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

Sponsor

Asociacion para el Estudio de las Enfermedades Infecciosas (Other)

Overall Status

Completed

CT.gov ID

NCT04402827

Collaborator

(none)

140

Enrollment

Location

Actual Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Health Care Worker Patient Transmission Receptor Site Alteration Susceptibility, Disease Immune Response	Diagnostic Test: Susceptibility to infection

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:

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.

Study Design

Study Type:

Observational

Actual Enrollment :

140 participants

Observational Model:

Case-Control

Time Perspective:

Prospective

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.

Actual Study Start Date :

Aug 1, 2020

Actual Primary Completion Date :

Aug 30, 2021

Actual Study Completion Date :

Sep 30, 2021

Arms and Interventions

Arm	Intervention/Treatment
Cases HCW highly exposed (defined as more than 15 days of continued personal attention in ICU, anaesthesia, or Infectious Diseases wards) to patients with a diagnosis of COVID-19 (PCR confirmed), who remained asymptomatic and with a negative serology (IgM and IgG negative). Transient entry or stay in the zone (kitchen personnel, rehab members,...) will be not included.	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 Names: KIR measurements
Controls HCW highly exposed to PCR-confirmed patients with a diagnosis of COVID-19, as defined above, matched by age and sex, who had suffered confirmed SARS CoV-2 disease (positive PCR or after, positive IgG)	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 Names: KIR measurements

Arm

Intervention/Treatment

Cases

HCW highly exposed (defined as more than 15 days of continued personal attention in ICU, anaesthesia, or Infectious Diseases wards) to patients with a diagnosis of COVID-19 (PCR confirmed), who remained asymptomatic and with a negative serology (IgM and IgG negative). Transient entry or stay in the zone (kitchen personnel, rehab members,...) will be not included.

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 Names:

KIR measurements

Controls

HCW highly exposed to PCR-confirmed patients with a diagnosis of COVID-19, as defined above, matched by age and sex, who had suffered confirmed SARS CoV-2 disease (positive PCR or after, positive IgG)

Diagnostic Test: Susceptibility to infection

Other Names:

KIR measurements

Outcome Measures

Primary Outcome Measures

Susceptibility to SARS CoV-2 infection according to ACE2 receptor [1 month]
ACE2 analysis
Cellular immune response to SARS CoV-2 infection [1 month]
Activation of CD4-CD8 by viral peptides
Susceptibility to infections according to KIR phenoytpes [2 months]
Analysis of KIR in NK cells

Secondary Outcome Measures

Characteristics of exposure in time and intensity of HCW with SARS CoV-2 infection [1 month]
Survey
Cellular immune response in HCW with positive IgG against SARS CoV-2 [1 month]
Activation of CD4-CD8 by viral peptides

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital Ramon y Cajal	Madrid		Spain	28034

Sponsors and Collaborators

Asociacion para el Estudio de las Enfermedades Infecciosas

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Asociacion para el Estudio de las Enfermedades Infecciosas

ClinicalTrials.gov Identifier:

NCT04402827

Other Study ID Numbers:

EC 162/20

First Posted:

May 27, 2020

Last Update Posted:

Oct 26, 2021

Last Verified:

Oct 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Undecided

Plan to Share IPD:

Undecided

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Asociacion para el Estudio de las Enfermedades Infecciosas

coronavirus, susceptibility, transmission, HCW

Additional relevant MeSH terms:

COVID-19

Disease Susceptibility

Study Results

No Results Posted as of Oct 26, 2021