Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 7 de 7
Filter
2.
Annals of Intensive Care ; 12(1), 2022.
Article in English | ProQuest Central | ID: covidwho-1837129

ABSTRACT

BackgroundLymphopenia is a hallmark of severe coronavirus disease 19 (COVID-19). Similar alterations have been described in bacterial sepsis and therapeutic strategies targeting T cell function such as recombinant human interleukin 7 (rhIL-7) have been proposed in this clinical context. As COVID-19 is a viral sepsis, the objectives of this study were to characterize T lymphocyte response over time in severe COVID-19 patients and to assess the effect of ex vivo administration of rhIL-7.ResultsPeripheral blood mononuclear cells from COVID-19 patients hospitalized in intensive care unit (ICU) were collected at admission and after 20 days. Transcriptomic profile was evaluated through NanoString technology. Inhibitory immune checkpoints expressions were determined by flow cytometry. T lymphocyte proliferation and IFN-γ production were evaluated after ex vivo stimulation in the presence or not of rhIL-7. COVID-19 ICU patients were markedly lymphopenic at admission. Mononuclear cells presented with inhibited transcriptomic profile prevalently with impaired T cell activation pathways. CD4 + and CD8 + T cells presented with over-expression of co-inhibitory molecules PD-1, PD-L1, CTLA-4 and TIM-3. CD4 + and CD8 + T cell proliferation and IFN-γ production were markedly altered in samples collected at ICU admission. These alterations, characteristic of a T cell exhaustion state, were more pronounced at ICU admission and alleviated over time. Treatment with rhIL-7 ex vivo significantly improved both T cell proliferation and IFN-γ production in cells from COVID-19 patients.ConclusionsSevere COVID-19 patients present with features of profound T cell exhaustion upon ICU admission which can be reversed ex vivo by rhIL-7. These results reinforce our understanding of severe COVID-19 pathophysiology and opens novel therapeutic avenues to treat such critically ill patients based of immunomodulation approaches. Defining the appropriate timing for initiating such immune-adjuvant therapy in clinical setting and the pertinent markers for a careful selection of patients are now warranted to confirm the ex vivo results described so far.Trial registration ClinicalTrials.gov identifier: NCT04392401 Registered 18 May 2020, http:// clinicaltrials.gov/ct2/show/NCT04392401.

3.
EBioMedicine ; 78: 103967, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1757276

ABSTRACT

BACKGROUND: In critically ill COVID-19 patients, the initial response to SARS-CoV-2 infection is characterized by major immune dysfunctions. The capacity of these severe patients to mount a robust and persistent SARS-CoV-2 specific T cell response despite the presence of severe immune alterations during the ICU stay is unknown. METHODS: Critically ill COVID-19 patients were sampled five times during the ICU stay and 9 and 13 months afterwards. Immune monitoring included counts of lymphocyte subpopulations, HLA-DR expression on monocytes, plasma IL-6 and IL-10 concentrations, anti-SARS-CoV-2 IgG levels and T cell proliferation in response to three SARS-CoV-2 antigens. FINDINGS: Despite the presence of major lymphopenia and decreased monocyte HLA-DR expression during the ICU stay, convalescent critically ill COVID-19 patients consistently generated adaptive and humoral immune responses against SARS-CoV-2 maintained for more than one year after hospital discharge. Patients with long hospital stays presented with stronger anti-SARS-CoV-2 specific T cell response but no difference in anti-SARS-CoV2 IgG levels. INTERPRETATION: Convalescent critically ill COVID-19 patients consistently generated a memory immune response against SARS-CoV-2 maintained for more than one year after hospital discharge. In recovered individuals, the intensity of SARS-CoV-2 specific T cell response was dependent on length of hospital stay. FUNDING: This observational study was supported by funds from the Hospices Civils de Lyon, Fondation HCL, Claude Bernard Lyon 1 University and Région Auvergne Rhône-Alpes and by partial funding by REACTing (Research and ACTion targeting emerging infectious diseases) INSERM, France and a donation from Fondation AnBer (http://fondationanber.fr/).


