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Bishir M, Vigorito M, Chan MH, Khan MAS, Chang SL. Alcohol Consumption Modulates the Development of Chronic Pain in COVID-19 Patients: A Network Meta-Analysis. ACS Pharmacol Transl Sci 2025; 8:409-422. [PMID: 39974632 PMCID: PMC11833718 DOI: 10.1021/acsptsci.4c00479] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2024] [Revised: 12/09/2024] [Accepted: 12/23/2024] [Indexed: 02/21/2025]
Abstract
The mechanisms underlying the onset and progression of chronic pain in COVID-19 patients have been understudied. Using network meta-analysis, we previously demonstrated that alcohol augments COVID-19 symptoms and pathologies possibly by inducing a severe cytokine storm. We and others have also reported that acute alcohol consumption produces analgesic effects, while chronic alcohol consumption results in hyperalgesia and chronic pain. This study aimed to identify the influence of alcohol consumption and COVID-19 on pain. Using publicly available curated gene expression data sets of differentially expressed genes (DEGs) in the prefrontal cortex (PFC) and amygdala of COVID-19 patients, we employed a bioinformatics application, QIAGEN ingenuity pathway analysis (IPA), to identify the key signaling pathways, upstream regulators, and biological functions in these brain areas known to play a role in pain. Canonical pathway analysis revealed activation of the neuropathic pain pathway and signaling pathways involving the cytokine storm, S100 family, IL-6, and neuroinflammation. IPA's network builder was employed to construct a network map of shared molecules between alcohol and pain-related constructs (discomfort, neuropathic pain, and inflammatory pain). The simulation of alcohol consumption inhibited pain in this network map. To study the influence of COVID-19, we overlaid the DEGs from the PFC and amygdala onto these networks, mimicking alcohol consumption during SARS-CoV-2 infection. Upregulation of molecules in the amygdala and PFC predicted an increase in neuropathic pain, as well as an increase in inflammatory pain in the PFC. Our results suggest that while alcohol consumption directly inhibits pain, the presence of COVID-19 exaggerates impaired cytokine signaling, neuroinflammation, and neuropathic pain signaling in the CNS providing novel insights into the signaling pathways associated with chronic pain of the COVID-19 patients.
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Affiliation(s)
- Muhammed Bishir
- Institute
of NeuroImmune Pharmacology, Seton Hall
University, South
Orange, New Jersey 07079, United States
- Department
of Biological Science, Seton Hall University, South Orange, New Jersey 07079, United States
| | - Michael Vigorito
- Institute
of NeuroImmune Pharmacology, Seton Hall
University, South
Orange, New Jersey 07079, United States
| | - Ming-Huan Chan
- Institute
of Neuroscience, National Chengchi University, Taipei 116,Taiwan
- Department
of Medical Research, China Medical University
Hospital, Taichung 40447, Taiwan
| | - Mohammed A S Khan
- Institute
of NeuroImmune Pharmacology, Seton Hall
University, South
Orange, New Jersey 07079, United States
- Department
of Neurosurgery, Brigham & Women’s
Hospital, Boston, Massachusetts 02115, United States
| | - Sulie L. Chang
- Institute
of NeuroImmune Pharmacology, Seton Hall
University, South
Orange, New Jersey 07079, United States
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Rengifo T, Bishir M, Huang W, Snyder M, Chang SL. Network meta-analysis of the molecular mechanisms and signaling pathways underlying alcohol-induced thymic atrophy. ALCOHOL, CLINICAL & EXPERIMENTAL RESEARCH 2024; 48:795-809. [PMID: 38553251 PMCID: PMC11161038 DOI: 10.1111/acer.15292] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/28/2023] [Revised: 01/28/2024] [Accepted: 02/22/2024] [Indexed: 05/02/2024]
Abstract
BACKGROUND Thymic atrophy is characterized by loss of thymocytes, destruction of thymic architecture, and a subsequent decrease in naïve T cells with compromised immunity. Thymic atrophy occurs during aging. Environmental factors including alcohol misuse also induce thymic atrophy. Despite the link between alcohol misuse and thymic atrophy, the underlying mechanism is understudied. We aimed to identify molecules and signaling pathways that underly alcohol-induced thymic atrophy during aging. METHODS F344 rats were given 3-day binge-ethanol (4.8 g/kg/day; 52% w/v; i.g.) and the thymus was collected and weighed. Molecular mechanisms underlying ethanol-induced thymic atrophy were investigated by network meta-analysis using the QIAGEN Ingenuity Pathway Analysis (IPA). The molecules associated with ethanol were identified from the QIAGEN Knowledge Base (QKB) and those associated with thymic atrophy were identified from QKB and Mouse Genome Informatics (MGI). Aging-mediated Differential Expression Genes (DEGs) from mouse thymocytes were obtained from the Gene Expression Omnibus (GEO) database (GSE132136). The relationship between the molecules and associated signaling pathways were studied using IPA. RESULTS Binge-ethanol decreased thymic weight in F344 rats. Our meta-analysis using IPA identified molecules commonly shared by ethanol and thymic atrophy through which simulation with ethanol increased thymic atrophy. We then obtained aging-mediated DEGs from the atrophied thymocytes. We found that ethanol contributed to thymic atrophy through modulation of the aging-mediated DEGs. Our network meta-analysis suggests that ethanol may augment thymic atrophy through increased expression of cytokines (e.g., IL-6, IL-17A and IL-33) along with their regulators (e.g., STAT1 and STAT3). CONCLUSIONS Exposure to alcohol may augment thymic atrophy by altering the activity of key inflammatory mediators, such as STAT family members and inflammatory cytokines. These findings provide insights into the signaling pathways and upstream regulators that underly alcohol-induced thymic atrophy during aging, suggesting that alcohol consumption could prepone thymic atrophy.
