Report #2886013

Overview

Sex

Male

Age

Age unknown

State

—

Recovered

Not recovered

Vaccinated

Mar 24, 2021

Onset

May 1, 2021

Days to onset

38

Hospital days

—

Symptoms (23)

Symptom narrative

pulmonary emboli; orange-yellow facial papules with telangiectasia; orange-yellow facial papules with telangiectasia; body aches; headaches; fatigue; bloating; sore throat; poor sleep; sensation of ear fluid; low-grade chest pain (typically ~2/10); malaise; shortness of breath; This is a literature report from License Party for the following literature source(s). Other Case identifier(s): AE-022566 (BIONTECH). Here, the authors report a case of multi-system post-COVID-19 vaccination syndrome supported by a uniquely extensive longitudinal molecular, immunologic, genetic, proteomic, transcriptomic, and tissue-level assessment. Case Presentation: Patient is a 55-year-old male with a history of postoperative venous thromboembolism, complicated by deep venous thrombosis and pulmonary embolism at age 46 following lumbar spine surgery. He completed three months of anticoagulation, with follow-up imaging demonstrating resolution; thrombophilia evaluation was unremarkable. Past medical history included mild hearing loss with tinnitus, intermittently elevated blood pressure treated at times with low-dose losartan, and occasional anxiety. Prior routine physical examinations, coronary calcium scoring, and a baseline cardiac stress test were reported as normal. Vaccination and Early Systemic Symptoms: The patient received a two-dose Pfizer-BioNTech COVID-19 mRNA vaccination series in Mar2021. Beginning in May2021, he developed episodic systemic symptoms including body aches, headaches, fatigue, and bloating, followed by intermittent ENT complaints (sore throat, poor sleep, and a sensation of ear fluid). During fall 2021, he developed persistent low-grade chest pain (typically 2/10), fatigue/malaise, and shortness of breath, prompting outpatient evaluation prior to his first emergency department visit. On 28Oct2021, he presented to the emergency department with abrupt, self-resolving tachycardia (heart rate 208 bpm) accompanied by dizziness, disorientation, shortness of breath, difficulty focusing, and diplopia. Testing was limited, and symptoms were attributed to anxiety. Pulmonary Embolism and Follow-Up: He re-presented to the emergency department on 08Nov2021, with tachycardia and shortness of breath; laboratory testing demonstrated an elevated D-dimer of 1.71 ug/mL FEU (reference range greater than 0.22 ug/mL FEU). Chest CT on 09Nov2021 demonstrated multiple small bilateral pulmonary emboli, prompting hospitalization, specialty referral, and initiation of anticoagulation. Two thrombophilia evaluations (Jan2022 and Dec2022) were unremarkable. The patient received a Pfizer-BioNTech mRNA booster on 20Feb2022; chest CT on 22Feb2022 demonstrated resolution of the pulmonary emboli and described clear lungs without inflammatory findings. Symptoms persisted and broadened across multiple systems. Dermatology documentation described orange-yellow facial papules with telangiectasia on 30Aug2021, which resolved over Fall 2021. Transcriptomic profiling: Biopsy skin: (24Apr2025) SARS-CoV-2 Spike S1 subunit positive, notes: in endothelial cells; Spike S1 subunit positive in perivascular macrophages; nucleocapsid not detected; (22Jul2025) SARS-CoV-2 Spike S1 subunit positive, notes: in perivascular macrophages; nucleocapsid not detected; (14Nov2025) Vaccine plasmid DNA positive, notes: (SV40, ori 1, ori 2: all positive); vaccine plasmid DNA fragments positive (sequence 1; sequence 2; sequence 3); SARS-CoV-2 Spike S1 subunit positive in nerve fibers; Spike S1 subunit positive in endothelial cells; Spike S1 subunit positive in perivascular macrophages; nucleocapsid not detected; Blood test: (26Aug2025) Plasmid