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1.
Front Med (Lausanne) ; 9: 837258, 2022.
Article in English | MEDLINE | ID: covidwho-1952364

ABSTRACT

Purpose: The objective of the present study was to provide a detailed histopathological description of fatal coronavirus disease 2019 (COVID 19), and compare the lesions in Intensive Care Unit (ICU) and non-ICU patients. Methods: In this prospective study we included adult patients who died in hospital after presenting with confirmed COVID-19. Multiorgan biopsies were performed. Data generated with light microscopy, transmission electron microscopy (TEM) and RT-PCR assays were reviewed. Results: 20 patients were enrolled in the study and the main pulmonary finding was alveolar damage, which was focal in 11 patients and diffuse in 8 patients. Chronic fibrotic and inflammatory lesions were observed in 18 cases, with acute inflammatory lesions in 12 cases. Diffuse lesions, collapsed alveoli and dystrophic pneumocytes were more frequent in the ICU group (62.5%, vs. 25%; 63%, vs. 55%; 87.5%, vs. 54%). Acute lesions (82%, vs. 37.5%; p = 0.07) with neutrophilic alveolitis (63.6% vs. 0%, respectively; p = 0.01) were observed more frequently in the non-ICU group. Viral RNA was detected in 12 lung biopsies (60%) up to 56 days after disease upset. TEM detected viral particles in the lung and kidney biopsy samples up to 27 days after disease upset. Furthermore, abundant networks of double-membrane vesicles (DMVs, a hallmark of viral replication) were observed in proximal tubular epithelial cells. Conclusion: Lung injury was different in ICU and non-ICU patients. Extrapulmonary damage consisting in kidney and myocardial injury were more frequent in ICU patients. Our TEM experiments provided the first description of SARS-CoV-2-induced DMVs in kidney biopsy samples-a sign of intense viral replication in this organ.

2.
Intensive Care Med ; 48(6): 667-678, 2022 06.
Article in English | MEDLINE | ID: covidwho-1899121

ABSTRACT

PURPOSE: Severely ill patients affected by coronavirus disease 2019 (COVID-19) develop circulatory failure. We aimed to report patterns of left and right ventricular dysfunction in the first echocardiography following admission to intensive care unit (ICU). METHODS: Retrospective, descriptive study that collected echocardiographic and clinical information from severely ill COVID-19 patients admitted to 14 ICUs in 8 countries. Patients admitted to ICU who received at least one echocardiography between 1st February 2020 and 30th June 2021 were included. Clinical and echocardiographic data were uploaded using a secured web-based electronic database (REDCap). RESULTS: Six hundred and seventy-seven patients were included and the first echo was performed 2 [1, 4] days after ICU admission. The median age was 65 [56, 73] years, and 71% were male. Left ventricle (LV) and/or right ventricle (RV) systolic dysfunction were found in 234 (34.5%) patients. 149 (22%) patients had LV systolic dysfunction (with or without RV dysfunction) without LV dilatation and no elevation in filling pressure. 152 (22.5%) had RV systolic dysfunction. In 517 patients with information on both paradoxical septal motion and quantitative RV size, 90 (17.4%) had acute cor pulmonale (ACP). ACP was associated with mechanical ventilation (OR > 4), pulmonary embolism (OR > 5) and increased PaCO2. Exploratory analyses showed that patients with ACP and older age were more likely to die in hospital (including ICU). CONCLUSION: Almost one-third of this cohort of critically ill COVID-19 patients exhibited abnormal LV and/or RV systolic function in their first echocardiography assessment. While LV systolic dysfunction appears similar to septic cardiomyopathy, RV systolic dysfunction was related to pressure overload due to positive pressure ventilation, hypercapnia and pulmonary embolism. ACP and age seemed to be associated with mortality in this cohort.


Subject(s)
COVID-19 , Heart Failure , Hypertension, Pulmonary , Pulmonary Embolism , Ventricular Dysfunction, Left , Ventricular Dysfunction, Right , Aged , Echocardiography , Female , Humans , Intensive Care Units , Male , Retrospective Studies , Ventricular Dysfunction, Right/diagnostic imaging
3.
Int J Mol Sci ; 23(11)2022 May 31.
Article in English | MEDLINE | ID: covidwho-1869643

