Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 21
Filter
1.
J Autoimmun ; 125: 102741, 2021 12.
Article in English | MEDLINE | ID: covidwho-1482678

ABSTRACT

The COVID-19 pandemic is still raging across the world and vaccination is expected to lead us out of this pandemic. Although the efficacy of the vaccines is beyond doubt, safety still remains a concern. We report a case of a 65-year-old woman who experienced acute severe autoimmune hepatitis two weeks after receiving the first dose of Moderna-COVID-19 vaccine. Serum immunoglobulin G was elevated and antinuclear antibody was positive (1:100, speckled pattern). Liver histology showed a marked expansion of the portal tracts, severe interface hepatitis and multiple confluent foci of lobular necrosis. She started treatment with prednisolone, with a favorable clinical and analytical evolution. Some recent reports have been suggested that COVID-19 vaccination can lead to the development of autoimmune diseases. It is speculated that the vaccine can disturb self-tolerance and trigger autoimmune responses through cross-reactivity with host cells. Therefore, healthcare providers must remain vigilant during mass COVID-19 vaccination.


Subject(s)
/adverse effects , COVID-19/prevention & control , Hepatitis, Autoimmune/etiology , Jaundice/etiology , Vaccination/adverse effects , Antibodies, Antinuclear/blood , Bilirubin/blood , Female , Fibrosis/pathology , Hepatitis, Autoimmune/immunology , Humans , Jaundice/diagnosis , Liver/enzymology , Middle Aged , Molecular Mimicry/immunology , Prednisolone/therapeutic use , SARS-CoV-2/immunology
2.
Iran J Med Sci ; 46(4): 237-255, 2021 07.
Article in English | MEDLINE | ID: covidwho-1395708

ABSTRACT

Background: The outbreak of the coronavirus disease-2019 (COVID-19) has become a global public health challenge. Assessing the effect of COVID-19 on liver injury is of great importance. A systematic review and meta-analysis were conducted to establish the characteristics of liver function tests in COVID-19 patients. Methods: A systematic search of publications from December 2019 up to April 2020 in Web of Science, Scopus, and Medline (via PubMed) databases was performed. Both cross-sectional and case series studies reporting an association between liver injury and COVID-19 infection were included. The data were analyzed using the STATA software (version 11.0) and the random-effects model for I2>50% was used to pool the results. Results: In this meta-analysis, 42 articles comprising a total of 6,557 COVID-19 patients were studied. The prevalence of increase in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels was 30% and 21% in non-severe patients and 38% and 48% in severe patients, respectively. Patients with severe COVID-19 infection were 4.22, 4.96, and 4.13 times more likely to have elevated AST, ALT, and lactate dehydrogenase (LDH) levels, respectively. Conclusion: Elevation in liver function tests was higher in patients with severe than non-severe COVID-19 infection. Given the widespread use of drugs that increases the risk of hepatotoxicity, healthcare providers should be aware of changes in liver enzymes in COVID-19 patients. The inclusion of other studies from outside China could confirm the pattern of elevation in liver function tests in COVID-19 patients across the globe. Preprint of this article is available on medRxiv, https://www.medrxiv.org/content/10.1101/2020.05.20.20108357v1.


Subject(s)
COVID-19/complications , Liver Diseases/virology , Liver Function Tests , Alanine Transaminase , Aspartate Aminotransferases , Humans , L-Lactate Dehydrogenase , Liver/enzymology , Liver Diseases/epidemiology
3.
Life Sci ; 284: 119881, 2021 Nov 01.
Article in English | MEDLINE | ID: covidwho-1347741

