Th1/Th2/Th17/TREG and TLRs Activation/KIR for COVID 19 Prediction of Outcome

Cytokine Release Syndrome Clinical Trial

— Resistir  

Official title:

Th1/Th2/Th17/TREG Response and TLRs Activation/KIR Receptors for Predicting the Evolution of the SARS Cov-2 Infected Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04403061
• Other study ID #: EC128/20
• Status: Completed
• Start date: May 22, 2020
• Est. completion date: January 10, 2021

Study information

• Verified date: January 2021
• Source: Asociacion para el Estudio de las Enfermedades Infecciosas
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

To ascertain globally the changes in the cytokines involved and TLRs/KIR activation in patients admitted to the hospital with a COVID-19 diagnosis, and the changes after initiation of the different therapies

Description:

COVID-19 is a disease with an initial viral phase followed, usually at the 7th day, of an inflammatory state (cytokine storm) leading to respiratory distress, ICU admission and risk of death. Thus, several biological agents, antagonists of the different cytokines (IL-6, IL-1) have been used for patients with severe disease. However, there are no data about the cytokine changes, at admission and after therapy, and its predictive value, a fundamental knowledge to establish the best therapeutic strategy.

The first line of immune defense is the interaction of the virus with innate immunity cell members. The toll like receptors (TLRs) family is a group of pattern recognition receptors that include many different molecules (21-23). These bindings can activate dendritic cells, monocytes, macrophages. There is an important RNA and DNA connection, activation of TLRs, the production of type I interferons, and the development of some autoimmune diseases. TLR7 and TLR8 specifically recognize simple-chain RNA of viruses and are expressed in endosomal membranes. TLR8 is expressed in regulatory cells (Treg) and its activation results in inhibition of its regulatory functions. Natural killer cells (NK) respond to alterations of class I HLA molecules present in infected cells (24-26). An increase in class I HLA expression could lead to an increase in NK activation by increasing its ability to produce IFN-gamma. Therefore, the reasons for KIR binding are often variable between individuals and between populations.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 106
• Est. completion date: January 10, 2021
• Est. primary completion date: December 22, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

Inclusion Criteria:

• Patients with a diagnosis of COVID-19 (PCR confirmed)

Exclusion Criteria:

• No informed consent

• Presence of chronic therapy with immunomodulators, corticoids or antineoplastic agents.

Related Conditions & MeSH terms

• Cytokine Release Syndrome
• Disease, Viral
• TLRs
• Virus Diseases

Intervention

Diagnostic Test:
• Cytokines measurement
Quantification of plasma cytokine levels of human GM-CSF, IFN-a, IFN-?, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12p70, IL-17A, and TNF-a using multiplex technol-ogy (quantitative measure).
• Cellular response
SARS-CoV-2 peptides (Prot-S, Pros-N and Port-M) will be used to activate CD4 and CD8 T cells. Cytokines released, such as IFNg, TNFa, IL4, IL17A, and IL2, from each cell subset will be measured by flow cytometry (quantitative measure).
• TLRs activation measurement
After specific cell activation through TLR7/8 receptors, such as resiquimod, ORN R-0002, ORN R-0006, ORN R-1263, ORN R-2336, and controls as Poly (I:C), the release of IFNa, IFNg, TNFa, IL12, and IL6 will be analyzed (quantitative measure).
• KIR phenotype evaluation
Characterization of the presence of 14 genes plus 2 pseudogenes of KIR gene family (qualitative genotyping) by PCR, mRNA expression profiling (quantitative measures) by RT-PCR, and phenotyping of human NK cells analyzing different KIR receptors (quantitative measure) by flow cytometry, will be analyzed.

Locations

Country	Name	City	State
Spain	Hospital Ramon y Cajal	Madrid

Sponsors (2)

Lead Sponsor	Collaborator
Asociacion para el Estudio de las Enfermedades Infecciosas	Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in cytokines associated with SARS CoV-2 infection		1 month
Primary	Evaluation of cellular response		1 month
Primary	TLRs activation		1 month
Primary	KIR phenotype determination		1 month