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Gan C, Yuan Y, Shen H, Gao J, Kong X, Che Z, Guo Y, Wang H, Dong E, Xiao J. Liver diseases: epidemiology, causes, trends and predictions. Signal Transduct Target Ther 2025; 10:33. [PMID: 39904973 PMCID: PMC11794951 DOI: 10.1038/s41392-024-02072-z] [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: 06/30/2024] [Revised: 10/06/2024] [Accepted: 11/12/2024] [Indexed: 02/06/2025] Open
Abstract
As a highly complex organ with digestive, endocrine, and immune-regulatory functions, the liver is pivotal in maintaining physiological homeostasis through its roles in metabolism, detoxification, and immune response. Various factors including viruses, alcohol, metabolites, toxins, and other pathogenic agents can compromise liver function, leading to acute or chronic injury that may progress to end-stage liver diseases. While sharing common features, liver diseases exhibit distinct pathophysiological, clinical, and therapeutic profiles. Currently, liver diseases contribute to approximately 2 million deaths globally each year, imposing significant economic and social burdens worldwide. However, there is no cure for many kinds of liver diseases, partly due to a lack of thorough understanding of the development of these liver diseases. Therefore, this review provides a comprehensive examination of the epidemiology and characteristics of liver diseases, covering a spectrum from acute and chronic conditions to end-stage manifestations. We also highlight the multifaceted mechanisms underlying the initiation and progression of liver diseases, spanning molecular and cellular levels to organ networks. Additionally, this review offers updates on innovative diagnostic techniques, current treatments, and potential therapeutic targets presently under clinical evaluation. Recent advances in understanding the pathogenesis of liver diseases hold critical implications and translational value for the development of novel therapeutic strategies.
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Affiliation(s)
- Can Gan
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
| | - Yuan Yuan
- Aier Institute of Ophthalmology, Central South University, Changsha, China
| | - Haiyuan Shen
- Department of Oncology, the First Affiliated Hospital; The Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Medical University, Hefei, China
| | - Jinhang Gao
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
| | - Xiangxin Kong
- Engineering and Translational Medicine, Medical College, Tianjin University, Tianjin, China
| | - Zhaodi Che
- Clinical Medicine Research Institute and Department of Anesthesiology, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Yangkun Guo
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
| | - Hua Wang
- Department of Oncology, the First Affiliated Hospital; The Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Medical University, Hefei, China.
| | - Erdan Dong
- Research Center for Cardiopulmonary Rehabilitation, University of Health and Rehabilitation Sciences Qingdao Hospital, School of Health and Life Sciences, University of Health and Rehabilitation Sciences, Qingdao, China.
- Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China.
| | - Jia Xiao
- Clinical Medicine Research Institute and Department of Anesthesiology, The First Affiliated Hospital of Jinan University, Guangzhou, China.
- Department of Gastroenterology, Qingdao Central Hospital, University of Health and Rehabilitation Sciences, Qingdao, China.
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Chen S, Zhang Y, Ashuo A, Song S, Yuan L, Wang W, Wang C, Du Z, Wu Y, Tan D, Huang C, Chen J, Li Y, Bai J, Guo H, Huang Z, Guan Y, Xia N, Yuan Z, Zhang J, Yuan Q, Fang Z. Combination of spatial transcriptomics analysis and retrospective study reveals liver infection of SARS-COV-2 is associated with clinical outcomes of COVID-19. EBioMedicine 2025; 111:105517. [PMID: 39709771 PMCID: PMC11732063 DOI: 10.1016/j.ebiom.2024.105517] [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: 07/11/2024] [Revised: 12/06/2024] [Accepted: 12/09/2024] [Indexed: 12/24/2024] Open
Abstract
BACKGROUND Liver involvement is a common complication of coronavirus disease 2019 (COVID-19), especially in hospitalized patients. However, the underlying mechanisms involved are not fully understood. METHODS Immunohistochemistry (IHC) staining of SARS-CoV-2 spike (S) and nucleocapsid (N) proteins was conducted on liver tissues from six patients with COVID-19. The 10x Genomics Visium CytAssist Spatial Gene Assay was designed to analyze liver transcriptomics. TCR CDR3 sequences were analyzed in DNA from liver tissues. Liver function indicators were retrospectively studied in 650 hospitalized patients with COVID-19. FINDINGS SARS-CoV-2 proteins were initially detected in the livers of naturally infected golden (Syrian) hamsters, prompting us to investigate the situation in clinical cases. Thus, we collected liver tissues from patients with abnormal liver biochemical values. Viral S and N proteins were detected in the livers of severe and deceased patients but not in those of moderate patients. We further demonstrated that hepatocytes and erythroid cells in hepatic sinusoids are major cells targeted by SARS-CoV-2. Immune cells, especially T cells, were enriched in surviving severe patients, characterized by enhanced CDR3α clonality and novel CDR3β recombination of the T-cell receptor. In contrast, hepatocyte apoptosis was triggered, and the transcription of albumin (ALB) was obviously impaired in the deceased patients. We then performed a retrospective study including patients with COVID-19. Serum aspartate aminotransferase (AST) and ALB levels at baseline significantly differed in the deceased cohort. However, AST regression did not decrease the risk of death. ALB recovery indicated clinical improvement, and declining or low serum ALB concentrations were associated with death. INTERPRETATION This study provides clinical evidence for liver infection with SARS-CoV-2, insight into the impact of SARS-CoV-2 on the liver, and a potential way to evaluate the risk of death via assessing serum ALB concentration fluctuations in patients with COVID-19. FUNDING National Key R&D Program of China (2021YFC2300602), National Natural Science Foundation of China (92369110), National Natural Science Foundation of China (U23A20474), Shanghai Municipal Science and Technology Major Project (ZD2021CY001), Shanghai Jinshan District Medical and Health Technology Innovation Fund Project (2023-WS-31).
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Affiliation(s)
- Shiqi Chen
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Shanghai Institute of Infectious Diseases and Biosecurity, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Yi Zhang
- Shanghai Public Health Clinical Center, Shanghai Medical College of Fudan University, Shanghai, China
| | - Asha Ashuo
- Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Research Unit of Cure of Chronic Hepatitis B Virus Infection (CAMS), Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China
| | - Shu Song
- Shanghai Public Health Clinical Center, Shanghai Medical College of Fudan University, Shanghai, China
| | - Lunzhi Yuan
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, Fujian, China
| | - Weixia Wang
- Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai, China
| | - Cong Wang
- Shanghai Public Health Clinical Center, Shanghai Medical College of Fudan University, Shanghai, China
| | - Zunguo Du
- Department of Pathology, Huashan Hospital, Fudan University, Shanghai, China
| | - Yangtao Wu
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, Fujian, China
| | - Dan Tan
- Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Research Unit of Cure of Chronic Hepatitis B Virus Infection (CAMS), Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China
| | - Chenlu Huang
- Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, China
| | - Jingna Chen
- Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Research Unit of Cure of Chronic Hepatitis B Virus Infection (CAMS), Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China
| | - Yaming Li
- Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Research Unit of Cure of Chronic Hepatitis B Virus Infection (CAMS), Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China
| | - Jinjin Bai
- Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, China
| | - Huilin Guo
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, Fujian, China
| | - Zehong Huang
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, Fujian, China
| | - Yi Guan
- State Key Laboratory of Emerging Infectious Diseases, University of Hong Kong, Hong Kong, China; Joint Institute of Virology (Shantou University and University of Hong Kong), Guangdong-Hongkong Joint Laboratory of Emerging Infectious Diseases, Shantou University, Shantou, China
| | - Ningshao Xia
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, Fujian, China.
| | - Zhenghong Yuan
- Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Research Unit of Cure of Chronic Hepatitis B Virus Infection (CAMS), Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
| | - Jiming Zhang
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Shanghai Institute of Infectious Diseases and Biosecurity, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.
| | - Quan Yuan
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, Fujian, China.
| | - Zhong Fang
- Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, China.
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Asri N, Mohammadi S, Jahdkaran M, Rostami-Nejad M, Rezaei-Tavirani M, Mohebbi SR. Viral infections in celiac disease: what should be considered for better management. Clin Exp Med 2024; 25:25. [PMID: 39731690 DOI: 10.1007/s10238-024-01542-6] [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: 11/26/2024] [Accepted: 12/20/2024] [Indexed: 12/30/2024]
Abstract
Following a gluten-free diet (GFD) is known as the main effective therapy available for celiac disease (CD) patients, which in some cases is not enough to heal all patients presentations completely. Accordingly, emerging researchers have focused on finding novel therapeutic/preventive strategies for this disorder. Moreover, previous studies have shown that celiac patients, especially untreated subjects, are at increased risk of developing viral and bacterial infections, which can become a challenge for the clinician. Viruses, such as Rotavirus, Reovirus, Adenovirus, Enterovirus, Rhinovirus, Astrovirus, Hepatitis virus, COVID-19, Norovirus, and Herpesvirus, have been related to CD pathogenesis. Therefore, clinicians need to pay more attention to evaluate CD patients' viral infection history (especially nonresponders to the GFD), to look for effective preventive strategies and educate patients about important risk factors. In addition, there are still viruses whose role in CD pathogenesis has not been fully studied. In this review, current information on the association between CD and various viral infections was gathered to improve knowledge in this subject area and draw researchers'/clinicians' attention to unstudied/less studied viruses in CD pathogenesis, which might guide future prevention approaches.
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Affiliation(s)
- Nastaran Asri
- Celiac Disease and Gluten Related Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Shahnaz Mohammadi
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mahtab Jahdkaran
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Rostami-Nejad
- Celiac Disease and Gluten Related Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Mostafa Rezaei-Tavirani
- Proteomics Research Center, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Seyed Reza Mohebbi
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Guo Y, Shen B, Lou C, Wang L, Li Y. IGSF1: a biomarker for predicting prognosis, immunotherapy response, and drug candidates in COVID-19 combined hepatocellular carcinoma. Discov Oncol 2024; 15:599. [PMID: 39470901 PMCID: PMC11522225 DOI: 10.1007/s12672-024-01483-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2024] [Accepted: 10/22/2024] [Indexed: 11/01/2024] Open
Abstract
Hepatocellular carcinoma (HCC) is a highly heterogeneous malignancy with poor prognosis and a common cause of cancer-related death worldwide, and despite ongoing therapeutic breakthroughs, patient survival benefits are limited. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19) and poses a major threat to humanity worldwide. As the epidemic continues to develop, more and more people are infected with SARS-CoV-2, including patients with HCC. However, the relationship between COVID-19 and HCC has not yet been fully elucidated. Our study aimed to identify the shared genetic characteristics and molecular mechanisms between COVID-19 and HCC. The data involved in this study come from Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression(GTEx), and Cancer Cell Line Encyclopedia(CCLE) databases. We used differentially expressed genes to perform enrichment analysis to reveal the biological landscape of COVID-19 combined with HCC. In addition, weighted gene co-expression network analysis (WGCNA) was used to study the co-expression network related to COVID-19 and HCC. We then combined the validation datasets to screen out immunoglobulin superfamily member 1 (IGSF1) as the most important core gene. Finally, we extensively studied the functional expression of IGSF1 in tumor samples, normal tissues, and cancer cell lines. The molecular mechanisms related to COVID-19 and HCC are rarely studied. Our study identifies IGSF1 as a potential therapeutic target and immune-related biomarker for patients with COVID-19 and HCC.
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Affiliation(s)
- Yuanhui Guo
- Henan Key Laboratory of Rare Diseases, Endocrinology and Metabolism Center, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003, China
| | - Baixuan Shen
- Henan Key Laboratory of Rare Diseases, Endocrinology and Metabolism Center, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003, China
| | - Chaoxuan Lou
- Department of Pharmacy, The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003, China
| | - Li Wang
- Department of Pharmacy, The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003, China
| | - Ying Li
- Department of Pharmacy, The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003, China.
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Nascimento LS, Marson FAL, dos Santos RDC. Epidemiological profile of patients hospitalized with Crohn's disease due to severe acute respiratory infection during the COVID-19 pandemic: a 2-year report from Brazil. Front Med (Lausanne) 2024; 11:1440101. [PMID: 39507710 PMCID: PMC11537927 DOI: 10.3389/fmed.2024.1440101] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Accepted: 09/16/2024] [Indexed: 11/08/2024] Open
Abstract
Background and aims The novel coronavirus-induced severe acute respiratory syndrome (COVID-19) led to one of the most significant global pandemics of the 21st century, causing substantial challenges for healthcare systems worldwide, including those in Brazil. This study aimed to investigate the demographic and clinical profiles of hospitalized patients in Brazil who had both COVID-19 and Crohn's disease (CD) over a 2-year period. Methods An epidemiological analysis was conducted using data from Open-Data-SUS. The study focused on describing the demographic characteristics, clinical manifestations, comorbidities, and hospitalization details of patients afflicted with severe acute respiratory syndrome due to COVID-19 and CD, with the aim of predicting mortality risk. Results The states of São Paulo, Paraná, and Minas Gerais accounted for 50% of the reported COVID-19 cases. The most affected racial group consisted of individuals who self-declared as mixed race. Common comorbidities included heart disease, diabetes mellitus, and obesity. The age group most affected was 25 to 60 years old, particularly among hospitalized patients with both CD and COVID-19 who ultimately succumbed to the illness. A multivariable analysis was conducted to identify the following significant risk factors for death: (a) the presence of neurological disorder (OR = 6.716; 95% CI = 1.954-23.078), (b) the need for intensive care (OR = 3.348; 95% CI = 1.770-6.335), and (c) the need for invasive mechanical ventilation (OR = 59.017; 95% CI = 19.796-175.944). Conclusion There was no discernible gender-based prevalence among hospitalized patients with CD and COVID-19; however, individuals of mixed race were disproportionately affected. The 25 to 60 age group emerged as the most vulnerable demographic group, with high risks of hospitalization and mortality. Moreover, the study highlights the potential for COVID-19 to induce systemic pathologies that may result in long-term degenerative effects and sequelae.
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Affiliation(s)
- Laís Silva Nascimento
- Laboratory of Natural Products, São Francisco University, Bragança Paulista, Brazil
- Laboratory of Molecular Biology and Genetics, São Francisco University, Bragança Paulista, Brazil
| | - Fernando Augusto Lima Marson
- Laboratory of Molecular Biology and Genetics, São Francisco University, Bragança Paulista, Brazil
- Laboratory of Clinical and Molecular Microbiology, São Francisco University, Bragança Paulista, Brazil
- LunGuardian Research Group-Epidemiology of Respiratory and Infectious Diseases, São Francisco University, Bragança Paulista, Brazil
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Wu H, Zhang Y, Tang W, Lv M, Chen Z, Meng F, Zhao Y, Xu H, Dai Y, Xue J, Wang J, Dong L, Wu D, Zhang S, Xue R. Liver function abnormality on admission predicts long COVID syndrome in digestive system. Heliyon 2024; 10:e37664. [PMID: 39386803 PMCID: PMC11462002 DOI: 10.1016/j.heliyon.2024.e37664] [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: 03/30/2024] [Revised: 08/06/2024] [Accepted: 09/07/2024] [Indexed: 10/12/2024] Open
Abstract
Background Clinical practice showed that many patients with SARS-CoV-2 infection presented with long COVID syndrome in digestive system. We sought to investigate the factor affecting the incidence of long COVID syndrome in digestive system. Methods and results Patients with SARS-CoV-2 infection diagnosed at two centers of Zhongshan Hospital and one center of Shanghai Pudong Hospital from March 01, 2022 to May 31, 2022 were enrolled, collected in the hospital database, and followed up until March 30, 2023. The primary outcome of the study was the occurrence of post-acute sequelae of COVID-19 in the digestive system (long COVID syndrome). Modified Poisson regression was used to calculate the relative risk (RR). This cohort study included 494 patients with SARS-CoV-2 infection, 144 (29.1 %) patients developed liver function abnormality on admission. During the follow-up period, the primary study outcome occurred in 30 (20.8 %) of the group presenting with liver function abnormality on admission and in 20 (5.7 %) of the group without liver function abnormality on admission (adjusted, RR = 3.550, 95%CI: 2.099-6.006, P ≤ 0.001). Conclusion Our study suggests that patients with COVID-19 who experience liver function abnormality on admission have an increased risk of developing long COVID syndrome in the digestive system.