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an infectious disease that has spread worldwide. Current treatments are limited in both availability and efficacy, such that improving our understanding of the factors that facilitate infection is urgently needed to more effectively treat infected individuals and to curb the pandemic. We and others have previously demonstrated the significance of interactions between the SARS-CoV-2 spike protein, integrin α5ß1, and human ACE2 to facilitate viral entry into host cells in vitro. We previously found that inhibition of integrin α5ß1 by the clinically validated small peptide ATN-161 inhibits these spike protein interactions and cell infection in vitro. In continuation with our previous findings, here we have further evaluated the therapeutic potential of ATN-161 on SARS-CoV-2 infection in k18-hACE2 transgenic (SARS-CoV-2 susceptible) mice in vivo. We discovered that treatment with single or repeated intravenous doses of ATN-161 (1 mg/kg) within 48 h after intranasal inoculation with SARS-CoV-2 lead to a reduction of lung viral load, viral immunofluorescence, and improved lung histology in a majority of mice 72 h post-infection. Furthermore, ATN-161 reduced SARS-CoV-2-induced increased expression of lung integrin α5 and αv (an α5-related integrin that has also been implicated in SARS-CoV-2 interactions) as well as the C-X-C motif chemokine ligand 10 (Cxcl10), further supporting the potential involvement of these integrins, and the anti-inflammatory potential of ATN-161, respectively, in SARS-CoV-2 infection. To the best of our knowledge, this is the first study demonstrating the potential therapeutic efficacy of targeting integrin α5ß1 in SARS-CoV-2 infection in vivo and supports the development of ATN-161 as a novel SARS-CoV-2 therapy.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , COVID-19/drug therapy , COVID-19/prevention & control , Oligopeptides/therapeutic use , SARS-CoV-2/physiology , Alanine Transaminase/metabolism , Animals , Aspartate Aminotransferases/metabolism , COVID-19/virology , Genome, Viral , Humans , Integrins/metabolism , Liver/enzymology , Liver/pathology , Lung/pathology , Lung/virology , Male , Mice, Inbred C57BL , Mice, Transgenic , Oligopeptides/pharmacology , SARS-CoV-2/genetics , Staining and Labeling , Viral Load/genetics
6.
J Med Virol ; 93(4): 2365-2373, 2021 04.
Article in English | MEDLINE | ID: covidwho-1217386

ABSTRACT

Coronavirus disease 2019 (COVID-19) is a newly emerging infectious disease. Our understanding of the clinical characteristics of liver damage and the relationship with disease severity in COVID-19 is still limited. To investigate the serum hepatic enzyme activities in different phenotypes of COVID-19 patients, evaluate their relationship with the illness severity and analyze the correlation of glycyrrhizin treatment and abnormal liver enzyme activities, one hundred and forty-seven patients with COVID-19 were enrolled in a retrospective study that investigated hepatic dysfunction. Liver alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactic dehydrogenase (LDH), Y-glutamyl transferase (GGT), superoxide dismutase (SOD), and alkaline phosphatase (ALP) were analyzed in these patients. Patients with diammonium glycyrrhizinate (DG) treatment were further investigated. Of the 147 patients, 56 (38.1%) had abnormal ALT activity and 80 (54.4%) had abnormal AST activity. The peak of abnormal hepatic enzyme activities occurred at 3 to 6 days after on admission. Serum AST and LDH levels were elevated, while the SOD level was decreased in severe and critical patients, compared with mild cases. DG treatment may alleviate the abnormal liver enzyme activities in non-critical COVID-19 patients. Abnormal liver functions may be observed in patients with COVID-19, and were associated with SARS-CoV-2-induced acute liver damage. Glycyrrhizin treatment may be an effective therapeutic approach for the outcome of abnormal hepatic enzyme activities in severe COVID-19 cases. Serum hepatic enzyme tests may reflect the illness severity and should be monitored.


Subject(s)
COVID-19/enzymology , Liver/enzymology , Adult , Aged , Aged, 80 and over , Alanine Transaminase/blood , Alkaline Phosphatase/blood , Aspartate Aminotransferases/blood , COVID-19/blood , COVID-19/metabolism , Female , Humans , Liver/metabolism , Liver Function Tests , Male , Middle Aged , Phenotype , Retrospective Studies , SARS-CoV-2 , Severity of Illness Index , Superoxide Dismutase/blood , Young Adult
7.
Int Immunopharmacol ; 97: 107701, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1198830

ABSTRACT

SARS-CoV-2 or Coronavirus disease 2019 (COVID-19) outbreak which caused by the severe acute respiratory syndrome, has rapidly spread over the world. The exact mechanism how this virus will affect the liver remained elusive. The aim of this study was to evaluate the liver function in patients with severe acute respiratory syndrome coronavirus 2 and potential causes of hepatic enzymes disease in these patients. Clinical characteristics and laboratory findings were collected from patients with COVID-19 who were admitted to the corona center in Erbil city/Kurdistan region of Iraq, from March 10 to July 10, 2020. Serum was collected from patients with COVID-19 and liver enzyme tests were measured. Liver alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TBIL) were analyzed in these patients. Of the 74 patients, 25 (34.7%) had abnormal ALT activity, 28 (40%) had abnormal AST activity, 12 (20.3%) had abnormal ALP activity, and 39 (52.7%) had abnormal total bilirubin P-value < 0.05. The inflammatory biomarkers CRP and IL-6 in COVID-19 patients with abnormal liver function test (4.9 ± 1.0 mg/dl) and (231.2 ± 35.7 pg/ml) respectively. The levels of both biomarkers were statistically significantly higher than COVID-19 patients with normal liver function test (2.1 ± 0.5 mg/dl) and (2.1 ± 0.5 mg/dl) respectively, P-value < 0.05. However, CRP and IL-6 were not statistically significant different between male and female COVID-19 patients P-value < 0.05. In conclusion, we found that most of the patients with SARS-CoV-2 have abnormal hepatic enzyme activities and that is might related to virus replication in the liver.


