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1
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Mataix RP, Morillo JSG, Martín JMS. Hepatic phenomena associated with SARS-CoV-2: Acute liver injury, autoimmune hepatitis and post-vaccination. Med Clin (Barc) 2025:S0025-7753(25)00011-9. [PMID: 39909769 DOI: 10.1016/j.medcli.2024.12.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2024] [Revised: 12/11/2024] [Accepted: 12/16/2024] [Indexed: 02/07/2025]
Abstract
The infection with SARS-CoV-2, primarily recognized for its respiratory effects, reveals itself as a multifaceted clinical phenomenon, extending beyond the pulmonary realm. Accompanied by gastrointestinal, neurological, thromboembolic, cardiovascular, and immune-related manifestations, the complexity of the systemic repercussions of the disease becomes apparent. Genetic predisposition is a significant factor in the development of autoimmune hepatitis, as both viruses, such as SARS-CoV-2, and drugs, including vaccines, can act as triggers in genetically susceptible individuals. A profound understanding of these mechanisms is essential to effectively address the clinical complexity of SARS-CoV-2 infection.
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Affiliation(s)
- Roberto Pertusa Mataix
- Unit of Systemic and Rare Autoimmune Diseases in Adults, Internal Medicine Service, Virgen del Rocío University Hospital, Manuel Siurot Avenue, S/n, 41013 Sevilla, Spain.
| | - José Salvador García Morillo
- Unit of Systemic and Rare Autoimmune Diseases in Adults, Internal Medicine Service, Virgen del Rocío University Hospital, Manuel Siurot Avenue, S/n, 41013 Sevilla, Spain
| | - José Manuel Sousa Martín
- Digestive Department, Virgen del Rocío University Hospital, Manuel Siurot Avenue, S/n, 41013 Sevilla, Spain
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2
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Yu C, Wang W, Zhang Q, Jin Z. Autoimmune hepatitis under the COVID-19 veil: an analysis of the nature of potential associations. Front Immunol 2025; 16:1510770. [PMID: 39958350 PMCID: PMC11825795 DOI: 10.3389/fimmu.2025.1510770] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2024] [Accepted: 01/14/2025] [Indexed: 02/18/2025] Open
Abstract
In recent years, the novel coronavirus infectious disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has led to over 670 million infections and nearly 7 million deaths worldwide. The global pandemic of COVID-19 has precipitated a significant public health crisis. The prevalence of liver function abnormalities associated with SARS-CoV-2 is as high as 53% among healthy individuals or patients with autoimmune hepatitis (AIH) and shows a positive correlation with disease severity; moreover, specific adaptive immune responses can influence the trajectory and outcomes of COVID-19. For instance, SARS-CoV-2 may impact autoimmunity through mechanisms such as excessive stimulation of immune responses and molecular mimicry, particularly in genetically predisposed individuals. Currently, the overall mutational trend of SARS-CoV-2 indicates heightened infectivity and immune evasion capabilities. Consequently, vaccination remains crucial for universal protection against this disease. Nevertheless, alongside the widespread implementation of vaccination programs globally, an increasing number of cases have been documented where COVID-19 vaccination appears to trigger new-onset autoimmune hepatitis; yet definitive evidence is still pending elucidation regarding causality. In this review, we analyse the clinical-immunological characteristics, risks associated with severe disease progression, and prognosis for AIH patients infected with SARS-CoV-2; discuss the detrimental effects exerted by SARS-CoV-2 on hepatic function; summarise the mechanisms and attributes leading to new-onset AIH; as well as provide insights into how vaccination may interfere with autoimmunity processes. We continue to underscore the significance of vaccination while aiming to enhance awareness concerning potential risks associated with it-this could facilitate better management strategies for autoimmune diseases along with appropriate adjustments in vaccination protocols. Although the precise triggering mechanism linking COVID-19-related events to AIH remains unclear, existing evidence suggests that this relationship is far from coincidental.
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Affiliation(s)
| | | | | | - Zhenjing Jin
- Department of Hepatopancreatobiliary Medicine, The Second Hospital of Jilin University, Changchun, Jilin, China
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3
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Xu JQ, Zhang WY, Fu JJ, Fang XZ, Gao CG, Li C, Yao L, Li QL, Yang XB, Ren LH, Shu HQ, Peng K, Wu Y, Zhang DY, Qiu Y, Zhou X, Yao YM, Shang Y. Viral sepsis: diagnosis, clinical features, pathogenesis, and clinical considerations. Mil Med Res 2024; 11:78. [PMID: 39676169 PMCID: PMC11648306 DOI: 10.1186/s40779-024-00581-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2024] [Accepted: 11/08/2024] [Indexed: 12/17/2024] Open
Abstract
Sepsis, characterized as life-threatening organ dysfunction resulting from dysregulated host responses to infection, remains a significant challenge in clinical practice. Despite advancements in understanding host-bacterial interactions, molecular responses, and therapeutic approaches, the mortality rate associated with sepsis has consistently ranged between 10 and 16%. This elevated mortality highlights critical gaps in our comprehension of sepsis etiology. Traditionally linked to bacterial and fungal pathogens, recent outbreaks of acute viral infections, including Middle East respiratory syndrome coronavirus (MERS-CoV), influenza virus, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), among other regional epidemics, have underscored the role of viral pathogenesis in sepsis, particularly when critically ill patients exhibit classic symptoms indicative of sepsis. However, many cases of viral-induced sepsis are frequently underdiagnosed because standard evaluations typically exclude viral panels. Moreover, these viruses not only activate conventional pattern recognition receptors (PRRs) and retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs) but also initiate primary antiviral pathways such as cyclic guanosine monophosphate adenosine monophosphate (GMP-AMP) synthase (cGAS)-stimulator of interferon genes (STING) signaling and interferon response mechanisms. Such activations lead to cellular stress, metabolic disturbances, and extensive cell damage that exacerbate tissue injury while leading to a spectrum of clinical manifestations. This complexity poses substantial challenges for the clinical management of affected cases. In this review, we elucidate the definition and diagnosis criteria for viral sepsis while synthesizing current knowledge regarding its etiology, epidemiology, and pathophysiology, molecular mechanisms involved therein as well as their impact on immune-mediated organ damage. Additionally, we discuss clinical considerations related to both existing therapies and advanced treatment interventions, aiming to enhance the comprehensive understanding surrounding viral sepsis.
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Affiliation(s)
- Ji-Qian Xu
- Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Wan-Ying Zhang
- Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Jia-Ji Fu
- Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Xiang-Zhi Fang
- Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Cheng-Gang Gao
- Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Chang Li
- Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Lu Yao
- Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Qi-Lan Li
- Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Xiao-Bo Yang
- Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Le-Hao Ren
- Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Hua-Qing Shu
- Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Ke Peng
- State Key Laboratory of Virology, Center for Antiviral Research, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 43007, China
| | - Ying Wu
- State Key Laboratory of Virology and Hubei Province Key Laboratory of Allergy and Immunology, Institute of Medical Virology, TaiKang Medical School, Wuhan University, Wuhan, 430072, China
| | - Ding-Yu Zhang
- Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Yang Qiu
- State Key Laboratory of Virology, Center for Antiviral Research, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 43007, China
| | - Xi Zhou
- State Key Laboratory of Virology, Center for Antiviral Research, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 43007, China.
| | - Yong-Ming Yao
- Translational Medicine Research Center, Medical Innovation Research Division and the Fourth Medical Center of Chinese, PLA General Hospital, Beijing, 100853, China.
| | - You Shang
- Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
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Hmimass S, Kadiri M, Borahma M, Chabib FZ, Berhili C, Lagdali N, Elbarhdadi IB, Ajana FZ. Acute severe hepatitis and COVID-19: case report. Pan Afr Med J 2024; 49:2. [PMID: 39372691 PMCID: PMC11453115 DOI: 10.11604/pamj.2024.49.2.44247] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2024] [Accepted: 08/11/2024] [Indexed: 10/08/2024] Open
Abstract
COVID-19, caused by SARS-CoV-2, has been declared an international public health emergency. Patients with COVID-19, even without a history of liver disease, frequently present with liver test disturbances. Due to the multisystemic involvement of COVID-19, the pathogenesis of liver injury is likely to be multifactorial, involving systemic inflammation, small vessel thrombosis, hepatic hypoxia, and potential drug toxicity, ruling out direct infection of hepatocytes by SARS-CoV-2. COVID-19 can cause severe acute hepatitis. We report the case of a 25-year-old man admitted to emergency with abdominal pain who presented with acute severe liver failure before respiratory signs.
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Affiliation(s)
- Saber Hmimass
- Department of Hepato-Gastroenterology C, Ibn Sina Hospital, Mohamed V University, Rabat, Morocco
| | - Maryeme Kadiri
- Department of Hepato-Gastroenterology C, Ibn Sina Hospital, Mohamed V University, Rabat, Morocco
| | - Mohamed Borahma
- Department of Hepato-Gastroenterology C, Ibn Sina Hospital, Mohamed V University, Rabat, Morocco
| | - Fatima-Zahra Chabib
- Department of Hepato-Gastroenterology C, Ibn Sina Hospital, Mohamed V University, Rabat, Morocco
| | - Camelia Berhili
- Department of Hepato-Gastroenterology C, Ibn Sina Hospital, Mohamed V University, Rabat, Morocco
| | - Nawa Lagdali
- Department of Hepato-Gastroenterology C, Ibn Sina Hospital, Mohamed V University, Rabat, Morocco
| | - Imane Ben Elbarhdadi
- Department of Hepato-Gastroenterology C, Ibn Sina Hospital, Mohamed V University, Rabat, Morocco
| | - Fatima-Zahra Ajana
- Department of Hepato-Gastroenterology C, Ibn Sina Hospital, Mohamed V University, Rabat, Morocco
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5
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Cheng L, Rui Y, Wang Y, Chen S, Su J, Yu XF. A glimpse into viral warfare: decoding the intriguing role of highly pathogenic coronavirus proteins in apoptosis regulation. J Biomed Sci 2024; 31:70. [PMID: 39003473 PMCID: PMC11245872 DOI: 10.1186/s12929-024-01062-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2024] [Accepted: 06/18/2024] [Indexed: 07/15/2024] Open
Abstract
Coronaviruses employ various strategies for survival, among which the activation of endogenous or exogenous apoptosis stands out, with viral proteins playing a pivotal role. Notably, highly pathogenic coronaviruses such as SARS-CoV-2, SARS-CoV, and MERS-CoV exhibit a greater array of non-structural proteins compared to low-pathogenic strains, facilitating their ability to induce apoptosis via multiple pathways. Moreover, these viral proteins are adept at dampening host immune responses, thereby bolstering viral replication and persistence. This review delves into the intricate interplay between highly pathogenic coronaviruses and apoptosis, systematically elucidating the molecular mechanisms underpinning apoptosis induction by viral proteins. Furthermore, it explores the potential therapeutic avenues stemming from apoptosis inhibition as antiviral agents and the utilization of apoptosis-inducing viral proteins as therapeutic modalities. These insights not only shed light on viral pathogenesis but also offer novel perspectives for cancer therapy.
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Affiliation(s)
- Leyi Cheng
- Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310009, China
- Cancer Center, Zhejiang University, Hangzhou, Zhejiang, 310058, China
| | - Yajuan Rui
- Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310009, China
- Cancer Center, Zhejiang University, Hangzhou, Zhejiang, 310058, China
| | - Yanpu Wang
- Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310009, China
- Cancer Center, Zhejiang University, Hangzhou, Zhejiang, 310058, China
| | - Shiqi Chen
- Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310009, China
- Cancer Center, Zhejiang University, Hangzhou, Zhejiang, 310058, China
| | - Jiaming Su
- Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310009, China.
- Cancer Center, Zhejiang University, Hangzhou, Zhejiang, 310058, China.
| | - Xiao-Fang Yu
- Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310009, China.
- Cancer Center, Zhejiang University, Hangzhou, Zhejiang, 310058, China.
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Ajmera A, Pernicone PJ, Patel N, Benabe SH. Coronavirus HKU1 infection and development of pediatric acute liver failure with immune dysregulation phenotype. JPGN REPORTS 2024; 5:204-207. [PMID: 38756108 PMCID: PMC11093931 DOI: 10.1002/jpr3.12065] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/12/2023] [Revised: 01/23/2024] [Accepted: 02/18/2024] [Indexed: 05/18/2024]
Abstract
Pediatric acute liver failure is a rare but serious complication of Coronavirus infections. Our patient is a previously healthy 8-year-old male who presented with acute liver failure in the setting of human coronavirus HKU1 (HCoV-HKU1) infection while asymptomatic from a respiratory perspective. During the hospital course, he developed acute hepatic encephalopathy and was listed for liver transplantation, but fortunately recovered remaining status 7 (inactive) on the transplant list. With a negative diagnostic evaluation other than his viral infection and hyperdense CD8 T-cells on liver immunohistochemical staining, pediatric acute liver failure (PALF) immune dysregulation phenotype was diagnosed.
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Affiliation(s)
- Arun Ajmera
- Center for Digestive Health and NutritionArnold Palmer Hospital for ChildrenOrlandoFloridaUSA
| | | | - Nishant Patel
- Center for Digestive Health and NutritionArnold Palmer Hospital for ChildrenOrlandoFloridaUSA
| | - Stefany Hernandez Benabe
- Advent Health Medical Group Pediatric Gastroenterology at OrlandoAdvent Health for ChildrenOrlandoFloridaUSA
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7
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Singh L, Kumar A, Rai M, Basnet B, Rai N, Khanal P, Lai KS, Cheng WH, Asaad AM, Ansari S. Spectrum of COVID-19 induced liver injury: A review report. World J Hepatol 2024; 16:517-536. [PMID: 38689748 PMCID: PMC11056898 DOI: 10.4254/wjh.v16.i4.517] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2023] [Revised: 01/20/2024] [Accepted: 02/28/2024] [Indexed: 04/24/2024] Open
Abstract
The coronavirus disease 2019 (COVID-19) pandemic has caused changes in the global health system, causing significant setbacks in healthcare systems worldwide. This pandemic has also shown resilience, flexibility, and creativity in reacting to the tragedy. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection targets most of the respiratory tract, resulting in a severe sickness called acute respiratory distress syndrome that may be fatal in some individuals. Although the lung is the primary organ targeted by COVID-19 viruses, the clinical aspect of the disease is varied and ranges from asymptomatic to respiratory failure. However, due to an unorganized immune response and several affected mechanisms, the liver may also experience liver cell injury, ischemic liver dysfunction, and drug-induced liver injury, which can result in respiratory failure because of the immune system's disordered response and other compromised processes that can end in multisystem organ failure. Patients with liver cirrhosis or those who have impaired immune systems may be more likely than other groups to experience worse results from the SARS-CoV-2 infection. We thus intend to examine the pathogenesis, current therapy, and consequences of liver damage concerning COVID-19.
