SARS-CoV-2: Is the liver merely a bystander to severe disease?

Bangash, Mansoor N.; Patel, Jaimin; Parekh, Dhruv; Murphy, Nick; Brown, Rachel M.; Elsharkawy, Ahmed M.; Mehta, Gautam; Armstrong, Matthew J.; Neil, Desley

doi:10.1016/j.jhep.2020.05.035

Cited by 47 publications

(48 citation statements)

References 10 publications

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“…Although the association between LEE and poorer outcome is now consolidated and supported by evidence on large cohorts of patients [ 17 , 18 , 20 , 25 , 26 ], the reasons for this are still to be clarified. In fact, LEE have been proposed to be innocent bystanders [ 32 ] of a systemic damage, while deaths linked to liver insufficiency have been rarely reported in the course of COVID-19 [ 33 , 34 ]. Although we found several factors associated with LEE, they showed an inverse association with factors commonly related to poor prognosis, such as older age [ 15 ], diabetes [ 35 ] or chronic kidney disease [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

Higher Mortality and Intensive Care Unit Admissions in COVID-19 Patients with Liver Enzyme Elevations

et al. 2020

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The aim of the present study is to evaluate if an independent association exists between liver enzyme elevations (LEE) and the risk of mortality or intensive care unit (ICU) admissions in patients with COVID-19. This was a single-center observational study, recruiting all consecutive adults with COVID-19. The elevation of aspartate aminotransferase (AST) or alanine aminotransferase (ALT) to the highest level between COVID-19 diagnosis and hospital discharge was categorized according to a standardized toxicity grade scale. In total, 799 patients were included in this study, 39% of which were female, with a mean age of 69.9 (±16.0) years. Of these patients, 225 (28.1%) developed LEE of grade ≥2 after a median of three days (interquartile range (IQR): 0–8 days) from the diagnosis of COVID-19, and they were estimated to have a higher hazard of death or ICU admission (adjusted hazard ratio (aHR): 1.46, 95% confidence interval (CI): 1.14–1.88). The clinical and laboratory variables associated with the development of LEE were male sex, higher respiratory rate, higher gamma glutamyl transpeptidase (GGT) and lower albumin levels at baseline. Among the analyzed treatments, steroids, tocilizumab and darunavir/ritonavir correlated with LEE. In conclusion, LEE were associated with mortality and ICU admission among COVID-19 patients. While the origin of LEE is probably multifactorial, LEE evaluation could add information to the clinical and laboratory variables that are commonly evaluated during the course of COVID-19.

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Section: Discussionmentioning

confidence: 99%

Higher Mortality and Intensive Care Unit Admissions in COVID-19 Patients with Liver Enzyme Elevations

et al. 2020

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“…Finally, electron microscopy of two post-mortem liver samples identified coronavirus-like particles in hepatocytes together with mitochondrial swelling, ER dilatation and massive hepatic apoptosis (19). However, no immunolabeling of these particles was performed raising concerns as to the specificity of these particles in post-mortem autolyzed samples (44). In summary, based on current knowledge, most liver-related pathological findings appear to be related to underlying co-morbidities such as NAFLD or ICU care rather than due to SARS-COV-2.…”

