Th1/Th2/Th17/TREG and TLRs Activation/KIR for COVID 19 Prediction of Outcome
Condition: Disease, Viral; Cytokine Release Syndrome; TLRs
MeSH terms: Virus Diseases; Cytokine Release Syndrome
Study type: Observational

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.
    

Intervention name(s): Cytokines measurement; Cellular response; TLRs activation measurement; KIR phenotype evaluation
Intervention type(s): Diagnostic Test; Diagnostic Test; Diagnostic Test; Diagnostic Test
Intervention description(s): 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).; 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).; 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).; 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.
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Patients with a diagnosis of COVID-19