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1.
JCI Insight ; 6(14)2021 07 22.
Article in English | MEDLINE | ID: covidwho-1320462

ABSTRACT

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains a pandemic. Severe disease is associated with dysfunction of multiple organs, but some infected cells do not express ACE2, the canonical entry receptor for SARS-CoV-2. Here, we report that the C-type lectin receptor L-SIGN interacted in a Ca2+-dependent manner with high-mannose-type N-glycans on the SARS-CoV-2 spike protein. We found that L-SIGN was highly expressed on human liver sinusoidal endothelial cells (LSECs) and lymph node lymphatic endothelial cells but not on blood endothelial cells. Using high-resolution confocal microscopy imaging, we detected SARS-CoV-2 viral proteins within the LSECs from liver autopsy samples from patients with COVID-19. We found that both pseudo-typed virus enveloped with SARS-CoV-2 spike protein and authentic SARS-CoV-2 virus infected L-SIGN-expressing cells relative to control cells. Moreover, blocking L-SIGN function reduced CoV-2-type infection. These results indicate that L-SIGN is a receptor for SARS-CoV-2 infection. LSECs are major sources of the clotting factors vWF and factor VIII (FVIII). LSECs from liver autopsy samples from patients with COVID-19 expressed substantially higher levels of vWF and FVIII than LSECs from uninfected liver samples. Our data demonstrate that L-SIGN is an endothelial cell receptor for SARS-CoV-2 that may contribute to COVID-19-associated coagulopathy.


Subject(s)
COVID-19 , Capillaries , Cell Adhesion Molecules/metabolism , Endothelial Cells , Lectins, C-Type/metabolism , Liver/blood supply , Lymphatic Vessels , Receptors, Cell Surface/metabolism , SARS-CoV-2/physiology , COVID-19/metabolism , COVID-19/pathology , COVID-19/virology , Capillaries/metabolism , Capillaries/pathology , Capillaries/virology , Endothelial Cells/metabolism , Endothelial Cells/pathology , Endothelial Cells/virology , Gene Expression Profiling/methods , Humans , Liver/pathology , Lymphatic Vessels/metabolism , Lymphatic Vessels/pathology , Lymphatic Vessels/virology , Spike Glycoprotein, Coronavirus , Virus Internalization
2.
World J Gastroenterol ; 26(48): 7693-7706, 2020 Dec 28.
Article in English | MEDLINE | ID: covidwho-1073508

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) disease can frequently affect the liver. Data on hepatic histopathological findings in COVID-19 is scarce. AIM: To characterize hepatic pathological findings in patients with COVID-19. METHODS: We conducted a systematic review with meta-analysis registered on PROSPERO (CRD42020192813), following PRISMA guidelines. Eligible trials were those including patients of any age and COVID-19 diagnosis based on a molecular test. Histopathological reports from deceased COVID-19 patients undergoing autopsy or liver biopsy were reviewed. Articles including less than ten patients were excluded. Proportions were pooled using random-effects models. Q statistic and I 2 were used to assess heterogeneity and levels of evidence, respectively. RESULTS: We identified 18 studies from 7 countries; all were case reports and case series from autopsies. All the patients were over 15 years old, and 67.2% were male. We performed a meta-analysis of 5 studies, including 116 patients. Pooled prevalence estimates of liver histopathological findings were hepatic steatosis 55.1% [95% confidence interval (CI): 46.2-63.8], congestion of hepatic sinuses 34.7% (95%CI: 7.9-68.4), vascular thrombosis 29.4% (95%CI: 0.4-87.2), fibrosis 20.5% (95%CI: 0.6-57.9), Kupffer cell hyperplasia 13.5% (95%CI: 0.6-54.3), portal inflammation 13.2% (95%CI: 0.1-48.8), and lobular inflammation 11.6% (95%CI: 0.3-35.7). We also identified the presence of venous outflow obstruction, phlebosclerosis of the portal vein, herniated portal vein, periportal abnormal vessels, hemophagocytosis, and necrosis. CONCLUSION: We found a high prevalence of hepatic steatosis and vascular thrombosis as major histological liver features. Other frequent findings included portal and lobular inflammation and Kupffer cell hyperplasia or proliferation. Further studies are needed to establish the mechanisms and implications of these findings.


Subject(s)
COVID-19/complications , Fatty Liver/epidemiology , Hepatic Veins/pathology , Liver/pathology , Venous Thrombosis/epidemiology , COVID-19/diagnosis , COVID-19/mortality , COVID-19/virology , Fatty Liver/etiology , Fatty Liver/pathology , Humans , Kupffer Cells/pathology , Liver/blood supply , Liver/cytology , Prevalence , SARS-CoV-2/isolation & purification , SARS-CoV-2/pathogenicity , Venous Thrombosis/etiology , Venous Thrombosis/pathology
4.
Am J Gastroenterol ; 116(5): 1077-1082, 2021 05 01.
Article in English | MEDLINE | ID: covidwho-1034416

ABSTRACT

INTRODUCTION: Liver chemistry abnormalities are a frequent manifestation of coronavirus disease 2019 (COVID-19) but are usually transient and resolve with disease resolution. METHODS: We describe the clinical course and histologic features of 3 adults who developed prolonged and severe cholestasis during recovery from critical cardiopulmonary COVID-19. RESULTS: These patients had clinical and histologic features similar to secondary sclerosing cholangitis of the critically ill patient, but with unique histologic features including severe cholangiocyte injury and intrahepatic microangiopathy suggestive of direct hepatic injury from COVID-19. DISCUSSION: We believe that these cases constitute a novel severe post-COVID-19 cholangiopathy with potential for long-term hepatic morbidity.


