Virological and Immunological Monitoring in Patients (Suspected of/Confirmed With) COVID-19 (Co-Vim)

This study is a prospective, observational multicentric study. The study population entails adult patients hospitalized with a high clinical suspicion of COVID-19 and consists of two study arms (SARS-CoV2- vs. SARS-CoV2+).This combined fundamental research project has a dual goal: on the one hand assessing immunological predisposing factors for severe infection and investigating the immunological impact of SARS-CoV2 infection, on the other hand studying viral characteristics. Furthermore, a substudy will examine the pharmacokinetics and pharmacodynamics of hydroxychloroquine in patients receiving this antiviral treatment (REVIVE susbstudy). To answer these research questions, samples will be collected from patients with a high clinical suspicion of COVID-19, hospitalized at UZ Gent and 2 participating hospitals in Ghent (AZ Maria Middelares en AZ Jan Palfijn).

Study Overview

• Status: Active, not recruiting
• Conditions: COVID-19
• Intervention / Treatment: Procedure: Blood draw; Procedure: Bronchoalveolar lavage; Procedure: SARS CoV-2 swabs

• Study Type: Observational
• Enrollment (Actual): 109

Contacts and Locations

Study Locations

• Belgium
  • Oost-Vlaanderen
    • Gent, Oost-Vlaanderen, Belgium, 9000
      • AZ Maria Middelares
    • Gent, Oost-Vlaanderen, Belgium, 9000
      • UZ Gent
    • Gent, Oost-Vlaanderen, Belgium, 9000
      • AZ Jan Palfijn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

The study population consists of patients hospitalised with symptoms with upper or lower respiratory symptoms and temperature ≥37.5°C, with high clinical suspicion of COVID-19, who require hospitalisation.

Description

Inclusion Criteria:

• Upper or lower respiratory symptoms and temperature ≥37.5°C, with high clinical suspicion of COVID-19
• Requiring hospitalization

Exclusion Criteria:

• Known pregnancy at the time of screening
• Inability to give informed consent or absence of legal representative who can give informed consent.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
COVID-19 positive; Peripheral blood draw: Day 1 of admission: blood draw.; Day 7-10 of hospitalization: blood draw.; Follow-up consultation: blood draw (selected patients). Bronchoscopic sampling: Material from bronchoscopic sampling (lavage fluid) will be collected only in those subjects in whom there is a diagnostic or therapeutic need for this procedure. Swabs for SARS-CoV-2 PCR: Day 1 of admission: Extra oropharyngeal, nasal and nasopharyngeal (NP) swabs will be collected after the result of the initial diagnostic swab is known. In case of shortage of swabs, sputum samples will be collected as an alternative.; Day 7-14 of hospitalization: NP swab or clinically available alternative will be executed on day 7 repeated weekly.	Procedure: Blood draw; 8x9mL EDTA tubes. In subjects treated with hydroxychloroquine treatment an extra EDTA tube (4mL) will be collected for the REVIVE substudy.; Procedure: Bronchoalveolar lavage; Only in case of diagnostic or therapeutic indication.; Procedure: SARS CoV-2 swabs; Nasopharyngeal, oropharyngeal and nasal swabs
COVID-19 negative; Peripheral blood draw: Day 1 of admission: blood draw.; Follow-up consultation: blood draw (selected patients). Bronchoscopic sampling: Material from bronchoscopic sampling (lavage fluid) will be collected only in those subjects in whom there is a diagnostic or therapeutic need for this procedure. Swabs for SARS-CoV-2 PCR: o Day 1 of admission: Extra oropharyngeal, nasal and nasopharyngeal (NP) swabs will be collected after the result of the initial diagnostic swab is known. In case of shortage of swabs, sputum samples will be collected as an alternative.	Procedure: Blood draw; 8x9mL EDTA tubes. In subjects treated with hydroxychloroquine treatment an extra EDTA tube (4mL) will be collected for the REVIVE substudy.; Procedure: Bronchoalveolar lavage; Only in case of diagnostic or therapeutic indication.; Procedure: SARS CoV-2 swabs; Nasopharyngeal, oropharyngeal and nasal swabs

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification of cytokines and chemokines associated with COVID-19 severity and outcome.	Cytokine and chemokine analysis (U-plex Mesoscale Diagnostics) on the plasma and BAL fluid will be correlated to disease severity and outcome	6 months
Identification of cellular subsets that can predict COVID-19 severity and outcome.	By using high-dimensional flow cytometry on cryopreserved PBMCs, the investigators will assess whether the phenotype and intracellular signaling can predict COVID-19 severity and disease outcome.	6 months
SARS CoV-2 sequencing.	Whole genome sequencing and viral metagenomics analysis will be performed on selected nasopharyngeal swabs and bronchoalveolar lavage fluid.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Single-cell RNA sequencing of BAL fluid and matched PBMC samples.	Single -cell RNA sequencing will be performed on fresh BAL fluid and matched PBMCs by using 10X Genomics technology. The aim of the project is to study the transcriptional activity in different immune cells in the lung in COVID-19 patients with differing disease severity and compare these to non-COVID-19 respiratory infections.	6 months
Measurement of plasma hydroxychloroquine and N-desethylhydroxychloroquine (REVIVE).	In this pilot substudy (REVIVE study), the investigators aim to measure plasma hydroxychloroquine, measuring range 10-2250 ng/mL, and the active metabolite, plasma N-desethylhydroxychloroquine, measuring range 2-2250 ng/m, in patients treated with hydroxychloroquine.	6 months
Analysis of micronutrients Cu, Fe and Zn in plasma samples from COVID-19 + and COVID-19 - patients.	Total serum or plasma concentrations (mg/L) of Cu, Fe and Zn will be measured using a benchtop TXRF spectrometer (S4 T-STAR, Bruker Nano GmbH, Berlin, Germany) by prof. Gijs Du Laing and the laboratory of Prof. Lutz Schomburg.	12 months
Analysis of micronutrient Se in plasma samples from COVID-19 + and COVID-19 - patients.	Total serum or plasma concentrations (µg/L) of Se will be measured using a benchtop TXRF spectrometer (S4 T-STAR, Bruker Nano GmbH, Berlin, Germany) by prof. Gijs Du Laing and the laboratory of Prof. Lutz Schomburg.	12 months

Collaborators and Investigators

• Sponsor: University Hospital, Ghent
• Collaborators: Fund for Scientific Research, Flanders, Belgium; Chan Zuckerberg Initiative; Flanders Institute for Biotechnology
• Investigators: Principal Investigator: Linos Vandekerckhove, Prof. MD, University Hospital, Ghent

Study record dates

Study Major Dates

• Study Start (Actual): March 23, 2020
• Primary Completion (Actual): July 23, 2020
• Study Completion (Estimated): September 30, 2024

Study Registration Dates

• First Submitted: May 28, 2020
• First Submitted That Met QC Criteria: May 26, 2021
• First Posted (Actual): May 27, 2021

Study Record Updates

• Last Update Posted (Actual): December 8, 2023
• Last Update Submitted That Met QC Criteria: December 1, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Molecular Mechanisms of Pharmacological Action; Chelating Agents; Sequestering Agents; Dimercaprol
• Other Study ID Numbers: BC-07492

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Time Frame: 6 months
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No