Preliminary Report On Residual Lung Damage in Long COVID-19 Using AD-cSVF In Clinical Trial NCT# 04326036

   

Robert W Alexander^*

Northwest Institute of Cellular and Biocellular Research USA

Corresponding author: Robert W. Alexander, Northwest Institute of Cellular and Biocellular Research +1 (406) 375-5451 USA

Citation: Alexander RW. (2023) Preliminary Report On Residual Lung Damage in Long COVID-19 Using AD-cSVF In Clinical Trial NCT# 04326036

Received:  July 7,  2023 | Published: July 28, 2023

Copyright© 2023 genesis pub by Alexander RW. CC BY NC-ND 4.0 DEED. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-No Derivatives 4.0 International License., This allows others distribute, remix, tweak, and build upon the work, even commercially, as long as they credit the authors for the original creation.

DOI: https://doi.org/10.52793/JSCR.2023.4(2)-52

 Clinical Trial of Treatment Long COVID-19 Patient Residual Damage

• Overview Summary of Understanding & Management
• Explain Clinical Trial Of Use Of cSVF In Long COVID Lung 
• Brief Description of cSVF Use In COPD/FLD Patients
• Fluidda Analysis Of COVID Lungs (Functional Pulmonary Images) For Diagnosis, Prediction, Management & Outcome Tracking
• Brief Introduction Followed By COVID Background & Beliefs
• Brief Introduction Followed By COVID Background & Beliefs

Understanding COVID-19

• Discovered Wuhan, China November-December 2019
• Contagious & Spread by Coughing/Sneezing/Aerosolization
• Initially Thought Primarily A Novel Respiratory Virus
• Susceptible Patients Older, Immune Deficient, CVD, DM, etc.
• Now Known Immune Failure Led to “Unique” Form of ARDS
• Interstitial Edema Led To Alveolar Failure and Fibrosis (Long-Term)
• Now Understood Lung Damage Occurs, To Some Extent,  in ALL Post-COVID-19 Symptomatic Patients

Early Beliefs on COVID-19

• Thought Likely Aerosol and Contact Spread
• Was Uncertain If Man-To-Man Spread (Quickly Dispelled)
• Thought Lungs Were Primary Target Impacted (Is Primary Entry)
• Some Presented ARDS Symptoms (But NOT Respond The Same)
• Presented With Generalized Viral Flu-Like Symptoms/Cough
• High Temps, Dropping 02 Saturations (even on 02), Patient Not Always Aware Sats Falling Below 90
• Mostly Older Patients, Pre-Existing Illnesses, Nursing Homes

Evolved Understanding COVID-19

• Immune System Failure, Often Severe Atypical ARDS (ICU, Vent)
• Sudden Loss Lung Respiratory Functional Capacity  ***
• Later Stage Huge Immune/Inflammatory Reaction (Cytokine)
• ARDS Progression NOT Following Classic Pulmonary Viral Infections
• Clots-MicroThrombi (Lungs, Heart, Brain, Kidney, Extremities, Liver)
• DIC Noted EVEN In Patients With No Co-Morbidities
• Known Attack Point at ACE2 Cell Wall Receptors (Lungs, Blood Vessel Linings, Kidneys, Intestines, etc.)
• Oxidative Stresses Are Elevated Within COVID-19 Process (ROS)

Mechanisms Of Lung & Peripheral Clotting In Covid-19

• Damage Occurs In Endothelial Walls Vessels – Many ACE2 Receptors Yielding High Angiotensin II Levels – Same Target as COVID Lung
• Spike Protein Of Virus Targets the ACE2 Receptors (Lungs, Capillary Endothelial Cells & Lung Alveolar Type II Cells, etc.)
• Elevated vWF Levels (Subendothelial) + Factor 8 in Circulation = Clotting
• Increased D-Dimer Levels, Lowered Platelet Levels (Reflects Clotting)
• Patients Display Serious Oxidative Stress & Thrombus Symptoms
• Impaired Gas Diffusion (Vascular Inequality -  V/Q Ratio Changes)

Early Management Tried In Covid-19 Ars

• Ventilator Tidal Volumes Were Often Set TOO HIGH
• Often Tried Excessive PEEP Pressures  (Both Did Not Raise O2 Sat)
• Tried Supine Vs. Prone Positioning Which Helped (Ref: Guerin – NEJM)
• Failure If Induced Coma Levels Not Enough (Vent Override Issue)
• Caused Over-Distention Lungs + Fluid Leaks Into Alveoli (Lower Ventilation/Perfusion Resulted With The “Cytokine Storm” Damage
• Resulted in Infiltration Fibroblasts, Scarring & Alveolar Loss

Common Case Management In Covid-19

• Ventilatory Support Escalation:
• Medium & High Flow O2
• CPAP/BPAP and Select Use Of PEEP
• Intubation & Full Ventilator Monitored TV (Long Term Need Is Common)
• Induced Coma To Permit Ventilatory Support
• Longer Prone Positioning Scheduling (Improves Ventilation)
• Used Steroids, AntiOxidants, AntiCoagulants, Variety of Medications 
• NOTE: Often Resulted in Permanent Lung Air Exchange Damage

