SCF Multi-Omics Neuroimmune Connectomic Reconstruction Platform | Adaptive Biomarker-Guided Precision Acupuncture Clinical Administration Protocol — Post-Viral / Long COVID Encephalopathy

SCF-ECCA-PVLC-FIH-CTD-0003

First-in-Human Clinical Trial Design

Post-Viral / Long COVID Encephalopathy

Adaptive Biomarker-Guided Precision Acupuncture Clinical Administration Protocol

I. TRIAL OVERVIEW

Study Title:

A First-in-Human Adaptive Biomarker-Guided Precision Acupuncture Study for Post-Viral / Long COVID Encephalopathy Utilizing the SCF Encephalopathy Connectomic Collapse Atlas.

Study Phase: Phase 0/Ia

Design: Prospective, adaptive, biomarker-guided, open-label, dose-escalation neuromodulation study.

Duration: 16 weeks

Screening: 2 weeks

Active Treatment: 12 weeks

Follow-up: 2 weeks

II. PRIMARY OBJECTIVES

Safety

Evaluate:

  • Serious adverse events
  • Post-exertional malaise worsening
  • Dysautonomia exacerbation
  • Cognitive decline
  • Syncope or presyncope
  • Seizure occurrence
  • Cardiopulmonary instability
  • New neurologic deterioration

Feasibility

Evaluate:

  • Treatment adherence
  • Biomarker collection feasibility
  • HRV and autonomic monitoring compliance
  • Tolerability of graded acupuncture intensity
  • PEM-safe administration model

III. SECONDARY OBJECTIVES

Evaluate:

  • Brain fog reduction
  • Neuroimmune stabilization
  • Autonomic recovery
  • Connectomic restoration
  • Fatigue improvement
  • Sleep normalization
  • Mitochondrial-bioenergetic recovery
  • Quality-of-life improvement

IV. TARGET POPULATION

Eligible post-viral encephalopathy phenotypes:

  • Long COVID cognitive dysfunction
  • Post-viral brain fog syndrome
  • Post-viral dysautonomia
  • Post-viral fatigue with cognitive impairment
  • Post-viral neuroinflammatory phenotype
  • Post-viral POTS-like phenotype

V. INCLUSION CRITERIA

Criterion
Requirement
Age
18–75
Prior viral illness
Documented or clinically probable
Symptom duration
≥12 weeks
Cognitive symptoms
Brain fog, slowed processing, impaired attention
MoCA
16–28
Functional impairment
PROMIS cognitive/fatigue abnormality
Stability
No acute infection within 14 days
SCF PV Connectomic Score
20–80
Standard care
Stable medications ≥14 days

VI. EXCLUSION CRITERIA

  • Active acute infection
  • Unstable cardiopulmonary disease
  • Uncontrolled epilepsy
  • Acute stroke or CNS infection
  • Severe psychiatric instability
  • Active myocarditis
  • Severe oxygen desaturation
  • Pregnancy
  • Mechanical ventilation
  • Severe PEM triggered by minimal clinical contact
  • Any condition making acupuncture unsafe

VII. REAL-TIME BIOMARKER PANEL

Tier 1 Neuroimmune Panel

Biomarker
Assay
Frequency
IL-6
Multiplex
Weekly
TNF-α
Multiplex
Weekly
IL-1β
Multiplex
Weekly
hsCRP
Immunoassay
Weekly
CXCL10
Multiplex
Biweekly

Endpoint: Post-Viral Neuroimmune Activation Index

Tier 2 Neuroglial / Neuroaxonal Panel

Biomarker
Assay
Frequency
GFAP
Simoa
Weekly
NfL
Simoa
Weekly
S100B
Immunoassay
Weekly
UCH-L1
Immunoassay
Biweekly
Total Tau
Simoa
Biweekly

