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1.
Virchows Arch ; 479(1): 97-108, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1574264

ABSTRACT

Between April and June 2020, i.e., during the first wave of pandemic coronavirus disease 2019 (COVID-19), 55 patients underwent long-term treatment in the intensive care unit at the University Hospital of Regensburg. Most of them were transferred from smaller hospitals, often due to the need for an extracorporeal membrane oxygenation system. Autopsy was performed in 8/17 COVID-19-proven patients after long-term treatment (mean: 33.6 days). Autopsy revealed that the typical pathological changes occurring during the early stages of the disease (e.g., thrombosis, endothelitis, capillaritis) are less prevalent at this stage, while severe diffuse alveolar damage and especially coinfection with different fungal species were the most conspicuous finding. In addition, signs of macrophage activation syndrome was detected in 7 of 8 patients. Thus, fungal infections were a leading cause of death in our cohort of severely ill patients and may alter clinical management of patients, particularly in long-term periods of treatment.


Subject(s)
COVID-19/microbiology , Coinfection , Lung Diseases, Fungal/microbiology , Lung/microbiology , Multiple Organ Failure/microbiology , Adult , Aged , COVID-19/drug therapy , COVID-19/mortality , COVID-19/pathology , COVID-19/therapy , Cause of Death , Extracorporeal Membrane Oxygenation , Female , Humans , Intensive Care Units , Lung/pathology , Lung/virology , Lung Diseases, Fungal/mortality , Lung Diseases, Fungal/pathology , Macrophage Activation Syndrome/microbiology , Macrophage Activation Syndrome/pathology , Male , Middle Aged , Multiple Organ Failure/mortality , Multiple Organ Failure/pathology , Multiple Organ Failure/virology , Risk Factors , Time Factors , Treatment Outcome
2.
Front Immunol ; 12: 740260, 2021.
Article in English | MEDLINE | ID: covidwho-1506482

ABSTRACT

Increased left ventricular fibrosis has been reported in patients hospitalized with coronavirus disease 2019 (COVID-19). It is unclear whether this fibrosis is a consequence of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection or a risk factor for severe disease progression. We observed increased fibrosis in the left ventricular myocardium of deceased COVID-19 patients, compared with matched controls. We also detected increased mRNA levels of soluble interleukin-1 receptor-like 1 (sIL1-RL1) and transforming growth factor ß1 (TGF-ß1) in the left ventricular myocardium of deceased COVID-19 patients. Biochemical analysis of blood sampled from patients admitted to the emergency department (ED) with COVID-19 revealed highly elevated levels of TGF-ß1 mRNA in these patients compared to controls. Left ventricular strain measured by echocardiography as a marker of pre-existing cardiac fibrosis correlated strongly with blood TGF-ß1 mRNA levels and predicted disease severity in COVID-19 patients. In the left ventricular myocardium and lungs of COVID-19 patients, we found increased neuropilin-1 (NRP-1) RNA levels, which correlated strongly with the prevalence of pulmonary SARS-CoV-2 nucleocapsid. Cardiac and pulmonary fibrosis may therefore predispose these patients to increased cellular viral entry in the lung, which may explain the worse clinical outcome observed in our cohort. Our study demonstrates that patients at risk of clinical deterioration can be identified early by echocardiographic strain analysis and quantification of blood TGF-ß1 mRNA performed at the time of first medical contact.


Subject(s)
COVID-19/physiopathology , Heart Ventricles/pathology , Myocardium/pathology , Pulmonary Fibrosis/physiopathology , SARS-CoV-2/physiology , Adult , Aged , COVID-19/immunology , Female , Fibrosis , Heart Ventricles/metabolism , Humans , Interleukin-1 Receptor-Like 1 Protein/genetics , Interleukin-1 Receptor-Like 1 Protein/metabolism , Male , Middle Aged , Myocardium/metabolism , Neuropilin-1/genetics , Neuropilin-1/metabolism , Pulmonary Fibrosis/immunology , Risk , Severity of Illness Index , Transforming Growth Factor beta1/genetics , Transforming Growth Factor beta1/metabolism , Viral Load
4.
ESC Heart Fail ; 8(1): 309-316, 2021 02.
Article in English | MEDLINE | ID: covidwho-1064347

