SCF-LC-MNSS-TEMP-0010
Temporal Windows of Post-Viral / Long COVID Encephalopathy (PVCE)
SCF Multi-Neurosystems Shock State (MNSS) Atlas
Acute SARS-CoV-2 Infection → Post-Viral Neuroimmune Persistence → Long COVID Encephalopathy → Connectomic Reconstruction
Integrated Neuroimmune, Neurocardiac, Neurovascular, Neurometabolic, Neuroendocrine, Neuroglial, Neuroaxonal, Endothelial, Mitochondrial, and Connectomic Biomarker Framework
I. SCF POST-VIRAL / LONG COVID ENCEPHALOPATHY SHOCK CASCADE
Etiopathogenic Core
Acute Viral Infection
↓
Persistent Viral Antigen Reservoirs
↓
Chronic Innate Immune Activation
↓
Microvascular Endotheliopathy
↓
Microthrombosis
↓
BBB Dysfunction
↓
Microglial Priming
↓
Astrocytic Activation
↓
Mitochondrial Dysfunction
↓
Autonomic Dysregulation
↓
Neuroendocrine Disruption
↓
Connectomic Instability
↓
Long COVID Encephalopathy
↓
Neuroaxonal Injury
↓
Chronic Neurocognitive Syndrome
II. MASTER TEMPORAL PROGRESSION TABLE
SCF Phase | Temporal Window | Dominant Shock State | Clinical Stage | Reversibility |
MNSS-0 | Pre-Infection | Physiologic Homeostasis | Healthy | Very High |
MNSS-IA | Acute Viral Infection (0–4 Weeks) | Neuroimmune Priming | Acute COVID-19 | Very High |
MNSS-IB | Early Post-Viral Persistence (4–12 Weeks) | Neuroimmune-Endothelial Shock | Post-Acute COVID Syndrome | Very High |
MNSS-II | 2–6 Months | Neurovascular-Neurometabolic Shock | Early Long COVID | High |
MNSS-IIIA | 3–12 Months | Connectomic Dysfunction Phase | Long COVID Encephalopathy | High |
MNSS-IIIB | 6–24 Months | Neuroaxonal-Autonomic Shock | Established PVCE | Moderate |
MNSS-IV | Variable | Global Multi-Neurosystems Shock | Severe PVCE | Limited |
MNSS-R1 | Recovery Initiation | Neuroimmune Resolution | Partial Recovery | High |
MNSS-R2 | Months–Years | Connectomic Reconstruction | Functional Recovery | Moderate–High |
MNSS-R3 | Years | Neuroadaptive Compensation | Chronic Long COVID Syndrome | Variable |
III. PRE-ENCEPHALOPATHY WINDOW 1
MNSS-IA — ACUTE VIRAL NEUROIMMUNE PRIMING
Temporal Window
0–4 Weeks
Dominant Shock States
- Neuroimmune Shock (NIS-1)
- Neurovascular Shock (NVS-1)
SCF Biomarker Panel
Neuroimmune Biomarkers
Biomarker | Baseline | Alert Threshold |
IL-6 | <2 pg/mL | >10 pg/mL |
TNF-α | <5 pg/mL | >10 pg/mL |
IFN-γ | Normal | Elevated |
IL-1β | Normal | Elevated |
CRP | <5 mg/L | >20 mg/L |
Neurovascular Biomarkers
Biomarker | Threshold |
vWF | Elevated |
P-Selectin | Elevated |
Angiopoietin-2 | Elevated |
D-Dimer | >500 ng/mL |
Neurocardiac Biomarkers
Biomarker | Threshold |
HRV SDNN | <90 ms |
RMSSD | <25 ms |
Clinical Manifestations
- Fatigue
- Anosmia
- Headache
- Sleep disturbance
Therapeutic Objective
Prevent persistent neuroimmune activation.
