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Completed

NCT Number: NCT04402827

Different Susceptibility to SARS CoV-2 Infection Among Health Care Workers Highly Exposed to COVID-19.

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

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Key information

About this study

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:

  • 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.
  • 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
  • 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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Susceptibility to infection

Diagnostic Test

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 names: KIR measurements

Primary outcomes

  1. Susceptibility to SARS CoV-2 infection according to ACE2 receptor

    Time frame: 1 month

    ACE2 analysis

  2. Cellular immune response to SARS CoV-2 infection

    Time frame: 1 month

    Activation of CD4-CD8 by viral peptides

  3. Susceptibility to infections according to KIR phenoytpes

    Time frame: 2 months

    Analysis of KIR in NK cells

Secondary outcomes

  1. Characteristics of exposure in time and intensity of HCW with SARS CoV-2 infection

    Time frame: 1 month

    Survey

  2. Cellular immune response in HCW with positive IgG against SARS CoV-2

    Time frame: 1 month

    Activation of CD4-CD8 by viral peptides

Sponsors and collaborators

Lead sponsor

Asociacion para el Estudio de las Enfermedades Infecciosas

Network

Registry information

Official study 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.

Acronym: CoVEX

Important dates

Study start
2020
Primary completion
2021
Study completion
2021
First posted
May 27, 2020
Registry last updated
Oct 26, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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