Description

What is a COVID Long Haulers 14 Cytokine Panel Test?

Cytokines are small, secreted proteins released by cells have a specific effect on the interactions and communications between cells. Cytokine is a general name; other names include lymphokine (cytokines made by lymphocytes), monokine (cytokines made by monocytes), chemokine (cytokines with chemotactic activities), and interleukin (cytokines made by one leukocyte and acting on other leukocytes). Cytokines may act on the cells that secrete them (autocrine action), on nearby cells (paracrine action), or in some instances on distant cells (endocrine action). There are both pro-inflammatory cytokines and anti-inflammatory cytokines.

Proinflammatory cytokines are produced predominantly by activated macrophages and are involved in the upregulation of inflammatory reactions. There is abundant evidence that certain pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α are involved in the process of pathological pain.

The anti-inflammatory cytokines are a series of immunoregulatory molecules that control the proinflammatory cytokine response. Cytokines act in concert with specific cytokine inhibitors and soluble cytokine receptors to regulate the human immune response. Major anti-inflammatory cytokines include interleukin (IL)-1 receptor antagonist, IL-4, IL-6, IL-10, IL-11, and IL-13.

The Cytokine 14 panel tests for the elevation or decreased levels of cytokines following COVID-19 infection or post-COVID-19 vaccine injury leading to long haul symptoms. The results may be helpful in better understanding the pathophysiology of immunological, infectious, or inflammatory disorders or may be used for research purposes.

Abnormalities in the levels of 14 cytokines and chemokines have been identified in cytokine storms such as occur in COVID-19 infection, and in patients who have recovered from the acute phase of infection but are still experiencing symptoms characteristic of chronic COVID. IL-2, IL-4, CCL3, IL-6, IL-10, IFN- gamma and VEGF have been found to be elevated in chronic COVID patients, whereas CCL4 and GM- CSF are often found to be diminished.

Long Hauler Score:

In a recent publication by Patterson et al., an analysis was performed on 144 individuals (including 29 normal, 26 mild-moderate COVID-19, 25 severe COVID-19 and 64 individuals with chronic COVID) to try to identify possible immunologic signatures of COVID-19 severity and determine if chronic COVID-19 might represent a distinct immunologic entity compared to mild to moderate or severe /critical COVID-19.

Plasma levels of 14 cytokines were measured and then analyzed using neural networking and machine learning. A “long hauler score” was developed which demonstrated a sensitivity of 97% and a specificity of 100% for identifying chronic COVID.

The cytokines IL-2, IL-4, CCL3, IL-6, IL-10 INF-gamma and VEGF were all significantly elevated compared to normal controls. Conversely, GM-CSF and CCL4 were significantly lower than normal controls. Upon further analysis three key cytokines emerged as characteristically indicative of the chronic COVID group (Interferon-gamma, IL-2, CCL-4) and formed the basis for the establishment of a “long-hauler score”.

This analysis suggests chronic patients are characterized by a profile able to induce the activation of effector T cell with pro-inflammatory properties and the capacity of generating an effective immune response to eliminate the virus but without the proper recruitment signals to attract activated T cells.

This quantitative immunologic score may be useful in stratifying patients to therapy and/or non-subjectively measuring response to therapy.

Test method:

This test is based on flow cytometry methodology and involves following CPT codes: 88184,

88185, 88188.

Disclaimer:

This is a Laboratory Developed Test (LDT) and involves flow cytometry methodology. Its components were developed by incellDx and their performance characteristics were determined by Radiance Diagnostics, that is certified under the CLIA as qualified to perform high complexity laboratory testing. The LDT tests comprising this panel have not been reviewed by the U.S. Food and Drug Administration.

REFERENCES:

• Patterson BK, et al. CCR5 Inhibition in CriticalCOVID-19 Patients Decreases Inflammatory Cytokines, Increases CDS T- Cells, and Decreases SARS-CoV2 RNA in Plasma by Day 14. IntiJ Infect Dis 2020
• Patterson Bruce K., Guevara-Coto Jose, Yogendra Ram, Francisco Edgar B., Long Emily, Pise Amruta, Rodrigues Hallison, Parikh Purvi, Mora Javier, Mora-Rodríguez Rodrigo A.Immune-Based Prediction of COVID-19 Severity and Chronicity Decoded Using Machine Learning Frontiers in Immunology, 12, 2021;2520
• Patterson BK, et al. CCR5 Inhibition in Critical COVID-19 Patients Decreases Inflammatory Cytokines, Increases CDS T- Cells, and Decreases SARS-CoV2 RNA in Plasma by Day 14. Inti J Infect Dis 2020
• Patterson BK, et al. Immune-Based Prediction of COVID-19 Severity and Chronicity Decoded Using Machine Learning. BioRxiv 2020
• Zhang JM, An J. Cytokines, inflammation, and pain. Int Anesthesiol Clin. 2007 Spring;45(2):27-37
• Opal SM, DePalo VA. Anti-inflammatory cytokines. Chest. 2000 Apr;117(4):1162-72.