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1.
Vieillard-Baron, Antoine, Flicoteaux, Rémi, Salmona, Maud, Annane, Djillali, Ayed, Soufia, Azoulay, Elie, Bellaiche, Raphael, Beloucif, Sadek, Berti, Enora, Bertier, Astrid, Besset, Sébastien, Bret, Marlène, Cariou, Alain, Carpentier, Christophe, Chaouch, Oussama, Chariot, Appoline, Charron, Cyril, Charpentier, Julien, Cheurfa, Cherifa, Cholley, Bernard, Clerc, Sébastien, Combes, Alain, Chousterman, Benjamin, Cohen, Yves, Constantin, Jean-Michel, Damoisel, Charles, Darmon, Michael, Degos, Vincent, D’Ableiges, Bertrand De Maupeou, Demeret, Sophie, Montmollin, Etienne De, Demoule, Alexandre, Depret, Francois, Diehl, Jean-Luc, Djibré, Michel, Do, Chung-Hi, Dudoignon, Emmanuel, Duranteau, Jacques, Fartoukh, Muriel, Fieux, Fabienne, Gayat, Etienne, Gennequin, Mael, Guidet, Bertrand, Gutton, Christophe, Hamada, Sophie, Heming, Nicholas, Jouffroy, Romain, Keita-Meyer, Hawa, Langeron, Olivier, Lortat-Jacob, Brice, Marey, Jonathan, Mebazaa, Alexandre, Megarbane, Bruno, Mekontso-Dessap, Armand, Mira, Jean-Paul, Molle, Julie, Mongardon, Nicolas, Montravers, Philippe, Morelot-Panzini, Capucine, Nemlaghi, Safaa, Nguyen, Bao-long, Parrot, Antoine, Pasqualotto, Romain, Peron, Nicolas, Picard, Lucile, de Chambrun, Marc Pineton, Planquette, Benjamin, Plaud, Benoit, Pons, Stéphanie, Quesnel, Christophe, Raphalen, Jean-Herlé, Razazi, Keyvan, Ricard, Jean-Damien, Roche, Anne, Rohaut, Benjamin, Roux, Damien, Savale, Laurent, Sobotka, Jennifer, Teboul, Jean-Louis, Timsit, Jean-François, Voiriot, Guillaume, Weiss, Emmanuel, Wildenberg, Lucille, Zogheib, Elie, Riou, Bruno, Batteux, Frédéric.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-327150

ABSTRACT

Importance Information about the severity of Omicron is scarce. Objective To report the respective risk of ICU admission in patients hospitalized with Delta and Omicron variants and to compare the characteristics and disease severity of critically ill patients infected with both variants according to vaccination status. Design Analysis from the APHP database, called Reality, prospectively recording the following information in consecutive patients admitted in the ICU for COVID-19: age, sex, immunosuppression, vaccination, pneumonia, need for invasive mechanical ventilation, time between symptom onset and ICU admission, and in-ICU mortality. Retrospective analysis on an administrative database, “Système d’Information pour le Suivi des Victimes” (SI-VIC), which lists hospitalized COVID-19 patients. Setting 39 hospitals in the Paris area from APHP group. Participants Patients hospitalized from December 1, 2021 to January 18, 2022 for COVID-19. Main outcomes and measures Risk of ICU admission was evaluated in 3761 patients and Omicron cases were compared to Delta cases in the ICU in 888 consecutive patients. Results On January 18, 45% of patients in the ICU and 63.8% of patients in conventional hospital units were infected with the Omicron variant (p < 0.001). The risk of ICU admission with Omicron was reduced by 64% than with Delta (9.3% versus 25.8% of cases, respectively, p < 0.001). In critically ill patients, 400 had the Delta variant, 229 the Omicron variant, 98 had an uninformative variant screening test and 161 did not have information on variant screening test. 747 patients (84.1%) were admitted for pneumonia. Compared to patients infected with Delta, Omicron patients were more vaccinated (p<0.001), even with 3 doses, more immunocompromised (p<0.001), less admitted for pneumonia (p<0.001), especially when vaccinated (62.1% in vaccinated versus 80.7% in unvaccinated, p<0.001), and less invasively ventilated (p=0.02). Similar results were found in the subgroup of pneumonia but Omicron cases were older. Unadjusted in-ICU mortality did not differ between Omicron and Delta cases, neither in the overall population (20.0% versus 27.9%, p = 0.08), nor in patients with pneumonia (31.6% versus 29.7%, respectively) where adjusted in-ICU mortality did not differ according to the variant (HR 1.43 95%CI [0.89;2.29], p=0.14). Conclusion and relevance Compared to the Delta variant, the Omicron variant is less likely to result in ICU admission and less likely to be associated with pneumonia. However, when patients with the Omicron variant are admitted for pneumonia, the severity seems similar to that of patients with the Delta variant, with more immunocompromised and vaccinated patients and no difference in adjusted in-ICU mortality. Further studies are needed to confirm our results.

