COVID-19 Longitudinal Biomarkers in Lung Injury (COLOBILI)

Profile known and novel biomarkers in blood in COVID19 patients to characterize the host response to SARS-CoV-2 over time and in response to treatment.

The investigators aim to:

• Better understand the disease. The investigators will achieve this by characterizing the biology of COVID-19 infection and the pathophysiology of the host response using clinical data together with cellular and molecular measurements over the course of the disease. This will allow better insights for the discovery and development of novel therapeutics.
• Understand why different patients have different phenotypes and disease presentations over time. The investigators will achieve this by analyzing for patient subgroups. This will allow targeted patient stratification and better matching of resources.
• Understand how patients are responding to the different medications being tested in clinical trials. The investigators will achieve that by co-enrolling with therapeutic trials. This will allow an understanding of the biological effects of these interventions.

Study Design: Observational adaptive study of a translational nature, combining clinical data and basic science investigations in blood samples in the same patients, longitudinally, with serial interim analyses.

Primary outcomes: 90 day ICU mortality. Secondary outcomes: measures of ICU utilization and disease severity, and 90 day in-hospital mortality.

The study ends after 3 months from admission to the ICU, hospital discharge or death.

Location: St. Michael's Hospital (Unity Health Toronto), an academic center in downtown Toronto affiliated with the University of Toronto.

The investigators will collect: A) Detailed clinical data including investigations, mechanical ventilation and cardiovascular parameters. B) Blood samples for state-of-the-art multi-omics biomarker discovery and development: cytokines, anti-COVID19 antibodies, autoimmune serology, metabolomics, transcriptomics, epigenomics, deep immune phenotyping, viral loads. For those patients who die with COVID19 The investigators will perform bedside post-mortem biopsies of lung, heart, kidney and muscle.

Sampling times: From admission to the maximal severity phase through convalescence, in order to capture the evolution and dynamics of the disease and the recovery process: days 0,1, 3, 5, 7, 10, 15 and 22, and then every 2 weeks until the end of the study (3 months from admission to the ICU, hospital discharge or death).

Study Overview

• Status: Recruiting
• Conditions: Critical Illness; Covid19; Respiratory Disease
• Intervention / Treatment: Other: no interventions performed. Just collecting data, blood samples and post-mortem biopsies.

• Study Type: Observational
• Enrollment (Anticipated): 200

Contacts and Locations

• Study Contact: Name: Marlene Santos; Phone Number: 2322 416-360-4000; Email: Marlene.Santos@unityhealth.to
• Study Contact Backup: Name: Victoria Paz; Phone Number: 416-864-5559; Email: Victoria.Paz@unityhealth.to

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5B 1W8
      • Recruiting
      • St Michael's Hospital
      • Contact: Marlene Santos; Phone Number: 2322 416-360-4000; Email: Marlene.Santos@unityhealth.to
      • Contact: Victoria Paz; Phone Number: 416-864-5559; Email: Victoria.Paz@unityhealth.to
      • Principal Investigator: Andrew Baker, MD

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Patients admitted to the critical care unit or general medicine ward in a tertiary referral medical center.

Description

• Primary Cohort: Patients admitted to the ICU with respiratory deterioration suspected or confirmed to be due to SARS-CoV-2. Suspicion will be based on the clinical criteria in place at SMH, with the threshold for inclusion being a suspicion high enough to use PPE until confirmatory testing results are obtained. Only patients found to be COVID19 positive will stay in this cohort. This population will be called "ICU Positive".
• Secondary Cohort: Patients admitted to the ICU for any reason who are COVID19 positive, regardless of admission date or when they are found to be COVID19 positive. This population will be called "ICU Positive - delayed"
• Biological controls in the ICU: Any patients from the primary cohort who are found to be COVID19 negative. This population will be called "ICU negative".
• Biological controls outside the ICU: Patients admitted to the floor with respiratory deterioration suspected or confirmed to be due to SARS-CoV-2, or that develop such respiratory deterioration within 15 days of admission (i.e. become "persons under investigation"). Suspicion will be based on the clinical criteria in place at SMH, with the threshold for inclusion being a suspicion high enough to use PPE until confirmatory testing results are obtained. Only patients found to be COVID19 positive will stay in this cohort. If these patients require ICU admission within 15 days, they will cross-over to the "ICU positive" cohort and count towards that cohort (i.e. number of recruited patients). If they don't require ICU admission within 15 days, they will stay in this cohort and be called "never ICU".
• Healthy volunteers: The investigators will recruit healthy volunteers among healthcare workers and allied personnel in the hospital. They will provide peripheral blood to serve as: a) independent controls for experimental and laboratory variables, and b) references of healthy baseline state for experiments.
• A patient previously enrolled as a COVID negative can be re-enrolled in a subsequent hospitalization with a new study ID (i.e. counts as another encounter for the total enrollment). The records will be linked to indicate they represent the same person enrolled again.