DNA in PBMC positive, notes: (ori 1, 2); vaccine mRNA in exosomes positive (S1 and S2 SPIKE sequence); IgG4 spike protein Ab elevated 320.2 +- 4.4 ng/mL; Computerised tomogram thorax: (09Nov2021) multiple small bilateral pulmonary emboli; (22Feb2022) resolution of the pulmonary emboli, notes: and described clear lungs without inflammatory findings; Diagnostic procedure: (Jan2022) unremarkable; (Dec2022) unremarkable; Fibrin D dimer (normal high range 0.22): (08Nov2021) 1.71, notes: ug/mL FEU; Heart rate: (28Oct2021) 208, notes: bpm; Long Hauler & COVID-19 S1 Immune Subset Panel: (20Jun2024) S1-positive monocytes detected, notes: (CD14loCD16+ nonclassical 3.36 (reference range: 0.00); CD14++CD16- classical 0.77) (reference range: 0.00); cytokine abnormalities; (05Dec2024) S1-positive monocytes no longer detected, notes: Persistent cytokine abnormalities; (12Nov2025) Persistent cytokine abnormalities, notes: VEGF increased; Long Hauler Index (normal high range 0.71): (20Jun2024) 1.96, notes: Long Hauler Index 1.96 (elevated); (12Nov2025) 1.10, notes: Long Hauler Index 1.10 (elevated); (19Aug2025) Structural genomic instability, notes: redox and mitochondrial stress, endothelial activation and a proteomic signature of chronic inflammation and vascular injury; Pain assessment: (2021) typically ~2/10; SARS-CoV-2 antibody test: (08May2024) Nucleocapsid negative, notes: spike antibody greater than250 above assay upper reporting limit); (13Jun2024) Nucleocapsid negative, notes: spike antibody 5,579 U/mL (elevated); (23Dec2024) Nucleocapsid negative, notes: spike antibody 5,136 U/mL (elevated); (25Sep2025) Nucleocapsid negative, notes: spike antibody 4,130 U/mL (elevated); (23Jan2026) Nucleocapsid negative, notes: spike antibody 4,553 U/mL (elevated); Urine analysis: (17Sep2025) Systemic inflammatory proteomic signature, notes: consistent with immune activation and vascular leakage (non-renal). Scope of Diagnostic Evaluation: Over the course of his illness, the patient underwent an extensive and repeated diagnostic evaluation across specialties. This included more than 40 emergency department visits and over 200 outpatient encounters across multiple specialties. These figures underestimate the total scope of care, as general practice visits, physical therapy, and other supportive care encounters were not included in these counts. While the volume of encounters may appear excessive, this does not capture the frequency or severity of symptoms nor the numerous instances in which the patient elected not to seek care due to repeated nondiagnostic evaluations and perceived lack of benefit. Visit totals by specialty are listed in parentheses. Specialty care included cardiology (40+), emergency (40+), pulmonology (14), neurology (16), gastroenterology (24), hepatology (2), immunology (5), rheumatology (2), infectious disease (2), endocrinology (4), hematology (7), otolaryngology (19), ophthalmology (12), psychiatry (24), orthopedic medicine/physical medicine and rehabilitation (20+), urology (4), nephrology (3), bariatric medicine (1), multispecialty/general surgery (2), and vascular medicine (2). Multi-Omic Analysis: Whole-blood transcriptomics were analyzed by REViSS/aHI-PBIMA, which demonstrated marked dysregulation of genes aligned with the patient's symptom domains: GPX4 was downregulated (-2.2), indicating impaired redox control and mitochondrial stress; ACE was upregulated (+4.6), consistent with endothelial activation and RAAS imbalance; APC was markedly reduced (-6.1), aligning with gastrointestinal barrier disruption and dysbiosis; and LMNA was decreased (-3.7), suggesting nuclear structural stress relevant to cardiomyocyte and neuronal vulnerability. Hallmark scoring showed a predominance of unfavorable signals in vascular, mitochondrial, and gastrointestinal axes, concordant with the patient's