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Affiliation(s)
- Huibin Wu
- Department of Gastroenterology and Hepatology, Shanghai Institute of Liver Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
| | - Yunjie Zhang
- Department of Clinical Medicine, Shanghai Medical College, Fudan University, Shanghai, 200032, China
| | - Wenqing Tang
- Department of Gastroenterology and Hepatology, Shanghai Institute of Liver Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
| | - Minzhi Lv
- Department of Biostatistics, Clinical Research Unit, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
- Department of Biostatistics, Clinical Research Unit, Key Laboratory of Public Health Safety of Ministry of Education, Key Laboratory for Health Technology Assessment, National Commission of Health, School of Public Health, Center of Evidence-Based Medicine, Fudan University, Shanghai, 200032, China
| | - Zhixue Chen
- Department of Gastroenterology and Hepatology, Shanghai Institute of Liver Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
| | - Fansheng Meng
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
| | - Yitong Zhao
- School of Medicine, Anhui University of Science and Technology, Anhui, 232000, China
| | - Huajie Xu
- Department of Cardiology, Zhongshan Hospital, Shanghai Institute of Cardiovascular Diseases, National Clinical Research Center for Interventional Medicine, Fudan University, Shanghai, 200032, China
| | - Yuxin Dai
- NHC Key Laboratory of Glycoconjugate Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China
| | - Jindan Xue
- School of Medicine, Anhui University of Science and Technology, Anhui, 232000, China
| | - Jingya Wang
- Department of Biochemistry and Molecular Biology, Department of Forensic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China
| | - Ling Dong
- Department of Gastroenterology and Hepatology, Shanghai Institute of Liver Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
| | - Dejun Wu
- Department of Gastrointestinal Surgery, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, 201399, China
| | - Si Zhang
- NHC Key Laboratory of Glycoconjugate Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China
| | - Ruyi Xue
- Department of Gastroenterology and Hepatology, Shanghai Institute of Liver Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
- Shanghai Baoshan District Wusong Central Hospital (Zhongshan Hospital Wusong Branch, Fudan University), Shanghai, 200940, China
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Fan Z, Zhou H, Zhang J, Liu X, Wu T, Shi Y, Lin J, Liang J. Opportunistic infections changed before and after SARS-CoV-2 infection in inflammatory bowel disease patients: a retrospective single-center study in China. Front Med (Lausanne) 2024; 11:1461801. [PMID: 39380736 PMCID: PMC11460596 DOI: 10.3389/fmed.2024.1461801] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2024] [Accepted: 09/13/2024] [Indexed: 10/10/2024] Open
Abstract
Objective SARS-CoV-2 transmission has become a serious worldwide public health concern. However, there is currently insufficient data to determine whether SARS-CoV-2 infection would affect opportunistic infections in inflammatory bowel disease (IBD) patients. Methods A retrospective study included 451 IBD patients (294 UC and 157 CD). The IBD patients were divided into two groups: before SARS-CoV-2 infection and after SARS-CoV-2 infection, and outcomes were measured for these groups. The primary outcome was the presence and distribution of opportunistic infections. The secondary outcomes included factors associated with opportunistic infections, based on which a nomogram prediction model was developed and validated. Results After SARS-CoV-2 infection, the proportion of IBD patients with opportunistic infections by Clostridium difficile (21.31% vs. 14.01%, p = 0.044) and Epstein-Barr virus (13.93% vs. 4.35%, p = 0.001) was significantly higher compared to that before. Conversely, the proportion of patients with hepatitis B virus (3.69% vs. 10.14%, p = 0.006) and herpes simplex virus type I (1.23% vs. 4.35%, p = 0.04) infections was significantly lower after the infection. Additionally, pre-SARS-CoV-2 infection factors associated with opportunistic infections in IBD include duration of illness, red blood cell count, the presence of comorbid chronic illnesses, and alcohol consumption, while post-SARS-CoV-2 infection, the primary risk factors involve corticosteroid use, red blood cell count, protein level, and high-sensitivity C-reactive protein. Conclusion After the SARS-CoV-2 infection, there has been a shift in the occurrence of opportunistic infections among IBD patients. It might be attributed to the use of corticosteroids and also the strengthening of containment measures, heightened public health awareness, and widespread vaccination.
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Affiliation(s)
| | | | | | | | | | | | | | - Jie Liang
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, China
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Volcic M, Nchioua R, Pastorio C, Zech F, Haußmann I, Sauter D, Read C, Walther P, Kirchhoff F. Attenuated replication and damaging effects of SARS-CoV-2 Omicron variants in an intestinal epithelial barrier model. J Med Virol 2024; 96:e29783. [PMID: 38965890 DOI: 10.1002/jmv.29783] [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: 03/12/2024] [Revised: 05/31/2024] [Accepted: 06/19/2024] [Indexed: 07/06/2024]
Abstract
Many COVID-19 patients suffer from gastrointestinal symptoms and impaired intestinal barrier function is thought to play a key role in Long COVID. Despite its importance, the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on intestinal epithelia is poorly understood. To address this, we established an intestinal barrier model integrating epithelial Caco-2 cells, mucus-secreting HT29 cells and Raji cells. This gut epithelial model allows efficient differentiation of Caco-2 cells into microfold-like cells, faithfully mimics intestinal barrier function, and is highly permissive to SARS-CoV-2 infection. Early strains of SARS-CoV-2 and the Delta variant replicated with high efficiency, severely disrupted barrier function, and depleted tight junction proteins, such as claudin-1, occludin, and ZO-1. In comparison, Omicron subvariants also depleted ZO-1 from tight junctions but had fewer damaging effects on mucosal integrity and barrier function. Remdesivir, the fusion inhibitor EK1 and the transmembrane serine protease 2 inhibitor Camostat inhibited SARS-CoV-2 replication and thus epithelial barrier damage, while the Cathepsin inhibitor E64d was ineffective. Our results support that SARS-CoV-2 disrupts intestinal barrier function but further suggest that circulating Omicron variants are less damaging than earlier viral strains.
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Affiliation(s)
- Meta Volcic
- Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany
| | - Rayhane Nchioua
- Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany
| | - Chiara Pastorio
- Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany
| | - Fabian Zech
- Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany
| | - Isabell Haußmann
- Institute for Medical Virology and Epidemiology of Viral Diseases, University Hospital Tübingen, Tübingen, Germany
| | - Daniel Sauter
- Institute for Medical Virology and Epidemiology of Viral Diseases, University Hospital Tübingen, Tübingen, Germany
| | - Clarissa Read
- Central Facility for Electron Microscopy, Ulm University, Ulm, Germany
| | - Paul Walther
- Central Facility for Electron Microscopy, Ulm University, Ulm, Germany
| | - Frank Kirchhoff
- Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany
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Abdellatif Z, Abdel-Haleem H, Abdalaziz RA, Ramadan A, Al-Sharif AM, El-Korashy RIM, Soliman YMA, Hussein SA, Kamal MM, Abdullatif MMA, AbdelRazik MM, Eldessouky NMT, Atef M. Coronavirus disease 19 (Covid-19): A comparative study of pattern of liver injury in adult patients in different waves of Covid-19 infection. Arab J Gastroenterol 2024; 25:170-175. [PMID: 38378355 DOI: 10.1016/j.ajg.2024.01.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2022] [Revised: 10/10/2023] [Accepted: 01/07/2024] [Indexed: 02/22/2024]
Abstract
BACKGROUND AND STUDY AIMS Liver dysfunction is a common manifestation of the COVID-19 infection. We aimed to study transaminase abnormalities through different waves of COVID-19 and their relations to disease severity or mortality. PATIENTS AND METHODS A retrospective study included 521 Egyptian patients diagnosed with COVID-19. Data was retrieved from the medical records of patients who were admitted from April 2020 to October 2021 in Kasr Al-Ainy Hospitals, Cairo University, with categorization according to disease severity in correspondence to the four waves. RESULTS The median age was lower in the first wave compared to other waves, with male predominance across all waves. The most commonly encountered comorbidity overall was hypertension, followed by diabetes mellitus. White blood cells, ferritin, and interleukin-6 showed the highest median values in the second wave, with significantly higher median C-reactive protein on day 1 in the first wave. Forty percent of the patients showed elevated hepatic transaminases on admission in four waves, with no statistically significant difference between waves. On day 5, around half of the patients had elevated transaminases, with no significant difference between waves. Most CT findings were of moderate severity. Clinical severity was higher in the second wave. It was observed that the higher the disease severity, the greater the proportion of patients with elevated hepatic transaminases. The mortality rate was markedly high in cases who had elevated ALT or AST on day 5. The association between elevated enzymes on admission and mortality was seen in the first wave only, with a fatality rate of 22.5% in cases with increased baseline ALT and AST versus 5% in those with normal baseline enzymes. CONCLUSION There was no significant difference in transaminases between the four waves. Elevated transaminases were positively associated with increased mortality and severity, reflecting their prognostic value.
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Affiliation(s)
- Zeinab Abdellatif
- Hepatogastroenterology and Endemic Medicine Department - Faculty of Medicine, Cairo University, Egypt.
| | - Hanan Abdel-Haleem
- Hepatogastroenterology and Endemic Medicine Department - Faculty of Medicine, Cairo University, Egypt
| | - Rasha Ahmed Abdalaziz
- Hepatogastroenterology and Endemic Medicine Department - Faculty of Medicine, Cairo University, Egypt.
| | - Ahmed Ramadan
- Hepatogastroenterology and Endemic Medicine Department - Faculty of Medicine, Cairo University, Egypt.
| | - Aya Mohamed Al-Sharif
- Hepatogastroenterology and Endemic Medicine Department - Faculty of Medicine, Cairo University, Egypt
| | | | | | - Sabah Ahmed Hussein
- Pulmonary Medicine Department - Faculty of Medicine, Cairo University, Egypt.
| | - Manal Mohamed Kamal
- Clinical and Chemical Pathology Department, Faculty of Medicine, Cairo University, Egypt
| | | | | | | | - Mira Atef
- Hepatogastroenterology and Endemic Medicine Department - Faculty of Medicine, Cairo University, Egypt.
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10
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Nikhat S, Fazil M. Shortening the long-COVID: An exploratory review on the potential of Unani medicines in mitigating post-Covid-19 sequelae. PHYTOMEDICINE PLUS 2024; 4:100570. [DOI: 10.1016/j.phyplu.2024.100570] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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11
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Mattioli LB, Frosini M, Corazza I, Fiorino S, Zippi M, Micucci M, Budriesi R. Long COVID-19 gastrointestinal related disorders and traditional Chinese medicine: A network target-based approach. Phytother Res 2024; 38:2323-2346. [PMID: 38421118 DOI: 10.1002/ptr.8163] [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: 08/23/2023] [Revised: 01/30/2024] [Accepted: 02/03/2024] [Indexed: 03/02/2024]
Abstract
The significant number of individuals impacted by the pandemic makes prolonged symptoms after COVID-19 a matter of considerable concern. These are numerous and affect multiple organ systems. According to the World Health Organization (WHO), prolonged gastrointestinal issues are a crucial part of post-COVID-19 syndrome. The resulting disruption of homeostasis underscores the need for a therapeutic approach based on compounds that can simultaneously affect more than one target/node. The present review aimed to check for nutraceuticals possessing multiple molecular mechanisms helpful in relieving Long COVID-19-specific gastrointestinal symptoms. Specific plants used in Keywords Chinese Medicine (TCM) expected to be included in the WHO Global Medical Compendium were selected based on the following criteria: (1) they are widely used in the Western world as natural remedies and complementary medicine adjuvants; (2) their import and trade are regulated by specific laws that ensure quality and safety (3) have the potential to be beneficial in alleviating intestinal issues associated with Long COVID-19. Searches were performed in PubMed, Elsevier, Google Scholar, Scopus, Science Direct, and ResearchGate up to 2023. Cinnamomum cassia, Glycyrrhiza uralensis, Magnolia officinalis, Poria cocos, Salvia miltiorrhiza, Scutellaria baicalensis, and Zingiber officinalis were identified as the most promising for their potential impact on inflammation and oxidative stress. Based on the molecular mechanisms of the phytocomplexes and isolated compounds of the considered plants, their clinical use may lead to benefits in gastrointestinal diseases associated with Long COVID-19, thanks to a multiorgan and multitarget approach.
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Affiliation(s)
- Laura Beatrice Mattioli
- Department of Pharmacy and Biotechnology, Food Chemistry and Nutraceutical Lab, Alma Mater Studiorum-University of Bologna, Bologna, Italy
| | - Maria Frosini
- Department of Life Sciences, University of Siena, Siena, Italy
| | - Ivan Corazza
- Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum-University of Bologna, Bologna, Italy
| | - Sirio Fiorino
- Internal Medicine Unit, Azienda USL, Budrio Hospital, Bologna, Italy
| | - Maddalena Zippi
- Unit of Gastroenterology & Digestive Endoscopy, Sandro Pertini Hospital, Rome, Italy
| | - Matteo Micucci
- Department of Biomolecular Sciences, Università degli Studi di Urbino "Carlo Bo", Urbino, Italy
| | - Roberta Budriesi
- Department of Pharmacy and Biotechnology, Food Chemistry and Nutraceutical Lab, Alma Mater Studiorum-University of Bologna, Bologna, Italy
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12
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Pallari CT, Achilleos S, Quattrocchi A, Gabel J, Critselis E, Athanasiadou M, Rahmanian Haghighi MR, Papatheodorou S, Liu T, Artemiou A, Rodriguez-Llanes JM, Bennett CM, Zimmermann C, Schernhammer E, Bustos Sierra N, Ekelson R, Lobato J, Macedo L, Mortensen LH, Critchley J, Goldsmith L, Denissov G, Le Meur N, Kandelaki L, Athanasakis K, Binyaminy B, Maor T, Stracci F, Ambrosio G, Davletov K, Glushkova N, Martial C, Chan Sun M, Hagen TP, Chong M, Barron M, Łyszczarz B, Erzen I, Arcos Gonzalez P, Burström B, Pidmurniak N, Verstiuk O, Huang Q, Polemitis A, Charalambous A, Demetriou CA. Magnitude and determinants of excess total, age-specific and sex-specific all-cause mortality in 24 countries worldwide during 2020 and 2021: results on the impact of the COVID-19 pandemic from the C-MOR project. BMJ Glob Health 2024; 9:e013018. [PMID: 38637119 PMCID: PMC11029481 DOI: 10.1136/bmjgh-2023-013018] [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: 06/01/2023] [Accepted: 01/06/2024] [Indexed: 04/20/2024] Open
Abstract
INTRODUCTION To examine the impact of the COVID-19 pandemic on mortality, we estimated excess all-cause mortality in 24 countries for 2020 and 2021, overall and stratified by sex and age. METHODS Total, age-specific and sex-specific weekly all-cause mortality was collected for 2015-2021 and excess mortality for 2020 and 2021 was calculated by comparing weekly 2020 and 2021 age-standardised mortality rates against expected mortality, estimated based on historical data (2015-2019), accounting for seasonality, and long-term and short-term trends. Age-specific weekly excess mortality was similarly calculated using crude mortality rates. The association of country and pandemic-related variables with excess mortality was investigated using simple and multilevel regression models. RESULTS Excess cumulative mortality for both 2020 and 2021 was found in Austria, Brazil, Belgium, Cyprus, England and Wales, Estonia, France, Georgia, Greece, Israel, Italy, Kazakhstan, Mauritius, Northern Ireland, Norway, Peru, Poland, Slovenia, Spain, Sweden, Ukraine, and the USA. Australia and Denmark experienced excess mortality only in 2021. Mauritius demonstrated a statistically significant decrease in all-cause mortality during both years. Weekly incidence of COVID-19 was significantly positively associated with excess mortality for both years, but the positive association was attenuated in 2021 as percentage of the population fully vaccinated increased. Stringency index of control measures was positively and negatively associated with excess mortality in 2020 and 2021, respectively. CONCLUSION This study provides evidence of substantial excess mortality in most countries investigated during the first 2 years of the pandemic and suggests that COVID-19 incidence, stringency of control measures and vaccination rates interacted in determining the magnitude of excess mortality.
