Clinical trial NCT04402827: Different Susceptibility to SARS CoV-2 Infection Among Health Care Workers Highly Exposed to COVID-19.
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.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Health Care Worker Patient Transmission
Receptor Site Alteration
Susceptibility, Disease
Immune Response
Keywords: coronavirus, susceptibility, transmission, HCW
Lead sponsor: Asociacion para el Estudio de las Enfermedades Infecciosas
Sponsor class: NETWORK
First posted: 2020-05-27
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
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)

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.

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.

Primary outcomes:
measure: Susceptibility to SARS CoV-2 infection according to ACE2 receptor
timeFrame: 1 month
measure: Cellular immune response to SARS CoV-2 infection
timeFrame: 1 month
measure: Susceptibility to infections according to KIR phenoytpes
timeFrame: 2 months
Secondary outcomes:
measure: Characteristics of exposure in time and intensity of HCW with SARS CoV-2 infection
timeFrame: 1 month
measure: Cellular immune response in HCW with positive IgG against SARS CoV-2
timeFrame: 1 month
Other outcomes:
Locations:
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal
Study officials:
affiliation: Ramon y Cajal Physician
name: Jose L Casado, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Vizcarra P, Haemmerle J, Velasco H, Velasco T, Fernandez-Escribano M, Vallejo A, Casado JL. BNT162b2 mRNA COVID-19 vaccine Reactogenicity: The key role of immunity. Vaccine. 2021 Dec 17;39(51):7367-7374. doi: 10.1016/j.vaccine.2021.10.074. Epub 2021 Nov 11.