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1.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-318996

ABSTRACT

The objective of the present study was to identify biological signatures of severe COVID-19 predictive of admission in the intensive care unit (ICU). Over 170 immunological markers were investigated in a ‘discovery’ cohort (n=98 patients) of the Lausanne University Hospital (LUH-1). While cellular immunological markers lacked power in discriminating between ICU and non-ICU patients, 13 out of 49 cytokines were significantly associated with ICU admission in the three cohorts (P<0.05 to P<0.001). The cytokine results were confirmed in two ‘validation’ cohorts, i.e. the French COVID-19 Study (FCS;n=62) and a second LUH-2 cohort (n=47). Of note, HGF is a pleiotropic cytokine with anti-inflammatory properties playing a fundamental role in lung tissue repair, and CXCL13, a pro-inflammatory chemokine associated with pulmonary fibrosis and regulating the maturation of B cell response. The two cytokines in combination were the best predictors of ICU admission (positive and negative predictive values ranging from 81.8% to 93.1% and 85.2% to 94.4% in the 3 cohorts) and occurrence of death during patient follow-up (8.8 fold higher likelihood of death when both cytokines were increased). Up-regulation of HGF reflects the most powerful counter-regulatory mechanism of the host immune response to antagonize the pro-inflammatory cytokines including CXCL13 and to prevent lung fibrosis in COVID-19 patients.

2.
Nat Commun ; 12(1): 4888, 2021 08 09.
Article in English | MEDLINE | ID: covidwho-1349667

ABSTRACT

The objective of the present study was to identify biological signatures of severe coronavirus disease 2019 (COVID-19) predictive of admission in the intensive care unit (ICU). Over 170 immunological markers were investigated in a 'discovery' cohort (n = 98 patients) of the Lausanne University Hospital (LUH-1). Here we report that 13 out of 49 cytokines were significantly associated with ICU admission in the three cohorts (P < 0.05 to P < 0.001), while cellular immunological markers lacked power in discriminating between ICU and non-ICU patients. The cytokine results were confirmed in two 'validation' cohorts, i.e. the French COVID-19 Study (FCS; n = 62) and a second LUH-2 cohort (n = 47). The combination of hepatocyte growth factor (HGF) and C-X-C motif chemokine ligand 13 (CXCL13) was the best predictor of ICU admission (positive and negative predictive values ranging from 81.8% to 93.1% and 85.2% to 94.4% in the 3 cohorts) and occurrence of death during patient follow-up (8.8 fold higher likelihood of death when both cytokines were increased). Of note, HGF is a pleiotropic cytokine with anti-inflammatory properties playing a fundamental role in lung tissue repair, and CXCL13, a pro-inflammatory chemokine associated with pulmonary fibrosis and regulating the maturation of B cell response. Up-regulation of HGF reflects the most powerful counter-regulatory mechanism of the host immune response to antagonize the pro-inflammatory cytokines including CXCL13 and to prevent lung fibrosis in COVID-19 patients.


Subject(s)
COVID-19/immunology , COVID-19/mortality , Chemokine CXCL13/immunology , Cytokines/immunology , Hepatocyte Growth Factor/immunology , Biomarkers/blood , CD4-Positive T-Lymphocytes , COVID-19/blood , COVID-19/diagnosis , Chemokine CXCL13/genetics , Cytokines/blood , Hepatocyte Growth Factor/genetics , Hospitalization , Humans , Intensive Care Units , Pulmonary Fibrosis , SARS-CoV-2/isolation & purification , Severity of Illness Index
3.
Diagnostics (Basel) ; 11(8)2021 Jul 28.
Article in English | MEDLINE | ID: covidwho-1335020

