Post-Spike Syndrome (PSS): A Proposed Clinical Entity Associated with SARS-CoV-2 Spike Protein Exposure from Infection and mRNA Vaccination — Case Series and Therapeutic Insights

Summary:

More than four years following the emergence of COVID-19, a subset of individuals experience persistent, multisystem symptoms extending beyond three months post-infection or post-exposure to mRNA-based COVID-19 vaccines. This condition, historically termed "Long COVID," has recently been redefined by some researchers as "Post-Spike Syndrome" (PSS) or "SPIKEOPATHY," emphasizing the pathogenic role of the SARS-CoV-2 Spike protein derived from both viral infection and mRNA vaccination. PSS manifests with diverse clinical features attributable to systemic inflammation and immune dysregulation triggered by circulating Spike protein and vaccine-derived particles. Herein, we present a compilation of seven detailed case reports illustrating the heterogenous clinical spectrum of PSS, therapeutic interventions employed, and patient outcomes, aiming to enhance recognition, guide management, and stimulate further research into this emerging syndrome.

Keywords: Post-Spike Syndrome, Long COVID, SPIKEOPATHY, SARS-CoV-2 Spike protein, mRNA vaccines, chronic COVID-19 symptoms, case series, inflammation, immunomodulation

Introduction:

Since the onset of the COVID-19 pandemic, a proportion of patients have reported persistent symptoms lasting beyond the acute phase of infection, commonly referred to as Long COVID or post-acute sequelae of SARS-CoV-2 infection (PASC) (2, 4, 8). While definitions vary, symptoms persisting for three months or longer are generally considered chronic manifestations (4, 6). Recently, a novel conceptual framework termed "SPIKEOPATHY" has been proposed, highlighting the central role of the SARS-CoV-2 Spike protein—present in both the virus and mRNA vaccines—in driving chronic symptomatology (5). This has led to the designation "Post-Spike Syndrome" (PSS) to better characterize this condition.

Pathophysiology of Post-Spike Syndrome:

PSS is hypothesized to result from the systemic dissemination of Spike protein and mRNA vaccine particles beyond the injection site, eliciting widespread inflammatory responses across multiple organ systems5. The Spike protein may localize on host cells, potentially inducing autoimmune phenomena through molecular mimicry and immune confusion, thereby exacerbating inflammation5. This pathogenesis aligns with observed multisystem involvement, including neurological, cardiovascular, immunological, gastrointestinal, dermatological, and ocular manifestations.

Clinical Manifestations:

Symptoms of PSS are diverse and reflect multi-system involvement. Researchers have identified over 200 symptoms, but the most common and clinically relevant include (9, 10):

• General: Fatigue, weakness, post-exertional malaise (worsening after activity), hair loss, pain, rash
• Respiratory: Shortness of breath, chronic cough, chest pain
• Cardiovascular: Chest tightness, heart palpitations, postural orthostatic tachycardia syndrome (POTS)
• Neurological: Brain fog, memory loss, difficulty concentrating, headaches, dizziness, loss of smell or taste
• Gastrointestinal: Abdominal pain, diarrhea, constipation, nausea, heartburn
• Muscle and Bone: Muscle pain and weakness
• Mental Health: Anxiety, depression, insomnia, psychosis symptoms
• Others: Kidney problems, sexual dysfunction, abnormal movements

These symptoms may be ongoing, intermittent, or fluctuate in severity, making diagnosis and management challenging.

Case Series:

Case 1:
A 57-year-old female with interstitial granulomatous dermatitis (IGD) and classic PSS symptoms (fatigue, alopecia, cognitive decline, paresthesia) experienced symptom exacerbation post-Pfizer mRNA vaccination. Conventional corticosteroids failed; however, a 60-day regimen including ciprofloxacin, nattokinase, ivermectin, and multi-strain probiotics led to complete symptom and lesion resolution5.

Case 2:
A 44-year-old female developed severe fatigue, alopecia, cognitive impairment, and trigeminal neuralgia following two SARS-CoV-2 infections and prior Pfizer vaccination. Treatment combining the above regimen with pregabalin, opioids, and valacyclovir resulted in full remission of PSS symptoms and neuralgia within 60 days5.

Case 3:
A 52-year-old unvaccinated female diagnosed with polymyalgia rheumatica post-COVID-19 exhibited persistent fatigue, brain fog, and gastrointestinal symptoms despite corticosteroids. Addition of the therapeutic protocol yielded symptom resolution and significant inflammatory marker improvement, enabling steroid tapering5.

Case 4:
A 70-year-old female with prior AstraZeneca and Pfizer vaccinations developed neurological and systemic PSS symptoms after reinfection. Treatment excluding antibiotics due to recent usage, but including nattokinase, ivermectin, and probiotics, achieved symptom regression with mild residual neuropathy5.

Case 5:
A 50-year-old unvaccinated female with refractory myoclonic seizures and PSS symptoms post-COVID-19 showed dramatic improvement and seizure remission following the combined therapeutic approach over three weeks5.

Case 6:
A 21-year-old male with ASD and ADHD developed vaccine-induced myopericarditis following Moderna mRNA vaccination, complicated by recurrent cardiovascular symptoms and COVID-19 infections. A multimodal treatment including anti-inflammatory agents, spike detoxification supplements, corticosteroids, and later rapamycin led to resolution of cardiac inflammation and symptom stabilization over months (11).

Case 7:
A physician vaccinated thrice with Pfizer reported a decline in Spike antibody titers and symptom improvement following a tailored protocol, supporting the potential for antibody modulation in PSS management (12).

Therapeutic Strategy:

The employed therapeutic regimen across cases generally included:

• Enzymatic supplements: Nattokinase 100 mg twice daily for ≥90 days
• Antiparasitic: Ivermectin 6 mg/30 kg thrice weekly for ≥8 weeks
• Probiotics: Multi-strain formulations twice daily for 90 days
• Antibiotics: Ciprofloxacin (noted fluoroquinolone caution) tailored per patient
• Adjunct treatments: Antivirals (valacyclovir), corticosteroids, analgesics, and immunomodulators (rapamycin) as clinically indicated

This multimodal approach aimed to reduce inflammation, modulate immune responses, and promote microbial balance, resulting in symptom resolution in the majority of cases (5).

Discussion:

This case series underscores the potential pathogenic role of the Spike protein in driving prolonged, multisystem symptoms post SARS-CoV-2 infection or mRNA vaccination, warranting the recognition of Post-Spike Syndrome as a distinct clinical entity. The heterogeneity of presentations reflects systemic inflammatory and autoimmune mechanisms consistent with current understanding of Long COVID and related syndromes247. The observed therapeutic responses suggest that targeted anti-inflammatory and immunomodulatory strategies may be beneficial, though controlled studies are needed.

Conclusion:

Post-Spike Syndrome represents an emerging syndrome characterized by persistent multisystem symptoms linked to SARS-CoV-2 Spike protein exposure. Recognition of PSS and its clinical spectrum is critical for diagnosis and management. This case series provides preliminary evidence supporting a comprehensive therapeutic approach, highlighting the need for further research to elucidate pathophysiology and optimize treatment protocols.