Why 90% of Patients Should Start at Tier 2
Most Long COVID research focuses on Tier 1 (Viral Persistence)—but Harvard just confirmed this is the WRONG target for the majority. Here's how Understanding Long COVID actually works:
The Evidence:
10,598 patients across 11 independent studies converge on the antibody/autonomic mechanism:
TREATME (3,925 patients): IVIG 58%, Mestinon 41%, autonomic interventions cluster
Harvard Barouch (140+ patients): Chronic inflammation, NOT viral persistence
Johns Hopkins PTLD (210 patients): Autonomic dysfunction identical in post-Lyme
Lidocaine Study (103 patients): 80% improvement with sustained autonomic modulation
Metaxaki (129 patients, 40 months): Antibodies INCREASING, immune function maintained
5 Detailed Case Studies: 4 months to 8 years, self-resolution to full recovery
The Palladino Approach Starts at Tier 2:
✅ Remove ganglionic antibodies (IVIG/plasmapheresis)
→ Tier 3 improves (autonomic, vascular, secretory, motility restored)
→ Tier 4 resolves (GI heals, thrombosis stops, PEM disappears, absorption normalizes)
→ Tier 5 symptoms vanish (exercise tolerance returns, cognition improves, energy restores)
Treat the root cause of PASC. Everything downstream improves, leading to better outcomes for those experiencing autoimmune symptoms related to COVID19.
TIER 1 (EST. ~ 10%)
Antivirals such as Paxlovid and Pemivibart are important in the context of COVID19 treatment, especially for those experiencing symptoms related to Long Covid or Post-Acute Sequelae of SARS-CoV-2 infection (PASC). Understanding Long Covid is crucial for individuals with autoimmune conditions who may be at increased risk.
🎯 TIER 2 (~70 to 90% START HERE!!!) 🎯
⭐ START HERE FOR MOST PATIENTS ⭐ (Understanding Long Covid: Antibodies trigger a cascade - Move to Tier 3 for those experiencing Autoimmune responses related to COVID19 or Long Covid, often referred to as PASC.)
Tier 3 - Four Direct Consequences of Tier 2 Antibody Blockade
Tier 4 - Pathologies From Tier 3 Combine - Create New Disease States
Tier 5 - Tier 4 manifests as symptoms you experience
❌ Treating Tier 5 alone = Chasing symptoms endlessly ✅ Treating Tier 2 = All tiers can improve simultaneously
"You're fatigued?" → Stimulants
"Brain fog?" → Antidepressants
"Exercise intolerance?" → "Try to exercise more" (GET: -72% HARM)
"Metabolic deficiencies?" → Endless supplements (that don't absorb)
→ Result: Symptoms persist. Patients dismissed as "anxious" in the context of autoimmune conditions or Long Covid (PASC). No improvement in understanding Long Covid.
Harvard Barouch (Dec 2025): "Long COVID, characterized by chronic inflammatory pathways, is not primarily due to viral persistence for the majority of patients experiencing PASC (Post-Acute Sequelae of SARS-CoV-2). TREATME (3,925 patients) shows that IVIG offers a 58% benefit, indicating that antibody removal is effective in addressing autoimmune issues related to COVID19. Scholten-Peeters (103 patients) reports an 80% improvement with lidocaine, demonstrating the effectiveness of autonomic modulation in treating Long COVID symptoms. The AAG Literature indicates an 83.5% improvement with IVIG/plasmapheresis, establishing this as a reliable treatment option. If 90% of patients have an antibody-related problem (Tier 2), it is crucial to start with an antibody solution and not delay the cure for the majority by requiring everyone to go through Tier 1 first."
Five Independent Teams, Same Conclusion:
┌─────────────────────────────────────────────────────────────┐
HARVARD (Barouch) → Chronic inflammation, NOT virus, driving Autoimmune responses in Long Covid
CAMBRIDGE (Metaxaki) → Antibodies INCREASING over time in COVID19 patients
TREATME (3,925 patients) → IVIG/autonomic interventions for PASC
STANFORD (Yonker) → IFN-γ immune cascades from spike protein in COVID19
PALLADINO THEORY → AAG unifies all findings, enhancing our Understanding Long Covid
└─────────────────────────────────────────────────────────────┘
Understanding Long Covid is crucial, especially as we see a rise in cases related to COVID19. Many individuals are experiencing symptoms that fall under the umbrella of Post-Acute Sequelae of SARS-CoV-2 infection (PASC), which can be particularly challenging for those with autoimmune conditions. By gaining a better understanding of Long Covid and its effects, we can help support those affected by both COVID19 and the complexities of autoimmune responses.
The evidence is here. The mechanism is plausible. The treatment is available.
Content on this site is for informational and advocacy purposes only. It does not constitute medical advice, diagnosis, or treatment. Always consult qualified healthcare professionals.
The Palladino Theory: Autoimmune Autonomic Ganglionopathy as a Unifying Mechanism for Long COVID Symptom Heterogeneity and Universal Treatment Failure - Publish Date: 12/15/25
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