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

Immune Response Clinical Trial

— CoVEX  

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04402827
• Other study ID #: EC 162/20
• Status: Completed
• Start date: August 1, 2020
• Est. completion date: September 30, 2021

Study information

• Verified date: October 2021
• Source: Asociacion para el Estudio de las Enfermedades Infecciosas
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 140
• Est. completion date: September 30, 2021
• Est. primary completion date: August 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• COVID-19
• Disease Susceptibility
• Health Care Worker Patient Transmission
• Immune Response
• Receptor Site Alteration
• Susceptibility, Disease

Intervention

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.

Locations

Country	Name	City	State
Spain	Hospital Ramon y Cajal	Madrid

Sponsors (1)

Lead Sponsor	Collaborator
Asociacion para el Estudio de las Enfermedades Infecciosas

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Susceptibility to SARS CoV-2 infection according to ACE2 receptor	ACE2 analysis	1 month
Primary	Cellular immune response to SARS CoV-2 infection	Activation of CD4-CD8 by viral peptides	1 month
Primary	Susceptibility to infections according to KIR phenoytpes	Analysis of KIR in NK cells	2 months
Secondary	Characteristics of exposure in time and intensity of HCW with SARS CoV-2 infection	Survey	1 month
Secondary	Cellular immune response in HCW with positive IgG against SARS CoV-2	Activation of CD4-CD8 by viral peptides	1 month