Official Title
Differences in Susceptibility to SARS CoV-2 Infection According to ACE2 and CD26 Receptors, Specific CD4/CD8 T Cell Response to Viral Peptides, and KIR Receptors Among Health Care Workers Highly Exposed to Patients With COVID-19 Diagnosis.
Brief 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.

Completed
Health Care Worker Patient Transmission
Receptor Site Alteration
Susceptibility, Disease
Immune Response

Diagnostic Test: Susceptibility to infection

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 Name: KIR measurements

Eligibility Criteria

Inclusion criteria

- HCW older than 18 years

- Highly exposed to COVID-19 according to the definition

- Negative (cases) or positive (controls) serology against SARS-CoV-2 infection
Exclusion criteria

- Presence of any disease / treatment which could alter the susceptibility (corticoid
therapy, chemotherapy, monoclonal antibodies)

- Pregnancy

High exposure definition: direct and continued care of COVID-19 diagnosed patients for 2
weeks or more, without aerosol- generating procedures, with inappropriate personal
protective equipment (PPE), or unprotected exposure to patients with COVID-19 during
aerosol-generating procedures.

The definition of appropriate PPE was based on previous recommendations. The absence of any
part of the PPE constituted an unprotected exposure. We defined the following as
aerosol-generating procedures: airway suction, application of a high-flow O2 instrument,
bronchoscopy, endotracheal intubation, tracheostomy, nebulizer treatment, sputum induction,
positive pressure ventilation, manual ventilation and cardiopulmonary resuscitation.

Eligibility Gender
All
Eligibility Age
Minimum: 18 Years ~ Maximum: 65 Years
Countries
Spain
Locations

Hospital Ramon y Cajal
Madrid, Spain

Jose L Casado, MD, PhD, Principal Investigator
Ramon y Cajal Physician

Asociacion para el Estudio de las Enfermedades Infecciosas
NCT Number
Keywords
coronavirus, susceptibility, transmission, HCW
MeSH Terms
COVID-19
Disease Susceptibility