ABSTRACT

We report postmortem cardio-pulmonary findings including detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in formalin-fixed paraffin embedded tissue in 12 patients with COVID-19. The 5 women and 7 men (median age: 73 years; range 35-96) died 6-38 days after onset of symptoms (median: 14.5 days). Eight patients received mechanical ventilation. Ten patients showed diffuse alveolar damage (DAD), 7 as exudative and 3 as proliferative/organizing DAD. One case presented as acute fibrinous and organizing pneumonia. Seven patients (58%) had acute bronchopneumonia, 1/7 without associated DAD and 1/7 with aspergillosis and necrotic bronchitis. Microthrombi were present in 5 patients, only in exudative DAD. Reverse transcriptase quantitative PCR detected high virus amounts in 6 patients (50%) with exudative DAD and symptom-duration ≤14 days, supported by immunohistochemistry and in-situ RNA hybridization (RNAscope). The 6 patients with low viral copy levels were symptomatic for ≥15 days, comprising all cases with organizing DAD, the patient without DAD and one exudative DAD. We show the high prevalence of DAD as a reaction pattern in COVID-19, the high number of overlying acute bronchopneumonia, and high-level pulmonary virus detection limited to patients who died ≤2 weeks after onset of symptoms, correlating with exudative phase of DAD.

4.
N Engl J Med ; 384(24): 2283-2294, 2021 06 17.
Article in English | MEDLINE | ID: covidwho-1275997

ABSTRACT

BACKGROUND: Targeted temperature management is recommended for patients after cardiac arrest, but the supporting evidence is of low certainty. METHODS: In an open-label trial with blinded assessment of outcomes, we randomly assigned 1900 adults with coma who had had an out-of-hospital cardiac arrest of presumed cardiac or unknown cause to undergo targeted hypothermia at 33°C, followed by controlled rewarming, or targeted normothermia with early treatment of fever (body temperature, ≥37.8°C). The primary outcome was death from any cause at 6 months. Secondary outcomes included functional outcome at 6 months as assessed with the modified Rankin scale. Prespecified subgroups were defined according to sex, age, initial cardiac rhythm, time to return of spontaneous circulation, and presence or absence of shock on admission. Prespecified adverse events were pneumonia, sepsis, bleeding, arrhythmia resulting in hemodynamic compromise, and skin complications related to the temperature management device. RESULTS: A total of 1850 patients were evaluated for the primary outcome. At 6 months, 465 of 925 patients (50%) in the hypothermia group had died, as compared with 446 of 925 (48%) in the normothermia group (relative risk with hypothermia, 1.04; 95% confidence interval [CI], 0.94 to 1.14; P = 0.37). Of the 1747 patients in whom the functional outcome was assessed, 488 of 881 (55%) in the hypothermia group had moderately severe disability or worse (modified Rankin scale score ≥4), as compared with 479 of 866 (55%) in the normothermia group (relative risk with hypothermia, 1.00; 95% CI, 0.92 to 1.09). Outcomes were consistent in the prespecified subgroups. Arrhythmia resulting in hemodynamic compromise was more common in the hypothermia group than in the normothermia group (24% vs. 17%, P<0.001). The incidence of other adverse events did not differ significantly between the two groups. CONCLUSIONS: In patients with coma after out-of-hospital cardiac arrest, targeted hypothermia did not lead to a lower incidence of death by 6 months than targeted normothermia. (Funded by the Swedish Research Council and others; TTM2 ClinicalTrials.gov number, NCT02908308.).


Subject(s)
Fever/therapy , Hypothermia, Induced , Out-of-Hospital Cardiac Arrest/therapy , Aged , Body Temperature , Cardiopulmonary Resuscitation/methods , Coma/etiology , Coma/therapy , Female , Fever/etiology , Humans , Hypothermia, Induced/adverse effects , Kaplan-Meier Estimate , Male , Middle Aged , Out-of-Hospital Cardiac Arrest/complications , Out-of-Hospital Cardiac Arrest/mortality , Single-Blind Method , Treatment Outcome
5.
Front Immunol ; 12: 666163, 2021.
Article in English | MEDLINE | ID: covidwho-1273338

ABSTRACT

The reason why most individuals with COVID-19 have relatively limited symptoms while other develop respiratory distress with life-threatening complications remains unknown. Increasing evidence suggests that COVID-19 associated adverse outcomes mainly rely on dysregulated immunity. Here, we compared transcriptomic profiles of blood cells from 103 patients with different severity levels of COVID-19 with that of 27 healthy and 22 influenza-infected individuals. Data provided a complete overview of SARS-CoV-2-induced immune signature, including a dramatic defect in IFN responses, a reduction of toxicity-related molecules in NK cells, an increased degranulation of neutrophils, a dysregulation of T cells, a dramatic increase in B cell function and immunoglobulin production, as well as an important over-expression of genes involved in metabolism and cell cycle in patients infected with SARS-CoV-2 compared to those infected with influenza viruses. These features also differed according to COVID-19 severity. Overall and specific gene expression patterns across groups can be visualized on an interactive website (https://bix.unil.ch/covid/). Collectively, these transcriptomic host responses to SARS-CoV-2 infection are discussed in the context of current studies, thereby improving our understanding of COVID-19 pathogenesis and shaping the severity level of COVID-19.


