Immune Cells Phenotypes During COVID-19

NCT04816760 | Unknown

• 1 other identifier: 2020-A00756-33
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 2

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.

Conditions

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

Outcome Measures

Primary Outcomes (22)

• Profiling of innate and adaptive immune cells during SARS CoV-2 infection.

  Determination of cells population using spectral cytometry of PBMCs.

  Day 0

• Profiling of innate and adaptive immune cells during SARS CoV-2 infection.

  Determination of cells population using spectral cytometry of PBMCs.

  Day 7

• Profiling of innate and adaptive immune cells during SARS CoV-2 infection.

  Determination of cells population using spectral cytometry of PBMCs.

  Day 14

• Profiling of innate and adaptive immune cells during SARS CoV-2 infection.

  Determination of cells population using spectral cytometry of PBMCs.

  Day 28

• Profiling of innate and adaptive immune cells during SARS CoV-2 infection.

  Determination of cells population using spectral cytometry of PBMCs.

  Day 90

• Profiling of innate and adaptive immune cells during SARS CoV-2 infection.

  Determination of cells population using spectral cytometry of PBMCs.

  Day 180

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• Platelet activation and circulating microparticles assessment during SARS CoV-2 infection.

  Determination of platelet activation and circulating microparticles levels using flow cytometry.

  Day 0

• Platelet activation and circulating microparticles assessment during SARS CoV-2 infection.

  Determination of platelet activation and circulating microparticles levels using flow cytometry.

  Day 7

• Platelet activation and circulating microparticles assessment during SARS CoV-2 infection.

  Determination of platelet activation and circulating microparticles levels using flow cytometry.

  Day 14

• 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 Outcomes (22)

• Serum concentration of Pro-inflammatory and Anti-inflammatory cytokines in response to SARS CoV-2 infection.

  Day 0

• Serum concentration of Pro-inflammatory and Anti-inflammatory cytokines in response to SARS CoV-2 infection.

  Day 7

• Serum concentration of Pro-inflammatory and Anti-inflammatory cytokines in response to SARS CoV-2 infection.

  Day 14

• Serum concentration of Pro-inflammatory and Anti-inflammatory cytokines in response to SARS CoV-2 infection.

  Day 28

• Serum concentration of Pro-inflammatory and Anti-inflammatory cytokines in response to SARS CoV-2 infection.

  Day 90

Interventions

Peripheral blood samples BIOLOGICAL

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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

You may qualify if:

• Age \> 18 y
• Laboratory confirmed SARS CoV-2 infection (positive RT-PCR).
• Ground-glass opacity on chest computed-tomography

You may not qualify if:

• Pregnant
• Under legal restriction

Sponsors & Collaborators

• Institut Hospitalo-Universitaire Méditerranée Infection: lead
• Hôpital Européen Marseille: collaborator
• Assistance Publique Hopitaux De Marseille: collaborator
• Institut Paoli-Calmettes: collaborator
• Beckman Coulter, Inc.: collaborator

Study Sites (2)

Hopital Europeen Marseille

Marseille, 13003, France

RECRUITING

Hopital Nord

Marseille, 13015, France

RECRUITING

Related Publications (8)

• 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. No abstract available.

  PMID: 32091533 BACKGROUND

• 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):eabd7114. doi: 10.1126/sciimmunol.abd7114.

  PMID: 32669287 BACKGROUND

• 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.

  PMID: 32320677 BACKGROUND

• 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.

  PMID: 32161940 BACKGROUND

• 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. No abstract available.

  PMID: 32203188 BACKGROUND

• 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.

  PMID: 32866033 BACKGROUND

• 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.

  PMID: 32437596 BACKGROUND

• Gay L, Rouviere MS, Mezouar S, Richaud M, Gorvel L, Foucher E, La Scola B, Menard A, Allardet-Servent J, Halfon P, Frohna P, Cano C, Mege JL, Olive D. Vgamma9Vdelta2 T-cells Are Potent Inhibitors of SARS-CoV-2 Replication and Represent Effector Phenotypes in Patients With COVID-19. J Infect Dis. 2024 Jun 14;229(6):1759-1769. doi: 10.1093/infdis/jiae169.

  PMID: 38557809 DERIVED

Related Links

• WHO Coronavirus Disease (COVID-19) Dashboard

MeSH Terms

Conditions

Infections

Study Officials

• Jean-Louis MEGE, MD, PhD

  Institut Hospitalo-Universitaire Méditérranée Infection

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Line MEDDEB

CONTACT

0413732347; line.meddeb@ap-hm.fr

Joana VITTE, MD, PhD

CONTACT

joana.vitte@ap-hm.fr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 12, 2021
• First Posted: March 25, 2021
• Study Start: March 25, 2020
• Primary Completion: June 1, 2021
• Study Completion: December 1, 2021
• Last Updated: March 25, 2021

Record last verified: 2021-03

Locations

FR (2)