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Affiliation(s)
- Tatiana Rengifo
- Institute of NeuroImmune Pharmacology, Seton Hall University
- Department of Biological Sciences, Seton Hall University
| | - Muhammed Bishir
- Institute of NeuroImmune Pharmacology, Seton Hall University
- Department of Biological Sciences, Seton Hall University
| | - Wenfei Huang
- Institute of NeuroImmune Pharmacology, Seton Hall University
- Department of Biological Sciences, Seton Hall University
| | | | - Sulie L. Chang
- Institute of NeuroImmune Pharmacology, Seton Hall University
- Department of Biological Sciences, Seton Hall University
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Michalak A, Lach T, Szczygieł K, Cichoż-Lach H. COVID-19, Possible Hepatic Pathways and Alcohol Abuse-What Do We Know up to 2023? Int J Mol Sci 2024; 25:2212. [PMID: 38396888 PMCID: PMC10888568 DOI: 10.3390/ijms25042212] [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: 01/01/2024] [Revised: 01/23/2024] [Accepted: 01/26/2024] [Indexed: 02/25/2024] Open
Abstract
The pandemic period due to coronavirus disease 2019 (COVID-19) revolutionized all possible areas of global health. Significant consequences were also related to diverse extrapulmonary manifestations of this pathology. The liver was found to be a relatively common organ, beyond the respiratory tract, affected by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Multiple studies revealed the essential role of chronic liver disease (CLD) in the general outcome of coronavirus infection. Present concerns in this field are related to the direct hepatic consequences caused by COVID-19 and pre-existing liver disorders as risk factors for the severe course of the infection. Which mechanism has a key role in this phenomenon-previously existing hepatic disorder or acute liver failure due to SARS-CoV-2-is still not fully clarified. Alcoholic liver disease (ALD) constitutes another not fully elucidated context of coronavirus infection. Should the toxic effects of ethanol or already developed liver cirrhosis and its consequences be perceived as a causative or triggering factor of hepatic impairment in COVID-19 patients? In the face of these discrepancies, we decided to summarize the role of the liver in the whole picture of coronavirus infection, paying special attention to ALD and focusing on the pathological pathways related to COVID-19, ethanol toxicity and liver cirrhosis.
