Immune Cells Phenotypes During COVID-19

Endothelial Dysfunction Clinical Trial

— IMMUNO-COVID  

Official title:

Alterations of Innate and Adaptive Immune Cells During the Course of SARS CoV-2 Pneumonia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04816760
• Other study ID #: 2020-A00756-33
• Status: Recruiting
• Start date: March 25, 2020
• Est. completion date: December 2021

Study information

• Verified date: March 2021
• Source: Institut Hospitalo-Universitaire Méditerranée Infection
• Contact: Line MEDDEB
• Phone: 0413732347
• Email: line.meddeb[@]ap-hm.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 2021
• Est. primary completion date: June 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

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

Related Conditions & MeSH terms

• Alveolar Lung Disease
• Endothelial Dysfunction
• Immunization; Infection
• Innate Immunity
• Lung Diseases
• Sars-CoV2

Intervention

Biological:
• Peripheral blood samples
Peripheral blood samples at Day 0, Day 7, Day 14, Day 28, Day 90 and Day 180.

Locations

Country	Name	City	State
France	Hopital Europeen Marseille	Marseille
France	Hopital Nord	Marseille

Sponsors (5)

Lead Sponsor	Collaborator
Institut Hospitalo-Universitaire Méditerranée Infection	Assistance Publique Hopitaux De Marseille, Beckman Coulter, Inc., Hôpital Européen Marseille, Institut Paoli-Calmettes

Country where clinical trial is conducted

France, 

References & Publications (7)

Ackermann M, Verleden SE, Kuehnel M, Haverich A, Welte T, Laenger F, Vanstapel A, Werlein C, Stark H, Tzankov A, Li WW, Li VW, Mentzer SJ, Jonigk D. Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19. N Engl J Med. 2020 Jul 9;383(2):120-128. doi: 10.1056/NEJMoa2015432. Epub 2020 May 21. — View Citation

Giamarellos-Bourboulis EJ, Netea MG, Rovina N, Akinosoglou K, Antoniadou A, Antonakos N, Damoraki G, Gkavogianni T, Adami ME, Katsaounou P, Ntaganou M, Kyriakopoulou M, Dimopoulos G, Koutsodimitropoulos I, Velissaris D, Koufargyris P, Karageorgos A, Katrini K, Lekakis V, Lupse M, Kotsaki A, Renieris G, Theodoulou D, Panou V, Koukaki E, Koulouris N, Gogos C, Koutsoukou A. Complex Immune Dysregulation in COVID-19 Patients with Severe Respiratory Failure. Cell Host Microbe. 2020 Jun 10;27(6):992-1000.e3. doi: 10.1016/j.chom.2020.04.009. Epub 2020 Apr 21. — View Citation

Hue S, Beldi-Ferchiou A, Bendib I, Surenaud M, Fourati S, Frapard T, Rivoal S, Razazi K, Carteaux G, Delfau-Larue MH, Mekontso-Dessap A, Audureau E, de Prost N. Uncontrolled Innate and Impaired Adaptive Immune Responses in Patients with COVID-19 Acute Respiratory Distress Syndrome. Am J Respir Crit Care Med. 2020 Dec 1;202(11):1509-1519. doi: 10.1164/rccm.202005-1885OC. — View Citation

Kuri-Cervantes L, Pampena MB, Meng W, Rosenfeld AM, Ittner CAG, Weisman AR, Agyekum RS, Mathew D, Baxter AE, Vella LA, Kuthuru O, Apostolidis SA, Bershaw L, Dougherty J, Greenplate AR, Pattekar A, Kim J, Han N, Gouma S, Weirick ME, Arevalo CP, Bolton MJ, Goodwin EC, Anderson EM, Hensley SE, Jones TK, Mangalmurti NS, Luning Prak ET, Wherry EJ, Meyer NJ, Betts MR. Comprehensive mapping of immune perturbations associated with severe COVID-19. Sci Immunol. 2020 Jul 15;5(49). pii: eabd7114. doi: 10.1126/sciimmunol.abd7114. — View Citation

Qin C, Zhou L, Hu Z, Zhang S, Yang S, Tao Y, Xie C, Ma K, Shang K, Wang W, Tian DS. Dysregulation of Immune Response in Patients With Coronavirus 2019 (COVID-19) in Wuhan, China. Clin Infect Dis. 2020 Jul 28;71(15):762-768. doi: 10.1093/cid/ciaa248. — View Citation

Wu Z, McGoogan JM. Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention. JAMA. 2020 Apr 7;323(13):1239-1242. doi: 10.1001/jama.2020.2648. — View Citation