Section: Histopathological Findingsmentioning

confidence: 99%

Liver Disease and Coronavirus Disease 2019: From Pathogenesis to Clinical Care

et al. 2021

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Infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus that emerged in late 2019, is posing an unprecedented challenge to global health. Coronavirus disease 2019 (COVID-19), the clinical disease caused by SARS-CoV-2, has a variable presentation ranging from asymptomatic infection to life-threatening acute respiratory distress syndrome and multiorgan failure. Liver involvement is common during COVID-19 and exhibits a spectrum of clinical manifestations from asymptomatic elevations of liver function tests to hepatic decompensation. The presence of abnormal liver tests has been associated with a more severe presentation of COVID-19 disease and overall mortality. Although SARS-CoV-2 RNA has been detected in the liver of patients with COVID-19, it remains unclear whether SARS-CoV-2 productively infects and replicates in liver cells and has a direct liver-pathogenic effect. The cause of liver injury in COVID-19 can be attributed to multiple factors, including virus-induced systemic inflammation, hypoxia, hepatic congestion, and drug-induced liver disease. Among patients with cirrhosis, COVID-19 has been associated with hepatic decompensation and liver-related mortality. Additionally, COVID-19's impact on health care resources can adversely affect delivery of care and outcomes of patients with chronic liver disease. Understanding the underlying mechanisms of liver injury during COVID-19 will be important in the management of patients with COVID-19, especially those with advanced liver disease. This review summarizes our current knowledge of SARS-CoV-2 virus-host interactions in the liver as well the clinical impact of liver disease in COVID-19. (Hepatology 2021;74:1088-1100). Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was officially declared a pandemic by the World Health Organization in March 2020. COVID-19 has a variable presentation ranging from an asymptomatic illness to severe pneumonia with acute respiratory distress syndrome, accompanied by multiorgan failure, shock, and severe thromboembolic events. The most common clinical features reported among patients who were symptomatic include fever, dry cough, shortness of breath, anosmia and ageusia, and diarrhea.Coronaviruses are enveloped, positive-sense, singlestranded RNA viruses belonging to the Coronaviridae family, responsible for mild upper respiratory and gastrointestinal tract infections in humans. Two emerging members of the Coronaviridae family were previously demonstrated to pose a major public health threat, namely the severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle Eastern respiratory syndrome coronavirus (MERS)-CoV. In December 2019, the first cases of viral pneumonia caused by a novel coronavirus (SARS-CoV-2) was reported. Over the ensuing months, the virus has rapidly spread globally, resulting in over 50 million infected persons and one million deaths, exceeding other major infectious causes of death worldwide.

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“…Autopsy studies have established the morphological changes associated with COVID-19 and have tried to visualise the virus in tissues. [5][6][7][8][9] Transmission electron microscopy (TEM) seems to be a logical tool to look for SARS-CoV-2 infection, but some of the published results are highly contested (kidney, 8,[10][11][12][13][14][15][16][17][18][19][20][21][22] endothelium, 8,9,[23][24][25][26][27][28] intestine, 8 liver [29][30][31][32] and placenta [33][34][35][36][37] ). Because most of us are not virologists or electron microscopists dedicated to the study of viral diseases, this review aims at combining multidisciplinary expertise of SARS-CoV-2 pathology, virology and electron microscopy.…”

Section: Introductionmentioning

confidence: 99%

Hunting coronavirus by transmission electron microscopy – a guide to SARS‐CoV‐2‐associated ultrastructural pathology in COVID‐19 tissues

et al. 2020

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Transmission electron microscopy has become a valuable tool to investigate tissues of COVID‐19 patients because it allows visualisation of SARS‐CoV‐2, but the “virus‐like particles” described in several organs have been highly contested. Because most electron microscopists in pathology are not accustomed to analysing viral particles and subcellular structures, our review aims to discuss the ultrastructural changes associated with SARS‐CoV‐2 infection and COVID‐19 with respect to pathology, virology, and electron microscopy. Using micrographs from infected cell cultures and autopsy tissues, we show how coronavirus replication affects ultrastructure and put the morphological findings in the context of viral replication, which induces extensive remodelling of the intracellular membrane systems. Virions assemble by budding into the endoplasmic reticulum‐Golgi intermediate complex and are characterized by electron dense dots of cross‐sections of the nucleocapsid inside the viral particles. Physiological mimickers such as multivesicular bodies or coated vesicles serve as perfect decoys. Compared to other in‐situ techniques, transmission electron microscopy is the only method to visualize assembled virions in tissues and will be required to prove SARS‐CoV‐2 replication outside the respiratory tract. In practice, documenting in tissues the characteristic features seen in infected cell cultures, seems to be much more difficult than anticipated. In our view, the hunt for coronavirus by transmission electron microscopy is still on.

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SARS-CoV-2: Is the liver merely a bystander to severe disease?

Cited by 47 publications

References 10 publications

Higher Mortality and Intensive Care Unit Admissions in COVID-19 Patients with Liver Enzyme Elevations

Higher Mortality and Intensive Care Unit Admissions in COVID-19 Patients with Liver Enzyme Elevations

Liver Disease and Coronavirus Disease 2019: From Pathogenesis to Clinical Care

Hunting coronavirus by transmission electron microscopy – a guide to SARS‐CoV‐2‐associated ultrastructural pathology in COVID‐19 tissues

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