IV. PRE-ENCEPHALOPATHY WINDOW 2
MNSS-IB — POST-VIRAL IMMUNE PERSISTENCE
Temporal Window
4–12 Weeks
Dominant Shock States
- Neuroimmune Shock (NIS-2)
- Neurovascular Shock (NVS-2)
- Neuroendocrine Shock (NES-1)
SCF Biomarker Panel
Neuroimmune Biomarkers
Biomarker | Alert Threshold |
IL-6 | >15 pg/mL |
TNF-α | >15 pg/mL |
IFN-γ | Elevated |
CCL2 | Elevated |
CXCL10 | Elevated |
HMGB1 | Elevated |
Neurovascular Biomarkers
Biomarker | Alert Threshold |
vWF | Elevated |
Endothelin-1 | Elevated |
MMP-9 | >250 ng/mL |
S100B | >0.10 ng/mL |
Neuroendocrine Biomarkers
Biomarker | Alert Threshold |
Cortisol Rhythm | Flattening |
DHEA-S | Reduced |
Melatonin | Reduced |
Clinical Manifestations
- Persistent fatigue
- Exercise intolerance
- Brain fog
- Orthostatic symptoms
Therapeutic Objective
Prevent chronic endothelial-neuroimmune coupling.
V. EARLY LONG COVID ENCEPHALOPATHY
MNSS-II — NEUROVASCULAR-NEUROMETABOLIC SHOCK
Temporal Window
2–6 Months
Dominant Shock States
- Neurovascular Shock (NVS-3)
- Neurometabolic Shock (NMS-1)
- Neuroglial Shock (NGS-1)
SCF Biomarker Panel
Neurovascular Biomarkers
Biomarker | Threshold |
MMP-9 | >300 ng/mL |
S100B | >0.15 ng/mL |
Angiopoietin-2 | Elevated |
Endothelin-1 | Elevated |
Neurometabolic Biomarkers
Biomarker | Threshold |
Lactate | >2 mmol/L |
Lactate/Pyruvate Ratio | >25 |
ATP Production | ↓20% |
cf-mtDNA | Elevated |
Neuroglial Biomarkers
Biomarker | Threshold |
GFAP | >150 pg/mL |
YKL-40 | >100 ng/mL |
sTREM2 | Elevated |
Clinical Manifestations
- Brain fog
- Cognitive slowing
- Sleep disruption
- Memory complaints
Therapeutic Objective
Prevent connectomic destabilization.
VI. ESTABLISHED LONG COVID ENCEPHALOPATHY
MNSS-IIIA
Temporal Window
3–12 Months
Dominant Shock States
- Neuroimmune Shock (NIS-3)
- Neurocardiac Shock (NCS-1)
- Connectomic Shock (CCS-1)
SCF Biomarker Panel
Neuroimmune Biomarkers
Biomarker | Threshold |
IL-6 | >20 pg/mL |
TNF-α | >20 pg/mL |
CXCL10 | Elevated |
HMGB1 | Elevated |
Neurocardiac Biomarkers
Biomarker | Threshold |
SDNN | <80 ms |
RMSSD | <20 ms |
LF/HF Ratio | >4 |
Connectomic Biomarkers
Biomarker | Threshold |
qEEG Connectivity | >15% decline |
EEG Theta | Increased |
EEG Delta | Increased |
rs-fMRI DMN Connectivity | Reduced |
Clinical Manifestations
- Cognitive impairment
- Dysautonomia
- POTS-like symptoms
- Executive dysfunction
Therapeutic Objective
Preserve large-scale brain network integrity.
VII. ADVANCED LONG COVID ENCEPHALOPATHY
MNSS-IIIB
Temporal Window
6–24 Months
Dominant Shock States
- Neuroaxonal Shock (NAS-1)
- Neurocardiac Shock (NCS-2)
- Neuroendocrine Shock (NES-2)
SCF Biomarker Panel
Neuroaxonal Biomarkers
Biomarker | Threshold |
NfL | >20 pg/mL |
UCH-L1 | Elevated |
Total Tau | Elevated |
NSE | Elevated |
Neurocardiac Biomarkers
Biomarker | Threshold |
SDNN | <70 ms |
RMSSD | <15 ms |
Troponin | Mild elevation |
NT-proBNP | Elevated |
Neuroendocrine Biomarkers
Biomarker | Threshold |
Cortisol Rhythm | Severely disrupted |
DHEA-S | Markedly reduced |
Melatonin | Suppressed |
Clinical Manifestations
- Severe cognitive dysfunction
- Chronic dysautonomia
- Neurofatigue
- Functional disability
Therapeutic Objective
Prevent irreversible network degeneration.