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Affiliation(s)
- Chryso Th Pallari
- Department of Primary Care and Population Health, University of Nicosia Medical School, Nicosia, Cyprus
| | - Souzana Achilleos
- Department of Primary Care and Population Health, University of Nicosia Medical School, Nicosia, Cyprus
| | - Annalisa Quattrocchi
- Department of Primary Care and Population Health, University of Nicosia Medical School, Nicosia, Cyprus
| | - John Gabel
- Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
| | - Elena Critselis
- Department of Primary Care and Population Health, University of Nicosia Medical School, Nicosia, Cyprus
| | - Maria Athanasiadou
- Health Monitoring Unit, Government of the Republic of Cyprus Ministry of Health, Nicosia, Cyprus
| | | | - Stefania Papatheodorou
- Department of Biostatistics and Epidemiology, Rutgers School of Public Health, Piscataway, New Jersey, USA
- Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, Massachusetts, USA
| | - Tianyu Liu
- Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
| | - Andreas Artemiou
- School of Information Technologies, University of Limassol, Limassol, Cyprus
| | | | - Catherine M Bennett
- Institute for Health Transformation, Deakin University, Burwood, Victoria, Australia
| | - Claudia Zimmermann
- Department of Epidemiology, Medical University of Vienna Center for Public Health, Vienna, Austria
| | - Eva Schernhammer
- Department of Epidemiology, Medical University of Vienna Center for Public Health, Vienna, Austria
| | | | - Reindert Ekelson
- Department of Epidemiology and Public Health, Sciensano, Brussels, Belgium
| | - Jackeline Lobato
- Department of Epidemiology and Biostatistics, Institute of Collective Health (ISC), Federal Fluminense University, Niteroi, Brazil
| | - Laylla Macedo
- Institute of Studies in Collective Health (IESC), Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | | | - Julia Critchley
- Population Health Research Institute, St George's University of London, London, UK
| | - Lucy Goldsmith
- Division of Health Services Research and Management, School of Health and Psychological Sciences, University of London, City, London, UK
| | - Gleb Denissov
- Department of Registries, National Institute for Health Development, Tallinn, Estonia
| | - Nolwenn Le Meur
- UMR CNRS 6051 - INSERM U1309, Ecole des Hautes Etudes en Santé Publique, Rennes, France
| | - Levan Kandelaki
- Department of Medical Statistics, National Center for Disease Control and Public Health, Tbilisi, Georgia
| | - Kostas Athanasakis
- Laboratory for Health Technology Assessment, University of West Attica, Athens, Greece
| | - Binyamin Binyaminy
- Israeli Center of Disease Control, State of Israel Ministry of Health, Ramat Gan, Israel
| | - Tamar Maor
- Israeli Center of Disease Control, State of Israel Ministry of Health, Ramat Gan, Israel
| | - Fabrizio Stracci
- Department of Medicine, Public Health Section, University of Perugia, School of Medicine, Perugia, Italy
| | - Giuseppe Ambrosio
- Department of Cardiology, University of Perugia School of Medicine, Perugia, Italy
| | - Kairat Davletov
- Rector Administration, Asfendiyarov Kazakh National Medical University, Almaty, Kazakhstan
| | - Nataliya Glushkova
- Department of Epidemiology, Evidence-Based Medicine and Biostatistics, Al-Farabi Kazakh National University, Almaty, Kazakhstan
| | - Cyndy Martial
- Department of Medicine, University of Mauritius Faculty of Science, Reduit, Mauritius
| | - Marie Chan Sun
- Department of Medicine, University of Mauritius Faculty of Science, Reduit, Mauritius
| | - Terje P Hagen
- Department of Health Management and Health Economics, University of Oslo, Oslo, Norway
| | - Mario Chong
- Departamento de Ingeniería, Universidad del Pacifico, Lima, Peru
| | - Manuel Barron
- Departamento de Economia, Universidad del Pacifico, Lima, Peru
| | - Błażej Łyszczarz
- Department of Health Economics, Nicolaus Copernicus University in Torun, Bydgoszcz, Poland
| | - Ivan Erzen
- Public Health School, National Institute of Public Health of the Republic of Slovenia, Ljubljana, Slovenia
| | - Pedro Arcos Gonzalez
- Unit for Research in Emergency and Disaster, Department of Medicine, University of Oviedo, Oviedo, Spain
| | - Bo Burström
- Department of Global Public Health, Karolinska Institutet, Stockholm, Sweden
| | - Nataliia Pidmurniak
- Department of Internal Medicine, Bogomolets National Medical University, Kyiv, Ukraine
| | - Olesia Verstiuk
- Department of Medical Sciences, University of Nicosia Medical School, Nicosia, Cyprus
| | - Qian Huang
- Center for Rural Health Research, College of Public Health, East Tennessee State University, Johnson City, TN, USA
| | | | | | - Christiana A Demetriou
- Department of Primary Care and Population Health, University of Nicosia Medical School, Nicosia, Cyprus
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Yinzhi D, Jianhua H, Hesheng L. The roles of liver sinusoidal endothelial cells in liver ischemia/reperfusion injury. J Gastroenterol Hepatol 2024; 39:224-230. [PMID: 37939704 DOI: 10.1111/jgh.16396] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2022] [Revised: 09/01/2023] [Accepted: 10/18/2023] [Indexed: 11/10/2023]
Abstract
Liver ischemia/reperfusion injury (IRI) is a major complication after partial hepatectomy and liver transplantation and during hypovolemic shock and hypoxia-related diseases. Liver IRI is a current research hotspot. The early stage of liver IRI is characterized by injury and dysfunction of liver sinusoidal endothelial cells (LSECs), which, along with hepatocytes, are the major cells involved in liver injury. In this review, we elaborate on the roles played by LSECs in liver IRI, including the pathological features of LSECs, LSECs exacerbation of the sterile inflammatory response, LSECs interactions with platelets and the promotion of liver regeneration, and the activation of LSECs autophagy. In addition, we discuss the study of LSECs as therapeutic targets for the treatment of liver IRI and the existing problems when applying LSECs in liver IRI research.
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Affiliation(s)
- Deng Yinzhi
- Hubei Selenium and Human Health Institute, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, China
- Department of Gastroenterology, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, China
- Hubei Provincial Key Lab of Selenium Resources and Bioapplications, Enshi, China
| | - He Jianhua
- Department of Gastroenterology, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, China
| | - Luo Hesheng
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China
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14
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Mosaffa-Jahromi M, Molavi Vardanjani H, Fuzimoto A, Hunter J, Lankarani KB, Pasalar M. Efficacy and safety of aniseed powder for treating gastrointestinal symptoms of COVID-19: a randomized, placebo-controlled trial. Front Pharmacol 2024; 15:1331177. [PMID: 38292939 PMCID: PMC10824915 DOI: 10.3389/fphar.2024.1331177] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Accepted: 01/08/2024] [Indexed: 02/01/2024] Open
Abstract
Background: Gastrointestinal symptoms are prevalent amongst patients with a confirmed diagnosis of COVID-19 and may be associated with an increased risk of disease severity. This trial aimed to evaluate the efficacy and safety of aniseed (Pimpinella anisum L.) powder as an add-on therapy to standard care for treating gastrointestinal symptoms experienced by adults with an acute SARS-CoV-2 infection. Methods: The study was a randomized parallel-group double-blinded placebo-controlled add-on therapy trial. Adults with an acute SARS-CoV-2 infection who did not require hospitalization and reported at least one gastrointestinal symptom in the preceding 48 h were assigned to either the aniseed or placebo group in a 1:4 ratio. All 225 participants (45 in the aniseed group and 180 in the placebo group) were instructed to use 25 g of powdered aniseed or placebo twice daily for 2 weeks. The primary outcomes were the proportion of patients who experienced an improvement of at least one point in the symptom score after adjusting for age group, gender, and time. Backwards stepwise logistic regression was applied to calculate the risk ratios. The clinical symptoms and adverse events were assessed at the beginning, 1 week later, and at the end of the trial (week two). Results: Participants in the aniseed group were significantly more likely to report symptom improvement for abdominal pain [adjusted risk ratio (RR):0.55; 95% confidence interval (CI): 0.46-0.72], anorexia (RR:0.62; 95% CI: 0.47-0.82), and diarrhea (RR:0.19; 95% CI: 0.12-0.30), but not nausea/vomiting (RR:0.87; 95% CI: 0.71-1.08) or bloating (RR:0.87; 95% CI: 0.72-1.05). Two participants in the aniseed group and three participants in the placebo group reported mild to moderate adverse events. Conclusion: This study showed that 2 weeks of aniseed powder containing trans-anethole (87%-94%) may help improve abdominal pain, anorexia, and diarrhea in COVID-19 patients. The findings align with the known biological, multitargeted activity of P. anisum and trans-anethole, which includes inhibiting SARS-CoV-2 along with other anti-infective, anti-inflammatory, antioxidant, hepatoprotective, and anti-dysbiosis properties. Multicenter trials with larger sample sizes and longer follow-up are warranted to confirm these findings. Clinical Trial Registration: Iranian Registry of Clinical Trials (IRCT20120506009651N3).
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Affiliation(s)
- Maryam Mosaffa-Jahromi
- Research Center for Traditional Medicine and History of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Hossein Molavi Vardanjani
- Research Center for Traditional Medicine and History of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | | | | | | | - Mehdi Pasalar
- Research Center for Traditional Medicine and History of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
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15
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He KY, Lei XY, Zhang L, Wu DH, Li JQ, Lu LY, Laila UE, Cui CY, Xu ZX, Jian YP. Development and management of gastrointestinal symptoms in long-term COVID-19. Front Microbiol 2023; 14:1278479. [PMID: 38156008 PMCID: PMC10752947 DOI: 10.3389/fmicb.2023.1278479] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2023] [Accepted: 11/20/2023] [Indexed: 12/30/2023] Open
Abstract
Background Emerging evidence reveals that SARS-CoV-2 possesses the capability to disrupt the gastrointestinal (GI) homeostasis, resulting in the long-term symptoms such as loss of appetite, diarrhea, gastroesophageal reflux, and nausea. In the current review, we summarized recent reports regarding the long-term effects of COVID-19 (long COVID) on the gastrointestine. Objective To provide a narrative review of abundant clinical evidence regarding the development and management of long-term GI symptoms in COVID-19 patients. Results Long-term persistent digestive symptoms are exhibited in a majority of long-COVID patients. SARS-CoV-2 infection of intestinal epithelial cells, cytokine storm, gut dysbiosis, therapeutic drugs, psychological factors and exacerbation of primary underlying diseases lead to long-term GI symptoms in COVID-19 patients. Interventions like probiotics, prebiotics, fecal microbiota transplantation, and antibiotics are proved to be beneficial in preserving intestinal microecological homeostasis and alleviating GI symptoms. Conclusion Timely diagnosis and treatment of GI symptoms in long-COVID patients hold great significance as they may contribute to the mitigation of severe conditions and ultimately lead to the improvement of outcomes of the patients.
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Affiliation(s)
- Kai-Yue He
- School of Life Sciences, Henan University, Kaifeng, China
| | - Xin-Yuan Lei
- School of Life Sciences, Henan University, Kaifeng, China
| | - Lei Zhang
- School of Life Sciences, Henan University, Kaifeng, China
| | - Dan-Hui Wu
- School of Life Sciences, Henan University, Kaifeng, China
| | - Jun-Qi Li
- School of Life Sciences, Henan University, Kaifeng, China
| | - Li-Yuan Lu
- School of Life Sciences, Henan University, Kaifeng, China
| | - Umm E. Laila
- School of Life Sciences, Henan University, Kaifeng, China
| | - Cui-Yun Cui
- Department of Blood Transfusion, Henan Provincial People’s Hospital, Zhengzhou, Henan, China
| | - Zhi-Xiang Xu
- School of Life Sciences, Henan University, Kaifeng, China
| | - Yong-Ping Jian
- School of Life Sciences, Henan University, Kaifeng, China
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16
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Wang Y, Yang L, Xu G. New-Onset Acute Interstitial Nephritis Post-SARS-CoV-2 Infection and COVID-19 Vaccination: A Panoramic Review. J Epidemiol Glob Health 2023; 13:615-636. [PMID: 37870719 PMCID: PMC10686899 DOI: 10.1007/s44197-023-00159-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Accepted: 09/27/2023] [Indexed: 10/24/2023] Open
Abstract
The 2019 coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) has posed a considerable challenge to global healthcare. Acute interstitial nephritis (AIN) post SARS-CoV-2 infection and vaccination has been reported, but its clinical features and pathogenesis remained unclear. We reviewed so far the largest 22 cases of AIN post SARS-CoV-2 infection and 36 cases of AIN following COVID-19 vaccination. The onset of AIN was mainly related to messenger RNA vaccines (52.8%). Apart from fever, proteinuria (45.5%) was the main manifestation of AIN post SARS-CoV-2 infection, left acute kidney injury (AKI, 63.9%) in patients post COVID-19 vaccination. The potential mechanism of vaccination induced AIN was conjugating vaccines with proteins to form a hapten, which activated dendritic cells and promoted a cascade immunological reaction leading to AIN.
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Affiliation(s)
- Yu Wang
- Department of Nephrology, Donghu District, the Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, 330006, Jiangxi, China
| | - Ling Yang
- Department of Health Management Medicine, The Second Affiliated Hospital of Nanchang University, Jiangxi, China
| | - Gaosi Xu
- Department of Nephrology, Donghu District, the Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, 330006, Jiangxi, China.
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Wang Y, Shen M, Li Y, Shao J, Zhang F, Guo M, Zhang Z, Zheng S. COVID-19-associated liver injury: Adding fuel to the flame. Cell Biochem Funct 2023; 41:1076-1092. [PMID: 37947373 DOI: 10.1002/cbf.3883] [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: 08/23/2023] [Revised: 10/19/2023] [Accepted: 10/21/2023] [Indexed: 11/12/2023]
Abstract
COVID-19 is mainly characterized by respiratory disorders and progresses to multiple organ involvement in severe cases. With expansion of COVID-19 and SARS-CoV-2 research, correlative liver injury has been revealed. It is speculated that COVID-19 patients exhibited abnormal liver function, as previously observed in the SARS and MERS pandemics. Furthermore, patients with underlying diseases such as chronic liver disease are more susceptible to SARS-CoV-2 and indicate a poor prognosis accompanied by respiratory symptoms, systemic inflammation, or metabolic diseases. Therefore, COVID-19 has the potential to impair liver function, while individuals with preexisting liver disease suffer from much worse infected conditions. COVID-19 related liver injury may be owing to direct cytopathic effect, immune dysfunction, gut-liver axis interaction, and inappropriate medication use. However, discussions on these issues are infancy. Expanding research have revealed that angiotensin converting enzyme 2 (ACE2) expression mediated the combination of virus and target cells, iron metabolism participated in the virus life cycle and the fate of target cells, and amino acid metabolism regulated immune response in the host cells, which are all closely related to liver health. Further exploration holds great significance in elucidating the pathogenesis, facilitating drug development, and advancing clinical treatment of COVID-19-related liver injury. This article provides a review of the clinical and laboratory hepatic characteristics in COVID-19 patients, describes the etiology and impact of liver injury, and discusses potential pathophysiological mechanisms.