Subject(s)
COVID-19/enzymology , COVID-19/virology , Liver/enzymology , Liver/virology , Adolescent , Adult , Aged , Alanine Transaminase/blood , Alkaline Phosphatase/blood , Aspartate Aminotransferases/blood , Bilirubin/blood , Biomarkers/blood , COVID-19/blood , COVID-19/complications , Carrier State/blood , Child , Female , Humans , Interleukin-6/blood , Liver Diseases/blood , Liver Diseases/enzymology , Liver Diseases/etiology , Liver Diseases/virology , Liver Function Tests , Male , Middle Aged , Receptors, Immunologic/blood , Young Adult
8.
Gut Liver ; 15(4): 606-615, 2021 07 15.
Article in English | MEDLINE | ID: covidwho-1158426

ABSTRACT

Background/Aims: Recent data indicate the presence of liver enzyme abnormalities in patients with coronavirus disease 2019 (COVID-19). We aimed to evaluate the clinical features and treatment outcomes of COVID-19 patients with abnormal liver enzymes. Methods: We performed a retrospective, multicenter study of 874 COVID-19 patients admitted to five tertiary hospitals from February 20 to April 14, 2020. Data on clinical features, laboratory parameters, medications, and treatment outcomes were collected until April 30, 2020, and compared between patients with normal and abnormal aminotransferases. Results: Abnormal aminotransferase levels were observed in 362 patients (41.1%), of which 94 out of 130 (72.3%) and 268 out of 744 (36.0%) belonged to the severe and non-severe COVID- 19 categories, respectively. The odds ratios (95% confidence interval) for male patients, patients with a higher body mass index, patients with severe COVID-19 status, and patients with lower platelet counts were 1.500 (1.029 to 2.184, p=0.035), 1.097 (1.012 to 1.189, p=0.024), 2.377 (1.458 to 3.875, p=0.001), and 0.995 (0.993 to 0.998, p>0.001), respectively, indicating an independent association of these variables with elevated aminotransferase levels. Lopinavir/ ritonavir and antibiotic use increased the odds ratio of abnormal aminotransferase levels after admission (1.832 and 2.646, respectively, both p<0.05). The median time to release from quarantine was longer (22 days vs 26 days, p=0.001) and the mortality rate was higher (13.0% vs 2.9%, p<0.001) in patients with abnormal aminotransferase levels. Conclusions: Abnormal aminotransferase levels are common in COVID-19 patients and are associated with poor clinical outcomes. Multivariate analysis of patients with normal aminotransferase levels on admission showed that the use of lopinavir/ritonavir and antibiotics was associated with abnormal aminotransferase levels; thus, careful monitoring is needed.


Subject(s)
COVID-19 , Liver Diseases , Aged , COVID-19/complications , Female , Humans , Liver/enzymology , Liver Diseases/virology , Male , Middle Aged , Prognosis , Retrospective Studies , Transaminases/analysis
9.
J Gastroenterol ; 56(5): 409-420, 2021 05.
Article in English | MEDLINE | ID: covidwho-1147593

ABSTRACT

Although primarily a respiratory illness, several studies have shown that COVID-19 causes elevation of liver enzymes and various gastrointestinal (GI) symptoms. The aim of this study was to undertake a systematic review and meta-analysis to determine whether the presence of gastrointestinal (GI) symptoms contributed toward COVID-19 severity, and identify the GI symptoms characteristic of severe COVID-19. We conducted a literature search of PubMed from December 1, 2019, to June 30, 2020, and identified all reports with GI symptoms reported. A meta-analysis comparing the severity of COVID-19 with the presence of liver enzyme elevation and GI symptoms was performed using RevMan version 5.4. Pooled data from 15,305 unique reverse transcriptase-polymerase chain reaction positive COVID-19 patients from 44 studies were analyzed. We found that the severe COVID-19 patients significantly had abdominal pain compared to the non-severe COVID-19 patients (OR = 2.70, 95% CI 1.17-6.27, Z = 2.32, p = 0.02, I2 = 0%) by analyzed 609 patients of 4 studies who reported both abdominal pain and COVID-19 severity. However, there was no significant difference in the incidence of diarrhea, nausea, or vomiting between the two groups. Thus, this systematic review and meta-analysis demonstrated that abdominal pain could be characteristic of severe COVID-19 infections. Compared with other viral infections that primarily infect the respiratory system, patients with COVID-19 have a slightly lower frequency of diarrheal symptoms with abdominal pain. However, to confirm this, further studies with COVID-19 patients across various countries and ethnicities are required.


