Immunophenotyping Assessment in a COVID-19 Cohort

Study Overview
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Brief Summary
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This surveillance study will collect detailed clinical, laboratory, and radiographic data in coordination with biologic sampling of blood and respiratory secretions and viral shedding in nasal secretions in order to identify immunophenotypic and genomic features of COVID-19 -related susceptibility and/or progression. The aim: for the results obtained from this study to assist in generating hypotheses for effective host-directed therapeutic interventions, to help to prioritize proposals for such interventions, and/or optimize timing for administration of host-response directed therapeutics.

Detailed Description
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This is a prospective observational cohort surveillance study of up to 2,000 adult participants hospitalized with known or presumptive COVID-19. Detailed information will be collected regarding patient history and onset of illness upon enrollment. Participants will undergo longitudinal assessments of clinical status and pertinent clinical data (including clinical laboratory values, radiographic findings, medication use, oxygen and ventilatory support requirements, complications, etc.) will be recorded. In parallel, the study will conduct serial biologic sampling for detailed immunophenotyping to provide a comprehensive picture of immune changes that occur throughout the course of infection. The biologic samples to be collected for this observational study include blood, nasal swabs, and endotracheal aspirates. Participants will be followed in hospital through Day 28, unless discharged earlier. If a participant requires an escalation to Intensive Care Unit (ICU)-level care, either within or outside of a dedicated ICU, additional samples will be collected within 24 and 96 hours of care escalation. Convalescent questionnaires and biologic samples will be collected at 3-month intervals up to Month 12 after infection symptom onset, if available. In addition, if a participant is discharged from the hospital prior to Day 28, attempts will be made to collect additional scheduled assessments through Day 28 on an outpatient basis, if feasible.

Official Title
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A Prospective Cohort Study to Assess Longitudinal Immune Responses in Hospitalized Patients With COVID-19 (DAIT-COVID-19-002)

Conditions
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SARS-CoV-2, Coronavirus Disease 2019 (COVID-19)

Intervention / Treatment
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* Procedure: Biological sample collection
* Procedure: Data Collection: Clinical Care Assessments


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Individuals who meet all of the following criteria are eligible for enrollment as study participants: Participant and/or surrogate understands the data to be collected and the study procedures and is willing to participate in the surveillance cohort as described in the study information sheet; ≥ 18 years of age at the time of hospitalization; and Admitted to a hospital with presumptive or documented coronavirus disease 2019 (COVID-19), with confirmation of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection by Polymerase Chain Reaction (PCR). Exclusion Criteria: Individuals who meet any of these criteria are not eligible for enrollment as study participants: Underlying medical problems which, in the opinion of the investigator may be associated with mortality unrelated to COVID-19 within 48 hours of hospitalization, or a decision by the patient or surrogate prior to hospitalization to limit care to comfort measures; or Medical problems or conditions such as pregnancy which might impact interpretation of the immunologic data obtained.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Surveillance cohort<br>Cohort descriptive data will include demographic variables (e.g. age, sex, race, ethnicity), clinical information on enrollment and key aspects of medical history (e.g. concomitant medications, for example). Patients will be longitudinally followed, up to 12 months. | Procedure: Biological sample collection<br>* During patient hospitalization: Nasal secretion samples by nasal swabs (for non-intubated patients), whole blood (blood draw/phlebotomy) and sputum secretions by endotracheal aspiration (for intubated patients) will be obtained to proceed with immunologic analysis of samples. DNA will be collected from whole blood at enrollment for genetic analysis (e.g., genome-wide association study [GWAS]). After hospital discharge: Collection of biologic samples (involving nasal swabs and blood draw/phlebotomy) will occur up to 12 months.<br>Procedure: Data Collection: Clinical Care Assessments<br>* Baseline data and assessments obtained as part of ongoing clinical care will be collected throughout hospitalization for COVID-19. After hospital discharge, clinical status and activity assessments will occur up to 12 months.<br>* Other names: Baseline data, clinical care assessments;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality Rate Among COVID-19 Patients | The incidence of mortality in the first 28 days. | Day 1 to Day 28 | 
| Proportion of Patients with COVID-19 who Require Intensive Care Unit (ICU)-Level Care, Mechanical Ventilatory Support (MV), and/or Extracorporeal Membrane Oxygenation (ECMO) Over Time to Day 28 | As a measure of disease acuity and severity. | Day 1 to Day 28 | 
| Proportion of Patients with COVID-19 who Develop Shock, Secondary Organ Failure, or Secondary Infection Over Time to Day 28 | As a measure of disease acuity and severity. | Day 1 to Day 28 | 
| Mechanistic: Longitudinal Assessment of Viral Load by Semi-Quantitative Polymerase Chain Reaction (PCR) Over Time to Day 28 | Ribonucleic acid (RNA) from the nasal swab will be used to assess SARS-CoV-2 viral load. | Day 1 to Day 28 | 
| Mechanistic: Antibody Isotype/Subclass Classification and Functionality Over Time through Day 28 and at follow-up through month 12 | Focus on the immune response to SARS-CoV-2, seroconversion and immunoglobulin and transitions. Antibody isotypes present in a patient specimen(s) provide information about the timing of initial exposure and may provide insight on the progression of the disease and prognosis. | Up to 12 Months | 
| Mechanistic: Longitudinal Assessment of Inflammatory Mediators as Collected Over Time to Day 28 | Collected as part of clinical care. | Day 1 to Day 28 | 
| Mechanistic: Longitudinal Assessment of Markers of Myocardial Injury Over Time to Day 28 | Collected as part of clinical care. | Day 1 to Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Mechanical Ventilation in Patients with COVID-19 Over Time to Day 28 | A measure of disease morbidity. | Day 1 to Day 28 | 
| Proportion of Patients with COVID-19 with Requirement for New (Or Increased from Baseline if on Home Oxygen) Supplemental Oxygen Over Time to Day 28 | A measure of disease morbidity. | Day 1 to Day 28 | 
| Requirement for Extracorporeal Membrane Oxygenation (ECMO) in COVID-19 Patients with COVID-19 Over Time to Day 28 | A measure of disease morbidity. | Day 1 to Day 28 | 
| Mechanistic: Immune Cell Frequencies and Activation Status (CyTOF) in Blood and Endotracheal Aspirate over time Through Day 28 and In blood at Select Study Visits Through Month 12 | Method of immune profiling and quantitating the response to COVID-19 over time. | Up to 12 Months | 
| Mechanistic: Gene Expression (Transcriptomics) in Blood | To identify and quantitate differences in immune response associated with disease outcome. | Up to 12 Months | 
| Mechanistic: Gene Expression (Transcriptomics) in Respiratory Epithelium | To identify and quantitate differences in immune response associated with disease outcome. | Up to 12 Months | 
| Mechanistic: Gene Expression (Transcriptomics) in Plasma Protein | To identify and quantitate differences in immune response associated with disease outcome. | Up to 12 Months | 
| Mechanistic: Gene expression (Transcriptomics) in Metabolic Profiling | To identify and quantitate differences in immune response associated with disease outcome. | Up to 12 Months | 
| Mechanistic: Circulating Immune Mediators Assessed by OLINK Methodology | Circulating immune biomarkers will be explored by use of the OLINK® (name of brand), a multiplex protein biomarker discovery panel. | Up to 12 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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observational cohort surveillance study, immunologic assessments