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Affiliation(s)
- Yingqian Wang
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China
- Jiangsu Key Laboratory of Therapeutic Material of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Min Shen
- Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, China
| | - Yujia Li
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China
- Jiangsu Key Laboratory of Therapeutic Material of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Jiangjuan Shao
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China
- Jiangsu Key Laboratory of Therapeutic Material of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Feng Zhang
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China
- Jiangsu Key Laboratory of Therapeutic Material of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Mei Guo
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China
- Jiangsu Key Laboratory of Therapeutic Material of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Zili Zhang
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China
- Jiangsu Key Laboratory of Therapeutic Material of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Shizhong Zheng
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China
- Jiangsu Key Laboratory of Therapeutic Material of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China
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Kočar E, Katz S, Pušnik Ž, Bogovič P, Turel G, Skubic C, Režen T, Strle F, Martins dos Santos VA, Mraz M, Moškon M, Rozman D. COVID-19 and cholesterol biosynthesis: Towards innovative decision support systems. iScience 2023; 26:107799. [PMID: 37720097 PMCID: PMC10502404 DOI: 10.1016/j.isci.2023.107799] [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: 04/18/2023] [Revised: 07/12/2023] [Accepted: 08/29/2023] [Indexed: 09/19/2023] Open
Abstract
With COVID-19 becoming endemic, there is a continuing need to find biomarkers characterizing the disease and aiding in patient stratification. We studied the relation between COVID-19 and cholesterol biosynthesis by comparing 10 intermediates of cholesterol biosynthesis during the hospitalization of 164 patients (admission, disease deterioration, discharge) admitted to the University Medical Center of Ljubljana. The concentrations of zymosterol, 24-dehydrolathosterol, desmosterol, and zymostenol were significantly altered in COVID-19 patients. We further developed a predictive model for disease severity based on clinical parameters alone and their combination with a subset of sterols. Our machine learning models applying 8 clinical parameters predicted disease severity with excellent accuracy (AUC = 0.96), showing substantial improvement over current clinical risk scores. After including sterols, model performance remained better than COVID-GRAM. This is the first study to examine cholesterol biosynthesis during COVID-19 and shows that a subset of cholesterol-related sterols is associated with the severity of COVID-19.
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Affiliation(s)
- Eva Kočar
- Centre for Functional Genomics and Bio-Chips, Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Zaloška cesta 4, SI-1000 Ljubljana, Slovenia
| | - Sonja Katz
- LifeGlimmer GmbH, Markelstraße 38, 12163 Berlin, Germany
- Biomanufacturing and Digital Twins Group, Bioprocess Engineering Laboratory, Wageningen University and Research, Droevendaalsesteeg 1, 6708PB Wageningen, the Netherlands
| | - Žiga Pušnik
- Faculty of Computer and Information Science, University of Ljubljana, Večna pot 113, SI-1000 Ljubljana, Slovenia
| | - Petra Bogovič
- Department of Infectious Diseases, University Medical Centre Ljubljana, Japljeva ulica 2, SI-1000 Ljubljana, Slovenia
| | - Gabriele Turel
- Department of Infectious Diseases, University Medical Centre Ljubljana, Japljeva ulica 2, SI-1000 Ljubljana, Slovenia
| | - Cene Skubic
- Centre for Functional Genomics and Bio-Chips, Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Zaloška cesta 4, SI-1000 Ljubljana, Slovenia
| | - Tadeja Režen
- Centre for Functional Genomics and Bio-Chips, Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Zaloška cesta 4, SI-1000 Ljubljana, Slovenia
| | - Franc Strle
- Department of Infectious Diseases, University Medical Centre Ljubljana, Japljeva ulica 2, SI-1000 Ljubljana, Slovenia
| | - Vitor A.P. Martins dos Santos
- LifeGlimmer GmbH, Markelstraße 38, 12163 Berlin, Germany
- Biomanufacturing and Digital Twins Group, Bioprocess Engineering Laboratory, Wageningen University and Research, Droevendaalsesteeg 1, 6708PB Wageningen, the Netherlands
| | - Miha Mraz
- Faculty of Computer and Information Science, University of Ljubljana, Večna pot 113, SI-1000 Ljubljana, Slovenia
| | - Miha Moškon
- Faculty of Computer and Information Science, University of Ljubljana, Večna pot 113, SI-1000 Ljubljana, Slovenia
| | - Damjana Rozman
- Centre for Functional Genomics and Bio-Chips, Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Zaloška cesta 4, SI-1000 Ljubljana, Slovenia
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Ng CYJ, Bun HH, Zhao Y, Zhong LLD. TCM "medicine and food homology" in the management of post-COVID disorders. Front Immunol 2023; 14:1234307. [PMID: 37720220 PMCID: PMC10500073 DOI: 10.3389/fimmu.2023.1234307] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2023] [Accepted: 08/10/2023] [Indexed: 09/19/2023] Open
Abstract
Background The World Health Organization declared that COVID-19 is no longer a public health emergency of global concern on May 5, 2023. Post-COVID disorders are, however, becoming more common. Hence, there lies a growing need to develop safe and effective treatment measures to manage post-COVID disorders. Investigating the use of TCM medicinal foods in the long-term therapy of post-COVID illnesses may be beneficial given contemporary research's emphasis on the development of medicinal foods. Scope and approach The use of medicinal foods for the long-term treatment of post-COVID disorders is highlighted in this review. Following a discussion of the history of the TCM "Medicine and Food Homology" theory, the pathophysiological effects of post-COVID disorders will be briefly reviewed. An analysis of TCM medicinal foods and their functions in treating post-COVID disorders will then be provided before offering some insight into potential directions for future research and application. Key findings and discussion TCM medicinal foods can manage different aspects of post-COVID disorders. The use of medicinal foods in the long-term management of post-COVID illnesses may be a safe and efficient therapy choice because they are typically milder in nature than chronic drug use. These findings may also be applied in the long-term post-disease treatment of similar respiratory disorders.
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Affiliation(s)
- Chester Yan Jie Ng
- School of Biological Sciences, Nanyang Technological University, Singapore, Singapore
| | - Hung Hung Bun
- The University of Hong Kong (HKU) School of Professional and Continuing Education, Hong Kong, Hong Kong SAR, China
| | - Yan Zhao
- School of Biological Sciences, Nanyang Technological University, Singapore, Singapore
| | - Linda L. D. Zhong
- School of Biological Sciences, Nanyang Technological University, Singapore, Singapore
- School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, Hong Kong SAR, China
- Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, Hong Kong, Hong Kong SAR, China
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20
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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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21
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Han L, Shi H, Li Y, Qi H, Wang Y, Gu J, Wu J, Zhao S, Cao P, Xu L, Deng X, Yao XI, Ran J. Excess Deaths of Gastrointestinal, Liver, and Pancreatic Diseases During the COVID-19 Pandemic in the United States. Int J Public Health 2023; 68:1606305. [PMID: 37649691 PMCID: PMC10462779 DOI: 10.3389/ijph.2023.1606305] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Accepted: 08/02/2023] [Indexed: 09/01/2023] Open
Abstract
Objectives: To evaluate excess deaths of gastrointestinal, liver, and pancreatic diseases in the United States during the COVID-19 pandemic. Methods: We retrieved weekly death counts from National Vital Statistics System and fitted them with a quasi-Poisson regression model. Cause-specific excess deaths were calculated by the difference between observed and expected deaths with adjustment for temporal trend and seasonality. Demographic disparities and temporal-spatial patterns were evaluated for different diseases. Results: From March 2020 to September 2022, the increased mortality (measured by excess risks) for Clostridium difficile colitis, gastrointestinal hemorrhage, and acute pancreatitis were 35.9%; 24.8%; and 20.6% higher than the expected. For alcoholic liver disease, fibrosis/cirrhosis, and hepatic failure, the excess risks were 1.4-2.8 times higher among younger inhabitants than older inhabitants. The excess deaths of selected diseases were persistently observed across multiple epidemic waves with fluctuating trends for gastrointestinal hemorrhage and fibrosis/cirrhosis and an increasing trend for C. difficile colitis. Conclusion: The persistently observed excess deaths of digestive diseases highlights the importance for healthcare authorities to develop sustainable strategies in response to the long-term circulating of SARS-CoV-2 in the community.
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Affiliation(s)
- Lefei Han
- School of Global Health, Chinese Center for Tropical Diseases Research, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Haoting Shi
- Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yongxuan Li
- School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Hongchao Qi
- British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom
| | - Yuhua Wang
- School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jiawei Gu
- School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jiayin Wu
- Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Shi Zhao
- JC School of Public Health and Primary Care, Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China
| | - Peihua Cao
- Clinical Research Center, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Lan Xu
- School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiaobei Deng
- School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiaoxin I. Yao
- Department of Clinical Research, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Jinjun Ran
- School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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22
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Tomkinson S, Triscott C, Schenk E, Foey A. The Potential of Probiotics as Ingestible Adjuvants and Immune Modulators for Antiviral Immunity and Management of SARS-CoV-2 Infection and COVID-19. Pathogens 2023; 12:928. [PMID: 37513775 PMCID: PMC10384479 DOI: 10.3390/pathogens12070928] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2023] [Revised: 06/30/2023] [Accepted: 07/03/2023] [Indexed: 07/30/2023] Open
Abstract
Probiotic bacteria are able to modulate general antiviral responsiveness, including barrier functionality and innate and adaptive immune responses. The COVID-19 pandemic, resulting from SARS-CoV-2 infection, has created a need to control and treat this viral infection and its ensuing immunopathology with a variety of approaches; one such approach may involve the administration of probiotic bacteria. As with most viral infections, its pathological responses are not fully driven by the virus, but are significantly contributed to by the host's immune response to viral infection. The potential adoption of probiotics in the treatment of COVID-19 will have to appreciate the fine line between inducing antiviral immunity without over-provoking immune inflammatory responses resulting in host-derived immunopathological tissue damage. Additionally, the effect exerted on the immune system by SARS-CoV-2 evasion strategies will also have to be considered when developing a robust response to this virus. This review will introduce the immunopathology of COVID-19 and the immunomodulatory effects of probiotic strains, and through their effects on a range of respiratory pathogens (IAV, SARS-CoV, RSV), as well as SARS-CoV-2, will culminate in a focus on how these bacteria can potentially manipulate both infectivity and immune responsiveness via barrier functionality and both innate and adaptive immunity. In conclusion, the harnessing of induction and augmentation of antiviral immunity via probiotics may not only act as an ingestible adjuvant, boosting immune responsiveness to SARS-CoV-2 infection at the level of barrier integrity and innate and adaptive immunity, but also act prophylactically to prevent infection and enhance protection afforded by current vaccine regimens.
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Affiliation(s)
- Sophie Tomkinson
- School of Biomedical Sciences, Faculty of Health, University of Plymouth, Drake Circus, Plymouth PL4 8AA, UK
| | - Cloe Triscott
- School of Biomedical Sciences, Faculty of Health, University of Plymouth, Drake Circus, Plymouth PL4 8AA, UK
| | - Emily Schenk
- School of Biomedical Sciences, Faculty of Health, University of Plymouth, Drake Circus, Plymouth PL4 8AA, UK
- Peninsula Medical School, Faculty of Health, University of Plymouth, Drake Circus, Plymouth PL4 8AA, UK
| | - Andrew Foey
- School of Biomedical Sciences, Faculty of Health, University of Plymouth, Drake Circus, Plymouth PL4 8AA, UK
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23
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Jagirdhar GSK, Pattnaik H, Banga A, Qasba RK, Rama K, Reddy ST, Bucharles ACF, Kashyap R, Elmati PR, Bansal V, Bains Y, DaCosta T, Surani S. Association of Non-Alcoholic Fatty Liver Disease and Metabolic-Associated Fatty Liver Disease with COVID-19-Related Intensive Care Unit Outcomes: A Systematic Review and Meta-Analysis. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:1239. [PMID: 37512051 PMCID: PMC10386363 DOI: 10.3390/medicina59071239] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/19/2023] [Revised: 06/13/2023] [Accepted: 06/27/2023] [Indexed: 07/30/2023]
Abstract
Background and Objective: The association of non-alcoholic fatty liver disease (NAFLD) and metabolic-associated fatty liver disease (MAFLD) with intensive care unit (ICU) admissions and the need for mechanical ventilation and disease severity in COVID-19 patients. Material and Methods: A systematic literature review was conducted on the databases: Cochrane, Embase, PubMed, ScienceDirect, and the Web of Science from January 2019 to June 2022. Studies evaluating MAFLD using laboratory methods, non-invasive imaging, or liver biopsy were included. The study protocol was registered in PROSPERO (ID CRD42022313259), and PRISMA guidelines were followed. The NIH quality assessment tool was used for quality assessment. RevMan version 5.3 software was used for pooled analysis. A sensitivity analysis was performed to assess the result's stability. Results: A total of 37,974 patients from 17 studies were assessed for the association between MAFLD and ICU admission. A total of 3396 COVID-19 patients required ICU admission: 1236 (20.41%) in the MAFLD group and 2160 (6.77%) in the non-MAFLD group. The odds ratio was 1.86 for ICU admission, p = 0.007, and a (95% CI) of [1.18-2.91]. A total of 37,166 patients from 13 studies were included in the need for invasive mechanical ventilation analysis. A total of 1676 patients required mechanical ventilation: 805 in the MAFLD group (14.20% of all MAFLD patients) and 871 patients in the non-MAFLD group (2.76% of all non-MAFLD patients). The odds ratio was 2.05, p = 0.02, and a (95% CI) of [1.12-3.74]. A total of 5286 patients from 14 studies were included in the COVID-19 disease severity analysis. Severe COVID-19 was seen in 1623 patients, with 33.17% (901/2716) of MAFLD patients and 28.09% (722/2570) of non-MAFLD patients having severe disease. The odds ratio was 1.59 for disease severity, p = 0.010, and a (95% CI) of [1.12-2.26]. Conclusions: Our meta-analysis suggests that there are significantly increased odds of ICU admissions, a need for invasive mechanical ventilation, and disease severity in MAFLD patients who acquire COVID-19.
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Affiliation(s)
| | | | - Akshat Banga
- Sawai Man Singh Medical College, Jaipur 302004, India
| | - Rakhtan K Qasba
- Green Life Medical College and Hospital, Dhaka 1205, Bangladesh
| | | | | | | | - Rahul Kashyap
- Critical Care Medicine, Department of Anesthesiology, Mayo Clinic, Rochester, MN 55905, USA
| | - Praveen Reddy Elmati
- Interventional Pain Medicine, University of Louisville, Louisville, KY 40202, USA
| | - Vikas Bansal
- Division of Nephrology and Critical Care Medicine, Department of Internal Medicine, Mayo Clinic, Rochester, MN 55905, USA
| | - Yatinder Bains
- Department of Gastroenterology, Saint Michaels Medical Center, Newark, NJ 07102, USA
| | - Theodore DaCosta
- Department of Gastroenterology, Saint Michaels Medical Center, Newark, NJ 07102, USA
| | - Salim Surani
- Pulmonary, Critical Care & Pharmacy, Texas A&M University, College Station, TX 79016, USA
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24
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Luo H, Chen J, Jiang Q, Yu Y, Yang M, Luo Y, Wang X. Comprehensive DNA methylation profiling of COVID-19 and hepatocellular carcinoma to identify common pathogenesis and potential therapeutic targets. Clin Epigenetics 2023; 15:100. [PMID: 37309005 DOI: 10.1186/s13148-023-01515-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2023] [Accepted: 05/31/2023] [Indexed: 06/14/2023] Open
Abstract
BACKGROUND & AIMS The effects of SARS-CoV-2 infection can be more complex and severe in patients with hepatocellular carcinoma (HCC) as compared to other cancers. This is due to several factors, including pre-existing conditions such as viral hepatitis and cirrhosis, which are commonly associated with HCC. METHODS We conducted an analysis of epigenomics in SARS-CoV-2 infection and HCC patients, and identified common pathogenic mechanisms using weighted gene co-expression network analysis (WGCNA) and other analyses. Hub genes were identified and analyzed using LASSO regression. Additionally, drug candidates and their binding modes to key macromolecular targets of COVID-19 were identified using molecular docking. RESULTS The epigenomic analysis of the relationship between SARS-CoV-2 infection and HCC patients revealed that the co-pathogenesis was closely linked to immune response, particularly T cell differentiation, regulation of T cell activation and monocyte differentiation. Further analysis indicated that CD4+ T cells and monocytes play essential roles in the immunoreaction triggered by both conditions. The expression levels of hub genes MYLK2, FAM83D, STC2, CCDC112, EPHX4 and MMP1 were strongly correlated with SARS-CoV-2 infection and the prognosis of HCC patients. In our study, mefloquine and thioridazine were identified as potential therapeutic agents for COVID-19 in combined with HCC. CONCLUSIONS In this research, we conducted an epigenomics analysis to identify common pathogenetic processes between SARS-CoV-2 infection and HCC patients, providing new insights into the pathogenesis and treatment of HCC patients infected with SARS-CoV-2.