Zheng M, Gao Y, Wang G, Song G, Liu S, Sun D, Xu Y, Tian Z. Functional exhaustion of antiviral lymphocytes in COVID-19 patients. Cell Mol Immunol. 2020 May;17(5):533-535. doi: 10.1038/s41423-020-0402-2. Epub 2020 Mar 19. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Profiling of innate and adaptive immune cells during SARS CoV-2 infection.	Determination of cells population using spectral cytometry of PBMCs.	Day 0
Primary	Profiling of innate and adaptive immune cells during SARS CoV-2 infection.	Determination of cells population using spectral cytometry of PBMCs.	Day 7
Primary	Profiling of innate and adaptive immune cells during SARS CoV-2 infection.	Determination of cells population using spectral cytometry of PBMCs.	Day 14
Primary	Profiling of innate and adaptive immune cells during SARS CoV-2 infection.	Determination of cells population using spectral cytometry of PBMCs.	Day 28
Primary	Profiling of innate and adaptive immune cells during SARS CoV-2 infection.	Determination of cells population using spectral cytometry of PBMCs.	Day 90
Primary	Profiling of innate and adaptive immune cells during SARS CoV-2 infection.	Determination of cells population using spectral cytometry of PBMCs.	Day 180
Primary	Functional state of innate and adaptive immune cells during SARS CoV-2 infection.	Determination of the functional state of immune cells using spectral cytometry	Day 0
Primary	Functional state of innate and adaptive immune cells during SARS CoV-2 infection.	Determination of the functional state of immune cells using spectral cytometry	Day 7
Primary	Functional state of innate and adaptive immune cells during SARS CoV-2 infection.	Determination of the functional state of immune cells using spectral cytometry	Day 14
Primary	Functional state of innate and adaptive immune cells during SARS CoV-2 infection.	Determination of the functional state of immune cells using spectral cytometry	Day 28
Primary	Functional state of innate and adaptive immune cells during SARS CoV-2 infection.	Determination of the functional state of immune cells using spectral cytometry	Day 90
Primary	Functional state of innate and adaptive immune cells during SARS CoV-2 infection.	Determination of the functional state of immune cells using spectral cytometry	Day 180
Primary	Serum IgA, IgM and IgG antibodies during SARS CoV-2 infection.	Measurement of serum SARS CoV-2 IgA, IgM and IgG antibodies using Elisa.	Day 0
Primary	Serum IgA, IgM and IgG antibodies during SARS CoV-2 infection.	Measurement of serum SARS CoV-2 IgA, IgM and IgG antibodies using Elisa.	Day 7
Primary	Serum IgA, IgM and IgG antibodies during SARS CoV-2 infection.	Measurement of serum SARS CoV-2 IgA, IgM and IgG antibodies using Elisa.	Day 14
Primary	Serum IgA, IgM and IgG antibodies during SARS CoV-2 infection.	Measurement of serum SARS CoV-2 IgA, IgM and IgG antibodies using Elisa.	Day 28
Primary	Serum IgA, IgM and IgG antibodies during SARS CoV-2 infection.	Measurement of serum SARS CoV-2 IgA, IgM and IgG antibodies using Elisa.	Day 90
Primary	Serum IgA, IgM and IgG antibodies during SARS CoV-2 infection.	Measurement of serum SARS CoV-2 IgA, IgM and IgG antibodies using Elisa.	Day 180
Primary	Platelet activation and circulating microparticles assessment during SARS CoV-2 infection.	Determination of platelet activation and circulating microparticles levels using flow cytometry.	Day 0
Primary	Platelet activation and circulating microparticles assessment during SARS CoV-2 infection.	Determination of platelet activation and circulating microparticles levels using flow cytometry.	Day 7
Primary	Platelet activation and circulating microparticles assessment during SARS CoV-2 infection.	Determination of platelet activation and circulating microparticles levels using flow cytometry.	Day 14
Primary	Platelet activation and circulating microparticles assessment during SARS CoV-2 infection.	Determination of platelet activation and circulating microparticles levels using flow cytometry.	Day 28
Secondary	Serum concentration of Pro-inflammatory and Anti-inflammatory cytokines in response to SARS CoV-2 infection.	Measurement of IL1ß, IL-6, IL-10, IL-17A, IL-18, TNFa, IFN?, CRTP-6 using Elisa.	Day 0
Secondary	Serum concentration of Pro-inflammatory and Anti-inflammatory cytokines in response to SARS CoV-2 infection.	Measurement of IL1ß, IL-6, IL-10, IL-17A, IL-18, TNFa, IFN?, CRTP-6 using Elisa.	Day 7