ABSTRACT

AIMS: We aimed to assess whether expression of whole-blood RNA of sodium proton exchanger 1 (NHE1) and glucose transporter 1 (GLUT1) is associated with COVID-19 infection and outcome in patients presenting to the emergency department with respiratory infections. Furthermore, we investigated NHE1 and GLUT1 expression in the myocardium of deceased COVID-19 patients. METHODS AND RESULTS: Whole-blood quantitative assessment of NHE1 and GLUT1 RNA was performed using quantitative PCR in patients with respiratory infection upon first contact in the emergency department and subsequently stratified by SARS-CoV-2 infection status. Assessment of NHE1 and GLUT1 RNA using PCR was also performed in left ventricular myocardium of deceased COVID-19 patients. NHE1 expression is up-regulated in whole blood of patients with COVID-19 compared with other respiratory infections at first medical contact in the emergency department (control: 0.0021 ± 0.0002, COVID-19: 0.0031 ± 0.0003, P = 0.01). The ratio of GLUT1 to NHE1 is significantly decreased in the blood of COVID-19 patients who are subsequently intubated and/or die (severe disease) compared with patients with moderate disease (moderate disease: 0.497 ± 0.083 vs. severe disease: 0.294 ± 0.0336, P = 0.036). This ratio is even further decreased in the myocardium of patients who deceased from COVID-19 in comparison with the myocardium of non-infected donors. CONCLUSIONS: NHE1 and GLUT1 may be critically involved in the disease progression of SARS-CoV-2 infection. We show here that SARS-CoV-2 infection critically disturbs ion channel expression in the heart. A decreased ratio of GLUT1/NHE1 could potentially serve as a biomarker for disease severity in patients with COVID-19.


Subject(s)
COVID-19/metabolism , Glucose Transporter Type 1/blood , Sodium-Hydrogen Exchanger 1/blood , COVID-19/blood , COVID-19/diagnosis , Case-Control Studies , Emergency Service, Hospital , Female , Glucose Transporter Type 1/metabolism , Humans , Male , Middle Aged , Polymerase Chain Reaction , Predictive Value of Tests , Prospective Studies , RNA, Messenger/blood , Severity of Illness Index , Sodium-Hydrogen Exchanger 1/metabolism
5.
Int J Infect Dis ; 103: 624-627, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-1065181

ABSTRACT

A 21-year-old woman was hospitalized due to coronavirus disease 2019 (COVID-19)-associated respiratory and hepatic impairment concomitant with severe hemolytic anemia. Upon diagnosis of secondary hemophagocytic lymphohistiocytosis, immunosuppression with anakinra and steroids was started, leading to a hepatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and viremia. Subsequent liver biopsy revealed virus particles in hepatocytes by electron microscopy and SARS-CoV-2 virus could be isolated and cultured. Immunosuppression was stopped and convalescent donor plasma given. In the differential diagnosis, an acute crisis of Wilson's disease was raised by laboratory and genetic testing. This case highlights the complexity of balancing immunosuppression to control hyperinflammation versus systemic SARS-CoV-2 dissemination.


Subject(s)
COVID-19/complications , Hepatolenticular Degeneration/diagnosis , Liver/virology , Lymphohistiocytosis, Hemophagocytic/etiology , SARS-CoV-2 , Diagnosis, Differential , Female , Humans , Lymphohistiocytosis, Hemophagocytic/diagnosis , Young Adult
6.
EJHaem ; 2020 Jun 29.
Article in English | MEDLINE | ID: covidwho-629713

ABSTRACT

The clinical course of coronavirus disease 2019 (COVID-19) varies from mild symptoms to acute respiratory distress syndrome, hyperinflammation, and coagulation disorder. The hematopoietic system plays a critical role in the observed hyperinflammation, particularly in severely ill patients. We conducted a prospective diagnostic study performing a blood differential analyzing morphologic changes in peripheral blood of COVID-19 patients. COVID-19 associated morphologic changes were defined in a training cohort and subsequently validated in a second cohort (n = 45). Morphologic aberrations were further analyzed by electron microscopy (EM) and flow cytometry of lymphocytes was performed. We included 45 COVID-19 patients in our study (median age 58 years; 82% on intensive care unit). The blood differential showed a specific pattern of pronounced multi-lineage aberrations in lymphocytes (80%) and monocytes (91%) of patients. Overall, 84%, 98%, and 98% exhibited aberrations in granulopoiesis, erythropoiesis, and thrombopoiesis, respectively. Electron microscopy revealed the ultrastructural equivalents of the observed changes and confirmed the multi-lineage aberrations already seen by light microscopy. The morphologic pattern caused by COVID-19 is characteristic and underlines the serious perturbation of the hematopoietic system. We defined a hematologic COVID-19 pattern to facilitate further independent diagnostic analysis and to investigate the impact on the hematologic system during the clinical course of COVID-19 patients.

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