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OUR LONG COVID RESEARCH IS

unlocking understanding of the role chronic inflammation plays in immune-mediated diseases

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INFLAMMATORY
PATHOLOGY

The CCR5/Fractalkine Immune Pathway mediates Vascular Inflammation

 

Recently, our team of researchers solved a piece of the Long Covid puzzle. In Long Covid patients, the SI protein of the COVID-19 virus remains in their monocytes, leading to a persistent immune response despite the absence of the active COVID-19 infection.

 

These monocytes have many CCR5 and fractalkine receptors on their surface, which promote vascular inflammation and immune dysregulation through the monocytic-endothelial-platelet axis.

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We investigated the presence of SARS-COV-2 S1 protein in 46 individuals. We analyzed T-cell, B-cell, and monocytic subsets in both severe COVID-19 patients and in patients with post-acute sequelae of COVID-19 (PASC). A statistically  significant number of non-classical monocytes contained SARS-C0V-2 S1 protein in both severe (P=0.004) and PASC patients (P=0.02) out to 15 months post-infection. The research published in Jan, 2022 in Frontiers in Immunology is listed below.

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RESOURCE ARTICLE

Frontiers in Immunology

Persistent of Sars CoV-2 S1 Protein in CD16+ Monocytes in Post-Acute Sequelae of COVID-19 (PASC) up to 15 Months Post-Infection

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RUO DIAGNOSTIC INNOVATION

IncellKINE™,  is designed to detect a unique or individual signature for each patient tested for Long-Covid and other immune-mediated diseases.

 

HealthBioAI developed a bioinformatics pipeline that analyzed cytokines of the immunological landscape of COVID-19 using machine learning methods to discriminate between PASC and Severe individuals from other classes.

 

The implementation of random forest classifiers allowed for the identification of the critical cytokines for this discrimination, which in turn was used to calculate highly sensitive heuristics for PASC and Severe individuals.

 

These models, which can be incorporated into clinical laboratory information systems, are intended to assist in the measurement of immune-based classification of severe COVID-19 infection and PASC. 

 

 

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RESOURCE ARTICLE

National Library of Medicine

Immune-Based Prediction of COVID-19 Severity and Chronicity Decoded Using Machine Learning

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INCELLKINE™

Test

 

WHAT ARE WE MEASURING?

