOE4 & Prevotella (exploratory association)
- Pretorius Video - Microclots
- X - Nicholas Fabiano Thread on Brain Persistence
- X - Jessica Rose (JesslovesMJK) Endorsement
- Jessica Rose's Substack - Unacceptable Jessica
- X - Jessica Rose (@JesslovesMJK)
- X - Annelise Bocquet (@AnneliseBocquet)
- X - Annelise Bocquet on SARS-CoV-2 Latency/Reactivation
- X - Annelise Bocquet on Spike Persistence and Immunodeficiency
- X - Annelise Bocquet on Fatal SARS-CoV-2 Reactivation
- Thread Reader App - Annelise Bocquet's Threads
- X - Genome Defense
Media & Commentary (clearly non-primary)
These links are useful for context/discussion but are not primary evidence. Keep them separate from references.
- PNAS Nexus — APOE4 & Prevotella (exploratory association)
- Pretorius — Microclots (video overview)
- Thread Reader — Annelise Bocquet's Threads
- Jessica Rose — Substack
- X — Nicholas Fabiano on brain-border S1
- X — Jessica Rose (JesslovesMJK)
- X — Annelise Bocquet (@AnneliseBocquet)
- X — Bocquet on SARS-CoV-2 latency/reactivation
- X — Bocquet on spike persistence & immunodeficiency
- X — Bocquet on fatal SARS-CoV-2 reactivation
- X — Genome Defense
How to cite
MeasslainteIRL. The Slow Burn: How Persistent Spike Protein, Reactivated Viruses, and Microclots Drive Long-Term Health Issues. Published 20 Oct 2025. Available at: measslainte.com (accessed ).
⚖️ Ethical Declaration (Purpose & Scope)
This article exists to promote scientific transparency, informed consent, and open discussion on biomedical safety. All data are cited from primary or peer-reviewed sources where available. No medical advice is given.
Contested / Active-Debate Notes
- Microclots: Assay methods and clinical utility are evolving; causality vs correlation remains under study.
- PVS spike detection: LISTEN findings are preprint data; interpretation may change post peer review.
- RAGE/S1 and brain persistence: Human autopsy signals exist; translation to population-level risk needs larger, multi-centre studies.
Quick FAQ
Is "persistence" the same as ongoing infection?
Not necessarily. Studies detect RNA/antigen or protein fragments in tissues/cells; that can reflect residual antigen, low-level replication, or compartmentalized reservoirs. Clinical significance varies by context.
Do vaccines stop brain-border S1 entirely?
Mouse data suggest prior vaccination reduces but does not eliminate S1 accumulation/leak at the skull–meninges–brain interface.
Are microclots unique to COVID?
No—fibrin(ogen) amyloid has been reported in other inflammatory states. What's debated is extent, persistence, and impact in Long COVID/PVS.
What's reasonable for self-care?
General terrain supports (diet quality, oral health, sleep, graded activity) are low-risk adjuncts. Diagnosis/treatment decisions belong with clinicians.
Plain Talk Add-On: The Slow Burn, in real-world language
If science chat makes your eyes glaze over, start here.
The short version (30 seconds):
- Pieces of the virus (or its spike) can hang around longer than expected in some people.
- That can keep the immune system slightly “on,” so you feel unwell even after “recovering.”
- Old viruses like EBV/HSV can “wake up” when your system is stressed.
- Tiny, stubborn microclots can slow oxygen delivery — think thick sludge in skinny pipes.
- Some folks’ brain “filter” (BBB) is leakier by genetics (e.g., APOE4), so inflammation hits harder.
A simple analogy:
- Imagine you spilled glitter in your house. You clean, but weeks later, glitter is still turning up in corners.
- Meanwhile, the pipes have a bit of sludge (microclots), so water pressure (oxygen delivery) isn’t great.
- If your air filter (brain barrier) is older or thinner, dust gets through more easily.
How it can feel day to day:
- Brain fog, short breath on stairs, heavy legs, weird heart flutters, sleep that doesn’t refresh, headaches after minor effort, and “good days / crash days” that don’t follow a pattern.
What this isn’t saying:
- Not everyone has this.
- It’s not proof of one single cause or a one-size-fits-all cure.
- Research is ongoing; some findings are early or debated.
Practical supports (common-sense, not medical advice):
- Sleep & pacing: Respect your “energy budget” and avoid boom-and-bust cycles.
- Gentle movement: Short walks, light mobility work; increase slowly if tolerated.
- Oral health: Treat gum issues; better mouth health = less background inflammation.
- Food basics: Protein, colorful plants, minimal ultra-processed foods; hydrate.
- Nervous system downshift: Sunlight, breath work, time outdoors, low-stress routines.
- When to get help: New chest pain, severe headaches, one-sided leg swelling, fainting, or stroke-like signs → urgent care. For persistent symptoms, talk to a clinician who takes post-viral issues seriously.
Is “persistence” the same as chronic infection?
Not always. Studies detect genetic fragments or protein; sometimes it’s leftover debris, sometimes low-level activity in hard-to-reach tissues. That’s why the science is careful with wording.
Are microclots unique to COVID?
No. They show up in other inflammatory states, too. The debate is how often, how stubborn, and how much they matter here.
Why do some people get hit harder?
Different genetics (like APOE4), different immune histories, other health conditions, timing, and simple bad luck can all play a role.
This section is for understanding, not diagnosis. Always work with a clinician for medical decisions.
Microclots & platelet pathology
- Prof. Resia Pretorius — microcirculation & microclots:
- Pretorius & Prof. Doug Kell — latest research and methods:
- Clinical perspective (Laubscher + Pretorius):
Brain/BBB context (APOE4)
- Axel Montagne, PhD — BBB dysfunction & APOE4:
- USC Zilkha Seminar (recording link): APOE4 → BBB breakdown
Brain border / persistence
- Spike at skull–meninges–brain interface (paper walk-through)Why: Ties directly to your brain-border section; quick ref recap.
EBV / latent virus reactivation (mini-series)
- EBV & Long COVID (Part 1 overview)
- Evidence of EBV reactivation in long haul (study walk-through)
BBB & APOE4 (context for vulnerability)
- APOE4 & blood–brain barrier leaks (lay explainer)
Neuro / autoimmunity angle
- Brain autoimmunity in Long COVID (MBP, MOG)
PVS / LISTEN signals
- Yale LISTEN immune signatures in post-vax syndrome (recap)
Clinic-facing overview
- Long-COVID management (broad symptom & systems talk)
Clotting/microclots (mechanisms) — external link
- Spikeopathies: how spike can drive platelet activation & clotting
Watch on React19 →
Disclaimer: Informational only; not medical advice.