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Affiliation(s)
- Agata Michalak
- Department of Gastroenterology with Endoscopy Unit, Medical University of Lublin, Jaczewskiego 8, 20-954 Lublin, Poland;
| | - Tomasz Lach
- Department of Orthopedics and Traumatology, Medical University of Lublin, Jaczewskiego 8, 20-954 Lublin, Poland;
| | - Karolina Szczygieł
- Clinical Dietetics Unit, Department of Bioanalytics, Medical University of Lublin, Chodźki 7, 20-093 Lublin, Poland;
| | - Halina Cichoż-Lach
- Department of Gastroenterology with Endoscopy Unit, Medical University of Lublin, Jaczewskiego 8, 20-954 Lublin, Poland;
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Lawler T, Warren Andersen S, Trentham-Dietz A, Sethi AK, Tevaarwerk AJ, Malecki KMC, Litzelman K, Pophali PA, Gangnon RE, Hampton JM, Kwekkeboom K, LoConte NK. Change in alcohol consumption during the Covid-19 pandemic and associations with mental health and financial hardship: results from a survey of Wisconsin patients with cancer. J Cancer Surviv 2023:10.1007/s11764-023-01502-1. [PMID: 38017319 PMCID: PMC11130075 DOI: 10.1007/s11764-023-01502-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Accepted: 11/15/2023] [Indexed: 11/30/2023]
Abstract
PURPOSE Alcohol consumption increases health risks for patients with cancer. The Covid-19 pandemic may have affected drinking habits for these individuals. We surveyed patients with cancer to examine whether changes in drinking habits were related to mental health or financial effects of the pandemic. METHODS From October 2020 to April 2021, adult patients (age 18-80 years at diagnosis) treated for cancer in southcentral Wisconsin were invited to complete a survey. Age-adjusted percentages for history of anxiety or depression, emotional distress, and financial impacts of Covid-19 overall and by change in alcohol consumption (non-drinker, stable, decreased, or increased) were obtained via logistic regression. RESULTS In total, 1,875 patients were included in the analysis (median age 64, range 19-87 years), including 9% who increased and 23% who decreased drinking. Compared to stable drinkers (32% of sample), a higher proportion of participants who increased drinking alcohol also reported anxiety or depression (45% vs. 26%), moderate to severe emotional distress (61% vs. 37%) and viewing Covid-19 as a threat to their community (67% vs. 55%). Decreased (vs. stable) drinking was associated with higher prevalence of depression or anxiety diagnosis, emotional distress, and negative financial impacts of the pandemic. Compared to non-drinkers (36% of sample), participants who increased drinking were more likely to report emotional distress (61% vs. 48%). CONCLUSIONS Patients with cancer from Wisconsin who changed their alcohol consumption during the Covid-19 pandemic were more likely to report poor mental health including anxiety, depression, and emotional distress than persons whose alcohol consumption was stable. IMPLICATIONS FOR CANCER SURVIVORS Clinicians working with cancer survivors should be aware of the link between poor mental health and increased alcohol consumption and be prepared to offer guidance or referrals to counseling, as needed.
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Affiliation(s)
- Thomas Lawler
- School of Medicine and Public Health, University of Wisconsin Carbone Cancer Center, Madison, WI, USA.
| | - Shaneda Warren Andersen
- School of Medicine and Public Health, University of Wisconsin Carbone Cancer Center, Madison, WI, USA
- Department of Population Health Sciences, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA
| | - Amy Trentham-Dietz
- School of Medicine and Public Health, University of Wisconsin Carbone Cancer Center, Madison, WI, USA
- Department of Population Health Sciences, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA
| | - Ajay K Sethi
- Department of Population Health Sciences, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA
| | | | - Kristen M C Malecki
- Department of Population Health Sciences, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA
- Division of Environmental and Occupational Health Sciences, School of Public Health, University of Illinois Chicago, Chicago, IL, USA
| | - Kristin Litzelman
- School of Medicine and Public Health, University of Wisconsin Carbone Cancer Center, Madison, WI, USA
- School of Human Ecology, University of Wisconsin-Madison, Madison, WI, USA
| | - Priyanka A Pophali
- Division of Hematology, Medical Oncology and Palliative Care, University of Wisconsin Carbone Cancer Center, Madison, WI, USA
| | - Ronald E Gangnon
- School of Medicine and Public Health, University of Wisconsin Carbone Cancer Center, Madison, WI, USA
- Department of Population Health Sciences, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA
- Department of Biostatistics and Medical Informatics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA
| | - John M Hampton
- School of Medicine and Public Health, University of Wisconsin Carbone Cancer Center, Madison, WI, USA
| | - Kristine Kwekkeboom
- School of Medicine and Public Health, University of Wisconsin Carbone Cancer Center, Madison, WI, USA
- School of Nursing, University of Wisconsin-Madison, Madison, WI, USA
| | - Noelle K LoConte
- School of Medicine and Public Health, University of Wisconsin Carbone Cancer Center, Madison, WI, USA
- Department of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA
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Bramness JG, Pandey S, Moe JS, Toft H, Lien L, Walby FA, Myhre MØ, Bolstad I. Levels of IL-6 are Associated with Lifetime Attempted Suicide in Alcohol Use Disorder Patients. Neuropsychiatr Dis Treat 2023; 19:2141-2148. [PMID: 37849526 PMCID: PMC10578180 DOI: 10.2147/ndt.s413101] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2023] [Accepted: 09/06/2023] [Indexed: 10/19/2023] Open
Abstract
Background Patients with alcohol use disorder (AUD) have an increased risk of suicide. Neuroimmunological measures, such as cytokines, are shown to deviate in people with attempted suicide. Few studies have investigated this among AUD patients. Patients and Methods One-hundred and fourteen patients undergoing residential treatment for AUD were interviewed on lifetime suicide attempts (SA) along with several other background variables and clinical characteristics. Serum blood samples were drawn for analysis of cytokines. Results Thirty-one patients (27%) reported at least one SA. These patients had more symptoms of current affective disorders and more severe dependence. In bivariate analysis only IL-6 and IL-10 appeared to be associated with lifetime SA but without reaching statistical significance. In multivariate linear regression, adjusting for sex, nicotine use, somatic illness, and the use of anti-inflammatory drugs, IL-6 was associated to SA (p = 0.033). Conclusion The cytokine IL-6 has repeatedly been found to be associated with suicidality. The present study concurs with this role of IL-6 in a naturalistic observational study of AUD patients.
