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Cell Death Differ ; 2022 Jan 22.
Article in English | MEDLINE | ID: covidwho-1641945


Severe SARS-CoV-2 infections are characterized by lymphopenia, but the mechanisms involved are still elusive. Based on our knowledge of HIV pathophysiology, we hypothesized that SARS-CoV-2 infection-mediated lymphopenia could also be related to T cell apoptosis. By comparing intensive care unit (ICU) and non-ICU COVID-19 patients with age-matched healthy donors, we found a strong positive correlation between plasma levels of soluble FasL (sFasL) and T cell surface expression of Fas/CD95 with the propensity of T cells to die and CD4 T cell counts. Plasma levels of sFasL and T cell death are correlated with CXCL10 which is part of the signature of 4 biomarkers of disease severity (ROC, 0.98). We also found that members of the Bcl-2 family had modulated in the T cells of COVID-19 patients. More importantly, we demonstrated that the pan-caspase inhibitor, Q-VD, prevents T cell death by apoptosis and enhances Th1 transcripts. Altogether, our results are compatible with a model in which T-cell apoptosis accounts for T lymphopenia in individuals with severe COVID-19. Therefore, a strategy aimed at blocking caspase activation could be beneficial for preventing immunodeficiency in COVID-19 patients.

Anaesth Crit Care Pain Med ; 40(4): 100931, 2021 08.
Article in English | MEDLINE | ID: covidwho-1306763


AIM: Describing acute respiratory distress syndrome patterns, therapeutics management, and outcomes of ICU COVID-19 patients and indentifying risk factors of 28-day mortality. METHODS: Prospective multicentre, cohort study conducted in 29 French ICUs. Baseline characteristics, comorbidities, adjunctive therapies, ventilatory support at ICU admission and survival data were collected. RESULTS: From March to July 2020, 966 patients were enrolled with a median age of 66 (interquartile range 58-73) years and a median SAPS II of 37 (29-48). During the first 24 h of ICU admission, COVID-19 patients received one of the following respiratory supports: mechanical ventilation for 559 (58%), standard oxygen therapy for 228 (24%) and high-flow nasal cannula (HFNC) for 179 (19%) patients. Overall, 721 (75%) patients were mechanically ventilated during their ICU stay. Prone positioning and neuromuscular blocking agents were used in 494 (51%) and 460 (48%) patients, respectively. Bacterial co-infections and ventilator-associated pneumonia were diagnosed in 79 (3%) and 411 (43%) patients, respectively. The overall 28-day mortality was 18%. Age, pre-existing comorbidities, severity of respiratory failure and the absence of antiviral therapy on admission were identified as independent predictors of 28-day outcome. CONCLUSION: Severity of hypoxaemia on admission, older age (> 70 years), cardiovascular and renal comorbidities were associated with worse outcome in COVID-19 patients. Antiviral treatment on admission was identified as a protective factor for 28-day mortality. Ascertaining the outcomes of critically ill COVID-19 patients is crucial to optimise hospital and ICU resources and provide the appropriate intensity level of care.

COVID-19 , SARS-CoV-2 , Aged , Cohort Studies , Critical Care , Humans , Intensive Care Units , Middle Aged , Prospective Studies , Respiration, Artificial
Curr Opin Anaesthesiol ; 34(2): 119-124, 2021 Apr 01.
Article in English | MEDLINE | ID: covidwho-1038304


PURPOSE OF REVIEW: The severe acute respiratory syndrome coronavirus 2 associated coronavirus disease 2019 (COVID-19) illness combines a syndrome of viral replication and a host dysregulated inflammatory response. Despite sharing a similar etiology, COVID-19 patients present different patterns from asymptomatic to severely hypoxemic patients. In some patients, patterns of multiorgan failure have been observed similarly to patients with bacterial sepsis. This review aimed to analyze the currently available data on the treatment of COVID-19, specifically the most studied antiviral agents and therapies targeting the immune system including those that have been investigated in sepsis. RECENT FINDINGS: In the last months, several trials have been conducted worldwide to try to identify optimal antiviral treatments against COVID-19. Antiviral agents such as lopinavir/ritonavir, remdesivir, hydroxychloroquine have been investigated as well as specific and non-specific immunomodulators in order to determine their potential efficacy against SARS-Cov2. SUMMARY: To date, the vast majority of the studied antiviral and immunomodulatory agents have failed to improve outcomes of patients with COVID-19 except for dexamethasone. Many other trials are currently underway with new antiviral agents and various immunomodulatory agents with potential clinical benefit for COVID-19 patients. Despite these emerging data, robust controlled clinical trials assessing patient-centered outcomes remain imperative.

COVID-19 , Shock, Septic , COVID-19/complications , Humans , Intensive Care Units , RNA, Viral , SARS-CoV-2 , Shock, Septic/drug therapy , Shock, Septic/etiology