Subject(s)
COVID-19/complications , Gastrointestinal Diseases/epidemiology , Liver/enzymology , Abdominal Pain/etiology , COVID-19/physiopathology , Diarrhea/epidemiology , Diarrhea/virology , Gastrointestinal Diseases/virology , Humans , Liver/virology , Nausea/epidemiology , Nausea/virology , Severity of Illness Index , Vomiting/epidemiology , Vomiting/virology
10.
Sci Rep ; 11(1): 5494, 2021 03 09.
Article in English | MEDLINE | ID: covidwho-1125236

ABSTRACT

It is important to pay attention to the indirect effects of the social distancing implemented to prevent the spread of coronavirus disease 2019 (COVID-19) pandemic on children and adolescent health. The aim of the present study was to explore impacts of a reduction in physical activity caused by COVID-19 outbreak in pediatric patients diagnosed with obesity. This study conducted between pre-school closing and school closing period and 90 patients aged between 6- and 18-year-old were included. Comparing the variables between pre-school closing period and school closing period in patients suffering from obesity revealed significant differences in variables related to metabolism such as body weight z-score, body mass index z-score, liver enzymes and lipid profile. We further evaluated the metabolic factors related to obesity. When comparing patients with or without nonalcoholic fatty liver disease (NAFLD), only hemoglobin A1c (HbA1c) was the only difference between the two time points (p < 0.05). We found that reduced physical activity due to school closing during COVID-19 pandemic exacerbated obesity among children and adolescents and negatively affects the HbA1C increase in NAFLD patients compared to non-NAFLD patients.


Subject(s)
COVID-19/pathology , Glucose Intolerance/diagnosis , Pediatric Obesity/diagnosis , Adolescent , Alanine Transaminase/analysis , Aspartate Aminotransferases/analysis , Body Mass Index , Body Weight , COVID-19/virology , Child , Exercise , Female , Glucose Intolerance/complications , Glycated Hemoglobin A/analysis , Humans , Lipids/analysis , Liver/enzymology , Male , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/diagnosis , Pediatric Obesity/complications , Quarantine , SARS-CoV-2/isolation & purification
11.
BMJ Open Gastroenterol ; 8(1)2021 03.
Article in English | MEDLINE | ID: covidwho-1119308

ABSTRACT

BACKGROUND AND AIMS: Patients infected with the SARS-CoV-2 usually report fever and respiratory symptoms. However, multiple gastrointestinal (GI) manifestations such as diarrhoea and abdominal pain have been described. The aim of this study was to evaluate the prevalence of GI symptoms, elevated liver enzymes and mortality of patients with COVID-19. METHODS: A systematic review and meta-analysis of published studies that included a cohort of patients infected with SARS-CoV-2 were performed from 1 December 2019 to 15 December 2020. Data were collected by conducting a literature search using PubMed, Embase, Scopus, and Cochrane according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We analysed pooled data on the prevalence of individual GI symptoms and elevated liver enzymes and performed subanalyses to investigate the relationship between GI symptoms/elevated liver enzymes, geographical location, mortality, and intensive care unit (ICU) admission. RESULTS: The available data of 78 798 patients positive for SARS-CoV-2 from 158 studies were included in our analysis. The most frequent manifestations were diarrhoea (16.5%, 95% CI 14.2% to 18.4%), nausea (9.7%, 95% CI 9.0% to 13.2%) and elevated liver enzymes (5.6%, 95% CI 4.2% to 9.1%). The overall mortality and GI mortality were 23.5% (95% CI 21.2% to 26.1%) and 3.5% (95% CI 3.1% to 6.2%), respectively. Subgroup analysis showed non-statistically significant associations between GI symptoms/elevated liver enzymes and ICU admissions (OR=1.01, 95% CI 0.55 to 1.83). The GI mortality was 0.9% (95% CI 0.5% to 2.2%) in China and 10.8% (95% CI 7.8% to 11.3%) in the USA. CONCLUSION: GI symptoms/elevated liver enzymes are common in patients with COVID-19. Our subanalyses showed that the presence of GI symptoms/elevated liver enzymes does not appear to affect mortality or ICU admission rate. Furthermore, the proportion of GI mortality among patients infected with SARS-CoV-2 varied based on geographical location.


