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

NCT ID: NCT04403061

Last Updated: 2021-01-12

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 106 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2020-05-22
• Study Completion Date: 2021-01-10

Brief 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

Detailed 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.

Conditions

Disease, Viral; Cytokine Release Syndrome; TLRs

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Interventions

Cytokines measurement

Quantification of plasma cytokine levels of human GM-CSF, IFN-α, IFN-γ, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12p70, IL-17A, and TNF-α using multiplex technol-ogy (quantitative measure).

Intervention Type: DIAGNOSTIC_TEST

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).

Intervention Type: DIAGNOSTIC_TEST

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).

Intervention Type: DIAGNOSTIC_TEST

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.

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal

OTHER

Sponsor Role: collaborator

Asociacion para el Estudio de las Enfermedades Infecciosas

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Hospital Ramon y Cajal

Madrid, , Spain

Countries

Spain

Other Identifiers

EC128/20

Identifier Type: -

Identifier Source: org_study_id