myocarditis, prior pulmonary emboli, chronic fatigue with dysautonomia, dermatologic inflammation, and intestinal symptoms. These transcriptomic findings corroborate the contemporaneous proteomic evidence of systemic inflammation and support a persistent spike- associated inflammatory state. Discussion: Importantly, this molecular profile aligns with the patient's clinical course, which included pulmonary embolism, myocarditis confirmed by cardiac MRI despite normal troponin and natriuretic peptide levels, and a progressive constellation of multisystem symptoms consistent with post-vaccination syndrome. Persistent spike protein in circulation and within exosomes may contribute to continued endothelial activation, immune dysregulation, and microvascular injury-mechanisms implicated in thrombotic and cardiac complications following mRNA vaccination. The patient received three Pfizer-BioNTech COVID-19 mRNA vaccine doses, each traceable to specific lot numbers associated with documented severe adverse events. Using the VAERS linked How Bad Is My Batch search tool, the authors identified significant numbers of reported cases of myocarditis, pulmonary embolism (PE), hospitalizations, and deaths for each lot: dose 1 with 11 myocarditis, 17 PE, 830 hospitalizations, 180 deaths and dose 2 with 5 myocarditis, 13 PE, 463 hospitalizations, 97 deaths. These data suggest non-random clustering of serious adverse event reports that warrants further formal pharmacovigilance analysis. After suspecting a vaccine-related injury, the patient reported the case to the Vaccine Adverse Event Reporting System (VAERS). After suspecting a vaccine-related injury, the patient reported the case to the Vaccine Adverse Event Reporting System (VAERS). VAERS intake staff did not capture in detail the multi-system, longitudinal nature of the illness and instead emphasized identifying the hospital where a diagnosis occurred for follow-up. The patient reports being informed by VAERS staff and the Compensation Program that reporting and claim eligibility were limited to one year after vaccination. In this case, suspicion did not arise until more than two years post-vaccination, and assembling corroborating records required substantially longer. In this case, delayed recognition of a vaccine-associated, multisystem condition intersected with time-limited post-authorization reporting and compensation pathways, including VAERS reporting norms and the PREP Act-linked Compensation Program. Because suspicion of a vaccine-related etiology emerged more than two years after vaccination, the patient's clinical timeline did not align with several time-dependent administrative processes despite persistent impairment. This timing mismatch may influence access to compensation mechanisms and employment-related benefit determinations, including workers' compensation, long-term disability, and supplemental critical illness coverage. Transcriptomic profiling further supported the patient's clinical presentation by revealing dysregulation of key genes associated with mitochondrial, vascular, intestinal, and structural integrity. Downregulation of GPX4, a key antioxidant enzyme, suggests impaired redox homeostasis and increased susceptibility to ferroptosis, consistent with mitochondrial oxidative stress observed in myocarditis and chronic fatigue. Upregulation of ACE indicates a renin- angiotensin system imbalance and endothelial injury, mechanisms that promote vascular inflammation and thrombosis, consistent with the diagnosis of pulmonary embolism. Reduced APC expression compromises intestinal epithelial integrity and immune regulation, aligning with the patient's dysbiosis and chronic inflammation. Finally, decreased LMNA, essential for nuclear stability in cardiomyocytes and neurons, may underlie persistent cardiac dysfunction and