Subject(s)
COVID-19/complications , Gastrointestinal Diseases/epidemiology , Gastrointestinal Diseases/virology , Liver Diseases/epidemiology , Liver Diseases/virology , COVID-19/mortality , Critical Care/statistics & numerical data , Gastrointestinal Diseases/mortality , Hospitalization/statistics & numerical data , Humans , Liver/enzymology , Liver Diseases/mortality , Pandemics , Prevalence , SARS-CoV-2 , Severity of Illness Index
12.
Expert Rev Vaccines ; 20(5): 623-634, 2021 05.
Article in English | MEDLINE | ID: covidwho-1118865

ABSTRACT

OBJECTIVE: Infectious disease emergencies like the 2013-2016 Ebola epidemic and the 2009 influenza and current SARS-CoV-2 pandemics illustrate that vaccines are now given to diverse populations with preexisting pathologies requiring pharmacological management. Many natural biomolecules (steroid hormones, fatty acids, vitamins) and ~60% of prescribed medications are processed by hepatic cytochrome P450 (CYP) 3A4. The objective of this work was to determine the impact of infection and vaccines on drug metabolism. METHODS: The impact of an adenovirus-based vaccine expressing Ebola glycoprotein (AdEBO) and H1N1 and H3N2 influenza viruses on hepatic CYP 3A4 and associated nuclear receptors was evaluated in human hepatocytes (HC-04 cells) and in mice. RESULTS: CYP3A activity was suppressed by 55% in mice 24 h after administration of mouse-adapted H1N1, while ˂10% activity remained in HC-04 cells after infection with H1N1 and H3N2 due to global suppression of cellular translation capacity, indicated by reduction (70%, H1N1, 56%, H3N2) of phosphorylated eukaryotic translation initiation factor 4e (eIF4E). AdEBO suppressed CYP3A activity in vivo (44%) and in vitro (26%) 24 hours after infection. CONCLUSION: As the clinical evaluation of vaccines for SARS-CoV-2 and other global pathogens rise, studies to evaluate the impact of new vaccines and emerging pathogens on CYP3A4 and other metabolic enzymes are warranted to avoid therapeutic failures that could further compromise the public health during infectious disease emergencies.


Subject(s)
Cytochrome P-450 CYP3A/metabolism , Hepatocytes/enzymology , Hepatocytes/metabolism , Liver/enzymology , Liver/metabolism , Pharmaceutical Preparations/metabolism , Animals , Cells, Cultured , Eukaryotic Initiation Factor-4E , Humans , Immunization/methods , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL
13.
Rev Esp Enferm Dig ; 113(7): 555, 2021 07.
Article in English | MEDLINE | ID: covidwho-1079863

ABSTRACT

After the publication of our meta-analysis, in which we demonstrated that aspartate aminotransferase (AST), alanine aminotransferase (ALT) and total bilirubin were related to a poor prognosis in patients suffering COVID-19, some authors raised the question about whether these findings are directly linked, or they are epiphenomena.


Subject(s)
COVID-19 , Liver/enzymology , Alanine Transaminase , Aspartate Aminotransferases , Humans , Prognosis , SARS-CoV-2
14.
Int J Biol Macromol ; 172: 418-428, 2021 Mar 01.
Article in English | MEDLINE | ID: covidwho-1033569

ABSTRACT

The major antioxidant enzyme catalase is downregulated and the enzyme activity is compromised in various disease conditions such as malarial and cancer. Hence, the restoration and protection of catalase is a promising therapeutic strategy in disease management. In the present study, for the first time we have demonstrated the protective role of well-known anti-malarial drug Artemisinin (ART) on the time and temperature-induced degradation of bovine liver catalase (BLC) activity. The findings at different time intervals and at higher temperature showed the protective role of ART on BLC activity. Molecular docking studies suggested specific binding of ART on BLC through heme group interface which was further supported by cyclic voltammetry and dynamic light scattering study. The stabilization of BLC in presence of ART was mediated through forming a BLC-ART complex with reduced and shifted electrochemical peak and increased hydrodynamic diameter. ART substantially prevents the temperature-induced reduction in α-helical content with simultaneous increment in other secondary structures like antiparallel, parallel, ß-turn and random coils. Nevertheless, the protective role of ART was accepted from the enhanced thermal stability and increased Tm value of BLC in presence of ART at higher temperatures. Our results uncover the mechanism of interaction between ART with BLC and suggest the protective role of ART towards spatiotemporal alteration of BLC by preventing the structural and molecular change in BLC. Thus, the findings advocate ART as a potential therapeutic drug for diseases associated with reduced catalase activity.


