Health Care Worker Patient Transmission, Immune Response, Receptor Site Alteration, Susceptibility, Disease
Conditions
Keywords
coronavirus, susceptibility, transmission, HCW
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.
Interventions
DIAGNOSTIC_TESTSusceptibility 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.
Sponsors
Asociacion para el Estudio de las Enfermedades Infecciosas
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
Spain
Outcome results
None listed