Immune Changes in Severe COVID-19 Pulmonary Infections (COVIDIMM)
Whole Blood Immune Cells Characterization in Critically Ill COVID-19 Patients: A Prospective Study
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.
Обзор исследования
Статус
Подробное описание
The most severe form of COVID-19 treated in intensive care for acute respiratory failure may have a poor prognosis. Both the level of IL-6 and the severity of the lymphopenia have been associated to the poor prognosis. Better knowledge of the time evolution of the circulating immune cells subpopulations and functions will help to best tailor the treatment: anti-inflammatory strategy at the initial phase might be rapidly shifted to immune stimulation when immunodepression is diagnosed.
It is then essential to assess the patients' immune status using flowcytometry methods to characterize both innate and adaptive immunity of the whole blood circulating immune peripheral blood mononuclear cells (PBMC). After cell staining with the adequate cell markers, the flowcytometry (NAVIOS® Flow Cytometer (Beckman Coulter) allowed to analyze the number and the function of the cells with an adequate gating strategy and the Kaluza® software v2.1 (Beckman Coulter). The data were then grouped by time intervals referring to the onset of symptoms and also to the ICU admission. The trend for innate immunity (monocytes number and subpopulations, HLA-DR expression) and for adaptive immunity (lymphocytes and subpopulations) will be analyzed. Since it is unknown if whole blood CD3/CD4 and CD3/CD8 lymphocytes elicit an "exhaustion" pattern and/or an abnormal response, an ex vivo testing of their reactivity for SARS-CoV-2 viral proteins will be performed. This test of polyfunctionality will characterize the intracellular cytokine expression (IL-1 beta, TNFalpha, and INFgamma) both for CD4 and CD8 T cells.
Тип исследования
Регистрация (Действительный)
Контакты и местонахождение
Места учебы
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Vandoeuvre-les-Nancy, Франция, 54511
- Centre Hospitalier Universitaire Nancy
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Критерии участия
Критерии приемлемости
Возраст, подходящий для обучения
Принимает здоровых добровольцев
Полы, имеющие право на обучение
Метод выборки
Исследуемая популяция
Описание
Inclusion Criteria: confirmed COVID-19
- a positive RT- PCR,
- a highly suggestive thoracic CTScan,
- severe hypoxemia
Exclusion Criteria:
- none
Учебный план
Как устроено исследование?
Детали дизайна
Когорты и вмешательства
Группа / когорта |
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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
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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
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Что измеряет исследование?
Первичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
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Changes in monocytes HLA-DR expression
Временное ограничение: through ICU stay, an average of 30 days
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circulating immune cell characterization
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through ICU stay, an average of 30 days
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Changes in lymphocytes subpopulations numbers
Временное ограничение: through ICU stay, an average of 30 days
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circulating immune cell characterization
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through ICU stay, an average of 30 days
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Changes in monocytes number
Временное ограничение: through ICU stay, an average of 30 days
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circulating immune cell characterization
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through ICU stay, an average of 30 days
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Вторичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
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TNFalpha level
Временное ограничение: 4 hours
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stimulation by SARS-CoV-2 viral proteins
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4 hours
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INFgamma level
Временное ограничение: 4 hours
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stimulation by SARS-CoV-2 viral proteins
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4 hours
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IL1beta level
Временное ограничение: 4 hours
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stimulation by SARS-CoV-2 viral proteins
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4 hours
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SOFA score
Временное ограничение: through ICU stay, an average of 30 days
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Sequential Organ dysfunction assessement, ranging from 0 (better) to 24 (worst) outcome
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through ICU stay, an average of 30 days
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number of recorded deaths
Временное ограничение: through study completion, an average of 6 months
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mortality
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through study completion, an average of 6 months
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presence of pneumonia
Временное ограничение: through ICU stay, an average of 30 days
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infectious complications
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through ICU stay, an average of 30 days
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presence of bacteremia
Временное ограничение: through ICU stay, an average of 30 days
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infectious complications
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through ICU stay, an average of 30 days
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presence of urinary tract infection
Временное ограничение: through ICU stay, an average of 30 days
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infectious complications
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through ICU stay, an average of 30 days
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C reactive protein
Временное ограничение: through ICU stay, an average of 30 days
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inflammation marker
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through ICU stay, an average of 30 days
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D Dimers
Временное ограничение: through ICU stay, an average of 30 days
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inflammation marker
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through ICU stay, an average of 30 days
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Соавторы и исследователи
Спонсор
Следователи
- Главный следователь: MARIE REINE LOSSER, MD, PhD, Central Hospital, Nancy, France
Публикации и полезные ссылки
Общие публикации
- 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.
- 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. Erratum In: Signal Transduct Target Ther. 2020 Apr 29;5(1):61.
- 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.
- 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.
- 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.
- 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.
Даты записи исследования
Изучение основных дат
Начало исследования (Действительный)
Первичное завершение (Действительный)
Завершение исследования (Действительный)
Даты регистрации исследования
Первый отправленный
Впервые представлено, что соответствует критериям контроля качества
Первый опубликованный (Действительный)
Обновления учебных записей
Последнее опубликованное обновление (Действительный)
Последнее отправленное обновление, отвечающее критериям контроля качества
Последняя проверка
Дополнительная информация
Термины, связанные с этим исследованием
Дополнительные соответствующие термины MeSH
Другие идентификационные номера исследования
- CHRU NANCY : 2020PI080_1
Информация о лекарствах и устройствах, исследовательские документы
Изучает лекарственный продукт, регулируемый FDA США.
Изучает продукт устройства, регулируемый Управлением по санитарному надзору за качеством пищевых продуктов и медикаментов США.
Эта информация была получена непосредственно с веб-сайта clinicaltrials.gov без каких-либо изменений. Если у вас есть запросы на изменение, удаление или обновление сведений об исследовании, обращайтесь по адресу register@clinicaltrials.gov. Как только изменение будет реализовано на clinicaltrials.gov, оно будет автоматически обновлено и на нашем веб-сайте. .
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