Subject(s)
Antioxidants/chemistry , Artemisinins/chemistry , Catalase/chemistry , Animals , Antioxidants/metabolism , Artemisinins/metabolism , Catalase/isolation & purification , Catalase/metabolism , Catalytic Domain , Cattle , Humans , Hydrogen Bonding , Liver/chemistry , Liver/enzymology , Molecular Docking Simulation , Protein Binding , Protein Conformation, alpha-Helical , Protein Conformation, beta-Strand , Protein Interaction Domains and Motifs , Protein Structure, Tertiary , Thermodynamics
15.
Clin Sci (Lond) ; 134(23): 3137-3158, 2020 12 11.
Article in English | MEDLINE | ID: covidwho-962239

ABSTRACT

Twenty years ago, the discovery of angiotensin-converting enzyme 2 (ACE2) was an important breakthrough dramatically enhancing our understanding of the renin-angiotensin system (RAS). The classical RAS is driven by its key enzyme ACE and is pivotal in the regulation of blood pressure and fluid homeostasis. More recently, it has been recognised that the protective RAS regulated by ACE2 counterbalances many of the deleterious effects of the classical RAS. Studies in murine models demonstrated that manipulating the protective RAS can dramatically alter many diseases including liver disease. Liver-specific overexpression of ACE2 in mice with liver fibrosis has proved to be highly effective in antagonising liver injury and fibrosis progression. Importantly, despite its highly protective role in disease pathogenesis, ACE2 is hijacked by SARS-CoV-2 as a cellular receptor to gain entry to alveolar epithelial cells, causing COVID-19, a severe respiratory disease in humans. COVID-19 is frequently life-threatening especially in elderly or people with other medical conditions. As an unprecedented number of COVID-19 patients have been affected globally, there is an urgent need to discover novel therapeutics targeting the interaction between the SARS-CoV-2 spike protein and ACE2. Understanding the role of ACE2 in physiology, pathobiology and as a cellular receptor for SARS-CoV-2 infection provides insight into potential new therapeutic strategies aiming to prevent SARS-CoV-2 infection related tissue injury. This review outlines the role of the RAS with a strong focus on ACE2-driven protective RAS in liver disease and provides therapeutic approaches to develop strategies to prevent SARS-CoV-2 infection in humans.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , COVID-19/virology , Liver Diseases/enzymology , Liver/enzymology , Renin-Angiotensin System/physiology , SARS-CoV-2/pathogenicity , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Animals , Biomarkers/metabolism , COVID-19/enzymology , COVID-19/etiology , COVID-19/therapy , Genetic Therapy , Humans , Liver/physiopathology , Liver/virology , Liver Diseases/therapy , Liver Diseases/virology , Mice
16.
BMC Infect Dis ; 20(1): 845, 2020 Nov 16.
Article in English | MEDLINE | ID: covidwho-926350

ABSTRACT

BACKGROUND: In December 2019, a new disease (COVID-19) caused by a novel coronavirus called SARS-CoV-2 emerged in China and spread to many other countries. There is only limited data about the clinical features of COVID-19 during pregnancy, especially in first trimester. CASE PRESENTATION: We report a COVID-19 infection in a 35 years-old patient in first trimester of pregnancy and its consequent medical care. At 7 weeks of pregnancy, the patient, who did not have any pregestational comorbidities, complained of intense nausea and asthenia. An important liver cytolysis was discovered with biological perturbations of transaminases levels. No respiratory symptoms were recorded. Classical viral aetiologies and drug-related toxicity were discarded. Because of the aggravation of the symptoms and the occurrence of the breathlessness, the patient was tested for the COVID-19 in a nasopharyngeal swab. The RTq-PCR assay indicated the presence of SARS-CoV-2 RNA. In the absence of severe symptoms, the patient was monitored at home according to the French government guidelines. After a few days, the symptoms resolved without any complications. The pregnancy is still ongoing without any visible sequelae on the foetus so far. CONCLUSIONS: This first case illustrated the difficulty of COVID-19 diagnosis in patients with isolated digestive symptoms in first trimester of pregnancy that could be confused with gravida hyperemesis. Monitoring of pregnancy after an episode of COVID-19 should be strengthened with bimonthly foetal growth ultrasounds and doppler assessments because of the risks for intrauterine growth restriction. Comprehensive data on larger numbers of first trimester gravid women with COVID-19 are required to better understanding the overall impact of SARS-CoV-2 on maternal and birth outcomes.