Secondary	Serum concentration of Pro-inflammatory and Anti-inflammatory cytokines in response to SARS CoV-2 infection.	Measurement of IL1ß, IL-6, IL-10, IL-17A, IL-18, TNFa, IFN?, CRTP-6 using Elisa.	Day 14
Secondary	Serum concentration of Pro-inflammatory and Anti-inflammatory cytokines in response to SARS CoV-2 infection.	Measurement of IL1ß, IL-6, IL-10, IL-17A, IL-18, TNFa, IFN?, CRTP-6 using Elisa.	Day 28
Secondary	Serum concentration of Pro-inflammatory and Anti-inflammatory cytokines in response to SARS CoV-2 infection.	Measurement of IL1ß, IL-6, IL-10, IL-17A, IL-18, TNFa, IFN?, CRTP-6 using Elisa.	Day 90
Secondary	Serum concentration of Pro-inflammatory and Anti-inflammatory cytokines in response to SARS CoV-2 infection.	Measurement of IL1ß, IL-6, IL-10, IL-17A, IL-18, TNFa, IFN?, CRTP-6 using Elisa.	Day 180
Secondary	Serum alveolar epithelial and endothelial cells biomarkers during SARS CoV-2 infection.	Measurement of KL-6, CC-16, S-RAGE, ANG-2 using ELISA.	Day 0
Secondary	Serum alveolar epithelial and endothelial cells biomarkers during SARS CoV-2 infection.	Measurement of KL-6, CC-16, S-RAGE, ANG-2 using ELISA.	Day 7
Secondary	Serum alveolar epithelial and endothelial cells biomarkers during SARS CoV-2 infection.	Measurement of KL-6, CC-16, S-RAGE, ANG-2 using ELISA.	Day 14
Secondary	Serum alveolar epithelial and endothelial cells biomarkers during SARS CoV-2 infection.	Measurement of KL-6, CC-16, S-RAGE, ANG-2 using ELISA.	Day 28
Secondary	Kinetic of surface biomarkers expression on neutrophils (C64) and monocytes (CD169, HLA-DR) during SARS CoV-2 infection.	Measurement of nCD64, mCD169 and mHLA-DR using the VersaPOC one-step rapid flow cytometry method.	Day 0
Secondary	Kinetic of surface biomarkers expression on neutrophils (C64) and monocytes (CD169, HLA-DR) during SARS CoV-2 infection.	Measurement of nCD64, mCD169 and mHLA-DR using the VersaPOC one-step rapid flow cytometry method.	Day 1
Secondary	Kinetic of surface biomarkers expression on neutrophils (C64) and monocytes (CD169, HLA-DR) during SARS CoV-2 infection.	Measurement of nCD64, mCD169 and mHLA-DR using the VersaPOC one-step rapid flow cytometry method.	Day 2
Secondary	Kinetic of surface biomarkers expression on neutrophils (C64) and monocytes (CD169, HLA-DR) during SARS CoV-2 infection.	Measurement of nCD64, mCD169 and mHLA-DR using the VersaPOC one-step rapid flow cytometry method.	Day 3
Secondary	Kinetic of surface biomarkers expression on neutrophils (C64) and monocytes (CD169, HLA-DR) during SARS CoV-2 infection.	Measurement of nCD64, mCD169 and mHLA-DR using the VersaPOC one-step rapid flow cytometry method.	Day 5
Secondary	Kinetic of surface biomarkers expression on neutrophils (C64) and monocytes (CD169, HLA-DR) during SARS CoV-2 infection.	Measurement of nCD64, mCD169 and mHLA-DR using the VersaPOC one-step rapid flow cytometry method.	Day 7
Secondary	Kinetic of surface biomarkers expression on neutrophils (C64) and monocytes (CD169, HLA-DR) during SARS CoV-2 infection.	Measurement of nCD64, mCD169 and mHLA-DR using the VersaPOC one-step rapid flow cytometry method.	Day 9
Secondary	Kinetic of surface biomarkers expression on neutrophils (C64) and monocytes (CD169, HLA-DR) during SARS CoV-2 infection.	Measurement of nCD64, mCD169 and mHLA-DR using the VersaPOC one-step rapid flow cytometry method.	Day 11
Secondary	Kinetic of surface biomarkers expression on neutrophils (C64) and monocytes (CD169, HLA-DR) during SARS CoV-2 infection.	Measurement of nCD64, mCD169 and mHLA-DR using the VersaPOC one-step rapid flow cytometry method.	Day 14
Secondary	Kinetic of surface biomarkers expression on neutrophils (C64) and monocytes (CD169, HLA-DR) during SARS CoV-2 infection.	Measurement of nCD64, mCD169 and mHLA-DR using the VersaPOC one-step rapid flow cytometry method.	Day 17
Secondary	Kinetic of surface biomarkers expression on neutrophils (C64) and monocytes (CD169, HLA-DR) during SARS CoV-2 infection.	Measurement of nCD64, mCD169 and mHLA-DR using the VersaPOC one-step rapid flow cytometry method.	Day 21
Secondary	Kinetic of surface biomarkers expression on neutrophils (C64) and monocytes (CD169, HLA-DR) during SARS CoV-2 infection.	Measurement of nCD64, mCD169 and mHLA-DR using the VersaPOC one-step rapid flow cytometry method.	Day 28

External Links

•   WHO Coronavirus Disease (COVID-19) Dashboard