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Affiliation(s)
- Jørgen G Bramness
- Norwegian National Advisory Unit on Concurrent Substance Abuse and Mental Health Disorders, Innlandet Hospital Trust, Brumunddal, Norway
- Norwegian Institute of Public Health, Department of Alcohol, Tobacco and Drugs, Oslo, Norway
- Institute of Clinical Medicine, UiT – The Arctic University of Norway, Tromsø, Norway
| | - Susmita Pandey
- Norwegian National Advisory Unit on Concurrent Substance Abuse and Mental Health Disorders, Innlandet Hospital Trust, Brumunddal, Norway
| | - Jenny Skumsnes Moe
- Norwegian National Advisory Unit on Concurrent Substance Abuse and Mental Health Disorders, Innlandet Hospital Trust, Brumunddal, Norway
- Institute of Clinical Medicine, UiT – The Arctic University of Norway, Tromsø, Norway
| | - Helge Toft
- Faculty of Social and Health Sciences, Inland Norway University of Applied Sciences, Elverum, Norway
| | - Lars Lien
- Norwegian National Advisory Unit on Concurrent Substance Abuse and Mental Health Disorders, Innlandet Hospital Trust, Brumunddal, Norway
- Faculty of Social and Health Sciences, Inland Norway University of Applied Sciences, Elverum, Norway
| | - Fredrik A Walby
- National Centre for Suicide Research and Prevention, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Martin Øverlien Myhre
- National Centre for Suicide Research and Prevention, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Ingeborg Bolstad
- Norwegian National Advisory Unit on Concurrent Substance Abuse and Mental Health Disorders, Innlandet Hospital Trust, Brumunddal, Norway
- Faculty of Social and Health Sciences, Inland Norway University of Applied Sciences, Elverum, Norway
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Antwi I, Watkins D, Pedawi A, Ghrayeb A, Van de Vuurst C, Cory TJ. Substances of abuse and their effect on SAR-CoV-2 pathogenesis. NEUROIMMUNE PHARMACOLOGY AND THERAPEUTICS 2023; 2:301-316. [PMID: 38013836 PMCID: PMC10474379 DOI: 10.1515/nipt-2023-0004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/17/2023] [Accepted: 07/19/2023] [Indexed: 11/29/2023]
Abstract
Following the emergence of SARS-CoV-2, various reports suggest that there has been a significant increase in substance abuse due to social distancing and related issues. Several reports have suggested the impact of chronic substance use on individuals' physiological and psychological health. Therefore, there is a need to know the impact of SARS-CoV-2 on persons with substance use disorders. Individuals with substance use disorders are the most vulnerable groups and are at a high risk of SARS-CoV-2 infection due to their already existing health issues associated with substance use. This review discusses some of the molecular and systemic/organic effects chronic substance use such as alcohol, nicotine, marijuana (cannabis), opioids, methamphetamine, and cocaine have on SARS-CoV-2 infectivity and its potential cause for worsened disease outcomes in persons with substance use disorder. This will provide healthcare providers, public health policies, and researchers with the needed knowledge to address some of the many challenges faced during the Covid-19 pandemic to facilitate treatment strategies for persons with substance use disorders.