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Affiliation(s)
- Huiyan Luo
- The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China
- Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Jixin Chen
- The Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Qiyin Jiang
- The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yifan Yu
- The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Miaolun Yang
- The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yuehua Luo
- The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Xiongwen Wang
- Department of Oncology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
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25
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Wang M, Yu F, Chang W, Zhang Y, Zhang L, Li P. Inflammasomes: a rising star on the horizon of COVID-19 pathophysiology. Front Immunol 2023; 14:1185233. [PMID: 37251383 PMCID: PMC10213254 DOI: 10.3389/fimmu.2023.1185233] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Accepted: 05/02/2023] [Indexed: 05/31/2023] Open
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a contagious respiratory virus that is the cause of the coronavirus disease 2019 (COVID-19) pandemic which has posed a serious threat to public health. COVID-19 is characterized by a wide spectrum of clinical manifestations, ranging from asymptomatic infection to mild cold-like symptoms, severe pneumonia or even death. Inflammasomes are supramolecular signaling platforms that assemble in response to danger or microbial signals. Upon activation, inflammasomes mediate innate immune defense by favoring the release of proinflammatory cytokines and triggering pyroptotic cell death. Nevertheless, abnormalities in inflammasome functioning can result in a variety of human diseases such as autoimmune disorders and cancer. A growing body of evidence has showed that SARS-CoV-2 infection can induce inflammasome assembly. Dysregulated inflammasome activation and consequent cytokine burst have been associated with COVID-19 severity, alluding to the implication of inflammasomes in COVID-19 pathophysiology. Accordingly, an improved understanding of inflammasome-mediated inflammatory cascades in COVID-19 is essential to uncover the immunological mechanisms of COVID-19 pathology and identify effective therapeutic approaches for this devastating disease. In this review, we summarize the most recent findings on the interplay between SARS-CoV-2 and inflammasomes and the contribution of activated inflammasomes to COVID-19 progression. We dissect the mechanisms involving the inflammasome machinery in COVID-19 immunopathogenesis. In addition, we provide an overview of inflammasome-targeted therapies or antagonists that have potential clinical utility in COVID-19 treatment.
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Affiliation(s)
- Man Wang
- *Correspondence: Man Wang, ; Peifeng Li,
| | | | | | | | | | - Peifeng Li
- *Correspondence: Man Wang, ; Peifeng Li,
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26
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Zhuo J, Wang K, Shi Z, Yuan C. Immunogenic cell death-led discovery of COVID-19 biomarkers and inflammatory infiltrates. Front Microbiol 2023; 14:1191004. [PMID: 37228369 PMCID: PMC10203236 DOI: 10.3389/fmicb.2023.1191004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2023] [Accepted: 04/18/2023] [Indexed: 05/27/2023] Open
Abstract
Immunogenic cell death (ICD) serves a critical role in regulating cell death adequate to activate an adaptive immune response, and it is associated with various inflammation-related diseases. However, the specific role of ICD-related genes in COVID-19 remains unclear. We acquired COVID-19-related information from the GEO database and a total of 14 ICD-related differentially expressed genes (DEGs) were identified. These ICD-related DEGs were closely associated with inflammation and immune activity. Afterward, CASP1, CD4, and EIF2AK3 among the 14 DEGs were selected as feature genes based on LASSO, Random Forest, and SVM-RFE algorithms, which had reliable diagnostic abilities. Moreover, functional enrichment analysis indicated that these feature genes may have a potential role in COVID-19 by being involved in the regulation of immune response and metabolism. Further CIBERSORT analysis demonstrated that the variations in the immune microenvironment of COVID-19 patients may be correlated with CASP1, CD4, and EIF2AK3. Additionally, 33 drugs targeting 3 feature genes had been identified, and the ceRNA network demonstrated a complicated regulative association based on these feature genes. Our work identified that CASP1, CD4, and EIF2AK3 were diagnostic genes of COVID-19 and correlated with immune activity. This study presents a reliable diagnostic signature and offers an overview to investigate the mechanism of COVID-19.
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Affiliation(s)
- Jianzhen Zhuo
- Guangdong Medical University, Dongguan, Guangdong, China
- Clinical Laboratory, Boai Hospital of Zhongshan Affiliated to Southern Medical University, Zhongshan, China
| | - Ke Wang
- Clinical Laboratory, Boai Hospital of Zhongshan Affiliated to Southern Medical University, Zhongshan, China
| | - Zijun Shi
- Reproductive Medical Center, Boai Hospital of Zhongshan Affiliated to Southern Medical University, Zhongshan, China
| | - Chunlei Yuan
- Guangdong Medical University, Dongguan, Guangdong, China
- Clinical Laboratory, Boai Hospital of Zhongshan Affiliated to Southern Medical University, Zhongshan, China
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27
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Zhang M, Wu Q, Chen H, Heidari AA, Cai Z, Li J, Md Abdelrahim E, Mansour RF. Whale optimization with random contraction and Rosenbrock method for COVID-19 disease prediction. Biomed Signal Process Control 2023; 83:104638. [PMID: 36741073 PMCID: PMC9889265 DOI: 10.1016/j.bspc.2023.104638] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Revised: 12/01/2022] [Accepted: 01/25/2023] [Indexed: 02/04/2023]
Abstract
Coronavirus Disease 2019 (COVID-19), instigated by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has hugely impacted global public health. To identify and intervene in critically ill patients early, this paper proposes an efficient, intelligent prediction model based on the machine learning approach, which combines the improved whale optimization algorithm (RRWOA) with the k-nearest neighbor (KNN) classifier. In order to improve the problem that WOA is prone to fall into local optimum, an improved version named RRWOA is proposed based on the random contraction strategy (RCS) and the Rosenbrock method. To verify the capability of the proposed algorithm, RRWOA is tested against nine classical metaheuristics, nine advanced metaheuristics, and seven well-known WOA variants based on 30 IEEE CEC2014 competition functions, respectively. The experimental results in mean, standard deviation, the Friedman test, and the Wilcoxon signed-rank test are considered, proving that RRWOA won first place on 18, 24, and 25 test functions, respectively. In addition, a binary version of the algorithm, called BRRWOA, is developed for feature selection problems. An efficient prediction model based on BRRWOA and KNN classifier is proposed and compared with seven existing binary metaheuristics based on 15 datasets of UCI repositories. The experimental results show that the proposed algorithm obtains the smallest fitness value in eleven datasets and can solve combinatorial optimization problems, indicating that it still performs well in discrete cases. More importantly, the model was compared with five other algorithms on the COVID-19 dataset. The experiment outcomes demonstrate that the model offers a scientific framework to support clinical diagnostic decision-making. Therefore, RRWOA is an effectively improved optimizer with efficient value.
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Affiliation(s)
- Meilin Zhang
- Institute of Big Data and Information Technology, Wenzhou University, Wenzhou 325000, China
| | - Qianxi Wu
- Institute of Big Data and Information Technology, Wenzhou University, Wenzhou 325000, China
| | - Huiling Chen
- Institute of Big Data and Information Technology, Wenzhou University, Wenzhou 325000, China
| | - Ali Asghar Heidari
- Institute of Big Data and Information Technology, Wenzhou University, Wenzhou 325000, China
| | - Zhennao Cai
- Institute of Big Data and Information Technology, Wenzhou University, Wenzhou 325000, China
| | - Jiaren Li
- Wenzhou People's Hospital, Wenzhou, Zhejiang 325099, China
| | - Elsaid Md Abdelrahim
- Faculty of Science, Northern Border University, Arar, Saudi Arabia.,Faculty of Science, Tanta University, Tanta, Egypt
| | - Romany F Mansour
- Department of Mathematics, Faculty of Science, New Valley University, El-Kharga 72511, Egypt
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Yang K, Guo J, Møhlenberg M, Zhou H. SARS-CoV-2 surveillance in medical and industrial wastewater-a global perspective: a narrative review. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2023; 30:63323-63334. [PMID: 36988799 PMCID: PMC10049894 DOI: 10.1007/s11356-023-26571-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Accepted: 03/16/2023] [Indexed: 05/11/2023]
Abstract
The novel coronavirus SARS-CoV-2 has spread at an unprecedented rate since late 2019, leading to the global COVID-19 pandemic. During the pandemic, being able to detect SARS-CoV-2 in human populations with high coverage quickly is a huge challenge. As SARS-CoV-2 is excreted in human excreta and thus exposed to the aqueous environment through sewers, the goal is to develop an ideal, non-invasive, cost-effective epidemiological method for detecting SARS-CoV-2. Wastewater surveillance has gained widespread interest and is increasingly being investigated as an effective early warning tool for monitoring the spread and evolution of the virus. This review emphasizes important findings on SARS-CoV-2 wastewater-based epidemiology (WBE) in different continents and techniques used to detect SARS-CoV-2 in wastewater during the period 2020-2022. The results show that WBE is a valuable population-level method for monitoring SARS-CoV-2 and is a valuable early warning alert. It can assist policymakers in formulating relevant policies to avoid the negative impacts of early or delayed action. Such strategy can also help avoid unnecessary wastage of medical resources, rationalize vaccine distribution, assist early detection, and contain large-scale outbreaks.
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Affiliation(s)
- Kaiwen Yang
- College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Liutai Road 1166, Wenjiang, Chengdu, 610000, China
| | - Jinlin Guo
- College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Liutai Road 1166, Wenjiang, Chengdu, 610000, China
| | - Michelle Møhlenberg
- Department of Biomedicine, Høegh-Guldbergs Gade 10, Building 1115, DK-8000, Aarhus C, Denmark
| | - Hao Zhou
- College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Liutai Road 1166, Wenjiang, Chengdu, 610000, China.
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Jacob B, Sawhney M, Sridhar A, Jacob B, Muller J, Abu-Sbaih R, Yao SC. Potential therapeutic effects of adjunct osteopathic manipulative treatments in SARS-CoV-2 patients. J Osteopath Med 2023:jom-2022-0207. [PMID: 37079451 DOI: 10.1515/jom-2022-0207] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2022] [Accepted: 01/23/2023] [Indexed: 04/21/2023]
Abstract
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) affects various human organ systems, including the lymphatic, pulmonary, gastrointestinal, and neurologic systems. The utilization of osteopathic manipulative treatment (OMT) techniques has been clinically effective in the alleviation of various upper respiratory infection symptoms. Consequently, the use of osteopathic manipulative medicine (OMM) in SARS-CoV-2 patients as adjunct treatment can be beneficial in promoting overall recovery. This paper attempts to address the pathophysiology of SARS-CoV-2 infection at the cellular level and its downstream effects. Subsequently, osteopathic principles were investigated to evaluate potential therapeutic effects, providing a holistic approach in the SARS-CoV-2 treatment. Although the association between the benefits of OMT on clinical improvement during the 1918 Spanish influenza pandemic can be seen, further investigation is required to establish a direct correlation between OMT and symptom management in SARS-CoV-2.
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Affiliation(s)
- Benna Jacob
- New York Institute of Technology College of Osteopathic Medicine, Old Westbury, NY, USA
| | - Mehak Sawhney
- New York Institute of Technology College of Osteopathic Medicine, Old Westbury, NY, USA
| | - Aarthi Sridhar
- New York Institute of Technology College of Osteopathic Medicine, Old Westbury, NY, USA
| | - Berlin Jacob
- New York Institute of Technology College of Osteopathic Medicine, Old Westbury, NY, USA
| | - Jeffrey Muller
- Department of Clinical Specialties, New York Institute of Technology College of Osteopathic Medicine, Old Westbury, NY, USA
| | - Reem Abu-Sbaih
- Department of Osteopathic Manipulative Medicine, New York Institute of Technology College of Osteopathic Medicine, Old Westbury, NY, USA
| | - Sheldon C Yao
- Department of Osteopathic Manipulative Medicine, New York Institute of Technology College of Osteopathic Medicine, Old Westbury, NY, USA
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Montori M, Baroni GS, Santori P, Di Giampaolo C, Ponziani F, Abenavoli L, Scarpellini E. Liver Damage and COVID-19: At Least a “Two-Hit” Story in Systematic Review. Curr Issues Mol Biol 2023; 45:3035-3047. [PMID: 37185723 PMCID: PMC10136465 DOI: 10.3390/cimb45040199] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2023] [Revised: 03/29/2023] [Accepted: 03/30/2023] [Indexed: 04/07/2023] Open
Abstract
COVID-19 pandemic waves have hit on our lives with pulmonary and, also, gastrointestinal symptoms. The latter also includes acute liver damage linked to direct SARS-CoV-2 action and/or drug-induced (DILI) in the frame of pre-existing chronic liver disease. We aimed to review literature data regarding liver damage during COVID-19. We conducted a systematic search on the main medical databases for original articles, reviews, meta-analyses, randomized clinical trials and case series using the following keywords and acronyms and their associations: liver disease, COVID-19, acute liver damage, drug-induced liver injury, antivirals. Acute liver damage due to SARS-CoV-2 infection is common among COVID-19 patients and is generally self-limiting. However, chronic hepatic diseases, such as metabolic-associated fatty liver disease (MAFLD), are associated with a less favorable prognosis, especially when alkaline phosphatases show a significant rise. Pathophysiology of COVID-19 liver damage is multifaceted and helps understand differences in liver derangement among patients. Thus, early recognition, monitoring and treatment of liver damage are crucial in these patients. In the frame of a not-ending pandemic sustained by SARS-CoV-2, it is crucial to recognize acute hepatic decompensation due to the virus and/or drugs used for COVID-19 treatment.
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Affiliation(s)
- Michele Montori
- Transplant and Hepatic Damage Unit, Polytechincs University of Marche, 60121 Ancona, Italy
| | | | - Pierangelo Santori
- Hepatology and Internal Medicine Unit, Madonna del Soccorso General Hospital, 00168 San Benedetto del Tronto, Italy
| | - Catia Di Giampaolo
- Hepatology and Internal Medicine Unit, Madonna del Soccorso General Hospital, 00168 San Benedetto del Tronto, Italy
| | - Francesca Ponziani
- Digestive Disease Center (C.E.M.A.D.), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Translational Medicine and Surgery Department, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Ludovico Abenavoli
- Department of Health Sciences, University Magna Græcia, 88100 Catanzaro, Italy
| | - Emidio Scarpellini
- Hepatology and Internal Medicine Unit, Madonna del Soccorso General Hospital, 00168 San Benedetto del Tronto, Italy
- Translational Research Center for Gastrointestinal Disorders, Gasthuisberg University Hospital, KULeuven, 3000 Lueven, Belgium
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Askari H, Rabiei F, Lohrasbi F, Ghadir S, Ghasemi-Kasman M. The Latest Cellular and Molecular Mechanisms of COVID-19 on Non-Lung Organs. Brain Sci 2023; 13:brainsci13030415. [PMID: 36979225 PMCID: PMC10046222 DOI: 10.3390/brainsci13030415] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2023] [Revised: 02/24/2023] [Accepted: 02/25/2023] [Indexed: 03/06/2023] Open
Abstract
Understanding the transmission pathways of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) will aid in developing effective therapies directed at the virus’s life cycle or its side effects. While severe respiratory distress is the most common symptom of a coronavirus 2019 (COVID-19) infection, the virus is also known to cause damage to almost every major organ and system in the body. However, it is not obvious whether pathological changes in extra-respiratory organs are caused by direct infection, indirect, or combination of these effects. In this narrative review, we first elaborate on the characteristics of SARS-CoV-2, followed by the mechanisms of this virus on various organs such as brain, eye, and olfactory nerve and different systems such as the endocrine and gastrointestinal systems.