Endpoint: Neuroglial Injury Stability Index

Tier 3 Autonomic Panel

Biomarker
Assay
Frequency
HRV SDNN
Wearable/ECG
Daily
RMSSD
Wearable/ECG
Daily
LF/HF Ratio
HRV
Daily
Orthostatic HR
Active stand
Weekly
Orthostatic BP
Active stand
Weekly

Endpoint: Post-Viral Autonomic Collapse Index

Tier 4 Bioenergetic Panel

Biomarker
Assay
Frequency
Lactate
Chemistry
Weekly
Pyruvate
LC-MS/MS
Weekly
Lactate/Pyruvate Ratio
LC-MS/MS
Weekly
Acylcarnitine Profile
LC-MS/MS
Biweekly
cf-mtDNA
qPCR
Biweekly

Endpoint: Bioenergetic Failure Index

Tier 5 Endothelial / Coagulation Panel

Biomarker
Assay
Frequency
D-dimer
Coagulation
Weekly
Fibrinogen
Coagulation
Weekly
vWF Antigen
Immunoassay
Biweekly
Platelet Count
CBC
Weekly
Ferritin
Chemistry
Weekly

Endpoint: Thromboendothelial Stress Index

Tier 6 Connectomic Monitoring Panel

Biomarker
Assay
Frequency
qEEG Connectivity
qEEG
Weekly
EEG Delta Power
qEEG
Weekly
EEG Theta Excess
qEEG
Weekly
rs-fMRI Connectivity
MRI
Baseline/Week 12
DTI Fractional Anisotropy
MRI-DTI
Baseline/Week 12

Endpoint: Post-Viral Connectomic Collapse Index

VIII. ACUPUNCTURE ADMINISTRATION PROTOCOL

Cohort A — Low Intensity

Frequency: 1–2 sessions/weekDuration: 15–20 minutesPrimary Points:

  • GV20
  • PC6
  • ST36
  • HT7
  • Yintang

Goal: Initial autonomic and cognitive stabilization with PEM-safe exposure.

Cohort B — Moderate Intensity

Frequency: 2–3 sessions/weekDuration: 25–30 minutesAdditional Points:

  • GV24
  • LI11
  • LI4
  • CV17
  • SP6

Goal: Neuroimmune-autonomic modulation.

Cohort C — High Intensity

Frequency: 3 sessions/week maximumDuration: 30–35 minutesAdditional Points:

  • Sishencong
  • ST25
  • CV12
  • KI3
  • LV3
  • Auricular Shenmen

Goal: Connectomic, gut-brain, metabolic, and limbic stabilization.

Important: No 5-session/week escalation in Long COVID due to PEM risk.

IX. ESCALATION RULES

Escalation requires ALL criteria for 14 consecutive days:

Domain
Escalation Threshold
PEM
No worsening from baseline
HRV
SDNN increase ≥10%
Cognition
MoCA improvement ≥2 points or PROMIS cognition improvement
Neuroimmune
IL-6 decrease ≥15% and hsCRP stable/decreased
Neuroglial
GFAP and NfL stable or decreased
Connectomics
qEEG connectivity improvement ≥10%
Fatigue
Fatigue Severity Scale improves ≥10%

Escalation Action: Advance one cohort level within 7 days.

X. DE-ESCALATION RULES

Immediate de-escalation if ANY occur:

Domain
De-Escalation Threshold
PEM
≥2-point worsening on PEM severity diary for >48 hours
HRV
SDNN decrease ≥20% from baseline
Orthostatic HR
Increase ≥30 bpm with symptoms
GFAP
Increase ≥25%
NfL
Increase ≥25%
IL-6
Increase ≥50%
qEEG
Connectivity deterioration ≥20%
Cognition
MoCA decline ≥3 points
Cardiopulmonary
New chest pain, hypoxia, syncope

Action: Return to prior cohort and repeat biomarker review within 24–72 hours.