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Affiliation(s)
- Ivy Antwi
- Department of Clinical Pharmacy, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN, USA
| | - Destiny Watkins
- Department of Clinical Pharmacy, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN, USA
| | - Alahn Pedawi
- Department of Clinical Pharmacy, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN, USA
| | - Atheel Ghrayeb
- Department of Clinical Pharmacy, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN, USA
| | - Christine Van de Vuurst
- Department of Clinical Pharmacy, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN, USA
| | - Theodore J. Cory
- Department of Clinical Pharmacy, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN, USA
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7
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Testino G, Pellicano R. COVID-19 and alcohol consumption: recommendations in the Omicron era. Minerva Gastroenterol (Torino) 2023; 69:423-432. [PMID: 35511656 DOI: 10.23736/s2724-5985.22.03194-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
In the early stages of the pandemic, the first reports began that alcohol consumption could increase the risk of becoming infected and worsening the prognosis disease. This is for two reasons: behavioral and socio-economic factors that characterize a part of this population can be the cause of viral spread and a direct or indirect negative action of ethanol on the immune system. The data used for the preparation of these recommendations are based on a detailed analysis of the scientific literature published before March 31, 2022 (Web of Science, Scopus, Google Scholar). Furthermore, in the process of developing this work, we consulted the guidelines/position papers of the Italian Society on Alcohol and of the World Health Organization. It has been confirmed that AC is in COVID-19 era a risky behavior and that AUD and substance use disorder (SUD) patients are certainly at greater risk of contracting infection and also of having a worse course. In light of what has been said, some recommendations can be made: correctly inform the general population that AC negatively interacts with COVID-19 infection; reducing the COVID-19 risk by advocating healthy lifestyle habits (smoke, diet, physical exercise, etc.) and preferential policies in population with comorbidities; implement actions that reduce the average consumption of alcohol by avoiding hazardous/harmful consumption. Abstention is better; identify alcohol consumption through a more in-depth alcohol history, using the AUDIT; AUDs patients are frail patients deserving a complete vaccination course; suggest a period of alcoholic abstention of at least thirty days before vaccination to be maintained for the following fifteen days; promoting health education campaigns for young people in order to promote vaccination culture and correct lifestyles.
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Affiliation(s)
- Gianni Testino
- Unit of Addiction and Hepatology/Alcohological Regional Centre, ASL3 c/o San Martino Polyclinic Hospital, Genoa, Italy -
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Chang SL, Zhang J. Commentary on "Repeated ethanol exposure and withdrawal alters angiotensin-converting enzyme 2 expression in discrete brain regions: Implications for SARS-CoV-2 neuroinvasion". ALCOHOL, CLINICAL & EXPERIMENTAL RESEARCH 2023; 47:1447-1452. [PMID: 37526581 DOI: 10.1111/acer.15122] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Revised: 05/11/2023] [Accepted: 05/22/2023] [Indexed: 08/02/2023]
Affiliation(s)
- Sulie L Chang
- Institute of NeuroImmune Pharmacology, Seton Hall University, New Jersey, South Orange, USA
- Department of Biological Sciences, Seton Hall University, South Orange, New Jersey, USA
| | - Jonathan Zhang
- Institute of NeuroImmune Pharmacology, Seton Hall University, New Jersey, South Orange, USA
- Department of Biological Sciences, Seton Hall University, South Orange, New Jersey, USA
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Luu B, Wijesinghe S, Kassem T, Lien J, Luu D, Wijesinghe R, Luu L, Kayingo G. Drugs in primary care that may alter COVID-19 risk and severity. JAAPA 2023; 36:28-33. [PMID: 37097779 DOI: 10.1097/01.jaa.0000918768.11544.e5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/26/2023]
Abstract
ABSTRACT This article describes drugs used in primary care that could alter patients' risk for and severity of COVID-19. The risks and benefits of each drug class were differentiated according to the strength of evidence from 58 selected randomized controlled trials, systematic reviews, and meta-analyses. Most of the studies reported on drugs affecting the renin-angiotensin-aldosterone system. Other classes included opioids, acid suppressants, nonsteroidal anti-inflammatory drugs, corticosteroids, vitamins, biguanides, and statins. Current evidence has not fully differentiated drugs that may increase risk versus benefits in COVID-19 infection. Further studies are needed in this area.