Exclusion Criteria

• Refusal to participate.
• Inability to record the primary outcome during the first 2 weeks.
• For the ICU positive and ICU negative cohorts only: failure to obtain the day 0 or 1 blood sample (for example technical problems, or identification of COVID-19 after ICU admission i.e. there was no suspicion on admission).
• For the ward patients, inability to collect day 1 or 2 blood sample.
• Known to have had COVID in the past (>4 weeks) in any setting.
• Healthy volunteers only: COVID19 known or suspected infection, or unprotected exposure to a known acutely ill COVID19 patient in the past 4 weeks; and/or currently unwell or in the course of an acute illness.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
COVID positive; Patients admitted to the ICU with respiratory distress found to be COVID19 positive.	Other: no interventions performed. Just collecting data, blood samples and post-mortem biopsies.; no interventions performed. Just collecting data, blood samples and post-mortem biopsies.
COVID negative; Patients admitted to the ICU with respiratory distress found to be COVID19 negative	Other: no interventions performed. Just collecting data, blood samples and post-mortem biopsies.; no interventions performed. Just collecting data, blood samples and post-mortem biopsies.
COVID positive delayed; Patients admitted to the ICU for an indication other than respiratory distress, found to be COVID19 positive.	Other: no interventions performed. Just collecting data, blood samples and post-mortem biopsies.; no interventions performed. Just collecting data, blood samples and post-mortem biopsies.
never-ICU; Patients admitted to the internal medicine ward with respiratory distress found to be COVID19 positive.	Other: no interventions performed. Just collecting data, blood samples and post-mortem biopsies.; no interventions performed. Just collecting data, blood samples and post-mortem biopsies.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Death in ICU	Death in ICU	within 3 months from admission

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Days in ICU	Length of hospitalization	within 3 months from admission to the ICU
Mechanical ventilation days	Length of mechanical ventilation while in the ICU	within 3 months from admission to the ICU
Days of mechanical ventilation rescue measures	Number of days on which the patient was treated with one or more of the following rescue meaures: neuromuscular blockade, inhaled NO, proning.	within 3 months from admission to the ICU
APACHE II score on admission	Acute Physiology And Chronic Health Evaluation II. Min 0, Max 71. Higher scores impart higher mortality risk.	On admission to the ICU
SOFA score	Sequential Organ Failure Assessment, calculated daily. Min 6, Max 24. Higher scores impart higher mortality risk.	On the same days as blood sampling: days 0,1, 3, 5, 7, 10, 15 and 22, and then every 2 weeks until the end of the study (3 months from admission to the ICU, hospital discharge or death).
In hospital death	In hospital death	within 3 months from admission

Collaborators and Investigators

• Sponsor: Dr. Andrew Baker
• Investigators: Principal Investigator: Andrew J Baker, MD, Unity Health Toronto

Publications and helpful links

General Publications

• Trahtemberg U, Fritzler MJ; On behalf of the COVID-19 chapter of the "Longitudinal Biomarkers in Lung Injury" study group. COVID-19-associated autoimmunity as a feature of acute respiratory failure. Intensive Care Med. 2021 Jul;47(7):801-804. doi: 10.1007/s00134-021-06408-z. Epub 2021 Apr 30. No abstract available.
• Trahtemberg U, Rottapel R, Dos Santos CC, Slutsky AS, Baker A, Fritzler MJ. Anticardiolipin and other antiphospholipid antibodies in critically ill COVID-19 positive and negative patients. Ann Rheum Dis. 2021 Sep;80(9):1236-1240. doi: 10.1136/annrheumdis-2021-220206. Epub 2021 Apr 26.

Study record dates

Study Major Dates

• Study Start (Actual): March 23, 2020
• Primary Completion (Anticipated): October 1, 2021
• Study Completion (Anticipated): December 31, 2021

Study Registration Dates

• First Submitted: February 3, 2021
• First Submitted That Met QC Criteria: February 9, 2021
• First Posted (Actual): February 10, 2021

Study Record Updates

• Last Update Posted (Actual): February 10, 2021
• Last Update Submitted That Met QC Criteria: February 9, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Pneumonia, Viral; Pneumonia; Lung Diseases; Wounds and Injuries; Disease Attributes; Thoracic Injuries; COVID-19; Critical Illness; Lung Injury; Respiration Disorders; Respiratory Tract Diseases
• Other Study ID Numbers: COLOBILI v4.2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: Depends on the type of data requested

Drug and device information, study documents

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