Clinical Trial Background Using Csvf

• Proposal For Phase 0/I Based On Experiences With cSVF in COPD & Fibrotic Lung Disorders (FLD) in Clinical Trials
• Two Years Of Existing Trials + For Safety and Efficacy In Progress
• FLUIDDA Analytics Available For Functional Respiratory Imaging 
• Major Value In Diagnostics, Prognostications, Management
• Study Examines Lung Damage Changes Achieved with cSVF + Other Systemic Findings Common In Long-COVID (>12 Week, Persistent)
• Prognostication Value Permits Early Interventions Needed
• COPD/FLD Group Showing Clinical Improvement In Function 

Background & Logic Of Csvf Use

• Studied Homeostasis & Wound Healing
• Examined How We Remodel, Repair & Maintain
• Learning More Stem + Stromal Cells & Their Possible Roles
• Known Importance For Repair/Regen In ALL Tissues
• Site Specific Changes:   Microenvironment & Paracrine Functions Appear of Major Importance
• Concentrates Contribute Cells & Signal Proteins (Including Exosomes/MV) To React At Needed Sites 
• Has Produced An Excellent Safety Profile In Autologous Use cSVF

Understanding Adult Stem Cells

• Wikipedia:  “Adult Stem Cells are multipotent, undifferentiated cells found throughout the body after development, that multiply via Asymmetric Cell Division to replenish dying cells and regenerate damaged tissues”.
• Adult stem cells values center on ability to divide & self-renew indefinitely, either generating the SAME cell or OTHER cell types than the tissue from which they originate!  (Basis for Multipotency)

 Study NCT #04326036  

• Harvesting, Isolation/Concentration cSVF (Digestion) – IV Deploy
• FUNCTIONAL RESPIRATORY IMAGING (FRI) – Fluidda Analysis 
• Uses HRCT-LUNG (Low Radiation Dose, Thin CT (<1mm), Taken At Functional Full Inhalation/Exhalation) -- Not A Std CT Lung
• Baseline and 6-12 Month Samples For Comparative Analytics
• Baseline and 6 Month Sample Std. PFA For Comparative Analytics
• Monitoring 02 Sats, Supplemental 02 Changes, DOE, etc.

Cellular SVF Use In COPD/FLD

• Known Ability To Mitigate Inflammatory Reactions
• Known Mitigation Immune Responses (Immunomodulatory Effects) 
• Autologous, Heterogeneous Cellular, Paracrine, & Signaling Effects
• Elements Includes Innate & Adaptive Immune Response Cell Types
• Non-Designated Cells (MSC, Perivascular Group) + Paracrine Effects
• Known to “Home” To Damaged-Inflamed Areas
• Signaling Via Exosomes/MV Secretions From Key Reparative Cells & Native Local Damaged Area Cells (Cell-To-Cell Communication)

Accessing/Concentrating AD-SVF Components

• Disposable, Sterile Microcannula With Tulip GEMS (2.11 mm) 
• Usual Compressed Volume (After Centrifugation) 20-25 cc ATC
• Enzymatic Isolation/Incubation/Concentration Of AD-cSVF (Stem/Stromal Cell Elements)
• Neutralization/Rinsing Of cSVF (Removal Residual Enzyme)
• Resuspension In Normal Saline (Buffered) and Deployment
• Arbitrary Target Minimum Number Of 100 Million SVF Cells To Deploy IV Trial And Verified Flow Cytometry For Numbers, Cell Integrity (Viability Measure), Cell Size Averaging 

Fluidda Analytics

Functional Respiratory Imaging (FRI)

• Been Very Valuable In Analysis of cSVF in COPD/FLD & COVID-19
• High Resolution CT LUNGS (Functional Exam NOT Chest CT)
• Relatively Low Dose Radiation; Rapid, Thin Section Of Full Inspiration/Expiration 
• Proven Value In Diagnostics, Prediction, Tracking Management
• Shows Significant Air Perfusion/Exchange Changes
• Uses CT  Lung (at Both TLC and FRC) For Airways & Vascular
• Useful Both In Active & Post-Infection Populations

Example COVID-19 HRCT Images

 COVID-19 Moderate Damage

 COVID-19 Severe Damage (Scarring) 

 Vascular Patterns In Lung Diseases

Trial Patient #7:  Vascular Changes

Ventilation/Perfusion Changes With cSVF

Example: Actual Exam Baseline-6 Months         

Trial Patient #8 – Perfusion Impact              

Fluidda Analysis: FRC  (Actual COPD Patient)

Trial Patient #8:   Fluidda Analysis

 

Trial Patient #1:  Fluidda Analysis

Preliminary Long Covid-19 Clinical Trial

Thanks To Black Tie Medical For Sponsoring Clinical Trial. Appreciation of Efforts of Pat Alexander, Nancy Smith & Susan Riley For Their Very Important Contributions To Carry Out This Trial.