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Affiliation(s)
- Brent Luu
- Brent Luu is an associate clinical professor at the University of California Davis's Betty Irene Moore School of Nursing in Sacramento, Calif. Sampath Wijesinghe is a clinical assistant professor in the PA program at Stanford (Calif.) University. Tarek Kassem is an assistant professor at California Northstate University in Elk Grove, Calif. Justin Lien is a student at Western University's College of Osteopathic Medicine in Pomona, Calif. Darrick Luu is a student at California Northstate University College of Health Science in Rancho Cordova, Calif. Rynee Wijesinghe is a student at California State University in Fresno, Calif. Leianna Luu is a student at the University of California Riverside. Gerald Kayingo is assistant dean, executive director, and professor in the Physician Assistant Leadership and Learning Academy at the University of Maryland Baltimore. The authors have disclosed no potential conflicts of interest, financial or otherwise
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Hasankhani A, Bahrami A, Tavakoli-Far B, Iranshahi S, Ghaemi F, Akbarizadeh MR, Amin AH, Abedi Kiasari B, Mohammadzadeh Shabestari A. The role of peroxisome proliferator-activated receptors in the modulation of hyperinflammation induced by SARS-CoV-2 infection: A perspective for COVID-19 therapy. Front Immunol 2023; 14:1127358. [PMID: 36875108 PMCID: PMC9981974 DOI: 10.3389/fimmu.2023.1127358] [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: 12/19/2022] [Accepted: 02/08/2023] [Indexed: 02/19/2023] Open
Abstract
Coronavirus disease 2019 (COVID-19) is a severe respiratory disease caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that affects the lower and upper respiratory tract in humans. SARS-CoV-2 infection is associated with the induction of a cascade of uncontrolled inflammatory responses in the host, ultimately leading to hyperinflammation or cytokine storm. Indeed, cytokine storm is a hallmark of SARS-CoV-2 immunopathogenesis, directly related to the severity of the disease and mortality in COVID-19 patients. Considering the lack of any definitive treatment for COVID-19, targeting key inflammatory factors to regulate the inflammatory response in COVID-19 patients could be a fundamental step to developing effective therapeutic strategies against SARS-CoV-2 infection. Currently, in addition to well-defined metabolic actions, especially lipid metabolism and glucose utilization, there is growing evidence of a central role of the ligand-dependent nuclear receptors and peroxisome proliferator-activated receptors (PPARs) including PPARα, PPARβ/δ, and PPARγ in the control of inflammatory signals in various human inflammatory diseases. This makes them attractive targets for developing therapeutic approaches to control/suppress the hyperinflammatory response in patients with severe COVID-19. In this review, we (1) investigate the anti-inflammatory mechanisms mediated by PPARs and their ligands during SARS-CoV-2 infection, and (2) on the basis of the recent literature, highlight the importance of PPAR subtypes for the development of promising therapeutic approaches against the cytokine storm in severe COVID-19 patients.
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Affiliation(s)
- Aliakbar Hasankhani
- Department of Animal Science, College of Agriculture and Natural Resources, University of Tehran, Karaj, Iran
| | - Abolfazl Bahrami
- Department of Animal Science, College of Agriculture and Natural Resources, University of Tehran, Karaj, Iran
- Faculty of Agricultural Sciences and Engineering, University of Tehran, Karaj, Iran
| | - Bahareh Tavakoli-Far
- Dietary Supplements and Probiotic Research Center, Alborz University of Medical Sciences, Karaj, Iran
- Department of Physiology and Pharmacology, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran
| | - Setare Iranshahi
- School of Pharmacy, Shahid Beheshty University of Medical Sciences, Tehran, Iran
| | - Farnaz Ghaemi
- Department of Biochemistry, Faculty of Advanced Sciences and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Majid Reza Akbarizadeh
- Department of Pediatric, School of Medicine, Amir al momenin Hospital, Zabol University of Medical Sciences, Zabol, Iran
| | - Ali H. Amin
- Zoology Department, Faculty of Science, Mansoura University, Mansoura, Egypt
| | - Bahman Abedi Kiasari
- Virology Department, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran
| | - Alireza Mohammadzadeh Shabestari
- Department of Dental Surgery, Mashhad University of Medical Sciences, Mashhad, Iran
- Khorasan Covid-19 Scientific Committee, Mashhad, Iran
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Sui Y, Li S, Fu XQ, Zhao ZJ, Xing S. Bioinformatics analyses of combined databases identify shared differentially expressed genes in cancer and autoimmune disease. J Transl Med 2023; 21:109. [PMID: 36765396 PMCID: PMC9921081 DOI: 10.1186/s12967-023-03943-9] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2022] [Accepted: 01/30/2023] [Indexed: 02/12/2023] Open
