COVIDIMM: Immune Changes in Severe COVID-19 Pulmonary Infections

Sponsor
Central Hospital, Nancy, France (Other)
Overall Status
Completed
CT.gov ID
NCT04386395
Collaborator
(none)
50
1
15
3.3

Study Details

Study Description

Brief Summary

SARS-CoV-2 outbreak causes a spectrum of clinical patterns that varies from asymptomatic infection to mildly symptomatic manifestations and more-severe forms that need intensive care. Until now, the immune response to SARS-CoV-2 virus infection has been poorly reported to help decision for immune modulation therapies. As a consequence, trials have been designed to test both anti-inflammatory molecules as steroids or anti-bodies against IL-6, and others proposing to "boost" immunity with interferon beta based on similar inclusion criteria.

The immune response to infective agents including viruses may have a complex time evolution with early and late phases corresponding to different patterns, oscillating between pro-inflammation and immune-depression. The potential window to improve outcome in COVID-19 by therapeutic intervention aimed at a fine tuning between immune toxicity and immunodepression requires a longitudinal assessment during the course of illness, especially for the patients who develop acute respiratory failure. Immune monitoring of both innate and adaptive immunity would then be essential to appropriately design clinical trials.

The whole blood cells evaluation was recorded according to the time intervals between the onset of symptoms and the sampling after ICU admission. Patients' care was standardized, especially with regard to ventilation, sedation, and antimicrobial treatment.

In this study the investigators prospectively perform a longitudinal study of both innate and adaptive immunity on patients admitted to ICU for an COVID-19 related acute respiratory failure. The data will be analyzed in reference to the onset of initial symptoms and also to the admission in ICU.

The primary end point is the evolution of the characterization of monocytes and their subsets in term of number and expression of HLA-DR. A similar approach is used for lymphocytes and their subtypes with in addition, an ex vivo testing of their capabilities to be stimulated by SARS-CoV-2 viral proteins in term of TNFalpha, INFgamma, and IL1beta production.

The secondary end-point was to test the association with outcomes and other non-specific markers of inflammation as CRP (C reactive protein), PCT (procalcitonin), DDimers and ferritin.

Condition or Disease Intervention/Treatment Phase

    Detailed Description

    The most severe form of COVID-19 treated in intensive care for acute respiratory failure may have a poor prognosis. Both the level of IL-6 and the severity of the lymphopenia have been associated to the poor prognosis. Better knowledge of the time evolution of the circulating immune cells subpopulations and functions will help to best tailor the treatment: anti-inflammatory strategy at the initial phase might be rapidly shifted to immune stimulation when immunodepression is diagnosed.

    It is then essential to assess the patients' immune status using flowcytometry methods to characterize both innate and adaptive immunity of the whole blood circulating immune peripheral blood mononuclear cells (PBMC). After cell staining with the adequate cell markers, the flowcytometry (NAVIOS® Flow Cytometer (Beckman Coulter) allowed to analyze the number and the function of the cells with an adequate gating strategy and the Kaluza® software v2.1 (Beckman Coulter). The data were then grouped by time intervals referring to the onset of symptoms and also to the ICU admission. The trend for innate immunity (monocytes number and subpopulations, HLA-DR expression) and for adaptive immunity (lymphocytes and subpopulations) will be analyzed. Since it is unknown if whole blood CD3/CD4 and CD3/CD8 lymphocytes elicit an "exhaustion" pattern and/or an abnormal response, an ex vivo testing of their reactivity for SARS-CoV-2 viral proteins will be performed. This test of polyfunctionality will characterize the intracellular cytokine expression (IL-1 beta, TNFalpha, and INFgamma) both for CD4 and CD8 T cells.

    Study Design

    Study Type:
    Observational
    Actual Enrollment :
    50 participants
    Observational Model:
    Cohort
    Time Perspective:
    Prospective
    Official Title:
    Whole Blood Immune Cells Characterization in Critically Ill COVID-19 Patients: A Prospective Study
    Actual Study Start Date :
    Mar 30, 2020
    Actual Primary Completion Date :
    May 30, 2020
    Actual Study Completion Date :
    Jun 30, 2021

    Arms and Interventions

    Arm Intervention/Treatment
    Immuno Cohort

    COVID-19 confirmed ICU patients, sedated and ventilated, sequential characterization of circulating immune cells over their ICU stay. Every 2 to 3 days, fresh whole blood aliquots from routine blood counts were processed on a Flow Cytometer (Beckman Coulter) to determine immune cells subpopulations

    Cortico Cohort

    COVID-19 confirmed ICU patients, sedated and ventilated, sequential characterization of circulating immune cells over their ICU stay. According to RECOVERY study, early routine administration of dexamethasone 6 mg/day over 10 days. Every 2 to 3 days, fresh whole blood aliquots from routine blood counts were processed on a Flow Cytometer (Beckman Coulter) to determine immune cells subpopulations

    Outcome Measures

    Primary Outcome Measures

    1. Changes in monocytes HLA-DR expression [through ICU stay, an average of 30 days]

      circulating immune cell characterization

    2. Changes in lymphocytes subpopulations numbers [through ICU stay, an average of 30 days]

      circulating immune cell characterization

    3. Changes in monocytes number [through ICU stay, an average of 30 days]

      circulating immune cell characterization

    Secondary Outcome Measures

    1. TNFalpha level [4 hours]

      stimulation by SARS-CoV-2 viral proteins

    2. INFgamma level [4 hours]

      stimulation by SARS-CoV-2 viral proteins

    3. IL1beta level [4 hours]

      stimulation by SARS-CoV-2 viral proteins

    4. SOFA score [through ICU stay, an average of 30 days]

      Sequential Organ dysfunction assessement, ranging from 0 (better) to 24 (worst) outcome

    5. number of recorded deaths [through study completion, an average of 6 months]

      mortality

    6. presence of pneumonia [through ICU stay, an average of 30 days]

      infectious complications

    7. presence of bacteremia [through ICU stay, an average of 30 days]

      infectious complications

    8. presence of urinary tract infection [through ICU stay, an average of 30 days]

      infectious complications

    9. C reactive protein [through ICU stay, an average of 30 days]

      inflammation marker

    10. D Dimers [through ICU stay, an average of 30 days]

      inflammation marker

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No

    Inclusion Criteria: confirmed COVID-19

    • a positive RT- PCR,

    • a highly suggestive thoracic CTScan,

    • severe hypoxemia

    Exclusion Criteria:
    • none

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Centre Hospitalier Universitaire NANCY Vandoeuvre-les-Nancy France 54511

    Sponsors and Collaborators

    • Central Hospital, Nancy, France

    Investigators

    • Principal Investigator: MARIE REINE LOSSER, MD, PhD, Central Hospital, Nancy, France

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Central Hospital, Nancy, France
    ClinicalTrials.gov Identifier:
    NCT04386395
    Other Study ID Numbers:
    • CHRU NANCY : 2020PI080_1
    First Posted:
    May 13, 2020
    Last Update Posted:
    Jul 15, 2021
    Last Verified:
    Dec 1, 2020
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Jul 15, 2021