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Affiliation(s)
- Hamid Askari
- Student Research Committee, Babol University of Medical Sciences, Babol 47176-47745, Iran
| | - Fatemeh Rabiei
- Student Research Committee, Babol University of Medical Sciences, Babol 47176-47745, Iran
| | - Fatemeh Lohrasbi
- Student Research Committee, Babol University of Medical Sciences, Babol 47176-47745, Iran
| | - Sara Ghadir
- Student Research Committee, Babol University of Medical Sciences, Babol 47176-47745, Iran
| | - Maryam Ghasemi-Kasman
- Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol 47176-47745, Iran
- Department of Physiology, School of Medicine, Babol University of Medical Sciences, Babol 47176-47745, Iran
- Correspondence: ; Tel./Fax: +98-11-32190557
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Effectiveness and Safety of Lianhua Qingwen Capsules for COVID-19: A Propensity-Score Matched Cohort Study. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2023; 2023:6028554. [PMID: 36846053 PMCID: PMC9957644 DOI: 10.1155/2023/6028554] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Accepted: 09/05/2022] [Indexed: 02/19/2023]
Abstract
As a traditional Chinese medicine, Lianhua Qingwen capsules have been widely used to treat Coronavirus Disease 2019 (COVID-19). This study was aimed to demonstrate the association between treatment with Lianhua Qingwen capsules and the clinical outcomes of hospitalized patients with COVID-19. This retrospective study was conducted at four hospitals in Central China. Data of hospitalized COVID-19 patients were collected between December 19, 2019 and April 26, 2020. Based on whether Lianhua Qingwen capsules were used, patients were classified into Lianhua Qingwen and non-Lianhua Qingwen (control) groups. To control for confounding factors, we used conditional logistic regression in a propensity-score matched (PSM) cohort (1 : 1 balanced), as well as logistic regression without matching as sensitivity analysis. A total of 4918 patients were included, 2760 of whom received Lianhua Qingwen capsules and 2158 of whom did not. In the PSM model, after adjusting for confounders, the in-hospital mortality was similar between the Lianhua Qingwen group and the control group (6.8% vs. 3.3%, adjusted OR, 0.66 [95% CI, 0.38-1.15], p = 0.138). The negative conversion rate of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection was higher in the Lianhua Qingwen group (88.3% vs. 96.1%, adjusted OR, 4.02 [95% CI, 2.58-6.25], p < 0.001). The incidence of acute liver injury was comparable between the two groups (14.0% vs. 11.5%, adjusted OR: 0.85 [95% CI, 0.71-1.02], p = 0.083), and the incidence of acute kidney injury was lower in the Lianhua Qingwen group (5.3% vs. 3.0%, adjusted OR: 0.71 [95% CI, 0.50-1.00], p = 0.048). Treatment with Lianhua Qingwen capsules was not significantly associated with in-hospital mortality in COVID-19 patients. In the Lianhua Qingwen group, the negative conversion rate of SARS-CoV-2 infection was higher and the incidence of acute kidney injury was lower than in the control group.
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McQuaid C, Solorzano A, Dickerson I, Deane R. Uptake of severe acute respiratory syndrome coronavirus 2 spike protein mediated by angiotensin converting enzyme 2 and ganglioside in human cerebrovascular cells. Front Neurosci 2023; 17:1117845. [PMID: 36875642 PMCID: PMC9980911 DOI: 10.3389/fnins.2023.1117845] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2022] [Accepted: 01/30/2023] [Indexed: 02/18/2023] Open
Abstract
Introduction There is clinical evidence of neurological manifestations in coronavirus disease-19 (COVID-19). However, it is unclear whether differences in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)/spike protein (SP) uptake by cells of the cerebrovasculature contribute to significant viral uptake to cause these symptoms. Methods Since the initial step in viral invasion is binding/uptake, we used fluorescently labeled wild type and mutant SARS-CoV-2/SP to study this process. Three cerebrovascular cell types were used (endothelial cells, pericytes, and vascular smooth muscle cells), in vitro. Results There was differential SARS-CoV-2/SP uptake by these cell types. Endothelial cells had the least uptake, which may limit SARS-CoV-2 uptake into brain from blood. Uptake was time and concentration dependent, and mediated by angiotensin converting enzyme 2 receptor (ACE2), and ganglioside (mono-sialotetrahexasylganglioside, GM1) that is predominantly expressed in the central nervous system and the cerebrovasculature. SARS-CoV-2/SPs with mutation sites, N501Y, E484K, and D614G, as seen in variants of interest, were also differentially taken up by these cell types. There was greater uptake compared to that of the wild type SARS-CoV-2/SP, but neutralization with anti-ACE2 or anti-GM1 antibodies was less effective. Conclusion The data suggested that in addition to ACE2, gangliosides are also an important entry point of SARS-CoV-2/SP into these cells. Since SARS-CoV-2/SP binding/uptake is the initial step in the viral penetration into cells, a longer exposure and higher titer are required for significant uptake into the normal brain. Gangliosides, including GM1, could be an additional potential SARS-CoV-2 and therapeutic target at the cerebrovasculature.
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Affiliation(s)
| | | | | | - Rashid Deane
- Department of Neuroscience, Del Monte Institute Neuroscience, University of Rochester, University of Rochester Medical Center (URMC), Rochester, NY, United States
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Li X, Yin W, Li A, Li D, Gao X, Wang R, Cui B, Qiu S, Li R, Jia L, Zuo C, Zhang L, Li M. ACE2 PET to reveal the dynamic patterns of ACE2 recovery in an infection model with pseudocorona virus. J Med Virol 2023; 95:e28470. [PMID: 36606602 DOI: 10.1002/jmv.28470] [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: 10/13/2022] [Revised: 11/27/2022] [Accepted: 12/25/2022] [Indexed: 01/07/2023]
Abstract
Due to the COVID-19 pandemic, a series of sequelae, such as fatigue, tachypnea, and ageusia, appeared in long COVID patients, but the pathological basis was still uncertain. The targeted radiopharmaceuticals were of potential to systemically and dynamically trace the pathological changes. For the key ACE2 protein in the virus-host interaction, 68 Ga-cyc-DX600 was developed on the basis of DX600 as a PET tracer of ACE2 fluctuation and maintained the ability in differentiating ACE and ACE2. In the temporary infection model inhaled with the radio-traceable pseudovirus in the upper respiratory tract of male humanized ACE2 (hACE2) mice, organ-specific ACE2 dysfunction in acute period and the following ACE2 recovery in a relatively long period was visualized and quantified by ACE2 PET, revealing a complex pattern of virus concentration-dependent degree and time period-dependent tendency of ACE2 recovery, mainly a sudden decrease of apparent ACE2 in the heart, liver, kidneys, lungs, and so on, but the liver was of a quick functional compensation on ACE2 expression after a temporary decrease. ACE2 expression of most organs has recovered to a normal level at 15 days post inhalation, with brain and genitals still of a decreased SUVACE2 ; meanwhile, kidneys were of an increased SUVACE2 . These findings on ACE2 PET were further verified by western blot. When compared with high-resolution computed tomography on structural changes and FDG PET on glycometabolism, ACE2 PET was superior in an earlier diagnostic window during infection and more comprehensive understanding of functional dysfunction post-infection. In the respective ACE2 PET/CT and ACE2 PET/MR scans of a volunteer, the repeatability of SUVACE2 and the ACE2 specificity were further confirmed. In conclusion, 68 Ga-cyc-DX600 was developed as an ACE2-specific tracer, and the corresponding ACE2 PET revealed the dynamic patterns of functional ACE2 recovery and provided a reference and approach to explore the ACE2-related pathological basis of sequelae in long COVID.
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Affiliation(s)
- Xiao Li
- Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, China.,University of Chinese Academy of Sciences, Beijing, China.,Department of Nuclear Medicine, Shanghai Changhai Hospital, Shanghai, China
| | - Wei Yin
- Department of Radiology, Shanghai Changhai Hospital, Shanghai, China
| | - Ao Li
- Department of Nuclear Medicine, Shanghai Changhai Hospital, Shanghai, China
| | - Danni Li
- Department of Nuclear Medicine, Shanghai Changhai Hospital, Shanghai, China
| | - Xiaolong Gao
- Department of Radiology, Luodian Hospital, Baoshan District, Shanghai, China
| | - Ruizhi Wang
- Department of Radiology, Huadong Hospital, Fudan University, Shanghai, China
| | - Bin Cui
- Department of Nuclear Medicine, Shanghai Changhai Hospital, Shanghai, China
| | - Shuang Qiu
- Department of Nuclear Medicine, Shanghai Changhai Hospital, Shanghai, China
| | - Rou Li
- Department of Nuclear Medicine, Shanghai Changhai Hospital, Shanghai, China
| | - Lina Jia
- Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, China
| | - Changjing Zuo
- Department of Nuclear Medicine, Shanghai Changhai Hospital, Shanghai, China
| | - Lan Zhang
- Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, China
| | - Ming Li
- Department of Radiology, Huadong Hospital, Fudan University, Shanghai, China
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Sadretdinova LD, Gantseva KK, Galina II, Tyurin AV. The duration of gastrointestinal symptom persistence at various periods of coronavirus infection. ALMANAC OF CLINICAL MEDICINE 2023; 50:392-399. [DOI: 10.18786/2072-0505-2022-50-025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
Aim: To analyze prevalence and type of symptomatic gastrointestinal involvement during symptomatic COVID-19 (up to 412 weeks after the disease) and post-COVID-19 syndrome (more than 12 weeks from the disease onset).
Materials and methods: We retrospectively analyzed the data from 785 in-patients with the diagnosis of COVID-19, who were treated in the infectious disease hospital from May to December 2020. At the first phase of the study we analyzed how frequently they were referred for out-patient care by a gastroenterology specialist after they were discharged from the hospital (all 785 patient medical files). At the 2nd study phase we performed phone calls to 247 patients, that were discharged from the infectious disease hospital, during which a specially designed questionnaire was filled with items on their comorbidities, general and specific complaints, as well as the standardized Gastrointestinal Symptom Rating Scale (GSRS).
Results: Within 2 years after their discharge from the infectious disease hospital, 88 patients asked for specialized gastroenterological care on an out-patient basis. The most common diagnoses were pancreatic diseases (33%), gastric disorders (31%), intestinal disorders (25%), liver and biliary disorders (11%). At referral, the most common complaints were dyspeptic: nausea, bitter taste in the mouth, heartburn, bloating (25%), abdominal pains of various location (17%) and stool abnormalities, such as diarrhea and constipation (11%).
Among patients who participated in the phone survey (N = 247), symptomatic COVID-19 was observed in 90 (11.46%) cases, with predominant complaints being loss of taste, loss of smell, and fever. Post-COVID-19 syndrome was identified in 157 (20%) cases, with their main complaints being weakness, shortness of breath and joint pain. Stool abnormalities and abdominal pain occurred during symptomatic COVID-19 and in the post-COVID-19 period with the same frequency (9% and 10%, respectively). According to the GSRS results, the post-COVID-19 dyspeptic syndrome was characterized by prevailing complaints of heartburn (24%), upper abdominal pain and discomfort (20%), and bloating (15%).
Conclusion: In the patients with a history of COVID-19, along with respiratory syndromes, gastrointestinal symptoms are seen, with their types being variable at various period of the coronavirus infection. In the early COVID-19, these are stool abnormalities and abdominal pain, and during the post-COVID-19 syndrome, nausea, bitter taste in the mouth, heartburn and bloating are more common.
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Zheng L, Zhang L, Zheng Y, An J, Wen G, Jin H, Tuo B. Digestive system infection by SARS‑CoV‑2: Entry mechanism, clinical symptoms and expression of major receptors (Review). Int J Mol Med 2023; 51:19. [PMID: 36660939 PMCID: PMC9911086 DOI: 10.3892/ijmm.2023.5222] [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: 11/01/2022] [Accepted: 01/05/2022] [Indexed: 01/21/2023] Open
Abstract
Besides causing severe acute respiratory syndrome (SARS), SARS‑coronavirus 2 (SARS‑CoV‑2) also harms the digestive system. Given the appearance of numerous cases of SARS‑CoV‑2, it has been demonstrated that SARS‑CoV‑2 is able to harm target organs such as the gastrointestinal tract, liver and pancreas, and either worsen the condition of patients with basic digestive illnesses or make their prognosis poor. According to several previously published studies, angiotensin‑converting enzyme II (ACE2) and transmembrane serine protease II (TMPRSS2) are expressed either singly or in combination in the digestive system and in other regions of the human body. In order to change the viral conformation, create a fusion hole and release viral RNA into the host cell for replication and transcription, SARS‑CoV‑2 is capable of binding to these two proteins through the spike protein on its surface. As a result, the body experiences an immune reaction and an inflammatory reaction, which may lead to nausea, diarrhea, abdominal pain and even gastrointestinal bleeding, elevated levels of liver enzymes, acute liver injury, pancreatitis and other serious lesions. In order to provide possible strategies for the clinical diagnosis and treatment of digestive system diseases during the COVID‑19 pandemic, the molecular structure of SARS‑CoV‑2 and the mechanism via which SARS‑CoV‑2 enters the human body through ACE2 and TMPRSS2 were discussed in the present review, and the clinical manifestations of SARS‑CoV‑2 infection in the digestive system were also summarized. Finally, the expression characteristics of ACE2 and TMPRSS2 in the main target organs of the digestive system were described.
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Affiliation(s)
- Liming Zheng
- Department of Gastroenterology, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563003, P.R. China
| | - Li Zhang
- Department of Gastroenterology, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563003, P.R. China
| | - Yi Zheng
- Department of Gastroenterology, The Fifth People's Hospital of Zunyi, Zunyi, Guizhou 563000, P.R. China
| | - Jiaxing An
- Department of Gastroenterology, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563003, P.R. China
| | - Guorong Wen
- Department of Gastroenterology, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563003, P.R. China
| | - Hai Jin
- Department of Gastroenterology, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563003, P.R. China
| | - Biguang Tuo
- Department of Gastroenterology, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563003, P.R. China,Correspondence to: Dr Biguang Tuo, Department of Gastroenterology, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan, Zunyi, Guizhou 563003, P.R. China, E-mail:
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COVID-19-associated monocytic encephalitis (CAME): histological and proteomic evidence from autopsy. Signal Transduct Target Ther 2023; 8:24. [PMID: 36609561 PMCID: PMC9816522 DOI: 10.1038/s41392-022-01291-6] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2022] [Revised: 12/07/2022] [Accepted: 12/13/2022] [Indexed: 01/09/2023] Open
Abstract
Severe neurological symptoms are associated with Coronavirus disease 2019 (COVID-19). However, the morphologic features, pathological nature and their potential mechanisms in patient brains have not been revealed despite evidence of neurotropic infection. In this study, neuropathological damages and infiltrating inflammatory cells were quantitatively evaluated by immunohistochemical staining, ultrastructural examination under electron microscopy, and an image threshold method, in postmortem brains from nine critically ill COVID-19 patients and nine age-matched cadavers of healthy individuals. Differentially expressed proteins were identified by quantitative proteomic assays. Histopathological findings included neurophagocytosis, microglia nodules, satellite phenomena, extensive edema, focal hemorrhage, and infarction, as well as infiltrating mononuclear cells. Immunostaining of COVID-19 brains revealed extensive activation of both microglia and astrocytes, severe damage of the blood-brain barrier (BBB) and various degrees of perivascular infiltration by predominantly CD14+/CD16+/CD141+/CCR7+/CD11c+ monocytes and occasionally CD4+/CD8+ T lymphocytes. Quantitative proteomic assays combined with bioinformatics analysis identified upregulated proteins predominantly involved in immune responses, autophagy and cellular metabolism in COVID-19 patient brains compared with control brains. Proteins involved in brain development, neuroprotection, and extracellular matrix proteins of the basement membrane were downregulated, potentially caused by the activation of transforming growth factor β receptor and vascular endothelial growth factor signaling pathways. Thus, our results define histopathological and molecular profiles of COVID-19-associated monocytic encephalitis (CAME) and suggest potential therapeutic targets.
