Clinical trial NCT04816760: Immune Cells Phenotypes During COVID-19
Official title: Alterations of Innate and Adaptive Immune Cells During the Course of SARS CoV-2 Pneumonia
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Sars-CoV2
Innate Immunity
Immunization; Infection
Alveolar Lung Disease
Endothelial Dysfunction
Lead sponsor: Institut Hospitalo-Universitaire Méditerranée Infection
Sponsor class: OTHER
Collaborators: name: Hôpital Européen Marseille
name: Assistance Publique Hopitaux De Marseille
name: Institut Paoli-Calmettes
name: Beckman Coulter, Inc.
First posted: 2021-03-25
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients presenting with a first episode of SARS CoV-2 pneumonia and requiring hospitalization either in a ward or an Intensive Care Unit will constitute the COVID-19 group.

Healthy blood donors from the Etablissement Français du Sang (EFS) will constituted the control group

Brief summary: The ongoing pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV-2) has infected more than one hundred twenty million peoples worldwide one year after its onset with a case-fatality rate of almost 2%. The disease due to the coronavirus 2019 (i.e., COVID-19) is associated with a wide range of clinical symptoms. As the primary site of viral invasion is the upper respiratory airways, lung infection is the most common complication. Most infected patients are asymptomatic or experience mild or moderate form of the disease (80 %). A lower proportion (15%) develop severe pneumonia with variable level of hypoxia that may required hospitalization for oxygen therapy. In the most severe cases (5%), patients evolve towards critical illness with organ failure such as the acute respiratory distress syndrome (ARDS). At this stage, invasive mechanical ventilation is required in almost 70 % and the hospital mortality rises to 37 %.

Immune cells are key players during SARS CoV-2 infection and several alterations have been reported including lymphocytes (T, B and NK) and monocytes depletion, and cells exhaustion. Such alterations were much more pronounced in patients with the most severe form of the disease. Beside, a dysregulated proinflammatory response has also been pointed out as a potential mechanism of lung damage. Finally, COVID-19 is associated with an unexpectedly high incidence of thrombosis which probably results from the viral invasion of endothelial cells.

The investigators aim to explore prospectively the alterations of innate and adaptive immune cells during both the acute and the recovery phase of SARS CoV-2 pneumonia. Flow and Spectral cytometry will be used to perform deep subset profiling focusing on T, B, NK, NKT, gamma-gelta T, monocytes and dendritic cells. Each specific cell type will be further characterized using markers of activation/inhibition, maturation/differenciation and senescence as well as chemokines receptors.

T-cell memory specificity will be explore using specific SARS CoV-2 pentamer. Platelet activation and circulating microparticles will be explore using flow cytometry. Serum SARS CoV-2 antibodies (IgA, IgM, IgG), serum cytokines, and serum biomarkers of alveolar epithelial and endothelial cells will be analyze using ELISA and correlate with the severity of the disease.


Eligibility criteria: Inclusion Criteria:

* Age \> 18 y
* Laboratory confirmed SARS CoV-2 infection (positive RT-PCR).
* Ground-glass opacity on chest computed-tomography
* Time from hospital admission to inclusion \< or equal to 72 h

Exclusion Criteria:

* Pregnant
* Under legal restriction

Primary outcomes:
measure: Profiling of innate and adaptive immune cells during SARS CoV-2 infection.
timeFrame: Day 0
measure: Profiling of innate and adaptive immune cells during SARS CoV-2 infection.
timeFrame: Day 7
measure: Profiling of innate and adaptive immune cells during SARS CoV-2 infection.
timeFrame: Day 14
measure: Profiling of innate and adaptive immune cells during SARS CoV-2 infection.
timeFrame: Day 28
measure: Profiling of innate and adaptive immune cells during SARS CoV-2 infection.
timeFrame: Day 90
measure: Profiling of innate and adaptive immune cells during SARS CoV-2 infection.
timeFrame: Day 180
measure: Functional state of innate and adaptive immune cells during SARS CoV-2 infection.
timeFrame: Day 0
measure: Functional state of innate and adaptive immune cells during SARS CoV-2 infection.
timeFrame: Day 7
measure: Functional state of innate and adaptive immune cells during SARS CoV-2 infection.
timeFrame: Day 14
measure: Functional state of innate and adaptive immune cells during SARS CoV-2 infection.
timeFrame: Day 28
measure: Functional state of innate and adaptive immune cells during SARS CoV-2 infection.
timeFrame: Day 90
measure: Functional state of innate and adaptive immune cells during SARS CoV-2 infection.
timeFrame: Day 180
measure: Serum IgA, IgM and IgG antibodies during SARS CoV-2 infection.
timeFrame: Day 0
measure: Serum IgA, IgM and IgG antibodies during SARS CoV-2 infection.
timeFrame: Day 7
measure: Serum IgA, IgM and IgG antibodies during SARS CoV-2 infection.
timeFrame: Day 14
measure: Serum IgA, IgM and IgG antibodies during SARS CoV-2 infection.
timeFrame: Day 28
measure: Serum IgA, IgM and IgG antibodies during SARS CoV-2 infection.
timeFrame: Day 90
measure: Serum IgA, IgM and IgG antibodies during SARS CoV-2 infection.
timeFrame: Day 180
measure: Platelet activation and circulating microparticles assessment during SARS CoV-2 infection.
timeFrame: Day 0
measure: Platelet activation and circulating microparticles assessment during SARS CoV-2 infection.
timeFrame: Day 7
measure: Platelet activation and circulating microparticles assessment during SARS CoV-2 infection.
timeFrame: Day 14
measure: Platelet activation and circulating microparticles assessment during SARS CoV-2 infection.
timeFrame: Day 28
Secondary outcomes:
measure: Serum concentration of Pro-inflammatory and Anti-inflammatory cytokines in response to SARS CoV-2 infection.
timeFrame: Day 0
measure: Serum concentration of Pro-inflammatory and Anti-inflammatory cytokines in response to SARS CoV-2 infection.
timeFrame: Day 7
measure: Serum concentration of Pro-inflammatory and Anti-inflammatory cytokines in response to SARS CoV-2 infection.
timeFrame: Day 14
measure: Serum concentration of Pro-inflammatory and Anti-inflammatory cytokines in response to SARS CoV-2 infection.
timeFrame: Day 28
measure: Serum concentration of Pro-inflammatory and Anti-inflammatory cytokines in response to SARS CoV-2 infection.
timeFrame: Day 90
measure: Serum concentration of Pro-inflammatory and Anti-inflammatory cytokines in response to SARS CoV-2 infection.
timeFrame: Day 180
measure: Serum alveolar epithelial and endothelial cells biomarkers during SARS CoV-2 infection.
timeFrame: Day 0
measure: Serum alveolar epithelial and endothelial cells biomarkers during SARS CoV-2 infection.
timeFrame: Day 7
measure: Serum alveolar epithelial and endothelial cells biomarkers during SARS CoV-2 infection.
timeFrame: Day 14
measure: Serum alveolar epithelial and endothelial cells biomarkers during SARS CoV-2 infection.
timeFrame: Day 28
measure: Kinetic of surface biomarkers expression on neutrophils (C64) and monocytes (CD169, HLA-DR) during SARS CoV-2 infection.
timeFrame: Day 0
measure: Kinetic of surface biomarkers expression on neutrophils (C64) and monocytes (CD169, HLA-DR) during SARS CoV-2 infection.
timeFrame: Day 1
measure: Kinetic of surface biomarkers expression on neutrophils (C64) and monocytes (CD169, HLA-DR) during SARS CoV-2 infection.
timeFrame: Day 2
measure: Kinetic of surface biomarkers expression on neutrophils (C64) and monocytes (CD169, HLA-DR) during SARS CoV-2 infection.
timeFrame: Day 3
measure: Kinetic of surface biomarkers expression on neutrophils (C64) and monocytes (CD169, HLA-DR) during SARS CoV-2 infection.
timeFrame: Day 5
measure: Kinetic of surface biomarkers expression on neutrophils (C64) and monocytes (CD169, HLA-DR) during SARS CoV-2 infection.
timeFrame: Day 7
measure: Kinetic of surface biomarkers expression on neutrophils (C64) and monocytes (CD169, HLA-DR) during SARS CoV-2 infection.
timeFrame: Day 9
measure: Kinetic of surface biomarkers expression on neutrophils (C64) and monocytes (CD169, HLA-DR) during SARS CoV-2 infection.
timeFrame: Day 11
measure: Kinetic of surface biomarkers expression on neutrophils (C64) and monocytes (CD169, HLA-DR) during SARS CoV-2 infection.
timeFrame: Day 14
measure: Kinetic of surface biomarkers expression on neutrophils (C64) and monocytes (CD169, HLA-DR) during SARS CoV-2 infection.
timeFrame: Day 17
measure: Kinetic of surface biomarkers expression on neutrophils (C64) and monocytes (CD169, HLA-DR) during SARS CoV-2 infection.
timeFrame: Day 21
measure: Kinetic of surface biomarkers expression on neutrophils (C64) and monocytes (CD169, HLA-DR) during SARS CoV-2 infection.
timeFrame: Day 28
Other outcomes:
Locations:
city: Marseille
country: France
facility: Hopital Europeen Marseille
city: Marseille
country: France
facility: Hopital Nord
Study officials:
affiliation: Institut Hospitalo-Universitaire Méditérranée Infection
name: Jean-Louis MEGE, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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