VIII. ACUTE MULTI-NEUROSYSTEMS SHOCK
MNSS-IV
Temporal Window
Variable
Dominant Shock States
- Neuroimmune Shock (NIS-4)
- Neurocardiac Shock (NCS-3)
- Neurovascular Shock (NVS-4)
- Neurometabolic Shock (NMS-3)
- Neuroendocrine Shock (NES-3)
Peak Biomarker Panel
Shock Domain | Peak Biomarkers |
Neuroimmune | IL-6, TNF-α, IFN-γ, HMGB1, CXCL10 |
Neurocardiac | SDNN <50 ms, RMSSD severely reduced, Troponin ↑ |
Neurovascular | MMP-9 peak, S100B peak, Endothelin-1 peak |
Neurometabolic | Lactate >4 mmol/L, ATP failure, cf-mtDNA peak |
Neuroendocrine | Cortisol collapse, ACTH dysregulation, Melatonin suppression |
Neuroglial | GFAP peak, YKL-40 peak |
Neuroaxonal | NfL peak, Tau peak, UCH-L1 peak |
Clinical Manifestations
- Severe dysautonomia
- Profound cognitive dysfunction
- Neuropsychiatric collapse
- Bed-bound state
- Multi-system decompensation
Therapeutic Objective
Preserve neurologic function and prevent permanent disability.
IX. POST-ENCEPHALOPATHY RECOVERY WINDOW
MNSS-R1 — NEUROIMMUNE RESOLUTION
Temporal Window
Months
Recovery Biomarker Panel
Domain | Biomarker Trend |
Neuroimmune | IL-6 ↓, TNF-α ↓, HMGB1 ↓ |
Neurocardiac | SDNN ↑ |
Neurovascular | MMP-9 ↓ |
Neuroglial | GFAP ↓ |
Neuroendocrine | Cortisol normalization |
Therapeutic Objective
Suppress persistent neuroinflammation.
X. CONNECTOMIC RECONSTRUCTION WINDOW
MNSS-R2
Temporal Window
Months–Years
Reconstruction Biomarker Panel
Domain | Desired Trend |
Neuroaxonal | NfL ↓ |
Neuroglial | GFAP ↓ |
Connectomic | qEEG Connectivity ↑ |
Connectomic | rs-fMRI DMN Connectivity ↑ |
Neurocardiac | HRV SDNN ↑ |
Neuroendocrine | Circadian restoration |
Neurometabolic | ATP restoration |
Therapeutic Objective
Restore cognitive endurance, autonomic stability, and executive function.
XI. POST-LONG COVID NEUROCOGNITIVE SYNDROME
MNSS-R3
Temporal Window
Years
Persistent Risk Biomarker Panel
Shock Domain | Persistent Biomarkers |
Neuroimmune | IL-6, HMGB1, CXCL10 |
Neurocardiac | SDNN suppression |
Neurovascular | Endothelin-1, MMP-9 |
Neurometabolic | cf-mtDNA elevation |
Neuroendocrine | Cortisol rhythm abnormalities |
Neuroglial | GFAP elevation |
Neuroaxonal | NfL, Tau |
Connectomic | Persistent DMN dysconnectivity |
Clinical Manifestations
- Chronic brain fog
- Cognitive fatigue
- Dysautonomia
- Sleep dysfunction
- Executive impairment
- Reduced functional capacity
XII. MASTER SCF POST-VIRAL / LONG COVID ENCEPHALOPATHY BIOMARKER MATRIX
SCF Phase | Neuroimmune Shock | Neurocardiac Shock | Neurovascular Shock | Neurometabolic Shock | Neuroendocrine Shock |
MNSS-IA | IL-6, CRP | SDNN ↓ | D-Dimer ↑ | ATP ↓ | Cortisol ↑ |
MNSS-IB | HMGB1, CXCL10 | LF/HF ↑ | MMP-9 ↑ | cf-mtDNA ↑ | DHEA-S ↓ |
MNSS-II | IL-6 ↑↑ | HRV ↓↓ | S100B ↑ | Lactate ↑ | Circadian disruption |