Subject(s)
Antiviral Agents/therapeutic use , Betacoronavirus , Coronavirus Infections/pathology , Hydroxychloroquine/therapeutic use , Liver/pathology , Pneumonia, Viral/pathology , Pregnancy Complications, Infectious/pathology , Adult , Antiviral Agents/pharmacology , Betacoronavirus/genetics , Betacoronavirus/isolation & purification , COVID-19 , China , Diagnosis, Differential , Embryo Implantation/drug effects , Female , Humans , Hydroxychloroquine/pharmacology , Liver/enzymology , Pandemics , Pregnancy , Pregnancy Trimester, First , RNA, Viral/isolation & purification , Real-Time Polymerase Chain Reaction , SARS-CoV-2 , Transaminases/metabolism
17.
Immunol Lett ; 217: 25-30, 2020 01.
Article in English | MEDLINE | ID: covidwho-888577

ABSTRACT

In a previous work we demonstrated that inhibition of mouse indoleamine 2,3-dioxygenase (IDO) by methyltryptophan (MT) exacerbated the pathological actions of mouse hepatitis virus (MHV-A59) infection, suggesting that tryptophan (TRP) catabolism was involved in viral effects. Since there is a second enzyme that dioxygenates TRP, tryptophan-2, 3-dioxygenase (TDO), which is mainly located in liver, we decided to study its role in our model of MHV-infection. Results showed that in vivo TDO inhibition by LM10, a derivative of 3-(2-(pyridyl) ethenyl) indole, resulted in a decrease of anti- MHV Ab titers induced by the virus infection. Besides, a reduction of some alarmin release, i.e, uric acid and high-mobility group box1 protein (HMGB1), was observed. Accordingly, since alarmin liberation was related to the expression of autoantibodies (autoAb) to fumarylacetoacetate hydrolase (FAH), these autoAb also diminished. Moreover, PCR results indicated that TDO inhibition did not abolish viral replication. Furthermore, histological liver examination did not reveal strong pathologies, whereas mouse survival was hundred percent in control as well as in MHV-infected mice treated with LM10. Data presented in this work indicate that in spite of the various TDO actions already described, specific TDO blockage could also restrain some MHV actions, mainly suppressing autoimmune reactions. Such results should prompt further experiments with various viruses to confirm the possible use of a TDO inhibitor such as LM-10 to treat either viral infections or even autoimmune diseases triggered by a viral infection.


Subject(s)
Autoimmune Diseases/enzymology , Autoimmunity/drug effects , Coronavirus Infections/enzymology , Coronavirus Infections/immunology , Liver/enzymology , Murine hepatitis virus/immunology , Tryptophan Oxygenase/antagonists & inhibitors , Tryptophan Oxygenase/metabolism , Alarmins/metabolism , Animals , Autoantibodies/drug effects , Autoantibodies/immunology , Autoimmune Diseases/drug therapy , Autoimmune Diseases/immunology , Autoimmune Diseases/virology , Coronavirus Infections/drug therapy , Coronavirus Infections/virology , Female , HMGB1 Protein/blood , HMGB1 Protein/metabolism , Hydrolases/immunology , Indoles/therapeutic use , Liver/drug effects , Liver/immunology , Liver/pathology , Mice , Mice, Inbred BALB C , Murine hepatitis virus/drug effects , Murine hepatitis virus/growth & development , Tryptophan/metabolism , Tryptophan Oxygenase/genetics , Uric Acid/blood , Uric Acid/metabolism , Virus Replication/drug effects , Virus Replication/immunology
18.
Am J Trop Med Hyg ; 103(4): 1600-1603, 2020 10.
Article in English | MEDLINE | ID: covidwho-740526