Subject(s)
COVID-19/immunology , Influenza, Human/immunology , Humans , SARS-CoV-2/immunology , Transcriptome
6.
Swiss Med Wkly ; 150: w20387, 2020 11 02.
Article in English | MEDLINE | ID: covidwho-922917

ABSTRACT

A 22-year-old male with a typical history of pauci-symptomatic COVID-19 3 weeks earlier, confirmed by positive serology for SARS-CoV-2 (IgG), was admitted to the intensive care unit because of severe myocarditis with refractory cardiogenic shock that required extracorporeal life support. Due to a clinical presentation suggestive of Kawasaki-like disease with coronary aneurysm and severe systemic inflammation, intravenous immunoglobulins were administered in combination with tocilizumab. The initial clinical course was favourable with these treatments. However, the patient subsequently developed a severe mononeuritis multiplex leading to bilateral foot drop, which required intensive immunosuppressive therapy (corticosteroids, cyclophosphamide and rituximab). The clinical presentation meets the criteria for multisystem inflammatory syndrome associated with SARS-CoV-2, but includes very severe organ damages. Early recognition, a multidisciplinary approach and aggressive therapeutic intervention can lead to a favourable outcome.


Subject(s)
COVID-19/complications , Mononeuropathies/etiology , Myocarditis/etiology , Shock, Cardiogenic/etiology , Systemic Inflammatory Response Syndrome/etiology , Extracorporeal Membrane Oxygenation , Humans , Male , SARS-CoV-2 , Young Adult
8.
Revue medicale suisse ; 16(N° 691-2):863-868, 2020.
Article | WHO COVID | ID: covidwho-154687

ABSTRACT

The SARS-coronavirus 2 disease initially reported in December 2019 in China (COVID-19) represents a major challenge for intensive care medicine, due to the high number of ICU admission and the prolonged stay for many patients. Up to 5 % of COVID-19 infected patients develop severe acute hypoxemic respiratory failure requiring invasive mechanical ventilation as supportive treatment. Apart from early antiviral and anti-inflammatory treatment, the management of COVID-19 patients is mainly applying protective mechanical ventilation, to support the injured lungs. However recently acquired data and clinical experience suggest that COVID-19-related ARDS presents some specificities that will be summarized in the present article. La maladie a coronavirus SARS-Cov2 apparue en Chine en decembre 2019 (COVID-19) constitue un defi majeur pour les unites de soins intensifs en raison du nombre important dadmissions. En effet, pres de 5 % des patients infectes necessitent une ventilation invasive et une part importante de ces patients restent aux soins intensifs durant une longue periode. A part lapproche pharmacologique antivirale et anti-inflammatoire precoce, le traitement est centre sur la ventilation mecanique protectrice, qui a fait ses preuves dans le syndrome de detresse respiratoire (SDRA) et qui constitue la pierre angulaire du traitement de latteinte pulmonaire du COVID-19. Toutefois, en letat actuel des connaissances, le SDRA sur COVID-19 presente des caracteristiques particulieres qui necessitent une approche specifique que nous resumons dans cet article.

9.
Revue medicale suisse ; 16(N° 691-2):863-868, 2020.
Article | WHO COVID | ID: covidwho-141621

ABSTRACT

The SARS-coronavirus 2 disease initially reported in December 2019 in China (COVID-19) represents a major challenge for intensive care medicine, due to the high number of ICU admission and the prolonged stay for many patients. Up to 5 % of COVID-19 infected patients develop severe acute hypoxemic respiratory failure requiring invasive mechanical ventilation as supportive treatment. Apart from early antiviral and anti-inflammatory treatment, the management of COVID-19 patients is mainly applying protective mechanical ventilation, to support the injured lungs. However recently acquired data and clinical experience suggest that COVID-19-related ARDS presents some specificities that will be summarized in the present article.

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