XI. STOPPING RULES

Immediate study suspension or withdrawal evaluation for:

  • New myocarditis/pericarditis concern
  • Syncope with injury
  • New seizure
  • Acute neurologic deficit
  • Oxygen saturation <90% at rest
  • NfL doubles from baseline
  • GFAP doubles from baseline
  • SCF PV Connectomic Collapse Score worsens >30%
  • Unexpected serious adverse event

XII. PRIMARY ENDPOINTS

Safety Endpoints

  • SAE incidence
  • PEM exacerbation frequency
  • Dysautonomia worsening
  • Syncope/presyncope
  • Cognitive deterioration
  • Neurologic adverse events

Biomarker Safety Endpoints

  • NfL stability
  • GFAP stability
  • HRV stability
  • Cytokine stability
  • D-dimer/fibrinogen stability

XIII. SECONDARY ENDPOINTS

Connectomic Restoration

  • qEEG connectivity
  • rs-fMRI connectivity
  • DTI fractional anisotropy

Cognitive Recovery

  • MoCA
  • PROMIS Cognitive Function
  • Trail Making Test A/B
  • Digit Symbol Substitution

Autonomic Recovery

  • HRV SDNN
  • RMSSD
  • COMPASS-31
  • Orthostatic HR/BP

Fatigue / PEM Recovery

  • Fatigue Severity Scale
  • PEM diary
  • Activity tolerance
  • Wearable step variability

Quality of Life

  • EQ-5D-5L
  • PROMIS Fatigue
  • PROMIS Sleep Disturbance

XIV. COMPOSITE SCF POST-VIRAL RESPONSE SCORE

Domain
Weight
Neuroimmune Activity
15%
Neuroglial Injury
15%
Autonomics
20%
Bioenergetics
15%
Connectomics
15%
Cognition
10%
Fatigue/PEM
10%
Score Change
Response
>30% improvement
Major Response
15–30% improvement
Moderate Response
5–15% improvement
Minor Response
±5%
Stable
>10% worsening
Progression

XV. TRANSLATIONAL DECISION GATES

GO

  • No SAE signal
  • PEM stable or improved
  • HRV improved ≥10%
  • qEEG connectivity improved
  • MoCA or PROMIS cognition improved
  • GFAP/NfL stable

CONDITIONAL GO

  • Safety acceptable
  • Mixed biomarker response
  • No PEM worsening
  • Protocol refinement required

NO-GO

  • PEM worsening signal
  • Neuroglial biomarker worsening
  • Dysautonomia worsening
  • Connectomic deterioration
  • Increased hospitalization or urgent-care events

XVI. REAL-TIME SAFETY DASHBOARD

Zone
Criteria
Action
Green
HRV improved, PEM stable, GFAP/NfL stable, cognition improved
Continue
Yellow
Mild fatigue flare, HRV decrease <15%, mild cytokine rise
Hold escalation, increase monitoring
Red
PEM worsening >48h, HRV ↓ ≥20%, GFAP/NfL ↑ ≥25%, syncope, MoCA ↓ ≥3
De-escalate or withdraw evaluation

NEXT CLINICAL ADMINISTRATION PROTOCOL

SCF-ECCA-AE-FIH-CTD-0004

Autoimmune Encephalopathy FIH Clinical Trial Design

MASTER REGISTRY INDEX

  • SCF-ECCA-PVLC-FIH-CTD-0003 — Post-Viral / Long COVID Encephalopathy FIH Clinical Trial Design
  • SCF-ECCA-PV-BIO-0003 — Post-Viral / Long COVID Encephalopathy Biomarker Panel
  • SCF-ECCA-PV-ACU-0003 — Post-Viral / Long COVID Acupoint Neuro-Circuit Atlas
  • SCF-ECCA-0001 — Encephalopathy Connectomic Collapse Atlas
  • SCF-CLINDEV-0001 — SCF Clinical Development Framework
  • SCF-BIOMARKER-ENDPOINTS-0001 — SCF Biomarker Endpoint Validation Framework
  • SCF-ACU-NEURO-ATLAS-0001 — SCF Neural Mapping Schema