Abstract
BACKGROUND Inadequate immunity caused by poor immune surveillance leads to tumorigenesis, while excessive immunity due to breakdown of immune tolerance causes autoimmune genesis. Although the function of immunity during the onset of these two processes appears to be distinct, the underlying mechanism is shared. To date, gene expression data for large bodies of clinical samples are available, but the resemblances of tumorigenesis and autoimmune genesis in terms of immune responses remains to be summed up. METHODS Considering the high disease prevalence, we chose invasive ductal carcinoma (IDC) and systemic lupus erythematosus (SLE) to study the potential commonalities of immune responses. We obtained gene expression data of IDC/SLE patients and normal controls from five IDC databases (GSE29044, GSE21422, GSE22840, GSE15852, and GSE9309) and five SLE databases (GSE154851, GSE99967, GSE61635, GSE50635, and GSE17755). We intended to identify genes differentially expressed in both IDC and SLE by using three bioinformatics tools including GEO2R, the limma R package, and Weighted Gene Co-expression Network Analysis (WGCNA) to perform function enrichment, protein-protein network, and signaling pathway analyses. RESULTS The mRNA levels of signal transducer and activator of transcription 1 (STAT1), 2'-5'-oligoadenylate synthetase 1 (OAS1), 2'-5'-oligoadenylate synthetase like (OASL), and PML nuclear body scaffold (PML) were found to be differentially expressed in both IDC and SLE by using three different bioinformatics tools of GEO2R, the limma R package and WGCNA. From the combined databases in this study, the mRNA levels of STAT1 and OAS1 were increased in IDC while reduced in SLE. And the mRNA levels of OASL and PML were elevated in both IDC and SLE. Based on Kyoto Encyclopedia of Genes and Genomes pathway analysis and QIAGEN Ingenuity Pathway Analysis, both IDC and SLE were correlated with the changes of multiple components involved in the Interferon (IFN)-Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway. CONCLUSION The expression levels of STAT1 and OAS1 manifest the opposite expression tendency across cancer and autoimmune disease. They are components in the IFN-JAK-STAT signaling pathway related to both tumorigenesis and autoimmune genesis. STAT1 and OAS1-associated IFN-JAK-STAT signaling could explain the commonalities during tumorigenesis and autoimmune genesis and render significant information for more precise treatment from the point of immune homeostasis.
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Affiliation(s)
- Yuan Sui
- grid.64924.3d0000 0004 1760 5735Edmond H. Fischer Signal Transduction Laboratory, School of Life Sciences, Jilin University, Changchun, 130012 China
| | - Shuping Li
- grid.266902.90000 0001 2179 3618Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104 USA
| | - Xue-Qi Fu
- grid.64924.3d0000 0004 1760 5735Edmond H. Fischer Signal Transduction Laboratory, School of Life Sciences, Jilin University, Changchun, 130012 China
| | - Zhizhuang Joe Zhao
- Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA.
| | - Shu Xing
- Edmond H. Fischer Signal Transduction Laboratory, School of Life Sciences, Jilin University, Changchun, 130012, China.
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12
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Nevola R, Criscuolo L, Beccia D, Delle Femine A, Ruocco R, Imbriani S, Alfano M, Villani A, Russo A, Perillo P, Marfella R, Adinolfi LE, Sasso FC, Marrone A, Rinaldi L. Impact of chronic liver disease on SARS-CoV-2 infection outcomes: Roles of stage, etiology and vaccination. World J Gastroenterol 2023; 29:800-814. [PMID: 36816617 PMCID: PMC9932424 DOI: 10.3748/wjg.v29.i5.800] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Revised: 12/12/2022] [Accepted: 01/18/2023] [Indexed: 02/06/2023] Open
Abstract
Since the first identification in December of 2019 and the fast spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, it has represented a dramatic global public health concern. Though affecting mainly the respiratory system, SARS-CoV-2 disease, defined as coronavirus disease 2019 (COVID-19), may have a systemic involvement leading to multiple organ dysfunction. Experimental evidence about the SARS-CoV-2 tropism for the liver and the increasing of hepatic cytolysis enzymes during infection support the presence of a pathophysiological relationship between liver and SARS-CoV-2. On the other side, patients with chronic liver disease have been demonstrated to have a poor prognosis with COVID-19. In particular, patients with liver cirrhosis appear extremely vulnerable to infection. Moreover, the etiology of liver disease and the vaccination status could affect the COVID-19 outcomes. This review analyzes the impact of the disease stage and the related causes on morbidity and mortality, clinical outcomes during SARS-CoV-2 infection, as well as the efficacy of vaccination in patients with chronic liver disease.