Subject(s)
COVID-19/complications , Cholangitis , Liver Function Tests/methods , Liver , Adult , Biopsy/methods , COVID-19/blood , COVID-19/diagnosis , COVID-19/physiopathology , COVID-19/therapy , Cholangiopancreatography, Endoscopic Retrograde/methods , Cholangiopancreatography, Magnetic Resonance/methods , Cholangitis/diagnosis , Cholangitis/virology , Critical Care/methods , Critical Illness , Diagnosis, Differential , Endothelial Cells/pathology , Female , Humans , Liver/blood supply , Liver/diagnostic imaging , Liver/pathology , Male , SARS-CoV-2/isolation & purification , SARS-CoV-2/pathogenicity , Severity of Illness Index
5.
Discov Med ; 30(160): 107-112, 2020.
Article in English | MEDLINE | ID: covidwho-1001174

ABSTRACT

Liver injury has been reported as a common complication in Coronavirus disease 2019 (COVID-19). Recently, more and more studies reported that the degree of liver damages was associated with the severity of COVID-19. Although the exact mechanism of liver injury in COVID-19 patients is unknown, recent studies have made some explorations and investigations. In this review, we summarized the potential mechanisms of liver dysfunction in COVID-19 patients gleaned from recently published research reports, which suggested that the progression of pre-existing liver diseases, direct damage of liver by SARS-CoV-2, systemic inflammation caused by SARS-CoV-2 infection, anti-viral drug toxicity, and hypoxia-reperfusion may be associated with liver injury in patients with COVID-19. Hypoxic liver injury due to ischemia and shock, cholestasis-related liver injury due to altered bile metabolism, and hepatocellular injury due to drug toxicity or overwhelming inflammation might occur in severe COVID-19 patients with sepsis. To understand the pathogenesis of liver dysfunction in COVID-19 patients, further research is needed to focus on liver-related comorbidities, the evidence of viral replication in hepatocytes and bile duct cells, histological features of liver injury, and the influence of hepatotoxic antiviral drugs. We also suggested that special attention should be paid to monitoring inflammatory cytokines and hypoxia for the prevention and treatment of liver injury in severe COVID-19 patients. A deep understanding of the mechanism of liver injury is helpful for the management and treatment of COVID-19 patients.


Subject(s)
COVID-19/metabolism , Hypoxia/metabolism , Liver Diseases/metabolism , Liver/blood supply , Liver/metabolism , SARS-CoV-2/metabolism , Antiviral Agents/therapeutic use , COVID-19/complications , COVID-19/drug therapy , COVID-19/pathology , Humans , Hypoxia/drug therapy , Hypoxia/pathology , Inflammation/drug therapy , Inflammation/metabolism , Inflammation/pathology , Liver/pathology , Liver Diseases/drug therapy , Liver Diseases/etiology , Liver Diseases/pathology
6.
Liver Int ; 40(9): 2110-2116, 2020 09.
Article in English | MEDLINE | ID: covidwho-639586

ABSTRACT

SARS2-CoV-2 breakout in Italy caused a huge number of severely ill patients with a serious increase in mortality. Although lungs seem to be the main target of the infection, very few information are available about liver involvement, possibly evocating a systemic disease. Post-mortem wedge liver biopsies from 48 patients died from severe pulmonary COVID-19 disease with respiratory failure were collected from two main hospitals in northern Italy. No patient had clinical symptoms of liver disease or signs of liver failure before and during hospitalization; for each of them liver function tests were available. All liver samples showed minimal inflammation features. Histological pictures compatible with vascular alterations were observed, characterized by increase in number of portal vein branches associated with lumen massive dilatation, partial or complete luminal thrombosis of portal and sinusoidal vessels, fibrosis of portal tract, focally markedly enlarged and fibrotic. SARS-CoV-2 was found in 15 of 22 samples tested by in situ hybridization method. Our preliminary results confirm the clinical impression that liver failure is not a main concern and this organ is not the target of significant inflammatory damage. Histopathological findings are highly suggestive for marked derangement of intrahepatic blood vessel network secondary to systemic changes induced by virus that could target not only lung parenchyma but also cardiovascular system, coagulation cascade and endothelial layer of blood vessels. It still remains unclear if the mentioned changes are directly related to virus infection or if SARS-CoV-2 triggers a series of reactions leading to striking vascular alterations.


Subject(s)
Coronavirus Infections/pathology , Liver/pathology , Pneumonia, Viral/pathology , Portal Vein/pathology , Respiratory Insufficiency/pathology , Adult , Aged , Aged, 80 and over , Betacoronavirus , COVID-19 , Coronavirus Infections/complications , Female , Humans , Liver/blood supply , Liver/enzymology , Male , Middle Aged , Pandemics , Pneumonia, Viral/complications , Respiratory Insufficiency/virology , SARS-CoV-2
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