2.
J Thromb Haemost ; 19(7): 1823-1830, 2021 07.
Article in English | MEDLINE | ID: covidwho-1172713

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a respiratory disease associated with vascular inflammation and endothelial injury. OBJECTIVES: To correlate circulating angiogenic markers vascular endothelial growth factor A (VEGF-A), placental growth factor (PlGF), and fibroblast growth factor 2 (FGF-2) to in-hospital mortality in COVID-19 adult patients. METHODS: Consecutive ambulatory and hospitalized patients with COVID-19 infection were enrolled. VEGF-A, PlGF, and FGF-2 were measured in each patient ≤48 h following admission. RESULTS: The study enrolled 237 patients with suspected COVID-19: 208 patients had a positive diagnostic for COVID-19, of whom 23 were mild outpatients and 185 patients hospitalized after admission. Levels of VEGF-A, PlGF, and FGF-2 significantly increase with the severity of the disease (P < .001). Using a logistic regression model, we found a significant association between the increase of FGF-2 or PlGF and mortality (odds ratio [OR] 1.11, 95% confidence interval [CI; 1.07-1.16], P < .001 for FGF-2 and OR 1.07 95% CI [1.04-1.10], P < .001 for PlGF) while no association were found for VEGF-A levels. Receiver operating characteristic curve analysis was performed and we identified PlGF above 30 pg/ml as the best predictor of in-hospital mortality in COVID-19 patients. Survival analysis for PlGF confirmed its interest for in-hospital mortality prediction, by using a Kaplan-Meier survival curve (P = .001) and a Cox proportional hazard model adjusted to age, body mass index, D-dimer, and C-reactive protein (3.23 95% CI [1.29-8.11], P = .001). CONCLUSION: Angiogenic factor PlGF is a relevant predictive factor for in-hospital mortality in COVID-19 patients. More than a biomarker, we hypothesize that PlGF blocking strategies could be a new interesting therapeutic approach in COVID-19.


Subject(s)
COVID-19 , Vascular Endothelial Growth Factor A , Adult , Biomarkers , Female , Hospital Mortality , Humans , Placenta Growth Factor , SARS-CoV-2
3.
Angiogenesis ; 24(3): 505-517, 2021 08.
Article in English | MEDLINE | ID: covidwho-1032491

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a respiratory disease associated with endotheliitis and microthrombosis. OBJECTIVES: To correlate endothelial dysfunction to in-hospital mortality in a bi-centric cohort of COVID-19 adult patients. METHODS: Consecutive ambulatory and hospitalized patients with laboratory-confirmed COVID-19 were enrolled. A panel of endothelial biomarkers and von Willebrand factor (VWF) multimers were measured in each patient ≤ 48 h following admission. RESULTS: Study enrolled 208 COVID-19 patients of whom 23 were mild outpatients and 189 patients hospitalized after admission. Most of endothelial biomarkers tested were found increased in the 89 critical patients transferred to intensive care unit. However, only von Willebrand factor antigen (VWF:Ag) scaled according to clinical severity, with levels significantly higher in critical patients (median 507%, IQR 428-596) compared to non-critical patients (288%, 230-350, p < 0.0001) or COVID-19 outpatients (144%, 133-198, p = 0.007). Moreover, VWF high molecular weight multimers (HMWM) were significantly higher in critical patients (median ratio 1.18, IQR 0.86-1.09) compared to non-critical patients (0.96, 1.04-1.39, p < 0.001). Among all endothelial biomarkers measured, ROC curve analysis identified a VWF:Ag cut-off of 423% as the best predictor for in-hospital mortality. The accuracy of VWF:Ag was further confirmed in a Kaplan-Meier estimator analysis and a Cox proportional Hazard model adjusted on age, BMI, C-reactive protein and D-dimer levels. CONCLUSION: VWF:Ag is a relevant predictive factor for in-hospital mortality in COVID-19 patients. More than a biomarker, we hypothesize that VWF, including excess of HMWM forms, drives microthrombosis in COVID-19.


