Sars-CoV2, Innate Immunity, Immunization; Infection, Alveolar Lung Disease, Endothelial Dysfunction
Conditions
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.
Interventions
Peripheral blood samples at Day 0, Day 7, Day 14, Day 28, Day 90 and Day 180.
Sponsors
Study design
Eligibility
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Profiling of innate and adaptive immune cells during SARS CoV-2 infection. | Day 0 | Determination of cells population using spectral cytometry of PBMCs. |
| Functional state of innate and adaptive immune cells during SARS CoV-2 infection. | Day 0 | Determination of the functional state of immune cells using spectral cytometry |
| Serum IgA, IgM and IgG antibodies during SARS CoV-2 infection. | Day 0 | Measurement of serum SARS CoV-2 IgA, IgM and IgG antibodies using Elisa. |
| Platelet activation and circulating microparticles assessment during SARS CoV-2 infection. | Day 0 | Determination of platelet activation and circulating microparticles levels using flow cytometry. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum alveolar epithelial and endothelial cells biomarkers during SARS CoV-2 infection. | Day 0 | Measurement of KL-6, CC-16, S-RAGE, ANG-2 using ELISA. |
| Kinetic of surface biomarkers expression on neutrophils (C64) and monocytes (CD169, HLA-DR) during SARS CoV-2 infection. | Day 0 | Measurement of nCD64, mCD169 and mHLA-DR using the VersaPOC one-step rapid flow cytometry method. |
| Serum concentration of Pro-inflammatory and Anti-inflammatory cytokines in response to SARS CoV-2 infection. | Day 0 | Measurement of IL1β, IL-6, IL-10, IL-17A, IL-18, TNFα, IFNγ, CRTP-6 using Elisa. |
Countries
France