Immune Changes in Severe COVID-19 Pulmonary Infections

NCT04386395 | Completed

• 1 other identifier: CHRU NANCY : 2020PI080_1
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

SARS-CoV-2; Immune System Disorder

Outcome Measures

Primary Outcomes (3)

• Changes in monocytes HLA-DR expression

  circulating immune cell characterization

  through ICU stay, an average of 30 days

• Changes in lymphocytes subpopulations numbers

  circulating immune cell characterization

  through ICU stay, an average of 30 days

• Changes in monocytes number

  circulating immune cell characterization

  through ICU stay, an average of 30 days

Secondary Outcomes (10)

• TNFalpha level

  4 hours

• INFgamma level

  4 hours

• IL1beta level

  4 hours

• SOFA score

  through ICU stay, an average of 30 days

• number of recorded deaths

  through study completion, an average of 6 months

Study Arms (2)

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

COVID-19 ICU patients, sedated and mechanically ventilated within the 48 hrs of admission for the first sampling, and monitored all over their ICU stay

You may qualify if:

• a positive RT- PCR,
• a highly suggestive thoracic CTScan,
• severe hypoxemia

You may not qualify if:

• none

Sponsors & Collaborators

• Central Hospital, Nancy, France: lead

Study Sites (1)

Centre Hospitalier Universitaire NANCY

Vandœuvre-lès-Nancy, 54511, France

Location

Related Publications (6)

• Tan L, Wang Q, Zhang D, Ding J, Huang Q, Tang YQ, Wang Q, Miao H. Lymphopenia predicts disease severity of COVID-19: a descriptive and predictive study. Signal Transduct Target Ther. 2020 Mar 27;5(1):33. doi: 10.1038/s41392-020-0148-4. No abstract available.

  PMID: 32296069 BACKGROUND

• Payen D, Faivre V, Miatello J, Leentjens J, Brumpt C, Tissieres P, Dupuis C, Pickkers P, Lukaszewicz AC. Multicentric experience with interferon gamma therapy in sepsis induced immunosuppression. A case series. BMC Infect Dis. 2019 Nov 5;19(1):931. doi: 10.1186/s12879-019-4526-x.

  PMID: 31690258 BACKGROUND

• Ziegler-Heitbrock L, Ancuta P, Crowe S, Dalod M, Grau V, Hart DN, Leenen PJ, Liu YJ, MacPherson G, Randolph GJ, Scherberich J, Schmitz J, Shortman K, Sozzani S, Strobl H, Zembala M, Austyn JM, Lutz MB. Nomenclature of monocytes and dendritic cells in blood. Blood. 2010 Oct 21;116(16):e74-80. doi: 10.1182/blood-2010-02-258558. Epub 2010 Jul 13.

  PMID: 20628149 BACKGROUND

• Hotchkiss RS, Monneret G, Payen D. Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy. Nat Rev Immunol. 2013 Dec;13(12):862-74. doi: 10.1038/nri3552. Epub 2013 Nov 15.

  PMID: 24232462 BACKGROUND

• Alattar R, Ibrahim TBH, Shaar SH, Abdalla S, Shukri K, Daghfal JN, Khatib MY, Aboukamar M, Abukhattab M, Alsoub HA, Almaslamani MA, Omrani AS. Tocilizumab for the treatment of severe coronavirus disease 2019. J Med Virol. 2020 Oct;92(10):2042-2049. doi: 10.1002/jmv.25964. Epub 2020 May 10.

  PMID: 32369191 BACKGROUND

• Payen D, Cravat M, Maadadi H, Didelot C, Prosic L, Dupuis C, Losser MR, De Carvalho Bittencourt M. A Longitudinal Study of Immune Cells in Severe COVID-19 Patients. Front Immunol. 2020 Oct 23;11:580250. doi: 10.3389/fimmu.2020.580250. eCollection 2020.

  PMID: 33178207 BACKGROUND

MeSH Terms

Conditions

Immune System Diseases

Study Officials

• MARIE REINE LOSSER, MD, PhD

  Central Hospital, Nancy, France

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: May 6, 2020
• First Posted: May 13, 2020
• Study Start: March 30, 2020
• Primary Completion: May 30, 2020
• Study Completion: June 30, 2021
• Last Updated: July 15, 2021

Record last verified: 2020-12

Locations

FR (1)