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Affiliation(s)
- Lokjan Singh
- Department of Microbiology, Karnali Academy of Health Science, Teaching Hospital, Jumla 21200, Karnali, Nepal
| | - Anil Kumar
- Department of Microbiology, Karnali Academy of Health Science, Teaching Hospital, Jumla 21200, Karnali, Nepal
| | - Maya Rai
- Department of Microbiology, Karnali Academy of Health Science, Teaching Hospital, Jumla 21200, Karnali, Nepal
| | - Bibek Basnet
- Health Sciences, Asian College of Advance Studies, Purbanchal University, Satdobato 24122, Lalitpur, Nepal
| | - Nishant Rai
- Department of Biotechnology, Graphic Era (Deemed to be University), Dehradun 248002, Uttarakhand, India
| | - Pukar Khanal
- Department of Pharmacology & Toxicology, KLE College of Pharmacy, Belagavi, KLE Academy of Higher Education and Research, Belagavi 590010, Karnataka, India
| | - Kok-Song Lai
- Division of Health Sciences, Abu Dhabi Women's College, Higher Colleges of Technology, Abu Dhabi 41012, United Arab Emirates
| | - Wan-Hee Cheng
- Health and Life Sciences, INTI International University, Nilai 71800, Malaysia
| | - Ahmed Morad Asaad
- Department of Microbiology, College of Medicine, Zagazig University, Zagazig 44519, Egypt
| | - Shamshul Ansari
- Division of Health Sciences, Abu Dhabi Women's College, Higher Colleges of Technology, Abu Dhabi 41012, United Arab Emirates.
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8
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Luxenburger H, Thimme R. SARS-CoV-2 and the liver: clinical and immunological features in chronic liver disease. Gut 2023; 72:1783-1794. [PMID: 37316169 PMCID: PMC10423489 DOI: 10.1136/gutjnl-2023-329623] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Accepted: 05/24/2023] [Indexed: 06/16/2023]
Abstract
SARS-CoV-2 infection may affect the liver in healthy individuals but also influences the course of COVID-19 in patients with chronic liver disease (CLD). As described in healthy individuals, a strong SARS-CoV-2-specific adaptive immune response is important for the outcome of COVID-19, however, knowledge on the adaptive immune response in CLD is limited.Here, we review the clinical and immunological features of SARS-CoV-2 infection in individuals with CLD. Acute liver injury occurs in many cases of SARS-CoV-2 infection and may be induced by multiple factors, such as cytokines, direct viral infection or toxic effects of COVID-19 drugs. In individuals with CLD, SARS-CoV-2 infection may have a more severe course and promote decompensation and particularly in patients with cirrhosis. Compared with healthy individuals, the SARS-CoV-2-specific adaptive immune responses is impaired in patients with CLD after both, natural infection and vaccination but improves at least partially after booster vaccination.Following SARS-CoV-2 vaccination, rare cases of acute vaccine-induced liver injury and the development of autoimmune-like hepatitis have been reported. However, the concomitant elevation of liver enzymes is reversible under steroid treatment.
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Affiliation(s)
- Hendrik Luxenburger
- Department of Medicine II (Gastroenterology, Hepatology, Endocrinology and Infectious Diseases), Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Robert Thimme
- Department of Medicine II (Gastroenterology, Hepatology, Endocrinology and Infectious Diseases), Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany
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Krishnamoorthy Y, Karunakaran M, Ganesh K, Hariharan VS. Association between acute liver injury & severity and mortality of COVID-19 patients: A systematic review and meta-analysis. Heliyon 2023; 9:e20338. [PMID: 37809564 PMCID: PMC10560047 DOI: 10.1016/j.heliyon.2023.e20338] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2023] [Revised: 09/15/2023] [Accepted: 09/19/2023] [Indexed: 10/10/2023] Open
Abstract
BACKGROUND Acute liver injury (ALI), a complication often seen in COVID-19 patients, can lead to severe liver damage, multi-organ failure, acute vascular events, and can potentially escalate to patient mortality. Given this, we initiated a meta-analysis to investigate the correlation between ALI and adverse outcomes in COVID-19 patients. METHODS We conducted an exhaustive search of databases, including Medline, Embase, PubMed Central, ScienceDirect, Google Scholar, and the Cochrane Library, from the November 2019 until January 2022. The quality of the included studies was evaluated using the Newcastle Ottawa (NO) scale. Our meta-analysis was carried out using a random-effects model and results were presented as pooled odds ratios (ORs) with their corresponding 95% confidence intervals (CIs). RESULTS Our analysis incorporated 20 studies involving a total of 13,850 participants, predominantly from China and the United States. According to the NO scale, the majority of these studies were categorized as low-quality. Patients with ALI faced approximately 7 times higher odds of severe COVID-19 symptoms (pooled OR = 7.09; 95%CI: 4.97 to 10.12) and over 5 times higher odds of mortality (pooled OR = 5.50; 95%CI: 3.37 to 8.99) when compared to those without ALI. CONCLUSION Our findings affirm that ALI is a potent predictor of adverse outcomes, including severity and mortality, among COVID-19 patients. Recognizing and promptly addressing ALI in COVID-19 patients could be pivotal in improving prognosis and tailoring individualized patient management strategies. This underscores the need for clinicians to be vigilant about liver complications in the COVID-19 patients and integrate appropriate interventions in the treatment paradigm.
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Affiliation(s)
- Yuvaraj Krishnamoorthy
- Department of Community Medicine, ESIC Medical College and PGIMSR, K.K. Nagar, Chennai, Tamil Nadu, India
| | - Monica Karunakaran
- Department of Anaesthesiology and Pain Management, SRM Institute of Medical Sciences, Tamil Nadu, India
| | - Karthika Ganesh
- Department of Community Medicine, Sri Lakshmi Narayana Institute of Medical Sciences, Puducherry, India
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10
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Bostanghadiri N, Ziaeefar P, Mofrad MG, Yousefzadeh P, Hashemi A, Darban-Sarokhalil D. COVID-19: An Overview of SARS-CoV-2 Variants-The Current Vaccines and Drug Development. BIOMED RESEARCH INTERNATIONAL 2023; 2023:1879554. [PMID: 37674935 PMCID: PMC10480030 DOI: 10.1155/2023/1879554] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/03/2023] [Revised: 07/07/2023] [Accepted: 08/04/2023] [Indexed: 09/08/2023]
Abstract
The world is presently in crisis facing an outbreak of a health-threatening microorganism known as COVID-19, responsible for causing uncommon viral pneumonia in humans. The virus was first reported in Wuhan, China, in early December 2019, and it quickly became a global concern due to the pandemic. Challenges in this regard have been compounded by the emergence of several variants such as B.1.1.7, B.1.351, P1, and B.1.617, which show an increase in transmission power and resistance to therapies and vaccines. Ongoing researches are focused on developing and manufacturing standard treatment strategies and effective vaccines to control the pandemic. Despite developing several vaccines such as Pfizer/BioNTech and Moderna approved by the U.S. Food and Drug Administration (FDA) and other vaccines in phase 4 clinical trials, preventive measures are mandatory to control the COVID-19 pandemic. In this review, based on the latest findings, we will discuss different types of drugs as therapeutic options and confirmed or developing vaccine candidates against SARS-CoV-2. We also discuss in detail the challenges posed by the variants and their effect on therapeutic and preventive interventions.
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Affiliation(s)
- Narjess Bostanghadiri
- Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Pardis Ziaeefar
- School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Morvarid Golrokh Mofrad
- Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization (AREEO), Karaj, Iran
| | - Parsa Yousefzadeh
- School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ali Hashemi
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Davood Darban-Sarokhalil
- Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
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11
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Aghamohamadi N, Shahba F, Zarezadeh Mehrabadi A, Khorramdelazad H, Karimi M, Falak R, Emameh RZ. Age-dependent immune responses in COVID-19-mediated liver injury: focus on cytokines. Front Endocrinol (Lausanne) 2023; 14:1139692. [PMID: 37654571 PMCID: PMC10465349 DOI: 10.3389/fendo.2023.1139692] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2023] [Accepted: 07/21/2023] [Indexed: 09/02/2023] Open
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is potentially pathogenic and causes severe symptoms; in addition to respiratory syndromes, patients might experience other severe conditions such as digestive complications and liver complications injury. The abnormality in the liver is manifested by hepatobiliary dysfunction and enzymatic elevation, which is associated with morbidity and mortality. The direct cytopathic effect, immune dysfunction, cytokine storm, and adverse effects of therapeutic regimens have a crucial role in the severity of liver injury. According to aging and immune system alterations, cytokine patterns may also change in the elderly. Moreover, hyperproduction of cytokines in the inflammatory response to SARS-CoV-2 can lead to multi-organ dysfunction. The mortality rate in elderly patients, particularly those with other comorbidities, is also higher than in adults. Although the pathogenic effect of SARS-CoV-2 on the liver has been widely studied, the impact of age and immune-mediated responses at different ages remain unclear. This review discusses the association between immune system responses in coronavirus disease 2019 (COVID-19) patients of different ages and liver injury, focusing on cytokine alterations.
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Affiliation(s)
- Nazanin Aghamohamadi
- Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Faezeh Shahba
- Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Ali Zarezadeh Mehrabadi
- Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Hossein Khorramdelazad
- Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
- Department of Immunology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
| | - Milad Karimi
- Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Reza Falak
- Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Reza Zolfaghari Emameh
- Department of Energy and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran
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Pustake M, Giri P, Ganiyani MA, Mumtaz K, Deshmukh K, Saju M, Nunez JV, Orlova N, Das A. Drawing Parallels between SARS, MERS, and COVID-19: A Comparative Overview of Epidemiology, Pathogenesis, and Pathological Features. Indian J Community Med 2023; 48:518-524. [PMID: 37662119 PMCID: PMC10470569 DOI: 10.4103/ijcm.ijcm_460_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2022] [Accepted: 05/22/2023] [Indexed: 09/05/2023] Open
Abstract
Background Since November 2019, when the novel coronavirus arose in Wuhan City, over 188 million people worldwide have been infected with COVID-19. It is the third coronavirus outbreak in the twenty-first century. Until now, practically all coronavirus epidemics have occurred due to zoonotic spread from an animal or transitional host or through the consumption of their products. Coronaviruses can infect humans and cause severe illness and even death. Material and Methods This review was designed to help us recognize and harmonize the similarities and differences between these three coronaviridae family members. Result Measures aimed at containing the epidemic should be emphasized in this circumstance. Prioritizing and planning these activities require an understanding of the particulars of these three viruses. Given the pandemic's enormous death toll and rapid spread, we should be cognizant of the parallels and differences between these three viruses. Additionally, this pandemic warns us to be cautious against the possibility of a future pandemic. Conclusion We highlight the fundamental characteristics of coronaviruses that are critical for recognizing coronavirus epidemiology, pathogenesis, and pathological features that reveal numerous significant pathological attributes and evolutionary patterns in the viral genome that aid in better understanding and anticipating future epidemics.
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Affiliation(s)
- Manas Pustake
- Department of Internal Medicine, Grant Govt. Medical College and Sir JJ Group of Hospitals, Mumbai, Maharashtra, India
- Harvard Medical School, Harvard University, Boston, MA, USA
| | - Purushottam Giri
- Department of Community Medicine, IIMSR Medical College, Jalna, Maharashtra, India
| | - Mohammad Arfat Ganiyani
- Department of Internal Medicine, Grant Govt. Medical College and Sir JJ Group of Hospitals, Mumbai, Maharashtra, India
| | - Kahkashan Mumtaz
- Department of Pediatrics, Grant Govt. Medical College and Sir JJ Group of Hospitals, Mumbai, Maharashtra, India
| | - Krishna Deshmukh
- Department of Internal Medicine, Grant Govt. Medical College and Sir JJ Group of Hospitals, Mumbai, Maharashtra, India
| | - Michael Saju
- Department of Community Medicine, Grant Govt. Medical College and Sir JJ Group of Hospitals, Mumbai, Maharashtra, India
| | | | | | - Arghadip Das
- Department of Pathology, Nil Ratan Sircar Medical College and Hospital, Kolkata, West Bengal, India
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13
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Zippi M, Fiorino S, Hong W, de Biase D, Gallo CG, Grottesi A, Centorame A, Crispino P. Post-COVID-19 cholangiopathy: A systematic review. World J Meta-Anal 2023; 11:229-237. [DOI: 10.13105/wjma.v11.i5.229] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/28/2023] Open
Abstract
BACKGROUND The recent and still ongoing pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entailed various long-term complications, including post-infectious cholangiopathy.
AIM To identify the available studies concerning post-coronavirus disease 2019 (COVID-19) cholangiopathy.
METHODS An extensive bibliographical search was carried out in PubMed and in Cochrane Library to identify the articles (retrospective and prospective studies, cohort studies, case series and case reports) published between January 1, 2020 and August 22, 2022, using both MeSH terms and free-language keywords: cholangiopathy; COVID-19; post-COVID-19 cholangiopathy; SARS-CoV-2.
RESULTS Thirteen studies fulfilled the inclusion criteria, which included 64 patients suffering from this condition. The patients were male in 82.8% of cases. Liver transplant was executed in 6 patients and scheduled in 7 patients, while 2 patients refused the surgical approach. Therefore in 23.4% of the cases, performing this procedure appeared to be necessary.
CONCLUSION This review has revealed that generally the involvement of the liver in the course of SARS-CoV-2 infection is mild and transient, inducing cholestasis of cholangiocytes but can also be severe enough to cause organ failure in some cases.
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Affiliation(s)
- Maddalena Zippi
- Unit of Gastroenterology and Digestive Endoscopy, Sandro Pertini Hospital, Rome 00157, Italy
| | - Sirio Fiorino
- Unit of Internal Medicine, Maggiore Hospital, Local Health Unit of Bologna, Bologna 40133, Italy
| | - Wandong Hong
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, China
| | - Dario de Biase
- Department of Pharmacy and Biotechnology, University of Bologna, Bologna 40126, Italy
| | | | - Alfonso Grottesi
- Unit of General Surgery, Sandro Pertini Hospital, Rome 00157, Italy
| | | | - Pietro Crispino
- Unit of Emergency Medicine, Santa Maria Goretti Hospital, Latina 04100, Italy
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14
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Imam MT, Almalki ZS, Alzahrani AR, Al-Ghamdi SS, Falemban AH, Alanazi IM, Shahzad N, Muhammad Alrooqi M, Jabeen Q, Shahid I. COVID-19 and severity of liver diseases: Possible crosstalk and clinical implications. Int Immunopharmacol 2023; 121:110439. [PMID: 37315370 PMCID: PMC10247890 DOI: 10.1016/j.intimp.2023.110439] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Revised: 05/30/2023] [Accepted: 05/31/2023] [Indexed: 06/16/2023]
Abstract
COVID-19-infected individuals and those who recovered from the infection have been demonstrated to have elevated liver enzymes or abnormal liver biochemistries, particularly with preexisting liver diseases, liver metabolic disorders, viral hepatitis, and other hepatic comorbidities. However, possible crosstalk and intricate interplay between COVID-19 and liver disease severity are still elusive, and the available data are murky and confined. Similarly, the syndemic of other blood-borne infectious diseases, chemical-induced liver injuries, and chronic hepatic diseases continued to take lives while showing signs of worsening due to the COVID-19 crisis. Moreover, the pandemic is not over yet and is transitioning to becoming an epidemic in recent years; hence, monitoring liver function tests (LFTs) and assessing hepatic consequences of COVID-19 in patients with or without liver illnesses would be of paramount interest. This pragmatic review explores the correlations between COVID-19 and liver disease severity based on abnormal liver biochemistries and other possible mechanisms in individuals of all ages from the emergence of the COVID-19 pandemic to the post-pandemic period. The review also alludes to clinical perspectives of such interactions to curb overlapping hepatic diseases in people who recovered from the infection or living with long COVID-19.