ABSTRACT

The endothelium has a fundamental role in the cardiovascular complications of coronavirus disease 2019 (COVID-19). Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) particularly affects endothelial cells. The virus binds to the angiotensin-converting enzyme 2 (ACE-2) receptor (present on type 2 alveolar cells, bronchial epithelial cells, and endothelial cells), and induces a cytokine storm. The cytokines tumor necrosis factor alpha, interleukin-1 beta, and interleukin-6 have particular effects on endothelial cells-leading to endothelial dysfunction, endothelial cell death, changes in tight junctions, and vascular hyperpermeability. Under normal conditions, apoptotic endothelial cells are removed into the bloodstream. During COVID-19, however, endothelial cells are detached more rapidly, and do not regenerate as effectively as usual. The loss of the endothelium on the luminal surface abolishes all of the vascular responses mediated by the endothelium and nitric oxide production in particular, which results in greater contractility. Moreover, circulating endothelial cells infected with SARS-CoV-2 act as vectors for viral dissemination by forming clusters that migrate into the circulation and reach distant organs. The cell clusters and the endothelial dysfunction might contribute to the various thromboembolic pathologies observed in COVID-19 by inducing the formation of intravascular microthrombi, as well as by triggering disseminated intravascular coagulation. Here, we review the contributions of endotheliopathy and endothelial-cell-derived extracellular vesicles to the pathogenesis of COVID-19, and discuss therapeutic strategies that target the endothelium in patients with COVID-19.


Subject(s)
COVID-19 , Vascular Diseases , COVID-19/complications , Cytokines/metabolism , Endothelial Cells/metabolism , Endothelium, Vascular/metabolism , Humans , SARS-CoV-2 , Vascular Diseases/metabolism
4.
Crit Care ; 26(1): 12, 2022 01 04.
Article in English | MEDLINE | ID: covidwho-1608868

ABSTRACT

BACKGROUND: In the context of acute respiratory distress syndrome (ARDS), the response to lung recruitment maneuvers (LRMs) varies considerably from one patient to another and so is difficult to predict. The aim of the study was to determine whether or not the recruitment-to-inflation (R/I) ratio could differentiate between patients according to the change in lung mechanics during the LRM. METHODS: We evaluated the changes in gas exchange and respiratory mechanics induced by a stepwise LRM at a constant driving pressure of 15 cmH2O during pressure-controlled ventilation. We assessed lung recruitability by measuring the R/I ratio. Patients were dichotomized with regard to the median R/I ratio. RESULTS: We included 30 patients with moderate-to-severe ARDS and a median [interquartile range] R/I ratio of 0.62 [0.42-0.83]. After the LRM, patients with high recruitability (R/I ratio ≥ 0.62) presented an improvement in the PaO2/FiO2 ratio, due to significant increase in respiratory system compliance (33 [27-42] vs. 42 [35-60] mL/cmH2O; p < 0.001). In low recruitability patients (R/I < 0.62), the increase in PaO2/FiO2 ratio was associated with a significant decrease in pulse pressure as a surrogate of cardiac output (70 [55-85] vs. 50 [51-67] mmHg; p = 0.01) but not with a significant change in respiratory system compliance (33 [24-47] vs. 35 [25-47] mL/cmH2O; p = 0.74). CONCLUSION: After the LRM, patients with high recruitability presented a significant increase in respiratory system compliance (indicating a gain in ventilated area), while those with low recruitability presented a decrease in pulse pressure suggesting a drop in cardiac output and therefore in intrapulmonary shunt.


Subject(s)
COVID-19 , Lung , Respiratory Distress Syndrome , COVID-19/complications , Humans , Lung/physiopathology , Positive-Pressure Respiration , Respiratory Distress Syndrome/therapy , Respiratory Distress Syndrome/virology , SARS-CoV-2
5.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-296420