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Naeem M, Bano N, Manzoor S, Ahmad A, Munawar N, Razak SIA, Lee TY, Devaraj S, Hazafa A. Pathogenetic Mechanisms of Liver-Associated Injuries, Management, and Current Challenges in COVID-19 Patients. Biomolecules 2023; 13:99. [PMID: 36671484 PMCID: PMC9855873 DOI: 10.3390/biom13010099] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2022] [Revised: 11/28/2022] [Accepted: 12/10/2022] [Indexed: 01/06/2023] Open
Abstract
The global outbreak of COVID-19 possesses serious challenges and adverse impacts for patients with progression of chronic liver disease and has become a major threat to public health. COVID-19 patients have a high risk of lung injury and multiorgan dysfunction that remains a major challenge to hepatology. COVID-19 patients and those with liver injury exhibit clinical manifestations, including elevation in ALT, AST, GGT, bilirubin, TNF-α, and IL-6 and reduction in the levels of CD4 and CD8. Liver injury in COVID-19 patients is induced through multiple factors, including a direct attack of SARS-CoV-2 on liver hepatocytes, hypoxia reperfusion dysfunction, cytokine release syndrome, drug-induced hepatotoxicity caused by lopinavir and ritonavir, immune-mediated inflammation, renin-angiotensin system, and coagulopathy. Cellular and molecular mechanisms underlying liver dysfunction are not fully understood in severe COVID-19 attacks. High mortality and the development of chronic liver diseases such as cirrhosis, alcoholic liver disease, autoimmune hepatitis, nonalcoholic fatty liver disease, and hepatocellular carcinoma are also associated with patients with liver damage. COVID-19 patients with preexisting or developing liver disease should be managed. They often need hospitalization and medication, especially in conjunction with liver transplants. In the present review, we highlight the attack of SARS-CoV-2 on liver hepatocytes by exploring the cellular and molecular events underlying the pathophysiological mechanisms in COVID-19 patients with liver injury. We also discuss the development of chronic liver diseases during the progression of SARS-CoV-2 replication. Lastly, we explore management principles in COVID-19 patients with liver injury and liver transplantation.
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Affiliation(s)
- Muhammad Naeem
- College of Life Science, Hebei Normal University, Shijiazhuang 050024, China
| | - Naheed Bano
- Department of Fisheries and Aquaculture, Muhammad Nawaz Sharif University of Agriculture, Multan 60000, Pakistan
| | - Saba Manzoor
- Department of Zoology, University of Sialkot, Sialkot 51310, Pakistan
| | - Aftab Ahmad
- Biochemistry/Center for Advanced Studies in Agriculture and Food Security (CAS-AFS), University of Agriculture, Faisalabad 38040, Pakistan
| | - Nayla Munawar
- Department of Chemistry, College of Science, United Arab Emirates University, Al-Ain 15551, United Arab Emirates
| | - Saiful Izwan Abd Razak
- BioInspired Device and Tissue Engineering Research Group (BioInspira), Department of Biomedical Engineering and Health Sciences, Faculty of Electrical Engineering, Universiti Teknologi Malaysia, Johor Bahru 81310, Malaysia
- Sports Innovation & Technology Centre, Institute of Human Centred Engineering, Universiti Teknologi Malaysia, Johor Bahru 81310, Malaysia
| | - Tze Yan Lee
- School of Liberal Arts, Science and Technology (PUScLST) Perdana University, Suite 9.2, 9th Floor, Wisma Chase Perdana, Changkat Semantan Damansara Heights, Kuala Lumpur 50490, Malaysia
| | - Sutha Devaraj
- Faculty of Medicine, AIMST University, Bedong 08100, Malaysia
| | - Abu Hazafa
- Department of Medicine, Surgery and Dentistry, “Scuola Medica Salernitana”, University of Salerno, 84081 Baronissi, Italy
- Department of Biochemistry, University of Agriculture Faisalabad, Faisalabad 38040, Pakistan
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Armas F, Chandra F, Lee WL, Gu X, Chen H, Xiao A, Leifels M, Wuertz S, Alm EJ, Thompson J. Contextualizing Wastewater-Based surveillance in the COVID-19 vaccination era. ENVIRONMENT INTERNATIONAL 2023; 171:107718. [PMID: 36584425 PMCID: PMC9783150 DOI: 10.1016/j.envint.2022.107718] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Revised: 12/16/2022] [Accepted: 12/22/2022] [Indexed: 06/17/2023]
Abstract
SARS-CoV-2 wastewater-based surveillance (WBS) offers a tool for cost-effective oversight of a population's infections. In the past two years, WBS has proven to be crucial for managing the pandemic across different geographical regions. However, the changing context of the pandemic due to high levels of COVID-19 vaccination warrants a closer examination of its implication towards SARS-CoV-2 WBS. Two main questions were raised: 1) Does vaccination cause shedding of viral signatures without infection? 2) Does vaccination affect the relationship between wastewater and clinical data? To answer, we review historical reports of shedding from viral vaccines in use prior to the COVID-19 pandemic including for polio, rotavirus, influenza and measles infection and provide a perspective on the implications of different COVID-19 vaccination strategies with regard to the potential shedding of viral signatures into the sewershed. Additionally, we reviewed studies that looked into the relationship between wastewater and clinical data and how vaccination campaigns could have affected the relationship. Finally, analyzing wastewater and clinical data from the Netherlands, we observed changes in the relationship concomitant with increasing vaccination coverage and switches in dominant variants of concern. First, that no vaccine-derived shedding is expected from the current commercial pipeline of COVID-19 vaccines that may confound interpretation of WBS data. Secondly, that breakthrough infections from vaccinated individuals contribute significantly to wastewater signals and must be interpreted in light of the changing dynamics of shedding from new variants of concern.
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Affiliation(s)
- Federica Armas
- Antimicrobial Resistance Interdisciplinary Research Group, Singapore-MIT Alliance for Research and Technology, Singapore; Campus for Research Excellence and Technological Enterprise (CREATE), Singapore
| | - Franciscus Chandra
- Antimicrobial Resistance Interdisciplinary Research Group, Singapore-MIT Alliance for Research and Technology, Singapore; Campus for Research Excellence and Technological Enterprise (CREATE), Singapore
| | - Wei Lin Lee
- Antimicrobial Resistance Interdisciplinary Research Group, Singapore-MIT Alliance for Research and Technology, Singapore; Campus for Research Excellence and Technological Enterprise (CREATE), Singapore
| | - Xiaoqiong Gu
- Antimicrobial Resistance Interdisciplinary Research Group, Singapore-MIT Alliance for Research and Technology, Singapore; Campus for Research Excellence and Technological Enterprise (CREATE), Singapore
| | - Hongjie Chen
- Antimicrobial Resistance Interdisciplinary Research Group, Singapore-MIT Alliance for Research and Technology, Singapore; Campus for Research Excellence and Technological Enterprise (CREATE), Singapore
| | - Amy Xiao
- Department of Biological Engineering, Massachusetts Institute of Technology, USA; Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology
| | - Mats Leifels
- Singapore Centre for Environmental Life Sciences Engineering, Nanyang Technological University, Singapore
| | - Stefan Wuertz
- Singapore Centre for Environmental Life Sciences Engineering, Nanyang Technological University, Singapore; School of Civil and Environmental Engineering, Nanyang Technological University, Singapore
| | - Eric J Alm
- Antimicrobial Resistance Interdisciplinary Research Group, Singapore-MIT Alliance for Research and Technology, Singapore; Campus for Research Excellence and Technological Enterprise (CREATE), Singapore; Department of Biological Engineering, Massachusetts Institute of Technology, USA; Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
| | - Janelle Thompson
- Campus for Research Excellence and Technological Enterprise (CREATE), Singapore; Singapore Centre for Environmental Life Sciences Engineering, Nanyang Technological University, Singapore; Asian School of the Environment, Nanyang Technological University, Singapore.
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40
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Ozaka S, Kobayashi T, Mizukami K, Murakami K. COVID-19 vaccination and liver disease. World J Gastroenterol 2022; 28:6791-6810. [PMID: 36632314 PMCID: PMC9827578 DOI: 10.3748/wjg.v28.i48.6791] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2022] [Revised: 11/07/2022] [Accepted: 12/06/2022] [Indexed: 12/26/2022] Open
Abstract
Various vaccines against severe acute respiratory syndrome coronavirus 2 have been developed in response to the coronavirus disease 2019 (COVID-19) global pandemic, several of which are highly effective in preventing COVID-19 in the general population. Patients with chronic liver diseases (CLDs), particularly those with liver cirrhosis, are considered to be at a high risk for severe COVID-19 and death. Given the increased rates of disease severity and mortality in patients with liver disease, there is an urgent need to understand the efficacy of vaccination in this population. However, the data regarding efficacy and safety of COVID-19 vaccination in patients with CLDs is limited. Indeed, several organ-specific or systemic immune-mediated side effects following COVID-19 vaccination, including liver injury similar to autoimmune hepatitis, have been recently reported. Although the number of cases of vaccine-related liver injury is increasing, its frequency, clinical course, and mechanism remain unclear. Here, we review the current findings on COVID-19 vaccination and liver disease, focusing on: (1) The impact of COVID-19 in patients with CLD; (2) The efficacy, safety, and risk-benefit profiles of COVID-19 vaccines in patients with CLD; and (3) Liver injury following COVID-19 vaccination.
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Affiliation(s)
- Sotaro Ozaka
- Department of Gastroenterology, Faculty of Medicine, Oita University, Yufu 879-5593, Oita, Japan
- Department of Infectious Disease Control, Faculty of Medicine, Oita University, Yufu 879-5593, Oita, Japan
| | - Takashi Kobayashi
- Department of Infectious Disease Control, Faculty of Medicine, Oita University, Yufu 879-5593, Oita, Japan
| | - Kazuhiro Mizukami
- Department of Gastroenterology, Faculty of Medicine, Oita University, Yufu 879-5593, Oita, Japan
| | - Kazunari Murakami
- Department of Gastroenterology, Faculty of Medicine, Oita University, Yufu 879-5593, Oita, Japan
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Quarleri J, Delpino MV. Molecular mechanisms implicated in SARS-CoV-2 liver tropism. World J Gastroenterol 2022; 28:6875-6887. [PMID: 36632318 PMCID: PMC9827585 DOI: 10.3748/wjg.v28.i48.6875] [Citation(s) in RCA: 3] [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: 09/05/2022] [Revised: 11/07/2022] [Accepted: 11/27/2022] [Indexed: 12/26/2022] Open
Abstract
The coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Hepatic involvement is common in SARS-CoV-2-infected individuals. It is currently accepted that the direct and indirect hepatic effects of SARS-CoV-2 infection play a significant role in COVID-19. In individuals with pre-existing infectious and non-infectious liver disease, who are at a remarkably higher risk of developing severe COVID-19 and death, this pathology is most medically relevant. This review emphasizes the current pathways regarded as contributing to the gastrointestinal and hepatic ailments linked to COVID-19-infected patients due to an imbalanced interaction among the liver, systemic inflammation, disrupted coagulation, and the lung.
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Affiliation(s)
- Jorge Quarleri
- Institute for Biomedical Research on Retroviruses and AIDS, Faculty of Medical Sciences, National Scientific and Technical Research Council-University of Buenos Aires, Buenos Aires 1121, Argentina
| | - M. Victoria Delpino
- Institute for Biomedical Research on Retroviruses and AIDS, Faculty of Medical Sciences, National Scientific and Technical Research Council-University of Buenos Aires, Buenos Aires 1121, Argentina
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Steiner J, Kaufmann-Bühler AK, Fuchsjäger M, Schemmer P, Talakić E. Secondary sclerosing cholangitis in a young COVID-19 patient resulting in death: A case report. World J Gastrointest Surg 2022; 14:1411-1417. [PMID: 36632122 PMCID: PMC9827572 DOI: 10.4240/wjgs.v14.i12.1411] [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: 06/13/2022] [Revised: 07/28/2022] [Accepted: 10/05/2022] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND With the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in late 2019 in Wuhan, China, liver injury in patients with coronavirus disease 2019 (COVID-19) due to SARS-CoV-2 infection has been regularly reported in the literature. There are a growing number of publications describing the occurrence of secondary sclerosing cholangitis (SSC) after SARS-CoV-2 infection in various cases. We present a case of sudden onset SSC in a critically ill patient (SSC-CIP) following COVID-19 infection who was previously healthy.
CASE SUMMARY A 33-year old female patient was admitted to our University Hospital due to increasing shortness of breath. A prior rapid antigen test showed a positive result for SARS-CoV-2. The patient had no known preexisting conditions. With rapidly increasing severe hypoxemia she required endotracheal intubation and developed the need for veno-venous extracorporeal membrane oxygenation in a setting of acute respiratory distress syndrome. During the patient´s 154-d stay in the intensive care unit and other hospital wards she underwent hemodialysis and extended polypharmaceutical treatment. With increasing liver enzymes and the development of signs of cholangiopathy on magnetic resonance cholangiopancreatography (MRCP) as well as endoscopic retrograde cholangiopancreatography (ERCP), the clinical setting was suggestive of SSC. At an interdisciplinary meeting, the possibility of orthotopic liver transplantation and additional kidney transplantation was discussed due to the constant need for hemodialysis. Following a deterioration in her general health and impaired respiratory function with a reduced chance of successful surgery and rehabilitation, the plan for transplantation was discarded. The patient passed away due to multiorgan failure.
CONCLUSION SSC-CIP seems to be a rare but serious complication in patients with SARS-CoV-2 infection, of which treating physicians should be aware. Imaging with MRCP and/or ERCP seems to be indicated and a valid method for early diagnosis. Further studies on the effects of early and late SSC in (post-) COVID-19 patients needs to be performed.
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Affiliation(s)
- Jakob Steiner
- Department of General Radiology, Medical University of Graz, Graz 8036, Austria
| | | | - Michael Fuchsjäger
- Department of General Radiology, Medical University of Graz, Graz 8036, Austria
| | - Peter Schemmer
- Department of General Visceral and Transplant Surgery, Medical University of Graz, Graz 8036, Austria
| | - Emina Talakić
- Department of General Radiology, Medical University of Graz, Graz 8036, Austria
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Hu WS, Jiang FY, Shu W, Zhao R, Cao JM, Wang DP. Liver injury in COVID-19: A minireview. World J Gastroenterol 2022; 28:6716-6731. [PMID: 36620342 PMCID: PMC9813934 DOI: 10.3748/wjg.v28.i47.6716] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Revised: 11/02/2022] [Accepted: 11/23/2022] [Indexed: 12/19/2022] Open
Abstract
Coronavirus disease 2019 (COVID-19), caused by infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has escalated into a global tragedy afflicting human health, life, and social governance. Through the increasing depth of research and a better understanding of this disease, it has been ascertained that, in addition to the lungs, SARS-CoV-2 can also induce injuries to other organs including the liver. Liver injury is a common clinical manifestation of COVID-19, particularly in severe cases, and is often associated with a poorer prognosis and higher severity of COVID-19. This review focuses on the general existing information on liver injury caused by COVID-19, including risk factors and subpopulations of liver injury in COVID-19, the association between preexisting liver diseases and the severity of COVID-19, and the potential mechanisms by which SARS-CoV-2 affects the liver. This review may provide some useful information for the development of therapeutic and preventive strategies for COVID-19-associated liver injury.