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Affiliation(s)
- Mohammad T Imam
- Department of Clinical Pharmacy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al Kharj 11942, Saudi Arabia
| | - Ziyad S Almalki
- Department of Clinical Pharmacy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al Kharj 11942, Saudi Arabia
| | - Abdullah R Alzahrani
- Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Al-Abidiyah, Makkah 21955, Saudi Arabia
| | - Saeed S Al-Ghamdi
- Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Al-Abidiyah, Makkah 21955, Saudi Arabia
| | - Alaa H Falemban
- Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Al-Abidiyah, Makkah 21955, Saudi Arabia
| | - Ibrahim M Alanazi
- Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Al-Abidiyah, Makkah 21955, Saudi Arabia
| | - Naiyer Shahzad
- Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Al-Abidiyah, Makkah 21955, Saudi Arabia
| | | | - Qaisar Jabeen
- Department of Pharmacology, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, Pakistan
| | - Imran Shahid
- Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Al-Abidiyah, Makkah 21955, Saudi Arabia.
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15
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Seyoum F. Mechanisms of severe acute respiratory syndrome coronavirus-2 induced liver damage and alteration of some liver biomarkers: A review. Medicine (Baltimore) 2023; 102:e33517. [PMID: 37171303 PMCID: PMC10174413 DOI: 10.1097/md.0000000000033517] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/13/2023] Open
Abstract
The most serious problem for people suffering from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is liver damage. The liver is a frequently affected organ due to the metabolizing and detoxifying functions of several endogenous and exogenous molecules. In COVID-19-affected individuals, even moderate loss of hepatic function could dramatically affect the therapeutic efficacy of antiviral drugs metabolized in the liver. The clear mechanism of hepatocellular damage from SARS-CoV-2 infection is not fully understood. The main objective of this review is to identify potential mechanisms of SARS-2 induced liver damage, treatment outcomes in SARS-CoV-2-infected patients, and future direction. Electronic databases including Web of Science, Google Scholar, MEDLINE, Scopus, and Cochrane library were used to systematically search without limitation of publication date and status. Observational, retrospective cohort, prospective case-control, cohort studies, cross-sectional studies, or clinical trials were included. Liver damage in coronavirus patients is characterized by histopathological changes and abnormal elevation of some liver function tests. These abnormalities include elevation of Alanine aminotransferase, Aspartate aminotransferase, Gamma-glutamyl transferase, Alkaline phosphatase, and Serum bilirubin levels. Histopathological changes of the liver might consist of complete or partial thrombosis of the portal and sinusoidal vessels, portal tract fibrosis, and focally markedly enlarged and fibrotic hepatocytes. Understanding the fundamental molecular and immunological processes of COVID-19-related liver injury is essential for the selection of appropriate drugs and the logical development of successful treatment.
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Affiliation(s)
- Fikadu Seyoum
- Department of Medical Biochemistry, College of Medicine and Health Sciences, Ambo University, Addis Ababa, Ethiopia
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16
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Mohammedsaeed W, Ahmedseedi I, Alahmadey Z. Liver and Renal Impairments in COVID-19 Patients of Madinah City of Saudi Arabia: A Cross-Sectional Study (2020). Cureus 2023; 15:e39409. [PMID: 37362525 PMCID: PMC10287181 DOI: 10.7759/cureus.39409] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/22/2023] [Indexed: 06/28/2023] Open
Abstract
Purpose Most of the research on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (coronavirus disease 2019 [COVID-19]) has mainly focused on the lungs as a key organ involved in the disease, while very little data is available regarding the involvement of other organs including the liver and kidneys, which are also reported to be severely affected by the disease. The objective of this study was to analyze the effect of COVID-19 disease on liver and kidney functions and to determine their association with the severity and mortality of the disease. This was a retrospective cross-sectional analysis of medical records. Methods A total of 100 confirmed COVID-19 adult patients from Madinah, Saudi Arabia hospitalized between April 28 and June 30, 2020, were included and categorized into asymptomatic, mild to moderate, and severely ill patients. We analyzed the clinical status of liver and renal functioning in all three groups. Results Most patients (51%) were diagnosed with mild to moderate disease, 27% of patients were severely ill and 22% of patients were asymptomatic. The liver and renal functional analysis showed that the severity of the COVID-19 patients was significantly associated with renal impairments exhibiting higher levels of creatinine and urea (P<0.05) with high levels of liver enzymes as indicators for liver damage. Conclusion We concluded from the present study that severely ill COVID-19 patients were more prone to have abnormal liver and renal functions. The present findings, however, demand further study of the association between liver and kidney impairments with COVID-19 infection for better clinical management.
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Affiliation(s)
- Walaa Mohammedsaeed
- Department of Medical Laboratory Technology, Faculty of Applied Medical Science, Taibah University, Madinah, SAU
| | | | - Ziab Alahmadey
- Laboratory Department, Ohud Hospital Madinah, Madinah, SAU
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17
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Khullar N, Bhatti JS, Singh S, Thukral B, Reddy PH, Bhatti GK. Insight into the liver dysfunction in COVID-19 patients: Molecular mechanisms and possible therapeutic strategies. World J Gastroenterol 2023; 29:2064-2077. [PMID: 37122601 PMCID: PMC10130970 DOI: 10.3748/wjg.v29.i14.2064] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Revised: 10/23/2022] [Accepted: 03/21/2023] [Indexed: 04/13/2023] Open
Abstract
As of June 2022, more than 530 million people worldwide have become ill with coronavirus disease 2019 (COVID-19). Although COVID-19 is most commonly associated with respiratory distress (severe acute respiratory syndrome), meta-analysis have indicated that liver dysfunction also occurs in patients with severe symptoms. Current studies revealed distinctive patterning in the receptors on the hepatic cells that helps in viral invasion through the expression of angiotensin-converting enzyme receptors. It has also been reported that in some patients with COVID-19, therapeutic strategies, including repurposed drugs (mitifovir, lopinavir/ritonavir, tocilizumab, etc.) triggered liver injury and cholestatic toxicity. Several proven indicators support cytokine storm-induced hepatic damage. Because there are 1.5 billion patients with chronic liver disease worldwide, it becomes imperative to critically evaluate the molecular mechanisms concerning hepatotropism of COVID-19 and identify new potential therapeutics. This review also designated a comprehensive outlook of comorbidities and the impact of lifestyle and genetics in managing patients with COVID-19.
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Affiliation(s)
- Naina Khullar
- Department of Zoology, Mata Gujri College, Fatehgarh Sahib 140407, Punjab, India
| | - Jasvinder Singh Bhatti
- Laboratory of Translational Medicine and Nanotherapeutics, Department of Human Genetics and Molecular Medicine, School of Health Sciences, Central University of Punjab, Bathinda 151401, Punjab, India
| | - Satwinder Singh
- Department of Computer Science and Technology, Central University of Punjab, Bathinda 151401, Punjab, India
| | - Bhawana Thukral
- Department of Nutrition and Dietetics, University Institute of Applied Health Sciences, Chandigarh University, Mohali 140413, Punjab, India
| | - P Hemachandra Reddy
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, United States
| | - Gurjit Kaur Bhatti
- Department of Medical Lab Technology, University Institute of Applied Health Sciences, Chandigarh University, Mohali 140413, Punjab, India
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18
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Yu Y, Li X, Wan T. Effects of Hepatitis B Virus Infection on Patients with COVID-19: A Meta-Analysis. Dig Dis Sci 2023; 68:1615-1631. [PMID: 36085229 PMCID: PMC9462612 DOI: 10.1007/s10620-022-07687-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2022] [Accepted: 08/29/2022] [Indexed: 12/09/2022]
Abstract
BACKGROUND The COVID-19 pandemic has brought new problems to patients infected with hepatitis B virus (HBV). AIM We aim to know the effects of HBV infection on patients with COVID-19. METHODS We searched PubMed, Embase, and Web of Science for data and utilized Stata 14.0 software for this meta-analysis with a random-effects model. This paper was conducted in alignment with the preferred reporting items for systematic review and meta-analysis (PRISMA) guideline. RESULTS In total, 37,696 patients were divided into two groups: 2591 COVID-19 patients infected with HBV in the experimental group and 35,105 COVID-19 patients not infected with HBV in the control group. Our study showed that the in-hospital mortality of the experimental group was significant higher than that of the control group (OR = 2.04, 95% CI 1.49-2.79). We also found that COVID-19 patients infected with HBV were more likely to develop severe disease (OR = 1.90, 95% CI 1.32-2.73) than COVID-19 patients not infected with HBV. Upon measuring alanine aminotransferase (SMD = 0.62, 95% CI 0.25-0.98), aspartate aminotransferase (SMD = 0.60, 95% CI 0.30-0.91), total bilirubin (SMD = 0.45, 95% CI 0.23-0.67), direct bilirubin (SMD = 0.36, 95% CI 0.24-0.47), lactate dehydrogenase (SMD = 0.32, 95% CI 0.18-0.47), we found that HBV infection led to significantly higher laboratory results in COVID-19 patients. CONCLUSION COVID-19 patients infected with HBV should receive more attention, and special attention should be given to various liver function indices during treatment.
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Affiliation(s)
- Yang Yu
- Department of Hepatobiliary and Pancreatic Surgery, China-Japan Union Hospital of Jilin University, Changchun, 130033, Jilin Province, China
| | - Xingzhao Li
- Department of Ultrasound, China-Japan Union Hospital of Jilin University, Changchun, 130033, Jilin Province, China
| | - Taihu Wan
- Department of Radiology, China-Japan Union Hospital of Jilin University, Changchun, 130033, Jilin Province, China.
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19
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Said ZNA, El Habashy SA, Zaky S. COVID-19-induced transaminitis and hyperbilirubinemia: Presentation and outcomes. World J Gastroenterol 2023; 29:1123-1130. [PMID: 36926664 PMCID: PMC10011958 DOI: 10.3748/wjg.v29.i7.1123] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2022] [Revised: 12/29/2022] [Accepted: 02/13/2023] [Indexed: 02/21/2023] Open
Abstract
The risk of liver injury in patients with coronavirus disease 2019 (COVID-19) infection is quite evident. Furthermore, liver function test abnormalities are still detected in COVID-19 patients despite the development of antivirals and the availability of several types of vaccines. This editorial describes liver involvement during COVID-19 infection in patients with or without preexisting liver injury, such as chronic liver disease, to elucidate COVID-19-induced liver function abnormalities and their severity, pathophysiology, clinical manifestations, and clinical and laboratory outcomes. We also discuss the effect of vaccination against COVID-19 to better understand host factors, such as age, gender, and race, on the incidence and severity of liver dysfunction at initial presentation and during the illness. Finally, we summarize the results of relevant meta-analyses published to date and highlight the importance of adequate liver function monitoring in the current climate of the overwhelming COVID-19 pandemic.
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Affiliation(s)
- Zeinab Nabil Ahmed Said
- Department of Medical Microbiology and Immunology, Faculty of Medicine (For Girls), Al-Azhar University, Cairo 11754, Nasr City, Egypt
| | | | - Samy Zaky
- Department of Hepato-gastroenterology and Infectious Diseases, Faculty of Medicine (For Girls), Al-Azhar University, Cairo 11754, Egypt
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20
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Rabaan AA, Smajlović S, Tombuloglu H, Ćordić S, Hajdarević A, Kudić N, Mutai AA, Turkistani SA, Al-Ahmed SH, Al-Zaki NA, Al Marshood MJ, Alfaraj AH, Alhumaid S, Al-Suhaimi E. SARS-CoV-2 infection and multi-organ system damage: A review. BIOMOLECULES & BIOMEDICINE 2023; 23:37-52. [PMID: 36124445 PMCID: PMC9901898 DOI: 10.17305/bjbms.2022.7762] [Citation(s) in RCA: 22] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 06/27/2022] [Revised: 08/23/2022] [Accepted: 08/23/2022] [Indexed: 02/03/2023]
Abstract
The SARS-CoV-2 infection causes COVID-19, which has affected approximately six hundred million people globally as of August 2022. Organs and cells harboring angiotensin-converting enzyme 2 (ACE2) surface receptors are the primary targets of the virus. However, once it enters the body through the respiratory system, the virus can spread hematogenously to infect other body organs. Therefore, COVID-19 affects many organs, causing severe and long-term complications, even after the disease has ended, thus worsening the quality of life. Although it is known that the respiratory system is most affected by the SARS-CoV-2 infection, many organs/systems are affected in the short and long term. Since the COVID-19 disease simultaneously affects many organs, redesigning diagnostic and therapy policies to fit the damaged organs is strongly recommended. Even though the pathophysiology of many problems the infection causes is unknown, the frequency of COVID-19 cases rises with age and the existence of preexisting symptoms. This study aims to update our knowledge of SARS-CoV-2 infection and multi-organ dysfunction interaction based on clinical and theoretical evidence. For this purpose, the study comprehensively elucidates the most recent studies on the effects of SARS-CoV-2 infection on multiple organs and systems, including respiratory, cardiovascular, gastrointestinal, renal, nervous, endocrine, reproductive, immune, and parts of the integumentary system. Understanding the range of atypical COVID-19 symptoms could improve disease surveillance, limit transmission, and avoid additional multi-organ-system problems.