ABSTRACT

The COVID-19 pandemic has recently spread worldwide, presenting primarily in the form of pneumonia or other respiratory disease. In addition, gastrointestinal manifestations have increasingly been reported as one of the extrapulmonary features of the virus. We report two cases of SARS-CoV-2 infection complicated by paralytic ileus. The first patient was a 33-year-old man who was hospitalized with severe COVID-19 pneumonia requiring ventilator support and intensive care. He developed large bowel dilatation and perforation of the mid-transverse colon, and underwent laparotomy and colonic resection. Histopathology of the resected bowel specimen showed acute inflammation, necrosis, and hemorrhage, supporting a role for COVID-19-induced micro-thrombosis leading to perforation. The second patient was a 33-year-old man who had severe COVID-19 pneumonia, renal failure, and acute pancreatitis. His hospital course was complicated with paralytic ileus, and he improved with conservative management. Both cases were observed to have elevated liver transaminases, which is consistent with other studies. Several authors have postulated that the angiotensin-converting enzyme 2 receptors, the host receptors for COVID-19, that are present on enterocytes in both the small and large bowel might mediate viral entry and resultant inflammation. This is a potential mechanism of paralytic ileus in cases of severe COVID-19 infection. Recognizing paralytic ileus as a possible complication necessitates timely diagnosis and management.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/virology , Intestinal Perforation/virology , Intestinal Pseudo-Obstruction/virology , Pancreatitis/virology , Pneumonia, Viral/virology , Renal Insufficiency/virology , Adult , Biomarkers/metabolism , COVID-19 , Coronavirus Infections/diagnostic imaging , Coronavirus Infections/physiopathology , Coronavirus Infections/therapy , Humans , Intestinal Perforation/diagnostic imaging , Intestinal Perforation/physiopathology , Intestinal Perforation/therapy , Intestinal Pseudo-Obstruction/diagnostic imaging , Intestinal Pseudo-Obstruction/physiopathology , Intestinal Pseudo-Obstruction/therapy , Liver/enzymology , Liver/pathology , Liver/virology , Male , Pancreatitis/diagnostic imaging , Pancreatitis/physiopathology , Pancreatitis/therapy , Pandemics , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/physiopathology , Pneumonia, Viral/therapy , Positive-Pressure Respiration/methods , Renal Dialysis , Renal Insufficiency/diagnostic imaging , Renal Insufficiency/physiopathology , Renal Insufficiency/therapy , SARS-CoV-2 , Tomography, X-Ray Computed , Transaminases/metabolism
19.
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
20.
Hepatology ; 73(3): 890-900, 2021 03.
Article in English | MEDLINE | ID: covidwho-273691

ABSTRACT

BACKGROUND AND AIMS: Coronavirus disease 2019 (COVID-19) leads to elevated liver biochemistries in approximately half of patients on presentation. To date, data are limited regarding the trend of liver biochemistries over the course of illness. We aimed to evaluate the trend, etiology, and outcomes associated with liver biochemistries in COVID-19. APPROACH AND RESULTS: A total of 60 patients with COVID-19 were admitted between March 21 and March 28, 2020. The mean age was 57 years, 65% were male, and 28% were Hispanic. At the study conclusion, 6 patients were deceased, 28 were discharged, and 26 remained admitted. Patients who remained admitted were followed for a median of 12 days. Of 60 patients, 41 (69%) had at least one abnormal liver biochemistry on admission. Median aspartate aminotransferase (AST) was higher than alanine aminotransferase (ALT) at admission (46 vs. 30 U/L) and during the hospital course. Aminotransferases rose above normal in 54 (93%) patients, whereas alkaline phosphatase and total bilirubin elevations were rare. Ten (17%) patients developed aminotransferases more than 5 times the upper limit of normal. AST highly correlated with ALT throughout the illness course (r = 0.97; P < 0.0001), whereas correlations with markers of muscle injury and inflammation were weak. Statin use was common before (40%) and during admission (80%) at our center, with no difference in peak liver biochemistries between users and nonusers. No demographic or comorbid illness was associated with liver injury. Admission AST (69 vs. 49; P < 0.05), peak AST (364 vs. 77; P = 0.003), and peak ALT (220 vs. 52; P = 0.002) were higher in intubated patients. CONCLUSIONS: AST-dominant aminotransferase elevation is common in COVID-19, mirrors disease severity, and appears to reflect true hepatic injury.


Subject(s)
Aspartate Aminotransferases/blood , COVID-19/complications , Liver Diseases/virology , SARS-CoV-2 , Adult , Aged , Alanine Transaminase/blood , Biomarkers/blood , COVID-19/blood , Cohort Studies , Female , Hospitalization , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Inflammation/blood , Intensive Care Units , Length of Stay , Liver/enzymology , Liver/virology , Liver Diseases/blood , Liver Diseases/enzymology , Liver Function Tests , Male , Middle Aged , Severity of Illness Index
SELECTION OF CITATIONS
SEARCH DETAIL