IL-6
IL-6: This pro inflammatory cytokine has been found to be elevated in severe COVID-19 patients and in chronic COVID patients. [Patterson, et al., IJID 2020; Patterson, et al., Front. Immunol. 2021]
IFN-gamma
IFN-gamma: This pro inflammatory cytokine has been found to be elevated in chronic COVID patients. [Patterson, et al., IJID 2020; Patterson, et al., Front. Immunol. 2021]
IL-2
IL-2: This is responsible for proliferation and activation of T cells, B cells, and NK cells.
IL-4
IL-4: The interleukin 4 is a cytokine that induces differentiation of naive helper T cells to Th2 cells. Upon activation by IL-4, Th2 cells subsequently produce additional IL-4 in a positive feedback loop. IL-4 is produced primarily by mast cells, Th2 cells, eosinophils, and basophils.
CXCL8 (IL-8)
CXCL8 (IL-8): Interleukin 8 is a chemokine produced by macrophages and other cell types such as epithelial cells, airway smooth muscle cells, and endothelial cells. Endothelial cells store IL-8 in their storage vesicles, the Weibel-Palade bodies. In humans, the interleukin-8 protein is encoded by the CXCL8 gene.
IL-10
IL-10: This has been found to be elevated in chronic COVID patients. [Patterson, et al., Front. Immunol. 2021]
It has been observed that long-hauler patients demonstrate an elevation in IL-2 and IFN-gamma, and a reduction in CCL4.
IL-13
IL-13: This is a cytokine produced by Th2 cells, NK cells, mast cells, and basophils; it is a mediator of allergic inflammation and a key regulator of IgEsynthesis, mucus hypersecretion, and airway hyperresponsivesness. [Rael et al., Gulati, et al.,]
GM-CSF
GM-CSF: This is produced by T cells, macrophages and fibroblasts, and stimulates production of granulocytes, monocytes, and eosinophils
[Turner, et al.,]. GM-CSF has been found to be
reduced in chronic COVID patients.
[Patterson, et al., Front. Immunol. 2021]
CCL3
CCL3: This is involved in macrophage and NK-cell migration, as well as T-cell dendritic cell interactions [Sokol, et al.,]. It has also been found to be
elevated in chronic COVID patients.
[Patterson, et al., Front. Immunol. 2021]
CCL4
CCL4: This has been found to be reduced in chronic COVID patients. [Patterson, et al., Front. Immunol. 2021]
CCL4 is involved in macrophage and NK-cell migration, as well as T-cell/dendritic cell interactions [Sokol, et al.,]. CCL4 signals through the receptor CCR5 to attract T-cells to the site of inflammation and, depending on the immune context, can recruit differently activated T-cells [Patterson, et al., Front. Immunol. 2021; Liu, et al; Mukaida, et al.,]
CCL5
CCL5:This is involved in macrophage and NK-cell migration, as well as T-cell/dendritic cell interactions [Sokol, et al.,]. CCL5 levels have been found to be highly elevated in severe COVID-19 patients, but not in chronic COVID patients [Patterson, et al., IJID 2020; Patterson, et al., Front. Immunol. 2021].
VEGF
VEGF:  This has been found to be elevated in chronic COVID patients [Patterson, et al., Front. Immunol. 2021]. The presence of VEGF in inflammation neuropathies, such as CIOP, GBS, and vascular neuropathy may indicate a potential relation with vascular involvement. [Nobile-Orazio, et al.,] VEGF has been shown to be elevated in POEMS, but no other monoclonal gammopathies, and can be elevated in immune-mediated neuropathies.
TNF-alpha
TNF-alpha: This is a pro-inflammatory cytokine, associated with phagocyte cell activation and endotoxic shock. [Turner, et al.,] TNF-alpha has been shown to play a role in the process of pathological pain. [Zhang, et al.,]
sCD4oL
sCD4oL: Soluble CD40 ligand (sCD40L) is contained in platelet granules, and thus its presence in the blood is a marker of platelet activation. By interacting with CD40, which is found in endothelial and smooth muscle cells, sCD40L may trigger the release of inflammatory mediators, lead to increase activity of matrix metallproteinases, and activate the coagulation cascade.

S1

Immune Panel Test

 

The S1 Immune Subset looks for the presence of SARS COV 2-S1 protein in
monocytes resulting from either the COVID-19 vaccine or natural infection.

 

WHAT ARE WE MEASURING?

Classical monocytes: Exhibit the CD14++, CD16- phenotype. The classical monocytes express high levels of the ACE-2 receptor, the putative receptor for SARS-CoV-2. classical monocytes express low levels of the chemokine receptors CX3R1 and CCR5.
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Non-classical monocytes: Exhibit CD14lo, CD16+ phenotype, express very little ACE-2 receptor, express high levels of CX3R1.
Intermediate monocytes: Exhibit a CD14+, CD16+ phenotype, express very little ACE-2 receptor, and express high levels of CCR5.
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Maraviroc and Pravastatin show potential for treating Long Covid 

 

HealthBioAI  has developed a patented drug combination to address immune dysregulation in Long Covid.

 

Research has shown a combination of the small molecules maraviroc and pravastatin can reduce chronic inflammation.  Together maraviroc, a CCR5 antagonist, and pravastatin provide a new mechanism that could disrupt the moncytic-endothelial-platelet-axis that is central to many immune-mediated diseases beyond Long Covid.

 

This research has led to the acceptance by the FDA to proceed with a Randomized Clinical Trial for the treatment of Long Covid/Post Acute Sequelae of COVID (PASC). 

 

 

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RESOURCE ARTICLE

National Library of Medicine

Case Series: Maravioc and Pravastatin as a Therapeutic Option to treat Long Covid/Post-Acute Sequealae of Covid (PASC)

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ADDITIONAL RESOURCES

Long Covid Diagnosis, Treatment & Pathology

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