neurocognitive symptoms. Together, these transcriptomic abnormalities provide a molecular framework linking oxidative stress, endothelial activation, barrier disruption, and nuclear instability to the patient's post-mRNA vaccine multi-system pathology. Conclusion: To the authors' knowledge, this case documents the most comprehensive molecular evidence of long-term persistence of multiple vaccinederived components following COVID-19 mRNA vaccination. Spike protein, vaccine mRNA, and plasmid DNA fragments were all detected more than 3.5 years after the patient's final Pfizer-BioNTech COVID-19 mRNA vaccine dose-far exceeding the assumed biological lifespan of these molecules. These vaccine- and spike-related findings were generated across multiple independent laboratories at multiple time points using diverse analytical methodologies in both blood and tissue specimens, following an extensive and repeated diagnostic evaluation that included more than 40 emergency department visits, over 200 specialty encounters across 18 medical disciplines, more than 100 non-routine laboratory investigations, over 100 imaging and functional diagnostic studies, and systematic exclusion of underlying etiologic mechanisms across infectious, autoimmune, rheumatologic, endocrine, genetic, hematologic, malignant, toxic/medication-related, cardiovascular/vascular, metabolic, and primary neurologic domains. Clinically, the patient developed a progressive, multi-organ syndrome-pulmonary emboli, MRI-confirmed myocarditis, neurocognitive impairment, gastrointestinal dysbiosis, and chronic dermatologic inflammation-mirroring the molecular evidence of persistent antigen exposure, endothelial dysfunction, and systemic immune activation. Multi-omic analysis further revealed structural genomic instability, redox and mitochondrial stress, endothelial activation, and a proteomic signature of chronic inflammation and vascular injury. The patient's immunogenetic background (HLA-B07:02, HLA-DRB111:04) provides an additional framework for prolonged antigen presentation and heightened inflammatory responsiveness. Combined, these results outline a unified biological model: long-term persistence of spike protein and vaccine-derived nucleic acids, combined with genomic dysregulation, may drive chronic immune stimulation, tissue inflammation, and multi-system dysfunction in a subset of individuals. While these findings require validation in larger cohorts with matched controls, they highlight critical gaps in the authors' understanding of mRNA vaccine biodistribution, persistence, and long-term immunologic consequences. While limited to a single patient, this case underscores the need for sustained clinical surveillance, rigorous molecular biomonitoring, and comprehensive longitudinal studies to determine the prevalence, mechanisms, and clinical relevance of persistent vaccine-derived components. A re-evaluation of current assumptions regarding mRNA vaccine clearance, stability, and systemic impact is warranted to guide management of individuals presenting with chronic, unexplained post-vaccination symptoms. BNT162B2 is under agreement with BIONTECH SE.; Sender's Comments: The events Pulmonary embolism is considered related to the suspect BNT162b2 vaccine, based on temporal association following vaccination, and absence of alternative etiology. The impact of this report on the benefit/risk profile of the Pfizer product is evaluated as part of Pfizer procedures for safety evaluation, including the review and analysis of aggregate data for adverse events. Any safety concern identified as part of this review, as well as any appropriate action in response, will be promptly notified to regulatory authorities, Ethics Committees, and Investigators, as appropriate.,Linked Report(s) : US-PFIZER INC-202600028836 same patient, different dose/event;