Subject(s)
COVID-19 , Immunologic Memory , T-Lymphocytes , Antibodies, Viral/blood , COVID-19/immunology , Critical Illness , HLA-DR Antigens , Humans , Immunoglobulin G/blood , SARS-CoV-2 , T-Lymphocytes/immunology
4.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-319182

ABSTRACT

Background: The coronavirus disease 2019 (COVID-19) pandemic would have particularly affected acute stroke care. However, its impact is clearly inherent to the local stroke network conditions. We aimed to assess the impact of COVID-19 pandemic on acute stroke care in the Lyon comprehensive stroke center during this period. Methods: We conducted a prospective data collection of patients with acute ischemic stroke (AIS) treated with intravenous thrombolysis (IVT) and/or mechanical thrombectomy (MT) during the COVID-19 period (from 29/02/2020 to 10/05/2020) and a control period (from 29/02/2019 to 10/05/2019). The volume of reperfusion therapies and pre and intra-hospital delays were compared during both periods. Results: A total of 208 patients were included. The volume of IVT significantly decreased during the COVID-period (55 (54.5%) vs 74 (69.2%);p=0.03) and was mainly due to time delay among patients treated with MT. The volume of MT remains stable over the two periods (72 (71.3%) vs 65 (60.8%);p=0.14) but the door-to-groin puncture time increased in patients transferred for MT (237 [187-339] vs 210 [163-260];p<0.01). The daily number of Emergency Medical Dispatch calls considerably increased (1502 [1133-2238] vs 1023 [960-1410];p<0.01). Conclusions: Our study showed a decrease of the volume of IVT, whereas the volume of MT remained stable although intra-hospital delays increased for transferred patients during the COVID-19 pandemic. These results contrast in part with the national surveys and suggest that the impact of the pandemic may depend on local stroke care networks.

5.
Eur J Clin Microbiol Infect Dis ; 40(9): 2023-2028, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1122785

ABSTRACT

During an epidemic period, we compared patients hospitalized for initial suspicion of COVID-19 but for whom an alternative diagnosis was finally retained (n = 152) with those who had COVID-19 (n = 222). Most common diagnoses were another infectious disease and heart failure. COVID-19-negative patients were more often active smokers had less often cough, fever, and digestive symptoms, as compared to the 222 COVID-19-positive patients. They had higher median neutrophil and lymphocyte counts and lower CRP level. In multivariate analysis, no current smoking, neurocognitive disorder, myalgia, and fibrinogen ≥4g/L were independently associated with a final diagnosis of COVID-19.


Subject(s)
COVID-19/diagnosis , Adult , Aged , COVID-19/therapy , COVID-19/virology , Hospitalization , Humans , Male , Patients/statistics & numerical data , Retrospective Studies , SARS-CoV-2/physiology
7.
J Neurol ; 268(7): 2314-2319, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-754555

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic would have particularly affected acute stroke care. However, its impact is clearly inherent to the local stroke network conditions. We aimed to assess the impact of COVID-19 pandemic on acute stroke care in the Lyon comprehensive stroke center during this period. METHODS: We conducted a prospective data collection of patients with acute ischemic stroke (AIS) treated with intravenous thrombolysis (IVT) and/or mechanical thrombectomy (MT) during the COVID-19 period (from 29/02/2020 to 10/05/2020) and a control period (from 29/02/2019 to 10/05/2019). The volume of reperfusion therapies and pre and intra-hospital delays were compared during both periods. RESULTS: A total of 208 patients were included. The volume of IVT significantly decreased during the COVID-period [55 (54.5%) vs 74 (69.2%); p = 0.03]. The volume of MT remains stable over the two periods [72 (71.3%) vs 65 (60.8%); p = 0.14], but the door-to-groin puncture time increased in patients transferred for MT (237 [187-339] vs 210 [163-260]; p < 0.01). The daily number of Emergency Medical Dispatch calls considerably increased (1502 [1133-2238] vs 1023 [960-1410]; p < 0.01). CONCLUSIONS: Our study showed a decrease in the volume of IVT, whereas the volume of MT remained stable although intra-hospital delays increased for transferred patients during the COVID-19 pandemic. These results contrast in part with the national surveys and suggest that the impact of the pandemic may depend on local stroke care networks.


Subject(s)
Brain Ischemia , COVID-19 , Stroke , Thrombectomy , Thrombolytic Therapy , Brain Ischemia/complications , Brain Ischemia/epidemiology , Brain Ischemia/therapy , France , Humans , Pandemics , Prospective Studies , Reperfusion , Retrospective Studies , Stroke/epidemiology , Stroke/therapy , Treatment Outcome
SELECTION OF CITATIONS
SEARCH DETAIL