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Affiliation(s)
- Ali A Rabaan
- Molecular Diagnostic Laboratory, Johns Hopkins Aramco Healthcare, Dhahran, Saudi Arabia
- College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
- Department of Public Health and Nutrition, The University of Haripur, Haripur, Pakistan
| | - Samira Smajlović
- Laboratory Diagnostics Institute Dr. Dedić, Bihać, Bosnia and Herzegovina
| | - Huseyin Tombuloglu
- Department of Genetics Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Sabahudin Ćordić
- Cantonal Hospital “Dr. Irfan Ljubijankić”, Microbiological Laboratory, Bihać, Bosnia and Herzegovina
| | - Azra Hajdarević
- International Burch University, Faculty of Engineering and Natural Sciences, Department of Genetics and Bioengineering, Ilidža, Bosnia and Herzegovina
| | - Nudžejma Kudić
- University of Sarajevo, Faculty of Agriculture and Food Science, Sarajevo, Bosnia and Herzegovina
| | - Abbas Al Mutai
- Research Center, Almoosa Specialist Hospital, Al Mubarraz, Saudi Arabia
- College of Nursing, Princess Norah Bint Abdulrahman University, Riyadh, Saudi Arabia
- School of Nursing, Wollongong University, Wollongong, NSW, Australia
- Nursing Department, Prince Sultan Military College of Health Sciences, Dammam, Saudi Arabia
| | | | - Shamsah H Al-Ahmed
- Specialty Pediatric Medicine, Qatif Central Hospital, Qatif, Saudi Arabia
| | - Nisreen A Al-Zaki
- Specialty Pediatric Medicine, Qatif Central Hospital, Qatif, Saudi Arabia
| | - Mona J Al Marshood
- Specialty Pediatric Medicine, Qatif Central Hospital, Qatif, Saudi Arabia
| | - Amal H Alfaraj
- Pediatric Department, Abqaiq General Hospital, First Eastern Health Cluster, Abqaiq, Saudi Arabia
| | - Saad Alhumaid
- Administration of Pharmaceutical Care, Al-Ahsa Health Cluster, Ministry of Health, Al-Ahsa, Saudi Arabia
| | - Ebtesam Al-Suhaimi
- Biology Department, College of Science and Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
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21
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Abstract
Coronavirus disease (COVID-19) is an infectious airborne viral pneumonia caused by a novel virus belonging to the family coronaviridae. On February 11, 2019, the Internal Committee on Taxonomy of Virus (ICTV) announced the name of the novel virus as "severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). One of the proteins present on its membrane i.e. the Spike protein is responsible for the attachment of the virus to the host. It spreads through the salivary droplets released when an infected person sneezes or coughs. The best way to slow down the disease is by protecting self by washing hands and using the disinfectant. Most of the infected people experience mild to moderate breathing issues. Serious illness might develop in people with underlying cardiovascular problems, diabetes and other immuno-compromised diseases. To date, there is no effective medicine available in the market which is effective in COVID-19. However, healthcare professionals are using ritonavir, flavipiravir, lopinavir, hydroxychloroquine and remdesivir. Along with the medicines, some countries are using convalescent plasma and mesenchymal stem cells for treatment. Till date, it has claimed millions of death worldwide. In this detailed review, we have discussed the structure of SARS-CoV-2, essential proteins, its lifecycle, transmission, symptoms, pathology, clinical features, diagnosis, prevention, treatment and epidemiology of the disease.
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Affiliation(s)
- Heena Rehman
- Department of Biochemistry, Jamia Hamdard, New Delhi, India
| | - Md Iftekhar Ahmad
- Department of Pharmaceutics, Shri Gopichand College of Pharmacy, Baghpat, India
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22
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Liptak P, Nosakova L, Rosolanka R, Skladany L, Banovcin P. Acute-on-chronic liver failure in patients with severe acute respiratory syndrome coronavirus 2 infection. World J Hepatol 2023; 15:41-51. [PMID: 36744167 PMCID: PMC9896507 DOI: 10.4254/wjh.v15.i1.41] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Revised: 11/03/2022] [Accepted: 11/29/2022] [Indexed: 01/16/2023] Open
Abstract
The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a significant impact on the lives of millions of people, especially those with other concomitant diseases, such as chronic liver diseases. To date, seven coronaviruses have been identified to infect humans. The main site of pathological action of these viruses is lung tissue. However, a substantial number of studies have proven that SARS-CoV-2 shows affinity towards several organs, including the gastrointestinal tract and the liver. The current state of evidence points to several proposed mechanisms of liver injury in patients with COVID-19 and their combination. Liver impairment is considered to be the result of the direct effect of the virus on the hepatic tissue cells, a systemic reaction consisting of inflammation, hypoxia and cytokine storm, drug-induced liver injury, with the possible contribution of a perturbed gut-liver axis. Reactivation of chronic hepatic disease could be another factor for liver impairment in patients with SARS-CoV-2 infection. Acute-on-chronic liver failure (ACLF) is a relatively new syndrome that occurs in 10%–30% of all hospitalized patients with chronic liver disease. It is crucial to recognize high-risk patients due to the increased morbidity and mortality in these cases. Several published studies have reported virus infection as a trigger factor for ACLF. However, to date, there are few relevant studies describing the presence of ACLF in patients with acute SARS-CoV-2 infection. In this minireview we summarize the current state of knowledge regarding the relation between ACLF and acute SARS-CoV-2 infection.
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Affiliation(s)
- Peter Liptak
- Clinic of Internal Medicine-Gastroenterology, University Hospital in Martin, Jessenius Faculty of Medicine in Martin, Comenius University, Martin 03601, Slovakia
| | - Lenka Nosakova
- Clinic of Internal Medicine-Gastroenterology, University Hospital in Martin, Jessenius Faculty of Medicine in Martin, Comenius University, Martin 03601, Slovakia
| | - Robert Rosolanka
- Clinic of Infectology and Travel Medicine, University Hospital in Martin, Jessenius Faculty of Medicine in Martin, Comenius University, Martin 03601, Slovakia
| | - Lubomir Skladany
- Department of Internal Medicine II, Division Hepatology, Gastroenterology and Liver Transplantation, FD Roosevelt University Hospital of Slovak Medical University, Banska Bystrica 97517, Slovakia
| | - Peter Banovcin
- Clinic of Internal Medicine-Gastroenterology, University Hospital in Martin, Jessenius Faculty of Medicine in Martin, Comenius University, Martin 03601, Slovakia
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23
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Valsamaki A, Xanthoudaki M, Oikonomou KG, Vlachostergios PJ, Papadogoulas A, Katsiafylloudis P, Voulgaridi I, Skoura AL, Komnos A, Papamichalis P. Prevention, diagnostic evaluation, management and prognostic implications of liver disease in critically ill patients with COVID-19. World J Clin Cases 2023; 11:514-527. [PMID: 36793637 PMCID: PMC9923862 DOI: 10.12998/wjcc.v11.i3.514] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2022] [Revised: 12/05/2022] [Accepted: 01/10/2023] [Indexed: 01/23/2023] Open
Abstract
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, broke out in December 2019 in Wuhan city of China and spread rapidly worldwide. Therefore, by March 2020, the World Health Organization declared the disease a global pandemic. Apart from the respiratory system, various other organs of the human body are also seriously affected by the virus. Liver injury in patients with a severe form of COVID-19 is estimated to be 14.8%-53.0%. Elevated levels of total bilirubin, aspartate aminotransferase and alanine aminotransferase and low levels of serum albumin and prealbumin are the main laboratory findings. Patients with pre-existing chronic liver disease and cirrhosis are much more prone to develop severe liver injury. This literature review presented the recent scientific findings regarding the pathophysiological mechanisms responsible for liver injury in critically ill patients with COVID-19, the various interactions between drugs used to treat the disease and the function of the liver and the specific tests providing the possibility of early diagnosis of severe liver injury in these patients. Moreover, it highlighted the burden that COVID-19 put on health systems worldwide and its effect on transplant programs and the care provided to critically ill patients in general and particularly to those with chronic liver disease.
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Affiliation(s)
- Asimina Valsamaki
- Intensive Care Unit, General Hospital of Larissa, Larissa 41221, Greece
| | - Maria Xanthoudaki
- Intensive Care Unit, General Hospital of Larissa, Larissa 41221, Greece
| | | | - Panagiotis J Vlachostergios
- Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medicine, New York, NY 10065, United States
| | | | | | - Ioanna Voulgaridi
- Department of Microbiology, General Hospital of Larissa, Larissa 41221, Greece
| | | | - Apostolos Komnos
- Intensive Care Unit, General Hospital of Larissa, Larissa 41221, Greece
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Sharobaro VI, Malik VV, Kornalevskaya VA. Gastroenterological disorders in patients with COVID-19. EXPERIMENTAL AND CLINICAL GASTROENTEROLOGY 2023:147-151. [DOI: 10.31146/1682-8658-ecg-206-10-147-151] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
Introduction - It was found that the frequency of symptoms from the gastrointestinal tract (gastrointestinal tract) in COVID-19 infection varies between 11.4-50. Cases of manifestation of the disease with gastroenterological symptoms are reported, appearing on average 1-5 days before the development of respiratory symptoms. The course of the disease with the presence of diarrhea and vomiting without fever and other classical manifestations is described. The purpose is to review the scientific literature on the analysis of the leading pathogenetic factors in the formation of intestinal syndrome in a new coronavirus infection. Material and methods. The scientific literature was searched in the Web of Science, Scopus, PubMed and RSCI databases for the following keywords: coronavirus infection, intestinal syndrome. Search depth - 3 years. Results. The study revealed clinical manifestations of the gastrointestinal tract (gastrointestinal tract) in COVID-19 infection, their main mechanisms and the frequency of occurrence of certain symptoms in practice
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25
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Zippi M, Fiorino S, Hong W, de Biase D, Gallo CG, Grottesi A, Centorame A, Crispino P. Post-COVID-19 cholangiopathy: A systematic review. World J Meta-Anal 2023; 11:29-37. [DOI: 10.13105/wjma.v11.i1.29] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Revised: 10/13/2022] [Accepted: 11/23/2022] [Indexed: 01/11/2023] Open
Abstract
BACKGROUND The recent and still ongoing pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entailed various long-term complications, including post-infectious cholangiopathy.
AIM To identify the available studies concerning post-coronavirus disease 2019 (COVID-19) cholangiopathy.
METHODS An extensive bibliographical search was carried out in PubMed and in Cochrane Library to identify the articles (retrospective and prospective studies, cohort studies, case series and case reports) published between January 1, 2020 and August 22, 2022, using both MeSH terms and free-language keywords: cholangiopathy; COVID-19; post-COVID-19 cholangiopathy; SARS-CoV-2.
RESULTS Thirteen studies fulfilled the inclusion criteria, which included 64 patients suffering from this condition. The patients were male in 82.8% of cases. Liver transplant was executed in 6 patients and scheduled in 7 patients, while 2 patients refused the surgical approach. Therefore in 23.4% of the cases, performing this procedure appeared to be necessary.
CONCLUSION This review has revealed that generally the involvement of the liver in the course of SARS-CoV-2 infection is mild and transient, inducing cholestasis of cholangiocytes but can also be severe enough to cause organ failure in some cases.
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Affiliation(s)
- Maddalena Zippi
- Unit of Gastroenterology and Digestive Endoscopy, Sandro Pertini Hospital, Rome 00157, Italy
| | - Sirio Fiorino
- Unit of Internal Medicine, Maggiore Hospital, Local Health Unit of Bologna, Bologna 40133, Italy
| | - Wandong Hong
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, China
| | - Dario de Biase
- Department of Pharmacy and Biotechnology, University of Bologna, Bologna 40126, Italy
| | | | - Alfonso Grottesi
- Unit of General Surgery, Sandro Pertini Hospital, Rome 00157, Italy
| | | | - Pietro Crispino
- Unit of Emergency Medicine, Santa Maria Goretti Hospital, Latina 04100, Italy
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Khreefa Z, Barbier MT, Koksal AR, Love G, Del Valle L. Pathogenesis and Mechanisms of SARS-CoV-2 Infection in the Intestine, Liver, and Pancreas. Cells 2023; 12:cells12020262. [PMID: 36672197 PMCID: PMC9856332 DOI: 10.3390/cells12020262] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Revised: 12/30/2022] [Accepted: 01/05/2023] [Indexed: 01/11/2023] Open
Abstract
The novel coronavirus, SARS-CoV-2, rapidly spread worldwide, causing an ongoing global pandemic. While the respiratory system is the most common site of infection, a significant number of reported cases indicate gastrointestinal (GI) involvement. GI symptoms include anorexia, abdominal pain, nausea, vomiting, and diarrhea. Although the mechanisms of GI pathogenesis are still being examined, viral components isolated from stool samples of infected patients suggest a potential fecal-oral transmission route. In addition, viral RNA has been detected in blood samples of infected patients, making hematologic dissemination of the virus a proposed route for GI involvement. Angiotensin-converting enzyme 2 (ACE2) receptors serve as the cellular entry mechanism for the virus, and these receptors are particularly abundant throughout the GI tract, making the intestine, liver, and pancreas potential extrapulmonary sites for infection and reservoirs sites for developing mutations and new variants that contribute to the uncontrolled spread of the disease and resistance to treatments. This transmission mechanism and the dysregulation of the immune system play a significant role in the profound inflammatory and coagulative cascades that contribute to the increased severity and risk of death in several COVID-19 patients. This article reviews various potential mechanisms of gastrointestinal, liver, and pancreatic injury.
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Affiliation(s)
- Zaid Khreefa
- Department of Pathology, School of Medicine, Louisiana State University Health School of Medicine, New Orleans, LA 70112, USA
| | - Mallory T. Barbier
- Louisiana Cancer Research Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA
| | - Ali Riza Koksal
- Department of Pathology and Laboratory Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA
| | - Gordon Love
- Department of Pathology, School of Medicine, Louisiana State University Health School of Medicine, New Orleans, LA 70112, USA
| | - Luis Del Valle
- Department of Pathology, School of Medicine, Louisiana State University Health School of Medicine, New Orleans, LA 70112, USA
- Louisiana Cancer Research Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA
- Correspondence:
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Said KB, Alsolami A, Alreshidi FS, Fathuddin A, Alshammari F, Alrashid F, Aljadani A, Aboras R, Alreshidi F, Alghozwi MH, Alshammari SF, Alharbi NF. Profiles of Independent-Comorbidity Groups in Senior COVID-19 Patients Reveal Low Fatality Associated with Standard Care and Low-Dose Hydroxychloroquine over Antivirals. J Multidiscip Healthc 2023; 16:1215-1229. [PMID: 37153358 PMCID: PMC10162097 DOI: 10.2147/jmdh.s403700] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2023] [Accepted: 04/03/2023] [Indexed: 05/09/2023] Open
Abstract
Introduction The lack of feasible therapies and comorbidities aggravate the COVID-19 case-fatality rate (CFR). However, reports examining CFR associations with diabetes, concomitant cardiovascular diseases, chronic kidney disease, and chronic liver disease (CLD) are limited. More studies assessing hydroxychloroquine (Hcq) and antivirals are needed. Purpose To examine associations of COVID-19 CFR in comorbid patient groups each with single comorbidities and after treatment with Hcq, favipiravir, and dexamethasone (Dex), either alone or in combination versus standard care. Methods Using statistical analysis, we descriptively determined these associations among 750 COVID-19 patient groups during the last quarter of 2021. Results A diabetes comorbidity (40%, n=299) showed twice the fatality (CFR 14%) of the others (CFR 7%; P=0.001). Hypertension (Htn) was the second-commonest comorbidity (29.5%, n=221), with similar CFR to diabetes (15% and 7% for Htn and non-Htn, respectively), but with higher significance (P=0.0006167). Although only 4% (n=30) heart failure (HF) was reported, the CFR (40%) was much higher than in those without it (8%). A similar rate (4%) for chronic kidney disease was reported, with CFRs of 33% and 9% among those with and without it, respectively (P=0.00048). Ischemic heart disease was 11% (n=74), followed by chronic liver disease (0.4%) and history of smoking (1%); however, these were not significant due to the sample sizes. Treatment indicated standard care and Hcq alone or in combination were superior (CFR of 4% and 0.5%, respectively) compared to favipiravir (25%) or Dex (38.5%) independently or in combination (35.4%). Furthermore, Hcq performed well (CFR 9%) when combined with Dex (9%; P=4.28-26). Conclusion The dominance of diabetes and other comorbidities with significant association with CFR implied existence of a common virulence mechanism. The superiority of low-dose Hcq and standard care over antivirals warrants further studies.