Current illness

Hearing loss; Tinnitus

Medical history

Medical History/Concurrent Conditions: Anticoagulant therapy (completed three months. with follow-up imaging demonstrating resolution); Anxiety (occasional); Blood pressure increased (intermittently, treated at times with low-dose losartan); Cardiac stress test normal; Computerised tomogram heart normal; Deep vein thrombosis (at age 46); Physical examination normal; Pulmonary embolism (at age 46); Surgery (at age 46); Venous thromboembolism

Lab data

Test Date: 20250424; Test Name: Grover's lesion trunk biopsy (PCR + histology/IHC); Result Unstructured Data: Test Result:SARS-CoV-2 Spike S1 subunit positive; Comments: in endothelial cells; Spike S1 subunit positive in perivascular macrophages; nucleocapsid not detected; Test Date: 20250722; Test Name: Grover's lesion trunk biopsy (PCR + histology/IHC); Result Unstructured Data: Test Result:SARS-CoV-2 Spike S1 subunit positive; Comments: in perivascular macrophages; nucleocapsid not detected; Test Date: 20251114; Test Name: Grover's lesion trunk biopsy (PCR + histology/IHC); Result Unstructured Data: Test Result:Vaccine plasmid DNA positive; Comments: (SV40, ori 1, ori 2: all positive); vaccine plasmid DNA fragments positive (sequence 1; sequence 2; sequence 3); SARS-CoV-2 Spike S1 subunit positive in nerve fibers; Spike S1 subunit positive in endothelial cells; Spike S1 subunit positive in perivascular macrophages; nucleocapsid not detected; Test Date: 20250826; Test Name: Plasma/PBMC testing; Result Unstructured Data: Test Result:Plasmid DNA in PBMC positive; Comments: (ori 1, 2); vaccine mRNA in exosomes positive (S1 and S2 SPIKE sequence); IgG4 spike protein Ab elevated 320.2 +- 4.4 ng/mL; Test Date: 20211109; Test Name: Chest CT; Result Unstructured Data: Test Result:multiple small bilateral pulmonary emboli; Test Date: 20220222; Test Name: Chest CT; Result Unstructured Data: Test Result:resolution of the pulmonary emboli; Comments: and described clear lungs without inflammatory findings; Test Date: 202201; Test Name: thrombophilia evaluations; Result Unstructured Data: Test Result:unremarkable; Test Date: 202212; Test Name: thrombophilia evaluations; Result Unstructured Data: Test Result:unremarkable; Test Date: 20211108; Test Name: D-dimer; Result Unstructured Data: Test Result:1.71; Comments: ug/mL FEU; Test Date: 20211028; Test Name: heart rate; Result Unstructured Data: Test Result:208; Comments: bpm; Test Date: 20240620; Test Name: Long Hauler & COVID-19 S1 Immune Subset Panel; Result Unstructured Data: Test Result:S1-positive monocytes detected; Comments: (CD14loCD16+ nonclassical 3.36 (reference range: 0.00); CD14++CD16- classical 0.77) (reference range: 0.00); cytokine abnormalities; Test Date: 20241205; Test Name: Long Hauler & COVID-19 S1 Immune Subset Panel; Result Unstructured Data: Test Result:S1-positive monocytes no longer detected; Comments: Persistent cytokine abnormalities; Test Date: 20251112; Test Name: Long Hauler & COVID-19 S1 Immune Subset Panel; Result Unstructured Data: Test Result:Persistent cytokine abnormalities; Comments: VEGF increased; Test Date: 20240620; Test Name: Long Hauler Index; Result Unstructured Data: Test Result:1.96; Comments: Long Hauler Index 1.96 (elevated); Test Date: 20251112; Test Name: Long Hauler Index; Result Unstructured Data: Test Result:1.10; Comments: Long Hauler Index 1.10 (elevated); Test Date: 20250819; Test Name: Multi-Omic Analysis; Result Unstructured Data: Test Result:Structural genomic instability; Comments: redox and mitochondrial stress, endothelial activation and a proteomic signature of chronic inflammation and vascular injury.; Test Date: 2021; Test Name: low-grade chest pain; Result Unstructured Data: Test Result:typically ~2/10; Test Date: 20240508; Test Name: Nucleocapsid & Spike Antibodies; Result Unstructured Data: Test Result:Nucleocapsid negative; Comments: spike antibody greater than250 above assay upper reporting limit); Test Date: 20240613; Test Name: Nucleocapsid & Spike Antibodies; Result Unstructured Data: Test Result:Nucleocapsid negative; Comments: spike antibody 5,579 U/mL (elevated); Test Date: 20241223; Test Name: Nucleocapsid & Spike Antibodies; Result Unstructured Data: Test Result:Nucleocapsid negative; Comments: spike antibody 5,136 U/mL (elevated); Test Date: 20250925; Test Name: Nucleocapsid & Spike Antibodies; Result Unstructured Data: Test Result:Nucleocapsid negative; Comments: spike antibody 4,130 U/mL (elevated); Test Date: 20260123; Test Name: Nucleocapsid & Spike Antibodies; Result Unstructured Data: Test Result:Nucleocapsid negative; Comments: spike antibody 4,553 U/mL (elevated); Test Date: 20250917; Test Name: Urine proteomics; Result Unstructured Data: Test Result:Systemic inflammatory proteomic signature; Comments: consistent with immune activation and vascular leakage (non-renal)