Different Susceptibility to SARS CoV-2 Infection Among Health Care Workers Highly Exposed to COVID-19.
Condition: Health Care Worker Patient Transmission; Receptor Site Alteration; Susceptibility, Disease; Immune Response
MeSH terms: COVID-19; Disease Susceptibility
Study type: Observational

Summary: 
      The primary objective of this study is to establish differences in susceptibility to SARS
      CoV-2 infection among health care workers (HCW) highly exposed to patients with COVID-19
      diagnosis. To ascertain this issue, we evaluated:

        -  Changes in receptor polymorphism (ACE2 and CD26 receptor study.

        -  SARS-CoV-2 CD4/CD8 T cell response (CTL)

        -  Different KIR phenotypes
    

Detailed description: 
      Only 24% of health care workers (HCW) had developed inmunological response to SARS CoV-2
      infection in one centre attending thousands of COVID-19 patients, and with shorteness of
      personal protective equipments. Our hypothesis is that this relatively low number of infected
      HCW could be secondary to:

        1. Differences in susceptibility to infection mediated by changes in viral receptors. Thus,
           it is important to characterize and genotyping the main receptor for SARS-CoV-2, ACE2,
           and other related receptor, such as CD26.

        2. Increased cellular immune response, offering cross-immunity against SARS CoV-2 infection
           by previous exposure to other coronavirus or respiratory pathogens. A specific CD4/CD8 T
           cell response to viral peptides could respond this question

        3. Specific KIR phenotypes (Killer Immunoglobulin-like Receptors): Natural killer cells
           (NK) response to alterations of class I HLA molecules presented in infected cells. An
           increase in class I HLA expression could lead to an increase in NK activation by
           increasing its ability to produce IFN-gamma.
    

Intervention name(s): Susceptibility to infection
Intervention type(s): Diagnostic Test
Intervention description(s): ACE2 and CD26 receptor study: After genomic DNA extraction and quantification using a NanoDrop-1000, 14 ACE2 SNPs (rs1978124, rs2048683, rs2074192, rs2106809, rs2285666, rs233575, rs4240157, rs4646142, rs4646155, rs4646156, rs4646188, rs4830542, rs6632677, and rs879922) will be studied. In addition, one CD26 (DPP4) SNP (rs7608798) will be analysed (qualitative measure).
SARS-CoV-2 CD4/CD8 T cell 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).
KIR characterization: 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.
Other intervention name(s): KIR measurements
Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        -  Cases: HCW highly exposed to COVID-19 diagnosed patients (see definition) who remained
             free of symptoms of disease and had a negative serology against SARS-CoV-2 (both IgG
             and IgM)

          -  Controls: HCW highly exposed to COVID-19 diagnosed patients who had suffered the
             infection and/or had presence of antibodies in the serological test, paired by sex and
             age (5 year interval)
      
Keywords: coronavirus, susceptibility, transmission, HCW