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Affiliation(s)
- Kamaleldin B Said
- Department of Pathology and Microbiology, College of Medicine, University of Ha’il, Ha’il, 55476, Saudi Arabia
- Genomics, Bioinformatics and Systems Biology, Carleton University, Ottawa, ON K1S 5B6, Canada
- Correspondence: Kamaleldin B Said, Department of Pathology and Microbiology, College of Medicine, University of Ha’il, Ha’il, 55476, Saudi Arabia, Tel +966500771459, Email
| | - Ahmed Alsolami
- Department of Internal Medicine, College of Medicine, University of Ha’il, Ha’il, 55476, Saudi Arabia
| | - Fayez Saud Alreshidi
- Deparmtent of Family, Community Medicine, College of Medicine, University of Ha’il, Ha’il, 55476, Saudi Arabia
| | - Anas Fathuddin
- Department of Plastic Surgery, College of Medicine, University of Ha’il, Ha’il, 55476, Saudi Arabia
| | - Fawwaz Alshammari
- Department of Dermatology, College of Medicine, University of Ha’il, Ha’il, 55476, Saudi Arabia
| | - Fauwaz Alrashid
- Department of Surgery, College of Medicine, University of Ha’il, Ha’il, 55476, Saudi Arabia
| | - Ahmed Aljadani
- Department of Internal Medicine, College of Medicine, University of Ha’il, Ha’il, 55476, Saudi Arabia
| | - Rana Aboras
- Deparmtent of Family, Community Medicine, College of Medicine, University of Ha’il, Ha’il, 55476, Saudi Arabia
| | - Fatmah Alreshidi
- Deparmtent of Family, Community Medicine, College of Medicine, University of Ha’il, Ha’il, 55476, Saudi Arabia
| | - Mohammed H Alghozwi
- Department of Pathology and Microbiology, College of Medicine, University of Ha’il, Ha’il, 55476, Saudi Arabia
| | - Suliman F Alshammari
- Department of Pathology and Microbiology, College of Medicine, University of Ha’il, Ha’il, 55476, Saudi Arabia
| | - Nawaf F Alharbi
- Department of Pathology and Microbiology, College of Medicine, University of Ha’il, Ha’il, 55476, Saudi Arabia
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Xu KL, Randall PA. Alcohol, nicotine, and COVID-19: A retrospective study of health outcomes in central Pennsylvania. Brain Res Bull 2023; 192:175-183. [PMID: 36442695 PMCID: PMC9694354 DOI: 10.1016/j.brainresbull.2022.11.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Revised: 11/09/2022] [Accepted: 11/11/2022] [Indexed: 11/27/2022]
Abstract
Individuals with substance abuse disorder are at increased risk for the development of severe disease following COVID-19 infection. Furthermore, individuals in rural populations where access to healthcare is limited and rates of substance abuse tend to be higher are at increased risk compared to other regions. The Penn State Health Network serves 29 counties in central Pennsylvania that are largely rural. The current study assessed the electronic medical records for individuals in this population that were reported as having alcohol dependence, nicotine dependence or both (co-users) in addition to individuals with no history of drug use and the rate of developing primary and secondary health outcomes following COVID-19 infection. All patients in this study were determined to be COVID+ while in care. We found that overall, risk for requiring ventilation, developing pneumonia, and mortality within 30 days of diagnosis all increased with any substance use history, across both males and females and across all age groups. Moreover, rates of these outcomes were considerably higher in patients that were both alcohol and nicotine dependent suggesting additive effects of co-use. Rates of secondary effects also increased substantially across all use categories with these patients showing greater risk of developing liver, kidney, and pancreas maladies compared to patients with no history of substance use. Taken together, these findings reinforce previous studies showing that substance use increases the risks of significant disease following COVID-19 infection, giving insights into the health disparities that exist in rural populations.
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Affiliation(s)
- Kevin Lou Xu
- Department of Anesthesiology and Perioperative Medicine, Penn State College of Medicine, Hershey, PA 17033, USA,Program in Medical Education, Pennsylvania State University, College of Medicine, Hershey, PA 17033, USA
| | - Patrick Arthur Randall
- Department of Anesthesiology and Perioperative Medicine, Penn State College of Medicine, Hershey, PA 17033, USA,Department of Pharmacology, Penn State College of Medicine, Hershey, PA 17033, USA,Corresponding author at: Department of Anesthesiology and Perioperative Medicine, Penn State College of Medicine, Hershey, PA 17033, USA
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Jia FJ, Han J. Liver injury in COVID-19: Holds ferritinophagy-mediated ferroptosis accountable. World J Clin Cases 2022; 10:13148-13156. [PMID: 36683648 PMCID: PMC9850986 DOI: 10.12998/wjcc.v10.i36.13148] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Revised: 11/20/2022] [Accepted: 12/08/2022] [Indexed: 12/26/2022] Open
Abstract
Even in patients without a history of liver disease, liver injury caused by coronavirus disease 2019 (COVID-19) is gradually becoming more common. However, the precise pathophysiological mechanisms behind COVID-19's liver pathogenicity are still not fully understood. We hypothesize that inflammation may become worse by cytokine storms caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Elevated ferritin levels can initiate ferritinophagy mediated by nuclear receptor coactivator 4 (NCOA4), which leads to iron elevation, and ferroptosis. In COVID-19 patients, ferroptosis can be restricted to reduce disease severity and liver damage by targeting NCOA4-mediated ferritinophagy. To confirm the role of ferritinophagy-mediated ferroptosis in SARS-CoV-2 infection, further research is required.
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Affiliation(s)
- Feng-Ju Jia
- School of Nursing, Qingdao University, Qingdao 266071, Shandong Province, China
| | - Jing Han
- School of Nursing, Qingdao University, Qingdao 266071, Shandong Province, China
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30
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Domovitz T, Ayoub S, Werbner M, Alter J, Izhaki Tavor L, Yahalom-Ronen Y, Tikhonov E, Meirson T, Maman Y, Paran N, Israely T, Dessau M, Gal-Tanamy M. HCV Infection Increases the Expression of ACE2 Receptor, Leading to Enhanced Entry of Both HCV and SARS-CoV-2 into Hepatocytes and a Coinfection State. Microbiol Spectr 2022; 10:e0115022. [PMID: 36314945 PMCID: PMC9769977 DOI: 10.1128/spectrum.01150-22] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Accepted: 09/28/2022] [Indexed: 11/09/2022] Open
Abstract
Recent studies suggest the enhancement of liver injury in COVID-19 patients infected with Hepatitis C virus (HCV). Hepatocytes express low levels of angiotensin-converting enzyme 2 (ACE2), the SARS-CoV-2 entry receptor, raising the possibility of HCV-SARS-CoV-2 coinfection in the liver. This work aimed to explore whether HCV and SARS-CoV-2 coinfect hepatocytes and the interplay between these viruses. We demonstrate that SARS-CoV-2 coinfects HCV-infected Huh7.5 (Huh7.5HCV) cells. Both viruses replicated efficiently in the coinfected cells, with HCV replication enhanced in coinfected compared to HCV-mono-infected cells. Strikingly, Huh7.5HCV cells were eight fold more susceptible to SARS-CoV-2 pseudoviruses than naive Huh7.5 cells, suggesting enhanced SARS-CoV-2 entry into HCV-preinfected hepatocytes. In addition, we observed increased binding of spike receptor-binding domain (RBD) protein to Huh7.5HCV cells, as well as enhanced cell-to-cell fusion of Huh7.5HCV cells with spike-expressing Huh7.5 cells. We explored the mechanism of enhanced SARS-CoV-2 entry and identified an increased ACE2 mRNA and protein levels in Huh7.5HCV cells, primary hepatocytes, and in data from infected liver biopsies obtained from database. Importantly, higher expression of ACE2 increased HCV infection by enhancing its binding to the host cell, underscoring its role in the HCV life cycle as well. Transcriptome analysis revealed that shared host signaling pathways were induced in HCV-SARS-CoV-2 coinfection. This study revealed complex interactions between HCV and SARS-CoV-2 infections in hepatocytes, which may lead to the increased liver damage recently reported in HCV-positive COVID-19 patients. IMPORTANCE Here, we provide the first experimental evidence for the coexistence of SARS-CoV-2 infection with HCV, and the interplay between them. The study revealed a complex relationship of enhancement between the two viruses, where HCV infection increased the expression of the SARS-CoV-2 entry receptor ACE2, thus facilitating SARS-CoV-2 entry, and potentially, also HCV entry. Thereafter, SARS-CoV-2 infection enhanced HCV replication in hepatocytes. This study may explain the aggravation of liver damage that was recently reported in COVID-19 patients with HCV coinfection and suggests preinfection with HCV as a risk factor for severe COVID-19. Moreover, it highlights the possible importance of HCV treatment for coinfected patients. In a broader view, these findings emphasize the importance of identifying coinfecting pathogens that increase the risk of SARS-CoV-2 infection and that may accelerate COVID-19-related co-morbidities.
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Affiliation(s)
- Tom Domovitz
- Molecular Virology Lab, The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
| | - Samer Ayoub
- Molecular Virology Lab, The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
| | - Michal Werbner
- Molecular Virology Lab, The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
| | - Joel Alter
- The Laboratory of Structural Biology of Infectious Diseases, The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
| | - Lee Izhaki Tavor
- The Laboratory of Structural Biology of Infectious Diseases, The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
| | - Yfat Yahalom-Ronen
- Department of Infectious Diseases, Israel Institute for Biological Research, Ness Ziona, Israel
| | - Evgeny Tikhonov
- The Lab of Genomic Instability and Cancer, The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
| | - Tomer Meirson
- The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
- Davidoff Cancer Center, Rabin Medical Center-Beilinson Hospital, Petah Tikva, Israel
| | - Yaakov Maman
- The Lab of Genomic Instability and Cancer, The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
| | - Nir Paran
- Department of Infectious Diseases, Israel Institute for Biological Research, Ness Ziona, Israel
| | - Tomer Israely
- Department of Infectious Diseases, Israel Institute for Biological Research, Ness Ziona, Israel
| | - Moshe Dessau
- The Laboratory of Structural Biology of Infectious Diseases, The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
| | - Meital Gal-Tanamy
- Molecular Virology Lab, The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
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Liu Z, Fu Y, Huang Y, Zeng F, Rao J, Xiao X, Sun X, Jin H, Li J, Yang J, Du W, Liu L. Ubiquitination of SARS-CoV-2 ORF7a Prevents Cell Death Induced by Recruiting BclXL To Activate ER Stress. Microbiol Spectr 2022; 10:e0150922. [PMID: 36326498 PMCID: PMC9769937 DOI: 10.1128/spectrum.01509-22] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Accepted: 10/18/2022] [Indexed: 11/06/2022] Open
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19), which has emerged in the last 2 years. The accessory protein ORF7a has been proposed as an immunomodulating factor that can cause dramatic inflammatory responses, but it is unknown how ORF7a interacts with host cells. We show that ORF7a induces cell apoptosis by recruiting the prosurvival factor BclXL to the endoplasmic reticulum (ER) via the exposed C-terminal residues Lys117 and Lys119. Simultaneously, ORF7a activates ER stress via the PERK-elF2α-CHOP pathway and inhibits the expression of endogenous BclXL, resulting in enhanced cell apoptosis. Ubiquitination of ORF7a interrupts the interaction with BclXL in the ER and weakens the activation of ER stress, which to some extent rescues the cells. Our work demonstrates that SARS-CoV-2 ORF7a hires antiapoptosis protein and aggregates on the ER, resulting in ER stress and apoptosis initiation. On the other hand, ORF7a utilizes the ubiquitin system to impede and escape host elimination, providing a promising potential target for developing strategies for minimizing the COVID-19 pandemic. IMPORTANCE Viruses struggle to reproduce after infecting cells, and the host eliminates infected cells through apoptosis to prevent virus spread. Cells adopt a special ubiquitination code to protect against viral infection, while ORF7a manipulates and exploits the ubiquitin system to eliminate host cells' effect on apoptosis and redirect cellular pathways in favor of virus survival. Our results revealed that SARS-CoV-2-encoded accessory protein ORF7a recruits prosurvival factor BclXL to the ER and activates the cellular ER stress response resulting in the initiation of programmed death to remove virus-infected cells. Ubiquitination of ORF7a blocked the recruitment of BclXL and suppressed the ER stress response, which helps to counteract cell apoptosis and rescue cell fate. These findings help us understand the mechanism of SARS-CoV-2 invasion and contribute to a theoretical foundation for the clinical prevention of COVID-19.
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Affiliation(s)
- Zhixin Liu
- Department of Infectious Diseases, Renmin Hospital, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, China
- Institute of Virology, Hubei University of Medicine, Shiyan, China
- Hubei Key Laboratory of Embryonic Stem Cell Research, Hubei University of Medicine, Shiyan, China
| | - Yanan Fu
- Department of Infectious Diseases, Renmin Hospital, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, China
- Institute of Virology, Hubei University of Medicine, Shiyan, China
| | - Yanping Huang
- Department of Infectious Diseases, Renmin Hospital, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, China
- Institute of Virology, Hubei University of Medicine, Shiyan, China
| | - Feng Zeng
- Department of Infectious Diseases, Renmin Hospital, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, China
- Institute of Virology, Hubei University of Medicine, Shiyan, China
| | - Jingjing Rao
- Department of Infectious Diseases, Renmin Hospital, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, China
- Institute of Virology, Hubei University of Medicine, Shiyan, China
| | - Xiao Xiao
- Department of Infectious Diseases, Renmin Hospital, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, China
- Institute of Virology, Hubei University of Medicine, Shiyan, China
| | - Xiaoguang Sun
- Department of Infectious Diseases, Renmin Hospital, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, China
- Institute of Virology, Hubei University of Medicine, Shiyan, China
| | - Hao Jin
- Department of Infectious Diseases, Renmin Hospital, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, China
| | - Jian Li
- Department of Infectious Diseases, Renmin Hospital, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, China
- Institute of Virology, Hubei University of Medicine, Shiyan, China
| | - Jing Yang
- Department of Infectious Diseases, Renmin Hospital, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, China
- Institute of Virology, Hubei University of Medicine, Shiyan, China
| | - Weixing Du
- Department of Infectious Diseases, Renmin Hospital, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, China
| | - Long Liu
- Department of Infectious Diseases, Renmin Hospital, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, China
- Institute of Virology, Hubei University of Medicine, Shiyan, China
- Hubei Key Laboratory of Embryonic Stem Cell Research, Hubei University of Medicine, Shiyan, China
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32
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Choaib A, Issa E, El Choueiry F, Eldin JN, Shbaklo K, Alhajj M, Sawaya RT, Assi G, Nader M, Chatila R, Faour WH. SARS-CoV-2-mediated liver injury: pathophysiology and mechanisms of disease. Inflamm Res 2022; 72:301-312. [PMID: 36539655 PMCID: PMC9767399 DOI: 10.1007/s00011-022-01683-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2022] [Revised: 12/13/2022] [Accepted: 12/16/2022] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND SARS-CoV-2-induced severe inflammatory response can be associated with severe medical consequences leading to multi-organ failure, including the liver. The main mechanism behind this assault is the aggressive cytokine storm that induces cytotoxicity in various organs. Of interest, hepatic stellate cells (HSC) respond acutely to liver injury through several molecular mechanisms, hence furthering the perpetuation of the cytokine storm and its resultant tissue damage. In addition, hepatocytes undergo apoptosis or necrosis resulting in the release of pro-inflammatory and pro-fibrogenic mediators that lead to chronic liver inflammation. AIMS The aim of this review is to summarize available data on SARS-CoV-2-induced liver inflammation in addition to evaluate the potential effect of anti-inflammatory drugs in attenuating SARS-CoV-2-induced liver inflammation. METHODS Thorough PubMed search was done to gather and summarize published data on SARS-CoV-2-induced liver inflammation. Additionally, various anti-inflammatory potential treatments were also documented. RESULTS Published data documented SARS-CoV-2 infection of liver tissues and is prominent in most liver cells. Also, histological analysis showed various features of tissues damage, e.g., hepatocellular necrosis, mitosis, cellular infiltration, and fatty degeneration in addition to microvesicular steatosis and inflammation. Finally, the efficacy of the different drugs used to treat SARS-CoV-2-induced liver injury, in particular the anti-inflammatory remedies, are likely to have some beneficial effect to treat liver injury in COVID-19. CONCLUSION SARS-CoV-2-induced liver inflammation is a serious condition, and drugs with potent anti-inflammatory effect can play a major role in preventing irreversible liver damage in COVID-19.
