Health Care Worker Patient TransmissionCoVEXNCT04402827
Different Susceptibility to SARS CoV-2 Infection Among Health Care Workers Highly Exposed to COVID-19.
An observational study of Health Care Worker Patient Transmission and Receptor Site Alteration, run by Asociacion para el Estudio de las Enfermedades Infecciosas at 1 site in Spain.
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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Health Care Worker Patient Transmission, Receptor Site Alteration, Susceptibility, Disease
- What is being tested?
- Susceptibility to infection
- How many people
- 140 participants
- Where
- 1 siteSpain
- Study dates
- 1 Aug 2020to 30 Sep 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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)
Who may be able to join
- 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.
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
About this study
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.
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
Read the 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.
- Conditions
- Health Care Worker Patient Transmission, Receptor Site Alteration, Susceptibility, Disease, Immune Response
- Being tested
- Susceptibility to infection
- Keywords
- coronavirus, susceptibility, transmission, HCW
- Medical subject headings
- Disease Susceptibility, Coronavirus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Susceptibility to infectionDiagnostic test
Also called KIR measurements
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Diagnostic Test: Susceptibility to infection | |
| 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) Receives: Diagnostic Test: Susceptibility to infection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Susceptibility to SARS CoV-2 infection according to ACE2 receptor
ACE2 analysis
Measured: 1 month
Cellular immune response to SARS CoV-2 infection
Activation of CD4-CD8 by viral peptides
Measured: 1 month
Susceptibility to infections according to KIR phenoytpes
Analysis of KIR in NK cells
Measured: 2 months
Secondary outcomes (2)
Characteristics of exposure in time and intensity of HCW with SARS CoV-2 infection
Survey
Measured: 1 month
Cellular immune response in HCW with positive IgG against SARS CoV-2
Activation of CD4-CD8 by viral peptides
Measured: 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 May 2020
- Study start1 Aug 2020
- Primary completion30 Aug 2021
- Study completion30 Sep 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Health Care Worker Patient TransmissionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 140 participants (actual)
Sponsor and investigators
- Lead sponsor
- Asociacion para el Estudio de las Enfermedades Infecciosas
- Sponsor type
- Research network
- Responsible party
- Sponsor
- Investigators
- Jose L Casado, MD, PhD, Principal investigator, Ramon y Cajal Physician
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04402827
- Sponsor's protocol ID
- EC 162/20
- Acronym
- CoVEX
- Status last verified
- Oct 2021
- First submitted
- 23 May 2020
- Last updated
- 26 Oct 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Data about receptors could be shared with other investigators about the susceptiblity to SARS CoV-2 However, KIR phenotypes should be shared after ethical comitee approval
Publications
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.
PubMed 34802792
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT04402827
- Acronym / sponsor ID
- CoVEX / EC 162/20
- Conditions
- Health Care Worker Patient Transmission, Receptor Site Alteration, Susceptibility, Disease, Immune Response
- Keywords
- coronavirus, susceptibility, transmission, HCW
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 140 participants (actual)
- Lead sponsor
- Asociacion para el Estudio de las Enfermedades InfecciosasResearch network
- Study start
- 1 Aug 2020 (actual)
- Primary completion
- 30 Aug 2021 (actual)
- Study completion
- 30 Sep 2021 (actual)
- First posted
- 27 May 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cases | – | Diagnostic Test: Susceptibility to infectionHCW 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. |
| Controls | – | Diagnostic Test: Susceptibility to infectionHCW 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) |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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)
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Susceptibility to infectionAlso: KIR measurementsACE2 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. | Diagnostic test | Cases, Controls |
Primary outcome
Susceptibility to SARS CoV-2 infection according to ACE2 receptor
Time frame: 1 month
ACE2 analysis
Cellular immune response to SARS CoV-2 infection
Time frame: 1 month
Activation of CD4-CD8 by viral peptides
Susceptibility to infections according to KIR phenoytpes
Time frame: 2 months
Analysis of KIR in NK cells
2 secondary outcomes
Characteristics of exposure in time and intensity of HCW with SARS CoV-2 infection
Time frame: 1 month
Cellular immune response in HCW with positive IgG against SARS CoV-2
Time frame: 1 month
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2021.
- Derived from this study: PubMed 34802792Vizcarra 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.
- Individual participant dataSharing planned: Undecided. Data about receptors could be shared with other investigators about the susceptiblity to SARS CoV-2 However, KIR phenotypes should be shared after ethical comitee approval
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jose L Casado, MD, PhD principal investigator
Ramon y Cajal Physician
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Health Care Worker Patient Transmission and Receptor Site Alteration, run by Asociacion para el Estudio de las Enfermedades Infecciosas at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Susceptibility to SARS CoV-2 infection according to ACE2 receptor (time frame: 1 month). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04402827, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2021.