ABSTRACT

Purpose: The objective of the present study was to provide a detailed histopathological description of fatal coronavirus disease 2019 (COVID 19), and compare the lesions in Intensive Care Unit (ICU) and non-ICU patients.<br><br>Methods: In this prospective study we included adult patients who died in hospital after presenting with probable or confirmed COVID-19. Multiorgan biopsies were performed. Data generated with light microscopy, transmission electron microscopy (TEM) and RT-PCR assays were reviewed.Results20 patients were enrolled in the study and the main pulmonary finding was alveolar damage, which was focal in 11 patients and diffuse in 8 patients. Chronic fibrotic and inflammatory lesions were observed in 18 cases, with acute inflammatory lesions in 12 cases. Diffuse lesions, collapsed alveoli and dystrophic pneumocytes were more frequent in the ICU group (62.5%, vs. 25%;63%, vs. 55%;87.5%, vs. 54%). Acute lesions (82%, vs. 37.5%;p=0.07) with neutrophilic alveolitis (63.6% vs. 0%, respectively;p=0.01) were observed more frequently in the non-ICU group. Viral RNA was detected in 12 lung biopsies (60%) up to 56 days after disease upset. TEM detected viral particles in the lung and kidney biopsy samples up to 27 days after disease upset. Furthermore, abundant networks of double-membrane vesicles (DMVs, a hallmark of viral replication) were observed in proximal tubular epithelial cells.<br><br>Conclusion: Lung injury was different in ICU and non-ICU patients. Extrapulmonary damage was also involved. Our TEM experiments provided the first description of SARS-CoV-2-induced DMVs in kidney biopsy samples – a sign of intense viral replication in this organ.<br><br>Funding Information: This research did not receive any specific funding from agencies or organizations in the public, commercial, or not-for-profit sectors.<br><br>Declaration of Interests: The authors report no disclosures of relevance to the manuscript.<br><br>Ethics Approval Statement: The study was approved by the French Ministry of Health. Informed consent was obtained from all patient families.

6.
J Crit Care ; 64: 141-143, 2021 08.
Article in English | MEDLINE | ID: covidwho-1193376

ABSTRACT

Airway closure is a physiological phenomenon in which the distal airways are obstructed when the airway pressure drops below the airway opening pressure. We assessed this phenomenon in 27 patients with coronavirus disease 2019-related acute respiratory distress syndrome. Twelve (44%) patients had an airway opening pressure above 5 cmH2O. The median airway opening pressure was 8 cmH2O (interquartile range, 7-10), with a maximum value of 17 cmH2O. Three patients had a baseline positive end-expiratory pressure lower than the airway opening pressure.


Subject(s)
COVID-19/physiopathology , COVID-19/therapy , Positive-Pressure Respiration/methods , Respiratory Distress Syndrome/physiopathology , Respiratory Distress Syndrome/therapy , SARS-CoV-2 , Adult , Aged , Airway Obstruction/prevention & control , Critical Care , Female , France/epidemiology , Humans , Male , Middle Aged , Respiratory Mechanics
8.
Eur Heart J Cardiovasc Pharmacother ; 7(5): 426-434, 2021 09 21.
Article in English | MEDLINE | ID: covidwho-596784

ABSTRACT

AIMS: To describe the characteristics of patients hospitalized with COVID-19 (including their long-term at-home medication use), and compare them with regard to the course of the disease. To assess the association between renin-angiotensin system inhibitors (RASIs) and disease progression and critical outcomes. METHODS AND RESULTS: All consecutive hospitalized patients with laboratory-confirmed COVID-19 in a university hospital in Amiens (France) were included in this study. The primary composite endpoint was admission to an intensive care unit (ICU) or death before ICU admission. Univariable and multivariable logistic regression models were used to identify factors associated with the composite endpoint. Between 28 February 2020 and 30 March 2020, a total of 499 local patients tested positive for SARS-CoV-2. Of these, 231 were not hospitalized {males 33%; median [interquartile range (IQR)] age: 44 (32-54)}, and 268 were hospitalized [males 58%; median (IQR) age: 73 (61-84)]. A total of 116 patients met the primary endpoint: 47 died before ICU admission, and 69 were admitted to the ICU. Patients meeting the primary endpoint were more likely than patients not meeting the primary endpoint to have coronary heart disease and to have been taking RASIs; however, the two subsets of patients did not differ with regard to median age. After adjustment for other associated variables, the risk of meeting the composite endpoint was 1.73 times higher (odds ratio 1.73, 95% confidence interval 1.02-2.93) in patients treated at baseline with a RASI than in patients not treated with this drug class. This association was confirmed when the analysis was restricted to patients treated with antihypertensive agents. CONCLUSIONS: We highlighted a potential safety signal for RASIs, the long-term use of which was independently associated with a higher risk of severe COVID-19 and a poor outcome. Due to the widespread use of this important drug class, formal proof based on clinical trials is needed to better understand the association between RASIs and complications of COVID-19.


Subject(s)
Antihypertensive Agents/adverse effects , COVID-19/complications , Renin-Angiotensin System/drug effects , SARS-CoV-2 , Adult , Age Factors , Aged , Aged, 80 and over , Female , Humans , Hypertension/drug therapy , Intensive Care Units , Logistic Models , Male , Middle Aged , Retrospective Studies
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