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Affiliation(s)
- Ali Choaib
- Gilbert & Rose-Marie Chagoury School of Medicine, Lebanese American University, P.O. Box 36, Byblos, Lebanon
| | - Elio Issa
- Gilbert & Rose-Marie Chagoury School of Medicine, Lebanese American University, P.O. Box 36, Byblos, Lebanon
| | - Francesca El Choueiry
- Gilbert & Rose-Marie Chagoury School of Medicine, Lebanese American University, P.O. Box 36, Byblos, Lebanon
| | - Jade Nasser Eldin
- Gilbert & Rose-Marie Chagoury School of Medicine, Lebanese American University, P.O. Box 36, Byblos, Lebanon
| | - Khodor Shbaklo
- Gilbert & Rose-Marie Chagoury School of Medicine, Lebanese American University, P.O. Box 36, Byblos, Lebanon
| | - Maryline Alhajj
- Gilbert & Rose-Marie Chagoury School of Medicine, Lebanese American University, P.O. Box 36, Byblos, Lebanon
| | - Ramy Touma Sawaya
- Gilbert & Rose-Marie Chagoury School of Medicine, Lebanese American University, P.O. Box 36, Byblos, Lebanon
| | - Ghaith Assi
- Gilbert & Rose-Marie Chagoury School of Medicine, Lebanese American University, P.O. Box 36, Byblos, Lebanon
| | - Moni Nader
- Department of Physiology and Immunology, College of Medicine and Health Sciences, Khalifa University of Science and Technology, P.O. Box 127788, Abu Dhabi, United Arab Emirates
- Center for Biotechnology, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates
| | - Rajaa Chatila
- Gilbert & Rose-Marie Chagoury School of Medicine, Lebanese American University, P.O. Box 36, Byblos, Lebanon
- Internal Medicine-Gastroenterology, Lebanese American University Medical Center-Rizk Hospital (LAUMC-RH), Beirut, Lebanon
| | - Wissam H Faour
- Gilbert & Rose-Marie Chagoury School of Medicine, Lebanese American University, P.O. Box 36, Byblos, Lebanon.
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Payus AO, Mohd Noh M, Azizan N, Muthukaruppan Chettiar R. SARS-CoV-2-induced liver injury: A review article on the high-risk populations, manifestations, mechanisms, pathological changes, management, and outcomes. World J Gastroenterol 2022; 28:5723-5730. [PMID: 36338886 PMCID: PMC9627422 DOI: 10.3748/wjg.v28.i39.5723] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2022] [Revised: 08/24/2022] [Accepted: 10/10/2022] [Indexed: 02/06/2023] Open
Abstract
The novel coronavirus disease 2019 is an infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and was declared a global pandemic with more than 500 million reported cases and more than 6 million deaths worldwide to date. Although it has transitioned into the endemic phase in many countries, the mortality rate and overall prognosis of the disease are still abysmal and need further improvement. There has been evidence that shows the significance of SARS-CoV-2-related liver injury. Here, we review the literature on the various spectrum of SARS-CoV-2 infection-induced liver injury and the possible mechanisms of damage to the hepatobiliary system. This review aimed to illustrate the latest understanding regarding SARS-CoV-2-induced liver injury including the high-risk populations, the characteristic clinical manifestations, the possible pathogenic mechanism, the pathological changes, the current suggestions for clinical treatment for various spectrum of populations, and the prognosis of the condition. In conclusion, SARS-CoV-2 patients with a liver injury warrant close monitoring as it is associated with the more severe and poorer outcome of the infection.
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Affiliation(s)
- Alvin Oliver Payus
- Department of Medicine, Faculty of Medicine and Health Sciences, Universiti Malaysia Sabah, Kota Kinabalu 88400, Sabah, Malaysia
| | - Malehah Mohd Noh
- Department of Medicine, Faculty of Medicine and Health Sciences, Universiti Malaysia Sabah, Kota Kinabalu 88400, Sabah, Malaysia
| | - Nornazirah Azizan
- Department of Pathobiology and Medical Diagnostic, Faculty of Medicine and Health Sciences, Universiti Malaysia Sabah, Kota Kinabalu 88400, Malaysia
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Alnamshan MM. Potential histopathological and immunological effects of SARS-CoV-2 on the liver. BRAZ J BIOL 2022; 82:e262008. [PMID: 36074418 DOI: 10.1590/1519-6984.262008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2022] [Accepted: 07/05/2022] [Indexed: 12/15/2022] Open
Abstract
The coronavirus disease outbreak of 2019 (COVID-19) poses a serious threat to public health worldwide. Lung injury is the most common complication of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. However, other organs, including the liver, can also be affected. Currently, there is limited evidence that liver impairment is associated with severe SARS-CoV-2 infection. Clinicians will need to determine whether liver injury is caused by an underlying liver condition, COVID-19 therapy, the virus directly, or immune-mediated inflammation or represents a complicated disease course in the context of COVID-19. To address the scarcity of data on histopathological changes and immunological effects on the liver with COVID-19 positivity, we analyze and summarize recent findings. We searched PubMed, Medline, Google Scholar, Science Direct, Scopus, and Web of Science databases up to December 1, 2021, identifying published studies with the search terms "Histopathology in COVID-19," "COVID-19," "Pathological changes in liver in COVID-19," "Liver pathology in COVID-19," "immunological effects in liver in COVID-19," and "SARS-CoV-2." This concise review will aid clinicians and researchers in better understanding the tissue histopathology and immunological consequences of SARS-CoV-2 on the liver, enabling improved care planning and avoiding future dangers.
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Affiliation(s)
- M M Alnamshan
- Imam Abdulrahman Bin Faisal University, College of Science, Department of Biology, Dammam, Saudi Arabia
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35
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Coronaviruses exploit a host cysteine-aspartic protease for replication. Nature 2022; 609:785-792. [PMID: 35922005 DOI: 10.1038/s41586-022-05148-4] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Accepted: 07/26/2022] [Indexed: 11/08/2022]
Abstract
Highly pathogenic coronaviruses, including severe acute respiratory syndrome coronavirus 2 (refs. 1,2) (SARS-CoV-2), Middle East respiratory syndrome coronavirus3 (MERS-CoV) and SARS-CoV-1 (ref. 4), vary in their transmissibility and pathogenicity. However, infection by all three viruses results in substantial apoptosis in cell culture5-7 and in patient tissues8-10, suggesting a potential link between apoptosis and pathogenesis of coronaviruses. Here we show that caspase-6, a cysteine-aspartic protease of the apoptosis cascade, serves as an important host factor for efficient coronavirus replication. We demonstrate that caspase-6 cleaves coronavirus nucleocapsid proteins, generating fragments that serve as interferon antagonists, thus facilitating virus replication. Inhibition of caspase-6 substantially attenuates lung pathology and body weight loss in golden Syrian hamsters infected with SARS-CoV-2 and improves the survival of mice expressing human DPP4 that are infected with mouse-adapted MERS-CoV. Our study reveals how coronaviruses exploit a component of the host apoptosis cascade to facilitate virus replication.
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Denızlı R, Sakcak B, Farisoğulları N, Peker MEM, Sınacı S, Kara Ö, Tanacan A, Tekın ÖM, Şahın D. The İmpact of Elevated Liver Enzymes and İntrahepatic Cholestasis of Pregnancy on the Course of COVID-19 in Pregnant Women. SN COMPREHENSIVE CLINICAL MEDICINE 2022; 4:184. [PMID: 35971435 PMCID: PMC9366840 DOI: 10.1007/s42399-022-01267-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Accepted: 08/05/2022] [Indexed: 12/15/2022]
Abstract
This study aims to investigate the perinatal outcomes in COVID-19 pregnant women with intrahepatic cholestasis of pregnancy (ICP) and elevated liver enzymes. Present study was carried out on pregnant women with COVID-19 between March 11, 2020, and August 11, 2021. Patients with liver enzyme levels higher than twice the upper limit of the reference range for aspartate aminotransferase(AST) and/or alanine aminotransferase (ALT) were included. Patients with unexplained pruritus and elevated fasting biliary acid (FBA) levels were considered ICP. The remaining cases were used as the control group. There were a total of 1751 patients in the study period. Among them, 126 had elevated liver enzymes. Nineteen of these cases had also ICP. AST and ALT values were statistically higher in the ICP group. Demographic features, clinical characteristics, and perinatal outcomes were similar between the groups. The rate of ICP in pregnant women with COVID-19 was similar to the literature in this study. Although the preterm delivery rates for both groups were higher than in the current literature, the preterm delivery rates in the study and control groups were similar. Elevated liver enzymes can be observed in pregnant women with COVID-19 with higher rates of preterm delivery compared to the previous literature. However, the diagnosis of ICP in addition to elevated liver enzymes seems to have no significant impact on the perinatal outcomes. Future studies conducted on larger populations are necessary to confirm these results.
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Affiliation(s)
- Ramazan Denızlı
- Department of Obstetrics and Gynecology, Ministry of Health, Ankara City Hospital, Ankara, 06800 Turkey
| | - Bedri Sakcak
- Department of Obstetrics and Gynecology, Ministry of Health, Ankara City Hospital, Ankara, 06800 Turkey
| | - Nihat Farisoğulları
- Department of Obstetrics and Gynecology, Ministry of Health, Ankara City Hospital, Ankara, 06800 Turkey
| | - Melis Ece Men Peker
- Department of Obstetrics and Gynecology, Ministry of Health, Ankara City Hospital, Ankara, 06800 Turkey
| | - Selcan Sınacı
- Department of Obstetrics and Gynecology, Ministry of Health, Ankara City Hospital, Ankara, 06800 Turkey
| | - Özgür Kara
- Department of Obstetrics and Gynecology, Ministry of Health, Ankara City Hospital, Ankara, 06800 Turkey
| | - Atakan Tanacan
- Department of Obstetrics and Gynecology, Ministry of Health, Ankara City Hospital, Ankara, 06800 Turkey
| | - Özlem Moraloğlu Tekın
- Department of Obstetrics and Gynecology, Ministry of Health, Ankara City Hospital, Ankara, 06800 Turkey
- University of Health Sciences, Ankara City Hospital, Ankara, Turkey
| | - Dilek Şahın
- Department of Obstetrics and Gynecology, Ministry of Health, Ankara City Hospital, Ankara, 06800 Turkey
- University of Health Sciences, Ankara City Hospital, Ankara, Turkey
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Mukherjee MD, Kumar A, Solanki PR, Verma D, Yadav AK, Chaudhary N, Kumar P. Recent Advances in Understanding SARS-CoV-2 Infection and Updates on
Potential Diagnostic and Therapeutics for COVID-19. CORONAVIRUSES 2022; 3. [DOI: 10.2174/2666796703666220302143102] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/23/2021] [Revised: 11/09/2021] [Accepted: 12/13/2021] [Indexed: 09/25/2023]
Abstract
Abstract:
A more focused approach is needed to understand the SARS-CoV-2 virulence, structure, and
genomics to devise more effective diagnostic and treatment interventions as this virus can evade the immune
attack and causes life-threatening complications such as cytokine storm. The spread of the virus is
still amplifying and causing thousands of new cases worldwide. It is essential to review current diagnostics
and treatment approaches to pave the way to correct or modify our current practices to make more
effective interventions against COVID-19. COVID-19 vaccine development has moved at a breakneck
pace since the outbreak began, utilizing practically all possible platforms or tactics to ensure the success
of vaccines. A total of 42 vaccine candidates have already entered clinical trials, including promising
results from numerous vaccine candidates in phase 1 or phase 2 trials. Further, many existing drugs are
being explored on broad-spectrum antiviral medications for their use in clinical recovery against COVID-
19. The present review attempts to re-examine the SARS-CoV-2 structure, its viral life cycle, clinical
symptoms and pathogenesis, mode of transmission, diagnostics, and treatment strategies that may be useful
for resorting to more effective approaches for controlling COVID-19. Various antiviral drugs and
vaccination strategies with their strengths and weaknesses are also discussed in the paper to augment our
understanding of COVID-19 management.