Subject(s)
COVID-19/blood , COVID-19/mortality , Pandemics , SARS-CoV-2 , von Willebrand Factor/metabolism , Adult , Aged , Biomarkers/blood , Biomarkers/chemistry , COVID-19/physiopathology , Cross-Sectional Studies , Endothelium, Vascular/physiopathology , Female , Hospital Mortality , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Molecular Weight , Paris/epidemiology , Proportional Hazards Models , Protein Multimerization , Severity of Illness Index , Thrombosis/blood , Thrombosis/etiology , von Willebrand Factor/chemistry
4.
Front Med (Lausanne) ; 7: 586307, 2020.
Article in English | MEDLINE | ID: covidwho-954333

ABSTRACT

Background: Coronavirus disease 2019 (COVID-19) has been associated with cardiovascular complications and coagulation disorders. Objectives: To explore clinical and biological parameters of COVID-19 patients with hospitalization criteria that could predict referral to intensive care unit (ICU). Methods: Analyzing the clinical and biological profiles of COVID-19 patients at admission. Results: Among 99 consecutive patients that fulfilled criteria for hospitalization, 48 were hospitalized in the medicine department, 21 were first admitted to the medicine ward department and referred later to ICU, and 30 were directly admitted to ICU from the emergency department. At admission, patients requiring ICU were more likely to have lymphopenia, decreased SpO2, a D-dimer level above 1,000 ng/mL, and a higher high-sensitivity cardiac troponin (Hs-cTnI) level. A receiver operating characteristic curve analysis identified Hs-cTnI above 9.75 pg/mL as the best predictive criteria for ICU referral [area under the curve (AUC), 86.4; 95% CI, 76.6-96.2]. This cutoff for Hs-cTnI was confirmed in univariate [odds ratio (OR), 22.8; 95% CI, 6.0-116.2] and multivariate analysis after adjustment for D-dimer level (adjusted OR, 20.85; 95% CI, 4.76-128.4). Transthoracic echocardiography parameters subsequently measured in 72 patients showed an increased right ventricular (RV) afterload correlated with Hs-cTnI (r = 0.42, p = 0.010) and D-dimer (r = 0.18, p = 0.047). Conclusion: Hs-cTnI appears to be the best relevant predictive factor for referring COVID-19 patients to ICU. This result associated with the correlation of D-dimer with RV dilatation probably reflects a myocardial injury due to an increased RV wall tension. This reinforces the hypothesis of a COVID-19-associated microvascular thrombosis inducing a higher RV afterload.

5.
Angiogenesis ; 23(4): 611-620, 2020 11.
Article in English | MEDLINE | ID: covidwho-377964

ABSTRACT

BACKGROUND: Coronavirus disease-2019 (COVID-19), a respiratory disease has been associated with ischemic complications, coagulation disorders, and an endotheliitis. OBJECTIVES: To explore endothelial damage and activation-related biomarkers in COVID-19 patients with criteria of hospitalization for referral to intensive care unit (ICU) and/or respiratory worsening. METHODS: Analysis of endothelial and angiogenic soluble markers in plasma from patients at admission. RESULTS: Study enrolled 40 consecutive COVID-19 patients admitted to emergency department that fulfilled criteria for hospitalization. Half of them were admitted in conventional wards without any ICU transfer during hospitalization; whereas the 20 others were directly transferred to ICU. Patients transferred in ICU were more likely to have lymphopenia, decreased SpO2 and increased D-dimer, CRP and creatinine levels. In those patients, soluble E-selectin and angiopoietin-2 were significantly increased (p value at 0.009 and 0.003, respectively). Increase in SELE gene expression (gene coding for E-selectin protein) was confirmed in an independent cohort of 32 patients using a whole blood gene expression profile analysis. In plasma, we found a strong association between angiopoetin-2 and CRP, creatinine and D-dimers (with p value at 0.001, 0.001 and 0.003, respectively). ROC curve analysis identified an Angiopoietin-2 cut-off of 5000 pg/mL as the best predictor for ICU outcome (Se = 80.1%, Sp = 70%, PPV = 72.7%, NPV = 77%), further confirmed in multivariate analysis after adjustment for creatinine, CRP or D-dimers. CONCLUSION: Angiopoietin-2 is a relevant predictive factor for ICU direct admission in COVID-19 patients. This result showing an endothelial activation reinforces the hypothesis of a COVID-19-associated microvascular dysfunction.


Subject(s)
Angiopoietin-2/blood , Coronavirus Infections/blood , Coronavirus Infections/therapy , Endothelium, Vascular/metabolism , Intensive Care Units , Pneumonia, Viral/blood , Pneumonia, Viral/therapy , Aged , Betacoronavirus , Biomarkers/blood , COVID-19 , Critical Care/methods , E-Selectin/blood , Female , Gene Expression Profiling , Hospitalization , Humans , Male , Middle Aged , Pandemics , Patient Admission , Prospective Studies , Respiration, Artificial , SARS-CoV-2
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