MNSS-IIIA | Persistent cytokines | Dysautonomia | Endotheliopathy | ATP loss | HPA activation |
MNSS-IIIB | Chronic inflammation | Severe HRV impairment | Microvascular dysfunction | Mitochondrial dysfunction | Melatonin suppression |
MNSS-IV | Peak inflammatory burden | Severe autonomic collapse | Peak endothelial injury | Peak metabolic failure | HPA collapse |
MNSS-R1 | Resolution | HRV recovery | Endothelial repair | ATP recovery | Endocrine recovery |
MNSS-R2 | Low inflammation | SDNN ↑ | Vascular repair | Bioenergetic restoration | Circadian restoration |
MNSS-R3 | Residual inflammation | Persistent dysautonomia | Residual dysfunction | Chronic bioenergetic deficit | Neuroendocrine maladaptation |
XIII. HIGHEST-VALUE THERAPEUTIC WINDOWS
Rank | Window | SCF Phase | Reversibility | Primary Therapeutic Objective |
1 | Acute Viral Neuroimmune Priming | MNSS-IA | Very High | Prevent persistent immune activation |
2 | Post-Viral Immune Persistence | MNSS-IB | Very High | Prevent endothelial-neuroimmune coupling |
3 | Early Long COVID | MNSS-II | High | Prevent connectomic destabilization |
4 | Established PVCE | MNSS-IIIA | High | Preserve network integrity |
5 | Advanced PVCE | MNSS-IIIB | Moderate | Prevent neuroaxonal injury |
6 | Multi-Neurosystems Shock | MNSS-IV | Limited | Preserve neurologic function |
7 | Connectomic Reconstruction | MNSS-R2 | Moderate–High | Restore cognition and autonomic function |
XIV. EARLIEST PREDICTIVE SCF BIOMARKER PANEL FOR LONG COVID ENCEPHALOPATHY
Tier 1 — Neuroimmune Predictors
- IL-6
- TNF-α
- CXCL10
- IFN-γ
- HMGB1
Tier 2 — Neurovascular Predictors
- D-Dimer
- vWF
- Angiopoietin-2
- Endothelin-1
- MMP-9
Tier 3 — Neuroglial Predictors
- GFAP
- YKL-40
- S100B
- sTREM2
Tier 4 — Neurocardiac Predictors
- HRV SDNN
- RMSSD
- LF/HF Ratio
Tier 5 — Neurometabolic Predictors
- Lactate/Pyruvate Ratio
- ATP Production
- cf-mtDNA
Tier 6 — Neuroendocrine Predictors
- Cortisol Circadian Rhythm
- DHEA-S
- Melatonin
These biomarkers collectively identify the highest-value intervention window preceding persistent Long COVID encephalopathy, autonomic dysfunction, and connectomic collapse.
MASTER REGISTRY INDEX
- SCF-LC-MNSS-TEMP-0010 — Post-Viral / Long COVID Encephalopathy Disease Progression Timeline Mapping
- SCF-ECCA-LC-0003 — Post-Viral / Long COVID Encephalopathy Module
- SCF-ECCA-LC-BIO-0003 — Post-Viral / Long COVID Biomarker Panel
- SCF-ECCA-LC-FIH-CTD-0003 — Post-Viral / Long COVID FIH Clinical Trial Design
- SCF-MNSS-0001 — Multi-Neurosystems Shock State Framework
- SCF-CONNECTOMIC-RECONSTRUCTION-0001 — Neuroimmune Connectomic Reconstruction Framework
- SCF-BIOMARKER-ENDPOINTS-0001 — Biomarker Endpoint Validation Framework
- SCF-PATH-PROT-0001 — SCF Pathophysiology Protocol
- SCF-ACU-NEURO-ATLAS-0001 — SCF Neural Mapping Schema