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Affiliation(s)
- Maumita D. Mukherjee
- Amity Institute of Applied Sciences, Amity University, Noida, Uttar Pradesh-201313, India
| | - Anil Kumar
- National Institute of Immunology, New Delhi-110067, India
| | - Pratima R. Solanki
- Nano-Bio Laboratory, Special Centre for Nanoscience, Jawaharlal Nehru University, New Delhi-110067, India
| | - Damini Verma
- Nano-Bio Laboratory, Special Centre for Nanoscience, Jawaharlal Nehru University, New Delhi-110067, India
- Amity Institute of Applied Sciences, Amity University, Noida, Uttar Pradesh-201313, India
| | - Amit K. Yadav
- Nano-Bio Laboratory, Special Centre for Nanoscience, Jawaharlal Nehru University, New Delhi-110067, India
| | - Navneet Chaudhary
- Department of Biotechnology,
Delhi Technological University, Delhi-110042, India
| | - Pramod Kumar
- Sri Aurobindo College, Delhi University, New Delhi-110017,
India
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Khaswal A, Kumar V, Kumar S. Long-Term Health Consequences of SARS-CoV-2: Assumptions Based on SARS-CoV-1 and MERS-CoV Infections. Diagnostics (Basel) 2022; 12:diagnostics12081852. [PMID: 36010203 PMCID: PMC9406530 DOI: 10.3390/diagnostics12081852] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2022] [Revised: 07/25/2022] [Accepted: 07/27/2022] [Indexed: 01/08/2023] Open
Abstract
Coronavirus Disease-2019 (COVID-19) is one of the worst pandemics in the history of the world. It is the third coronavirus disease that has afflicted humans in a short span of time. The world appears to be recovering from the grasp of this deadly pandemic; still, its post-disease health effects are not clearly understood. It is evident that the vast majority of COVID-19 patients usually recovered over time; however, disease manifestation is reported to still exist in some patients even after complete recovery. The disease is known to have left irreversible damage(s) among some patients and these damages are expected to cause mild or severe degrees of health effects. Apart from the apparent damage to the lungs caused by SARS-CoV-1, MERS-CoV, and SARS-CoV-2 infection, COVID-19-surviving patients display a wide spectrum of dysfunctions in different organ systems that is similar to what occurs with SARS-CoV-1 and MERS diseases. The major long COVID-19 manifestations include the following aspects: (1) central nervous system, (2) cardiovascular, (3) pulmonary, (4) gastrointestinal, (5) hematologic, (6) renal and (7) psycho-social systems. COVID-19 has a disease display manifestation in these organs and its related systems amongst a large number of recovered cases. Our study highlights the expected bodily consequences of the pandemic caused by SARS-CoV-2 infection based on the understanding of the long-term effects of SARS-CoV-1 and MERS-CoV.
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Affiliation(s)
- Ashutosh Khaswal
- Department of Biotechnology, IMS Engineering College, NH-24, Ghaziabad 201009, Uttar Pradesh, India; (A.K.); (V.K.)
| | - Vivek Kumar
- Department of Biotechnology, IMS Engineering College, NH-24, Ghaziabad 201009, Uttar Pradesh, India; (A.K.); (V.K.)
| | - Subodh Kumar
- Center of Emphasis in Neuroscience, Department of Molecular and Translational Medicine, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, 5001 El Paso Drive, El Paso, TX 79905, USA
- Correspondence:
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Chen H, Chen Q. COVID-19 Pandemic: Insights into Interactions between SARS-CoV-2 Infection and MAFLD. Int J Biol Sci 2022; 18:4756-4767. [PMID: 35874945 PMCID: PMC9305262 DOI: 10.7150/ijbs.72461] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Accepted: 06/23/2022] [Indexed: 01/08/2023] Open
Abstract
COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become an ongoing global health pandemic. Since 2019, the pandemic continues to cast a long shadow on all aspects of our lives, bringing huge health and economic burdens to all societies. With our in-depth understanding of COVID-19, from the initial respiratory tract to the later gastrointestinal tract and cardiovascular systems, the multiorgan involvement of this infectious disease has been discovered. Metabolic dysfunction-associated fatty liver disease (MAFLD), formerly named nonalcoholic fatty liver disease (NAFLD), is a major health issue closely related to metabolic dysfunctions, affecting a quarter of the world's adult population. The association of COVID-19 with MAFLD has received increasing attention, as MAFLD is a potential risk factor for SARS-CoV-2 infection and severe COVID-19 symptoms. In this review, we provide an update on the interactions between COVID-19 and MAFLD and its underlying mechanisms.
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Affiliation(s)
- Hanfei Chen
- Cancer Center, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, China.,Centre for Precision Medicine Research and Training, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, China
| | - Qiang Chen
- Cancer Center, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, China.,Centre for Precision Medicine Research and Training, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, China.,MOE Frontier Science Centre for Precision Oncology, University of Macau, Taipa, Macau SAR, China
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Impact of COVID-19 in Chronic Viral Hepatitis B Patients on Virological, Clinical, and Paraclinical Aspects. Jundishapur J Microbiol 2022. [DOI: 10.5812/jjm-127312] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Background: Coronavirus disease 2019 (COVID-19) is caused by an infection in the respiratory tract leading to extrapulmonary manifestations, including dysregulation of the immune system and hepatic injury. Objectives: Given the high prevalence of viral hepatitis and a few studies carried out on severe acute respiratory syndrome coronavirus 2 and hepatitis B virus (HBV), this study investigated the impact of COVID-19 on chronic hepatitis B (CHB) patients in the northeast region of Iran. Methods: In this cross-sectional study, the blood samples were collected from 93 CHB patients registered in the Patient Detection Data Bank of Golestan University of Medical Sciences, Gorgan, Iran, and 62 healthy individuals as controls. Reverse transcription-polymerase chain reaction was adopted to detect COVID-19 infection in all the participants’ nasopharyngeal samples. All the participants were subjected to anti-hepatitis C virus, anti-hepatitis delta virus, and liver function tests. Then, HBV deoxyribonucleic acid load was detected in CHB patients. The collected data were analyzed by statistical tests using SPSS software (version 20). A P-value less than 0.05 was considered statistically significant. Results: In this study, 14% (13/93) and 32.25% (20/62) of CHB patients and control individuals were infected with COVID-19, respectively. The mean age of CHB patients was 39.69 ± 19.58 years, and 71% of them were female. The risk of developing COVID-19 in healthy controls was observed to be 2.3 times higher than in patients with CHB (0.95% confidence interval: 1.242 - 4.290). On the other hand, the mean values of aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase in CHB patients superinfected with COVID-19 were higher than other participants. Out of 35.4% of patients with viral hepatitis B that were taking antiviral drugs, only 5.4% had COVID-19. Conclusions: Although CHB infection did not predispose COVID-19 patients to more severe outcomes, the data of this study suggest that antiviral agents also decreased susceptibility to COVID-19 infection. Alternatively, careful assessment of hepatic manifestations and chronic viral hepatitis infections in COVID-19 patients can lead to more favorable health outcomes.
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Metabolite, protein, and tissue dysfunction associated with COVID-19 disease severity. Sci Rep 2022; 12:12204. [PMID: 35842456 PMCID: PMC9288092 DOI: 10.1038/s41598-022-16396-9] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2021] [Accepted: 07/08/2022] [Indexed: 01/09/2023] Open
Abstract
Proteins are direct products of the genome and metabolites are functional products of interactions between the host and other factors such as environment, disease state, clinical information, etc. Omics data, including proteins and metabolites, are useful in characterizing biological processes underlying COVID-19 along with patient data and clinical information, yet few methods are available to effectively analyze such diverse and unstructured data. Using an integrated approach that combines proteomics and metabolomics data, we investigated the changes in metabolites and proteins in relation to patient characteristics (e.g., age, gender, and health outcome) and clinical information (e.g., metabolic panel and complete blood count test results). We found significant enrichment of biological indicators of lung, liver, and gastrointestinal dysfunction associated with disease severity using publicly available metabolite and protein profiles. Our analyses specifically identified enriched proteins that play a critical role in responses to injury or infection within these anatomical sites, but may contribute to excessive systemic inflammation within the context of COVID-19. Furthermore, we have used this information in conjunction with machine learning algorithms to predict the health status of patients presenting symptoms of COVID-19. This work provides a roadmap for understanding the biochemical pathways and molecular mechanisms that drive disease severity, progression, and treatment of COVID-19.
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Kamal AM, Dumitrescu F, Mită A, Săbiescu DM, Alexandru DO, Gheorghe CE, Filip MM, Ionescu-Ciocâlteu A, Maria DT, Kamal D, Kamal CK. Liver Function Tests and FIB-4 Score as Predictors of Severity in COVID-19 Patients from the South-West of Romania. Life (Basel) 2022; 12:934. [PMID: 35888026 PMCID: PMC9318778 DOI: 10.3390/life12070934] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2022] [Revised: 06/19/2022] [Accepted: 06/20/2022] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND The coronavirus disease 2019 pandemic (COVID-19) is the most important global health crisis to date. In this study, we performed an analysis to find the association between liver damage, FIB-4 score and the severity of COVID-19 disease. METHODS We included a total of 580 patients that tested positive for SARS-CoV-2 infection and were hospitalized. No patient included had any known history of liver disease. Liver function tests were performed, and FIB-4 score was calculated in order to assess their involvement in the disease progression. RESULTS More than half of the patients had elevated liver function tests. Age, high body mass index, associated heart disease and diabetes were associated with poor outcome. Corticosteroids, antibiotics, and anticoagulants strongly correlated with liver injuries. Liver impairment and injury, as well as a FIB-4 score higher than 3.5, also correlated with higher degrees of disease severity. CONCLUSION Liver injury and elevated FIB-4 score were associated with poor clinical outcome and disease severity, as well as being a valuable tool to predict COVID-19-related mortality.
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Affiliation(s)
- Adina M. Kamal
- Department of Internal Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Florentina Dumitrescu
- Department of Infectious Disease, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania; (F.D.); (D.M.S.)
| | - Adrian Mită
- Department of Clinical Semiology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania;
| | - Denisa M. Săbiescu
- Department of Infectious Disease, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania; (F.D.); (D.M.S.)
| | - Dragoș O. Alexandru
- Department of Informatics and Biostatistics, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania;
| | - Codruța E. Gheorghe
- Department of Family Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania; (C.E.G.); (C.K.K.)
| | - Monalisa M. Filip
- Department of Gastroenterology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania; (M.M.F.); (A.I.-C.)
| | - Adriana Ionescu-Ciocâlteu
- Department of Gastroenterology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania; (M.M.F.); (A.I.-C.)
| | - Daniela T. Maria
- Department of Nephrology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania;
| | - Diana Kamal
- Department of Physical and Rehabilitation Medicine, Filantropia Municipal Hospital Craiova, 200516 Craiova, Romania;
| | - Constantin K. Kamal
- Department of Family Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania; (C.E.G.); (C.K.K.)
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Shih AR, Hatipoglu D, Wilechansky R, Goiffon R, Deshpande V, Misdraji J, Chung RT. Persistent Cholestatic Injury and Secondary Sclerosing Cholangitis in COVID-19 Patients. Arch Pathol Lab Med 2022; 146:1184-1193. [PMID: 35657750 DOI: 10.5858/arpa.2021-0605-sa] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/01/2022] [Indexed: 02/06/2023]
Abstract
CONTEXT.– Coronavirus disease 2019 (COVID-19) has been associated with liver injury, and a small subset of patients recovering from severe disease have shown persistent markedly elevated liver biochemistries for months after infection. OBJECTIVE.– To characterize persistent biliary injury after COVID-19. DESIGN.– A search of the pathology archives identified 7 post-COVID-19 patients with persistent biliary injury, and the clinical, radiologic, and pathologic features were assessed. RESULTS.– All patients in this cohort presented with respiratory symptoms and had a complicated clinical course with acute elevation of liver biochemistries. Alkaline phosphatase (ALP) was markedly and persistently elevated after discharge (median peak ALP: 1498 IU/L, at a median of 84 days from diagnosis). Magnetic resonance cholangiopancreatography (MRCP) showed 3 patients with irregularity, stricturing, and dilatation of intrahepatic ducts; no radiographic abnormalities were identified in the remaining 4 patients. Liver biopsies showed mild portal changes with features of cholestatic injury in 4 patients (bile duct injury and canalicular cholestasis) and marked biliary obstruction in 2 patients (profound cholestasis, ductular reaction, and bile infarcts), but no SARS-CoV-2 ribonucleic acid (RNA) was identified on in-situ hybridization. On follow-up, most patients had minimal intervention and showed marked improvement of liver biochemistries but with mild persistent elevation of ALP. CONCLUSIONS.– A subset of critically ill COVID-19 patients demonstrates marked and persistent cholestatic injury, with radiographic and histologic evidence of secondary sclerosing cholangitis, suggesting that cholestatic liver disease and secondary sclerosing cholangitis may be long-term sequelae of COVID-19 acute illness as a longstanding manifestation of critical illness.
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Affiliation(s)
- Angela R Shih
- Department of Pathology and Laboratory Medicine (Shih, Deshpande, Misdraji), at the Massachusetts General Hospital, Boston, Massachusetts
| | - Dilara Hatipoglu
- The Department of Medicine (Hatipoglu, Wilechansky, Chung), at the Massachusetts General Hospital, Boston, Massachusetts
| | - Robert Wilechansky
- Liver Center and Gastrointestinal Division (Wilechansky, Chung) at the Massachusetts General Hospital, Boston, Massachusetts.,The Department of Medicine (Hatipoglu, Wilechansky, Chung), at the Massachusetts General Hospital, Boston, Massachusetts
| | - Reece Goiffon
- Department of Radiology (Goiffon), at the Massachusetts General Hospital, Boston, Massachusetts
| | - Vikram Deshpande
- Department of Pathology and Laboratory Medicine (Shih, Deshpande, Misdraji), at the Massachusetts General Hospital, Boston, Massachusetts
| | - Joseph Misdraji
- Department of Pathology and Laboratory Medicine (Shih, Deshpande, Misdraji), at the Massachusetts General Hospital, Boston, Massachusetts
| | - Raymond T Chung
- Liver Center and Gastrointestinal Division (Wilechansky, Chung) at the Massachusetts General Hospital, Boston, Massachusetts.,The Department of Medicine (Hatipoglu, Wilechansky, Chung), at the Massachusetts General Hospital, Boston, Massachusetts
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Hammoud H, Bendari A, Bendari T, Bougmiza I. Histopathological Findings in COVID-19 Cases: A Systematic Review. Cureus 2022; 14:e25573. [PMID: 35784976 PMCID: PMC9249248 DOI: 10.7759/cureus.25573] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/01/2022] [Indexed: 11/05/2022] Open
Abstract
The ongoing coronavirus disease 2019 (COVID-19) pandemic has turned into one of the most serious public health crises of the last few decades. Although the disease can result in diverse and multiorgan pathologies, very few studies have addressed the postmortem pathological findings of COVID-19 cases. Active autopsy findings amid this pandemic could be an essential tool for diagnosis, surveillance, and research. We aimed to provide a comprehensive picture of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) histopathological features of different body organs through a systematic review of the published literature. A systematic search of electronic databases (PubMed, ScienceDirect, Google Scholar, medRxiv, and bioRxiv) for journal articles of different study designs reporting postmortem pathological findings in COVID-19 cases was performed. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used for conducting the review. A total of 50 articles reporting 430 cases were included in our analysis. Postmortem pathological findings were reported for different body organs: pulmonary system (42 articles), cardiovascular system (23 articles), hepatobiliary system (22 articles), kidney (16 articles), spleen and lymph nodes (12 articles), and central nervous system (seven articles). In lung samples, diffuse alveolar damage (DAD) was the most commonly reported finding in 239 cases (84.4%). Myocardial hypertrophy (87 cases, 51.2%), arteriosclerosis (121 cases, 62%), and steatosis (118 cases, 59.3%) were the most commonly reported pathological findings in the heart, kidney, and the hepatobiliary system respectively. Autopsy examination as an investigation tool could lead to a better understanding of SARS-CoV-2 pathophysiology, diagnosis, and management, subsequently improving patient care.
