Peer-Reviewed Literature Synthesis

PACVS Biomarker Atlas

Molecular, serologic, immunologic, and functional alterations reported in Post-Acute COVID-19 Vaccination Syndrome (PACVS) — from PACVS/PCVS primary studies and post-vaccination adverse-event literature only.

Literature Overview

PACVS research is emerging. This atlas includes only markers from post-vaccination syndrome primary studies — spike persistence after vaccination, GPCR autoantibodies, registry cohort laboratory findings, and PACVS trial protocols.

Searchable Alterations Database

Filter by category. HC = healthy controls. All entries cite PACVS/PCVS or post-vaccination adverse-event primary literature only.

Long COVID markers excluded

This atlas deliberately excludes infection-associated (Long COVID/PASC) biomarker literature. Shared-pathway markers documented only in post-infection cohorts — coagulation, complement, mitochondrial metabolites, and similar — are listed in the Long COVID Biomarker Atlas instead.

Related atlases: All Atlases · Long COVID · ME/CFS

Proposed diagnostic framework (Halma & Varon, 2025)

No single biomarker defines PACVS. Post-vaccination studies propose combining: (1) serology confirming vaccination exposure without prior infection (Anti-S+, Anti-N−); (2) spike antigenemia detection in vaccine adverse-event cohorts; (3) GPCR/RAS autoantibodies; (4) LC-MS/MS peptide profiling to distinguish vaccine-encoded spike (K986P/V987P "2P" mutations) from wild-type viral spike; and (5) optional qPCR for persistent vaccine mRNA sequences. Definitive diagnostic criteria remain under development.

Marker / Metabolite Direction Category vs. Comparison Associated Symptoms Key Reference

Category Deep Dives

PACVS-specific findings from post-vaccination primary studies and PACVS cohort registries.

💉 Spike Protein & Antigen Persistence

  • S1 in CD16+ monocytes ↑ up to 245d
  • Spike in post-mRNA myocarditis ↑ adolescents
  • Spike in cutaneous vaccine lesions ↑ tissue
  • Spike in neurological tissue ↑ post-vaccine AE
  • Vaccine mRNA (BNT162b2-specific) Detected in subset

🔬 Serologic Discrimination Panel

  • Anti-Spike (Anti-S) antibodies ↑ Expected+
  • Anti-Nucleocapsid (Anti-N) ↓ Expected−
  • 2P proteotypic peptides (LC-MS/MS) Vaccine-specific
  • Wild-type viral spike peptides Absent if no infection

🛡️ GPCR & RAS Autoantibodies (PACVS-specific)

  • Anti-ACE2 ↑ skin symptoms
  • Anti-AT1R (angiotensin II type 1 receptor) ↑ lymphadenopathy
  • Anti-MAS1 receptor ↑ burning sensation
  • Anti-STAB1 ↑ skin edema/rash
  • Anti-ADRA2A (α2B adrenergic) ↓ with brain fog
  • Anti-CHRM3 (muscarinic) Symptom-associated
  • Anti-idiotype mechanism (ACE2 ↔ Anti-S) Correlated

⚡ Metabolic & Inflammatory Alterations

  • Ferritin index ↓ >50% of subjects
  • Transferrin saturation ↓ subnormal
  • Blood lactate (exercise) ↑ earlier threshold
  • IL-6 / IL-8 ↑ >80% of cohort
  • Neurofilament light chain (NfL) ↑ >30% of cohort

📊 Functional & Clinical Markers

  • Heart rate variability (HRV) ↓ dysautonomia
  • Salivary nitric oxide ↓ NO pathway
  • Orthostatic HR increment ↑ POTS
  • 6-minute walk distance ↓ exercise capacity
  • Exertional SpO₂ nadir ↓ hypoxemia
  • Chester Step Test (VO₂ proxy) ↓ fitness
  • PAC-19QoL scores ↓ quality of life

Key References

Primary PACVS and post-vaccination adverse-event literature underpinning this atlas.

Perspective — PACVS Framework

Restoring Trust in Vaccination: Listening to Patients and Acknowledging Post-Acute COVID Vaccine Syndrome

Halma M, Varon J. Front Med. 2025;12:1688170 — Proposes 5-tier biomarker panel
DOI: 10.3389/fmed.2025.1688170 →
Primary Study — PACVS Autoantibodies

Autoantibodies Targeting GPCRs and RAS-Related Molecules in PACVS: A Retrospective Case Series

Mantovani M et al. Biomedicines. 2024;12(12):2852 — n=17, median 20 months post-vaccination
DOI: 10.3390/biomedicines12122852 →
Primary Study — Spike Persistence (PCVS)

Detection of S1 Spike Protein in CD16+ Monocytes up to 245 Days in SARS-CoV-2-Negative Post-COVID-19 Vaccine Syndrome

Patterson BK et al. Hum Vaccin Immunother. 2025 — PCVS cohort
DOI: 10.1080/21645515.2025.2494934 →
Primary Study — Vaccine Myocarditis

Circulating Spike Protein Detected in Post-mRNA Vaccine Myocarditis

Yonker LM et al. Circulation. 2023 — Adolescent post-vaccination cohort
DOI: 10.1161/CIRCULATIONAHA.122.061725 →
Primary Study — PACVS Cohort

Clinical and Diagnostic Features of Post-Acute COVID-19 Vaccination Syndrome (PACVS)

Mundorf AK et al. Vaccines. 2024;12(7):790 — n=191 registry cohort; iron storage, IL-6/8, dysautonomia phenotypes
DOI: 10.3390/vaccines12070790 →
Review — Treatment Strategies

Strategies for the Management of Spike Protein-Related Pathology

Halma MTJ et al. Microorganisms. 2023;11(5):1308
DOI: 10.3390/microorganisms11051308 →
Review — Susceptibility

The Possible Mechanistic Basis of Individual Susceptibility to Spike Protein Injury

Halma M et al. Adv Virol. 2025 — Genetic and physiological susceptibility factors
DOI: 10.1155/av/7990876 →
Disclaimer: This page is an educational synthesis of published peer-reviewed PACVS and post-vaccination literature and does not constitute medical advice. PACVS is an emerging nosological entity without validated diagnostic criteria or FDA-approved biomarker assays. Many findings derive from small case series or patient registries and require replication in larger, prospectively defined cohorts. Direction of change (↑/↓) reflects predominant findings in cited PACVS literature but may not apply to all patients. Anti-N nucleocapsid negativity is expected in vaccinated-only individuals but does not alone confirm PACVS. Consult qualified healthcare providers for clinical interpretation.