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Affiliation(s)
- Wen-Shu Hu
- Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
- Department of Physiology, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
| | - Fang-Ying Jiang
- Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
- Department of Physiology, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
| | - Wen Shu
- Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
- Department of Physiology, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
| | - Rong Zhao
- Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
- Department of Physiology, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
| | - Ji-Min Cao
- Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
- Department of Physiology, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
| | - De-Ping Wang
- Department of Physiology, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
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Grando M, Balbi M, Zeppieri M. COVID-19-induced liver injury in adult patients: A brief overview. World J Virol 2022; 11:443-452. [PMID: 36483102 PMCID: PMC9724208 DOI: 10.5501/wjv.v11.i6.443] [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: 08/17/2022] [Revised: 09/07/2022] [Accepted: 10/12/2022] [Indexed: 11/23/2022] Open
Abstract
Coronavirus disease has spread worldwide since 2019, causing important pandemic issues and various social health problems to date. Little is known about the origin of this virus and the effects it has on extra-pulmonary organs. The different mechanisms of the virus and the influence it has on humans are still being studied, with hopes of finding a cure for the disease and the pathologies associated with the infection. Liver damage caused by coronavirus disease 2019 (COVID-19) is sometimes underestimated and has been of important clinical interest in the past few years. Hepatic dysfunctions can manifest in different forms which can sometimes be mild and without specific signs and symptoms or be severe with important clinical implications. There are several studies that have tried to explain the mechanism of entry (hepatotropism) of the virus into hepatocytes and the effects the virus has on this important organ. What clearly emerges from the current literature is that hepatic injury represents an important clinical aspect in the management of patients infected with COVID-19, especially in frail patients and those with comorbidities. The aim of our brief overview is to summarize the current literature regarding the forms of hepatic damage, complications, mechanisms of pathology, clinical features of liver injury, influence of comorbidities and clinical management in patients with COVID-19 infection.
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Affiliation(s)
- Martina Grando
- Department of Internal Medicine, Azienda Sanitaria Friuli Occidentale, San Vito al Tagliamento 33078, Italy
| | - Massimiliano Balbi
- Department of Internal Medicine, Azienda Sanitaria Friuli Occidentale, San Vito al Tagliamento 33078, Italy
| | - Marco Zeppieri
- Department of Ophthalmology, University Hospital of Udine, Udine 33100, Italy
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LncRNA SNHG7 Knockdown Aggravates Hepatic Ischemia–Reperfusion Injury and Promotes Apoptosis in Hemorrhagic Shock Pregnant Rats by Modulating miR-34a-5p/YWHAG Axis. Mol Biotechnol 2022; 65:983-996. [DOI: 10.1007/s12033-022-00613-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2022] [Accepted: 11/14/2022] [Indexed: 11/26/2022]
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Iheanacho CO, Enechukwu OH. COVID-19-associated liver injury, role of drug therapy and management: a review. EGYPTIAN LIVER JOURNAL 2022; 12:66. [PMID: 36466933 DOI: 10.1186/s43066-022-00230-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Accepted: 11/15/2022] [Indexed: 11/27/2022] Open
Abstract
AbstractThe ongoing COVID-19 pandemic is known to affect several body organs, including the liver. This results from several factors such as direct effect of SARS-CoV-2 on the liver, side effects of drug therapy and pre-existing liver diseases. Drug-induced liver injury can result from a range of drugs used in the treatment of COVID-19 such as antiviral drugs, anti-inflammatory drugs, antibiotics, herbal medications and vaccines. Metabolism of most drugs occurs in the liver, and this leaves the liver at risk of medication-induced liver damage. Being among pathologies from the disease, COVID-19 liver injury presents with abnormally high liver-related enzymes, such as aspartate aminotransferase, alanine aminotransferase, alkaline phosphate (ALP), and gamma-glutamyl transferase. It is reversible, generally not severe and occurs more mildly in children. However, COVID-19-associated liver injury is worsened by chronic liver diseases and vice versa. There is a high risk of abnormal ALT and AST, in-hospital liver injury and prolonged SARS-CoV-2 shedding in COVID-19 patients with previously existing metabolic-associated fatty liver disease. COVID-19-associated liver injury also appears to be severe and significantly associated with life-threatening COVID-19 and mortality in persons with a history of liver transplant. Where necessary, only supportive management is usually indicated. This paper evaluates the aetiology, clinical and laboratory features, occurrence and management of COVID-19-associated liver injury. It also elaborated on the role of drug therapy in the development of COVID-19 liver injury.
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Prevalence of COVID-19 in Children with Gastrointestinal Manifestations: A Cross-Sectional Study of 184 Cases in 2020 - 2021. ARCHIVES OF PEDIATRIC INFECTIOUS DISEASES 2022. [DOI: 10.5812/pedinfect-121640] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Background: The coronavirus disease 2019 (COVID-19) pandemic has affected human life for more than a year. Coronavirus disease 2019 is well known for its respiratory manifestations; however, other important symptoms help with its diagnosis. Although clinical presentations in adults have been understood, clinical data in pediatric COVID-19 cases are still lacking. Objectives: We investigated gastrointestinal (GI) manifestations of COVID-19 in pediatric cases. Methods: This study included 184 cases with GI manifestations referred to the pediatric emergency department of Namazi hospital from 20 March to 20 November 2020. Their clinical and laboratory data were extracted and analyzed with SPSS22. Results: Of 184 patients, 51 had positive SARS-CoV-2 PCR results. The most common symptom in SARS-CoV-2-positive patients was vomiting in 22 (43%) patients, followed by watery diarrhea in 12 (23.5%) and dysentery in 11 (21%). Significantly elevated CRP (P value = 0.002), ESR (P value < 0.001), and lymphocyte count (P value = 0.037) were found in PCR-positive patients. Conclusions: Our result demonstrates that COVID-19 could present with different GI symptoms. Also, the symptoms and lab data could help clinicians diagnose COVID-19, besides other differential diagnoses in pediatric patients with GI symptoms.
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Liakina V, Stundiene I, Milaknyte G, Bytautiene R, Reivytyte R, Puronaite R, Urbanoviciute G, Kazenaite E. Effects of COVID-19 on the liver: The experience of a single center. World J Gastroenterol 2022; 28:5735-5749. [PMID: 36338891 PMCID: PMC9627423 DOI: 10.3748/wjg.v28.i39.5735] [Citation(s) in RCA: 3] [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: 06/22/2022] [Revised: 08/12/2022] [Accepted: 09/21/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The coronavirus disease 2019 (COVID-19) was perhaps the most severe global health crisis in living memory. Alongside respiratory symptoms, elevated liver enzymes, abnormal liver function, and even acute liver failure were reported in patients suffering from severe acute respiratory disease coronavirus 2 pneumonia. However, the precise triggers of these forms of liver damage and how they affect the course and outcomes of COVID-19 itself remain unclear.
AIM To analyze the impact of liver enzyme abnormalities on the severity and outcomes of COVID-19 in hospitalized patients.
METHODS In this study, 684 depersonalized medical records from patients hospitalized with COVID-19 during the 2020-2021 period were analyzed. COVID-19 was diagnosed according to the guidelines of the National Institutes of Health (2021). Patients were assigned to two groups: those with elevated liver enzymes (Group 1: 603 patients), where at least one out of four liver enzymes were elevated (following the norm of hospital laboratory tests: alanine aminotransferase (ALT) ≥ 40, aspartate aminotransferase (AST) ≥ 40, gamma-glutamyl transferase ≥ 36, or alkaline phosphatase ≥ 150) at any point of hospitalization, from admission to discharge; and the control group (Group 2: 81 patients), with normal liver enzymes during hospitalization. COVID-19 severity was assessed according to the interim World Health Organization guidance (2022). Data on viral pneumonia complications, laboratory tests, and underlying diseases were also collected and analyzed.
RESULTS In total, 603 (88.2%) patients produced abnormal liver test results. ALT and AST levels were elevated by a factor of less than 3 in 54.9% and 74.8% of cases with increased enzyme levels, respectively. Patients in Group 1 had almost double the chance of bacterial viral pneumonia complications [odds ratio (OR) = 1.73, P = 0.0217], required oxygen supply more often, and displayed higher biochemical inflammation indices than those in Group 2. No differences in other COVID-19 complications or underlying diseases were observed between groups. Preexisting hepatitis of a different etiology was rarely documented (in only 3.5% of patients), and had no impact on the severity of COVID-19. Only 5 (0.73%) patients experienced acute liver failure, 4 of whom died. Overall, the majority of the deceased patients (17 out of 20) had elevated liver enzymes, and most were male. All deceased patients had at least one underlying disease or combination thereof, and the deceased suffered significantly more often from heart diseases, hypertension, and urinary tract infections than those who made recoveries. Alongside male gender (OR = 1.72, P = 0.0161) and older age (OR = 1.02, P = 0.0234), diabetes (OR = 3.22, P = 0.0016) and hyperlipidemia (OR = 2.67, P = 0.0238), but not obesity, were confirmed as independent factors associated with more a severe COVID-19 infection in our cohort.
CONCLUSION In our study, the presence of liver impairment allows us to predict a more severe inflammation with a higher risk of bacterial complication and worse outcomes of COVID-19. Therefore, patients with severe disease forms should have their liver tests monitored regularly and their results should be considered when selecting treatment to avoid further liver damage or even insufficiency.
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Affiliation(s)
- Valentina Liakina
- Centre of Hepatology, Gastroenterology and Dietetics, Clinic of Gastroenterology, Nephrourology and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius 01513, Lithuania
- Department of Chemistry and Bioengineering, Faculty of Fundamental Sciences, VILNIUS TECH, Vilnius 10223, Lithuania
| | - Ieva Stundiene
- Centre of Hepatology, Gastroenterology and Dietetics, Clinic of Gastroenterology, Nephrourology and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius 01513, Lithuania
| | - Gabriele Milaknyte
- Centre of Hepatology, Gastroenterology and Dietetics, Clinic of Gastroenterology, Nephrourology and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius 01513, Lithuania
| | - Ramune Bytautiene
- Centre of Hepatology, Gastroenterology and Dietetics, Clinic of Gastroenterology, Nephrourology and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius 01513, Lithuania
| | - Rosita Reivytyte
- Faculty of Medicine, Vilnius University, Vilnius 01513, Lithuania
| | - Roma Puronaite
- Clinic of Cardiac and Vascular Diseases, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius 01513, Lithuania
- Institute of Data Science and Digital Technologies, Faculty of Mathematics and Informatics, Vilnius University, Vilnius 01513, Lithuania
| | | | - Edita Kazenaite
- Centre of Hepatology, Gastroenterology and Dietetics, Clinic of Gastroenterology, Nephrourology and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius 01513, Lithuania
- Department of Pathology, Forensic Medicine and Pharmacology, Institute of Biomedical Sciences, Faculty of Medicine, Vilnius University, Vilnius 01513, Lithuania
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Chen D, Ning M, Feng Y, Liu J. The early stage of COVID-19 pandemic: Gastrointestinal manifestations and liver injury in COVID-19 patients in Wuhan, China. Front Med (Lausanne) 2022; 9:997000. [PMID: 36341271 PMCID: PMC9630730 DOI: 10.3389/fmed.2022.997000] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Accepted: 09/27/2022] [Indexed: 12/15/2022] Open
Abstract
There are few and inconsistent data focusing on gastrointestinal (GI) manifestations and liver injury in China's early stage of COVID-19 pandemic. In this study, we research the prevalence and role of GI symptoms and liver injury in COVID-19 patients in Wuhan during the disease's first outbreak. We conducted a cross-sectional observational study in a non-ICU unit in Wuhan, China. COVID-19 patients were consecutively admitted from 23 February 2020 to 5 April 2020. Demographic and clinical data were retrieved and analyzed throughout the disease course. A total of 93 patients were enrolled, including 45.2% moderate, 54.8% severe, and 2.2% critical type patients. 69.9% of patients had at least one GI symptom; if excluding hyporexia/anorexia, 49.5% of patients showed at least one GI symptom. The incidence rate of hyporexia/anorexia, diarrhea, nausea/vomiting, abdominal discomfort/pain, and elevated liver enzymes were 67.7, 29.0, 28.0, 21.5, and 23.7%, respectively. Patients with GI symptoms or elevated liver enzymes have a higher risk of severe type disease than patients without GI symptoms or elevated liver enzymes (67.7 vs. 25.0%, p < 0.001; 77.3 vs. 47.9%, p = 0.016, respectively), and experienced longer disease duration. In multivariate analysis, hyporexia/anorexia was confirmed as an independent predictive factor of severe type disease (odds ratio: 5.912; 95% confidence interval: 2.247–15.559; p < 0.001). In conclusion, in the early stage of the COVID-19 pandemic, GI symptoms and elevated liver enzymes are common throughout the disease course, and associated with severer disease and longer disease duration.
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Affiliation(s)
- Dafan Chen
- Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Digestive Endoscopic Center, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- *Correspondence: Dafan Chen
| | - Min Ning
- Digestive Endoscopic Center, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yun Feng
- Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jun Liu
- Department of Nephrology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Jun Liu
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50
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Shen S, Gong M, Wang G, Dua K, Xu J, Xu X, Liu G. COVID-19 and Gut Injury. Nutrients 2022; 14:nu14204409. [PMID: 36297092 PMCID: PMC9608818 DOI: 10.3390/nu14204409] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Revised: 10/11/2022] [Accepted: 10/18/2022] [Indexed: 01/28/2023] Open
Abstract
COVID-19 induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently a pandemic and it has led to more than 620 million patients with 6.56 million deaths globally. Males are more susceptible to COVID-19 infection and associated with a higher chance to develop severe COVID-19 than females. Aged people are at a high risk of COVID-19 infection, while young children have also increased cases. COVID-19 patients typically develop respiratory system pathologies, however symptoms in the gastrointestinal (GI) tract are also very common. Inflammatory cell recruitments and their secreted cytokines are found in the GI tract in COVID-19 patients. Microbiota changes are the key feature in COVID-19 patients with gut injury. Here, we review all current known mechanisms of COVID-19-induced gut injury, and the most acceptable one is that SARS-CoV-2 binds to angiotensin-converting enzyme 2 (ACE2) receptor on host cells in the GI tract. Interestingly, inflammatory bowel disease (IBD) is an inflammatory disorder, but the patients with IBD do not have the increased risk to develop COVID-19. There is currently no cure for COVID-19, but anti-viruses and monoclonal antibodies reduce viral load and shorten the recovery time of the disease. We summarize current therapeutics that target symptoms in the GI tract, including probiotics, ACE2 inhibitors and nutrients. These are promising therapeutic options for COVID-19-induced gut injury.
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Affiliation(s)
- Sj Shen
- UNSW Microbiome Research Centre, St George and Sutherland Clinical Campus, University of New South Wales, Sydney, NSW 2217, Australia
| | - Muxue Gong
- School of Clinical Medicine, Bengbu Medicine College, Bengbu 233030, China
| | - Gang Wang
- Department of Respiratory and Critical Care Medicine, Clinical Research Center for Respiratory Disease, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Kamal Dua
- Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Ultimo, NSW 2007, Australia
- Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, NSW 2007, Australia
| | - Jincheng Xu
- Stomatology Department, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China
- School of Dental Medicine, Bengbu Medical College, Bengbu 233030, China
| | - Xiaoyue Xu
- School of Population Health, University of New South Wales, Sydney, NSW 2052, Australia
| | - Gang Liu
- School of Life Sciences, Faculty of Science, University of Technology Sydney, Ultimo, NSW 2007, Australia
- Centre for Inflammation, Centenary Institute, Camperdown, NSW 2050, Australia
- Correspondence:
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