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Affiliation(s)
- Hamed Hammoud
- Preventive Medicine, Hamad Medical Corporation, Doha, QAT
| | - Ahmed Bendari
- Department of Pathology, Lenox Hill Hospital, New York, USA
| | | | - Iheb Bougmiza
- Community Medicine Residency Program, Primary Health Care Corporation, Doha, QAT
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Choudhary A, Singh V, Bharadwaj M. Maternal and Neonatal Outcomes in Pregnant Women With SARS-CoV-2 Infection Complicated by Hepatic Dysfunction. Cureus 2022; 14:e25347. [PMID: 35761912 PMCID: PMC9233295 DOI: 10.7759/cureus.25347] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/26/2022] [Indexed: 01/09/2023] Open
Abstract
Background and objective The coronavirus disease 2019 (COVID-19) pandemic has caused one of the most devastating healthcare crises in recent times and presented many diagnostic challenges and uncertainties. COVID-19 complicated by acute hepatic dysfunction is a well-described phenomenon, but its impact on maternal and perinatal outcomes is not well documented. In this study, we aimed to evaluate the maternal and neonatal outcomes in pregnant women with COVID-19 complicated by liver dysfunction and compare those with pregnant women with COVID-19 and normal liver function. Methodology This was a retrospective observational cohort study conducted at the Tata Main Hospital, Jamshedpur, a tertiary care hospital in eastern India. All COVID-19-positive pregnant women (n=249) admitted to the hospital from May 15, 2020, to August 15, 2021, were included in this study. Retrospective data collection was done using the medical records of these COVID-19-positive pregnant women and included the baseline characteristics, past medical history, obstetric history, clinical presentation, laboratory results, management modalities, and maternal and neonatal outcomes. Of note, 107 women were found to have acute liver function abnormality on admission and 142 women had normal liver function tests (LFTs). Pregnant women with normal LFTs were classified as group one and those with deranged LFTs as group two. Characteristics such as age, period of gestation, symptoms, associated comorbidities, laboratory results, management, and outcomes were compared across both groups. Results Out of the total 249 pregnant women with COVID-19 admitted during the study period, 42.97% (n=107) women had laboratory findings consistent with liver dysfunction and 142 women (57.03%) had a normal liver function. Significantly higher levels of lactate dehydrogenase (LDH), C-reactive protein (CRP), neutrophil-lymphocyte ratio (NLR), alanine transaminase (ALT), aspartate aminotransferase (AST), and total bilirubin levels were seen in pregnant women with hepatic dysfunction when compared to those with normal liver function. Among the 249 patients, the majority were asymptomatic or had mild disease, 12 women had moderate disease, and six women had severe COVID-19. All women with severe COVID-19 had deranged LFTs. There was no statistical difference in terms of obstetric management between pregnant patients with and without liver dysfunction. Out of the 107 women with deranged liver function, 18 women had a preterm birth, four had intrauterine fetal death, and one had neonatal death. Complications such as postpartum hemorrhage, the need for blood transfusions, sepsis and multiorgan failure, and mortality were more commonly seen in the group of pregnant women with hepatic dysfunction associated with COVID-19. Conclusion COVID-19 in pregnancy may cause deranged LFTs in these women. Pregnant women with COVID-19 complicated by liver dysfunction have been reported to have worse inflammation, higher disease severity, and more morbidity and mortality when compared to those without liver dysfunction. They are also at a higher risk of complications such as postpartum hemorrhage, the need for blood transfusion, sepsis, and multiorgan dysfunction.
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Kariyawasam JC, Jayarajah U, Abeysuriya V, Riza R, Seneviratne SL. Involvement of the Liver in COVID-19: A Systematic Review. Am J Trop Med Hyg 2022; 106:1026-1041. [PMID: 35203056 PMCID: PMC8991364 DOI: 10.4269/ajtmh.21-1240] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Accepted: 01/16/2022] [Indexed: 01/11/2023] Open
Abstract
COVID-19, a respiratory viral infection, has affected 388 million individuals worldwide as of the February 4, 2022. In this review, we have outlined the important liver manifestations of COVID-19 and discussed the possible underlying pathophysiological mechanisms and their diagnosis and management. Factors that may contribute to hepatic involvement in COVID-19 include direct viral cytopathic effects, exaggerated immune responses/systemic inflammatory response syndrome, hypoxia-induced changes, vascular changes due to coagulopathy, endothelitis, cardiac congestion from right heart failure, and drug-induced liver injury. The majority of COVID-19-associated liver symptoms are mild and self-limiting. Thus management is generally supportive. Liver function tests and abdominal imaging are the primary investigations done in relation to liver involvement in COVID-19 patients. However, imaging findings are nonspecific. Severe acute respiratory syndrome coronavirus 2 RNA has been found in liver biopsies. However, there is limited place for liver biopsy in the clinical context, as it does not influence management. Although, the management is supportive in the majority of patients without previous liver disease, special emphasis is needed in those with nonalcoholic fatty liver disease, cirrhosis, hepatocellular carcinoma, hepatitis B and C infections, and alcoholic liver disease, and in liver transplant recipients.
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Affiliation(s)
| | - Umesh Jayarajah
- Postgraduate Institute of Medicine, University of Colombo, Colombo, Sri Lanka
| | - Visula Abeysuriya
- Nawaloka Hospital Research and Education Foundation, Nawaloka Hospitals, Colombo, Sri Lanka
| | - Rishdha Riza
- Colombo South Teaching Hospital, Colombo, Sri Lanka
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Mukherjee PK, Efferth T, Das B, Kar A, Ghosh S, Singha S, Debnath P, Sharma N, Bhardwaj PK, Haldar PK. Role of medicinal plants in inhibiting SARS-CoV-2 and in the management of post-COVID-19 complications. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2022; 98:153930. [PMID: 35114450 PMCID: PMC8730822 DOI: 10.1016/j.phymed.2022.153930] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/03/2021] [Revised: 12/30/2021] [Accepted: 01/03/2022] [Indexed: 05/07/2023]
Abstract
BACKGROUND The worldwide corona virus disease outbreak, generally known as COVID-19 pandemic outbreak resulted in a major health crisis globally. The morbidity and transmission modality of COVID-19 appear more severe and uncontrollable. The respiratory failure and following cardiovascular complications are the main pathophysiology of this deadly disease. Several therapeutic strategies are put forward for the development of safe and effective treatment against SARS-CoV-2 virus from the pharmacological view point but till date there are no specific treatment regimen developed for this viral infection. PURPOSE The present review emphasizes the role of herbs and herbs-derived secondary metabolites in inhibiting SARS-CoV-2 virus and also for the management of post-COVID-19 related complications. This approach will foster and ensure the safeguards of using medicinal plant resources to support the healthcare system. Plant-derived phytochemicals have already been reported to prevent the viral infection and to overcome the post-COVID complications like parkinsonism, kidney and heart failure, liver and lungs injury and mental problems. In this review, we explored mechanistic approaches of herbal medicines and their phytocomponenets as antiviral and post-COVID complications by modulating the immunological and inflammatory states. STUDY DESIGN Studies related to diagnosis and treatment guidelines issued for COVID-19 by different traditional system of medicine were included. The information was gathered from pharmacological or non-pharmacological interventions approaches. The gathered information sorted based on therapeutic application of herbs and their components against SARSCoV-2 and COVID-19 related complications. METHODS A systemic search of published literature was conducted from 2003 to 2021 using different literature database like Google Scholar, PubMed, Science Direct, Scopus and Web of Science to emphasize relevant articles on medicinal plants against SARS-CoV-2 viral infection and Post-COVID related complications. RESULTS Collected published literature from 2003 onwards yielded with total 625 articles, from more than 18 countries. Among these 625 articles, more than 95 medicinal plants and 25 active phytomolecules belong to 48 plant families. Reports on the therapeutic activity of the medicinal plants belong to the Lamiaceae family (11 reports), which was found to be maximum reported from 4 different countries including India, China, Australia, and Morocco. Other reports on the medicinal plant of Asteraceae (7 reports), Fabaceae (8 reports), Piperaceae (3 reports), Zingiberaceae (3 reports), Ranunculaceae (3 reports), Meliaceae (4 reports) were found, which can be explored for the development of safe and efficacious products targeting COVID-19. CONCLUSION Keeping in mind that the natural alternatives are in the priority for the management and prevention of the COVID-19, the present review may help to develop an alternative approach for the management of COVID-19 viral infection and post-COVID complications from a mechanistic point of view.
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Affiliation(s)
- Pulok K Mukherjee
- Institute of Bioresources and Sustainable Development, Imphal-795001, India; School of Natural Product Studies, Department of Pharmaceutical Technology, Jadavpur University, Kolkata -700 032, India.
| | - Thomas Efferth
- Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Mainz, Germany
| | - Bhaskar Das
- School of Natural Product Studies, Department of Pharmaceutical Technology, Jadavpur University, Kolkata -700 032, India
| | - Amit Kar
- Institute of Bioresources and Sustainable Development, Imphal-795001, India
| | - Suparna Ghosh
- School of Natural Product Studies, Department of Pharmaceutical Technology, Jadavpur University, Kolkata -700 032, India
| | - Seha Singha
- School of Natural Product Studies, Department of Pharmaceutical Technology, Jadavpur University, Kolkata -700 032, India
| | - Pradip Debnath
- School of Natural Product Studies, Department of Pharmaceutical Technology, Jadavpur University, Kolkata -700 032, India
| | - Nanaocha Sharma
- Institute of Bioresources and Sustainable Development, Imphal-795001, India
| | | | - Pallab Kanti Haldar
- School of Natural Product Studies, Department of Pharmaceutical Technology, Jadavpur University, Kolkata -700 032, India
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Human liver organoid derived intra-hepatic bile duct cells support SARS-CoV-2 infection and replication. Sci Rep 2022; 12:5375. [PMID: 35354880 PMCID: PMC8965546 DOI: 10.1038/s41598-022-09306-6] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2021] [Accepted: 03/21/2022] [Indexed: 12/18/2022] Open
Abstract
AbstractAlthough the main route of infection for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the respiratory tract, liver injury is also commonly seen in many patients, as evidenced by deranged parenchymal liver enzymes. Furthermore, the severity of liver damage has been shown to correlate with higher mortality. Overall, the mechanism behind the liver injury remains unclear. We showed in this study that intra-hepatic bile duct cells could be grown using a human liver organoid platform. The cholangiocytes were not only susceptible to SARS-CoV-2 infection, they also supported efficient viral replication. We also showed that SARS-CoV-2 replication was much higher than SARS-CoV. Our findings suggested direct cytopathic viral damage being a mechanism for SARS-CoV-2 liver injury.
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Tehrani AS, Mirakabad FST, Abdollahifar MA, Mollazadehghomi S, Darabi S, Forozesh M, Rezaei-Tavirani M, Mahmoudiasl GR, Ahrabi B, Azimzadeh Z, Abbaszadeh HA. Severe Acute Respiratory Syndrome Coronavirus 2 Induces Hepatocyte Cell Death, Active Autophagosome Formation and Caspase 3 Up-Regulation in Postmortem Cases: Stereological and Molecular Study. TOHOKU J EXP MED 2022; 256:309-319. [PMID: 35321977 DOI: 10.1620/tjem.2022.j007] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Affiliation(s)
- Atefeh Shirazi Tehrani
- Laser Application in Medical Sciences Research Center, Shahid Beheshti University of Medical Sciences.,Hearing disorders research center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences
| | | | - Mohammad-Amin Abdollahifar
- Laser Application in Medical Sciences Research Center, Shahid Beheshti University of Medical Sciences.,Hearing disorders research center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences
| | | | - Shahram Darabi
- Cellular and Molecular Research Center, Qazvin University of Medical Sciences
| | | | - Mostafa Rezaei-Tavirani
- Proteomics Research Center, Faculty of Para medicine, Shahid Beheshti University of Medical Sciences
| | | | - Behnaz Ahrabi
- Department of Biology and Anatomy, Shahid Beheshti University of Medical Sciences
| | - Zahra Azimzadeh
- Laser Application in Medical Sciences Research Center, Shahid Beheshti University of Medical Sciences
| | - Hojjat Allah Abbaszadeh
- Laser Application in Medical Sciences Research Center, Shahid Beheshti University of Medical Sciences.,Hearing disorders research center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences.,Department of Biology and Anatomy, Shahid Beheshti University of Medical Sciences
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Fataftah JZ, Tayyem R, Qandeel H, Baydoun HA, Al Manasra ARA, Tahboub A, Al-Dwairy SY, Al-Mousa A. The Effect of COVID 19 on Liver Parenchyma Detected and measured by CT scan Hounsfield Units. JOURNAL OF RESEARCH IN MEDICAL SCIENCES : THE OFFICIAL JOURNAL OF ISFAHAN UNIVERSITY OF MEDICAL SCIENCES 2022; 27:26. [PMID: 35419067 PMCID: PMC8995305 DOI: 10.4103/jrms.jrms_1228_20] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 11/18/2020] [Revised: 03/28/2021] [Accepted: 06/23/2021] [Indexed: 06/14/2023]
Abstract
BACKGROUND COVID 19 may affect organs other than lungs, including liver, leading to parenchymal changes. These changes are best assessed by unenhanced computed tomography (CT). We aim to investigate the effect of COVID 19 on liver parenchyma by measuring the attenuation in CT scan Hounsfield unit (HU). MATERIALS AND METHODS A cohort of patients, who tested COVID 19 polymerase chain reaction positive, were enrolled and divided into two groups: fatty liver (FL) group (HU ≤ 40) and nonfatty liver (NFL) group (HU > 40) according to liver parenchyma attenuation measurements by high resolution noncontrast CT scan. The CT scan was performed on admission and on follow up (10-14 days later). Liver enzyme tests were submitted on admission and follow up. RESULTS Three hundred and two patients were enrolled. Liver HU increased significantly from 48.9 on admission to 53.4 on follow up CT scan (P<0.001) in all patients. This increase was more significant in the FL group (increased from 31.9 to 42.9 [P =0.018]) Liver enzymes were abnormal in 22.6% of the full cohort. However, there was no significant change in liver enzymes between the admission and follow up in both groups. CONCLUSION The use of unenhanced CT scan for assessment of liver parenchymal represents an objective and noninvasive method. The significant changes in parenchymal HU are not always accompanied by significant changes in liver enzymes. Increased HU values caused by COVID 19 may be due to either a decrease in the fat or an increase in the fibrosis in the liver.
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Affiliation(s)
| | - Raed Tayyem
- Department of Surgery, Hashemite University, Zarqa, Jordan
| | | | | | | | - Ahmad Tahboub
- Department of Radiology, Hashemite University, Zarqa, Jordan
| | | | - Alaa Al-Mousa
- Department of Neurosurgery, Hashemite University, Zarqa, Jordan
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