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Affiliation(s)
- Riccardo Nevola
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, Naples 80138, Italy
- Internal Medicine and Hepatology Unit, Ospedale Evangelico Betania, Naples 80147, Italy
| | - Livio Criscuolo
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, Naples 80138, Italy
| | - Domenico Beccia
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, Naples 80138, Italy
| | - Augusto Delle Femine
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, Naples 80138, Italy
| | - Rachele Ruocco
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, Naples 80138, Italy
| | - Simona Imbriani
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, Naples 80138, Italy
| | - Maria Alfano
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, Naples 80138, Italy
| | - Angela Villani
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, Naples 80138, Italy
| | - Antonio Russo
- Department of Mental Health and Public Medicine, University of Campania “Luigi Vanvitelli”, Naples 80138, Italy
| | - Pasquale Perillo
- Internal Medicine and Hepatology Unit, Ospedale Evangelico Betania, Naples 80147, Italy
| | - Raffaele Marfella
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, Naples 80138, Italy
| | - Luigi Elio Adinolfi
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, Naples 80138, Italy
| | - Ferdinando Carlo Sasso
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, Naples 80138, Italy
| | - Aldo Marrone
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, Naples 80138, Italy
| | - Luca Rinaldi
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, Naples 80138, Italy
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13
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Wei B, Liu Y, Li H, Peng Y, Luo Z. Impact of alcohol consumption on coronavirus disease 2019 severity: A systematic review and meta-analysis. J Med Virol 2023; 95:e28547. [PMID: 36734064 DOI: 10.1002/jmv.28547] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2022] [Revised: 01/18/2023] [Accepted: 01/30/2023] [Indexed: 02/04/2023]
Abstract
Fear and misinformation lead to widespread myths in the coronavirus disease 2019 (COVID-19) pandemic, such as "consuming high-strength alcohol kills the virus in the inhaled air." However, whether alcohol consumption can affect COVID-19 has not been clarified yet. This study aims to investigate the impact of alcohol consumption on COVID-19 severity. PubMed, Embase, Cochrane Library, Central, CINAHL, ClinicalTrials.gov, and WHO-International Clinical Trials Registry Platform were searched until November 25, 2022. Forty studies (1,697,683 COVID-19 individuals) were analyzed. Brown (patients numbers: 1317, risk ratios [RR] = 1.58, 95% [confidence interval] CI = 1.31 to 1.90, I2 = 0.0%, p < 0.001), American (patients numbers: 3721, RR = 1.51, 95% CI = 1.30 to 1.75, I2 = 0.0%, p < 0.001), and European (patients numbers: 261,437, RR = 2.04, 95% CI = 1.96 to 2.13, I2 = 0.0%, p < 0.001) drinkers were at high risk of severe COVID-19, intensive care unit (ICU) admission, and invasive mechanical ventilation (IMV), respectively. Consistently, individuals with a drinking history were at high risk of severe COVID-19 (patients numbers: 5399, RR = 1.23, 95% CI = 1.02 to 1.48, I2 = 38.4%, p = 0.03) and ICU admission (patients numbers: 6995, RR = 1.32, 95% CI = 1.08 to 1.60, I2 = 46.6%, p = 0.01). In addition, current drinkers had an increased risk of symptomatic COVID-19. However, excessive drinkers were at high risk of COVID-19 hospitalization. Alcohol consumption intensifies COVID-19 severity and deteriorates its clinical outcomes. Here, we strongly propose that people do not drink alcohol during the COVID-19 pandemic.
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Affiliation(s)
- Baozhu Wei
- Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China
- Institute of Myocardial Injury and Repair, Wuhan University, Wuhan, China
| | - Yang Liu
- Department of Endocrinology, China Resources and WISCO General Hospital, Wuhan, China
| | - Hang Li
- Department of Geratology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China
| | - Yuanyuan Peng
- Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China
| | - Zhi Luo
- Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China
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14
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Zsichla L, Müller V. Risk Factors of Severe COVID-19: A Review of Host, Viral and Environmental Factors. Viruses 2023; 15:175. [PMID: 36680215 PMCID: PMC9863423 DOI: 10.3390/v15010175] [Citation(s) in RCA: 41] [Impact Index Per Article: 20.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Revised: 01/04/2023] [Accepted: 01/04/2023] [Indexed: 01/11/2023] Open
Abstract
The clinical course and outcome of COVID-19 are highly variable, ranging from asymptomatic infections to severe disease and death. Understanding the risk factors of severe COVID-19 is relevant both in the clinical setting and at the epidemiological level. Here, we provide an overview of host, viral and environmental factors that have been shown or (in some cases) hypothesized to be associated with severe clinical outcomes. The factors considered in detail include the age and frailty, genetic polymorphisms, biological sex (and pregnancy), co- and superinfections, non-communicable comorbidities, immunological history, microbiota, and lifestyle of the patient; viral genetic variation and infecting dose; socioeconomic factors; and air pollution. For each category, we compile (sometimes conflicting) evidence for the association of the factor with COVID-19 outcomes (including the strength of the effect) and outline possible action mechanisms. We also discuss the complex interactions between the various risk factors.
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Affiliation(s)
- Levente Zsichla
- Institute of Biology, Eötvös Loránd University, 1117 Budapest, Hungary
- National Laboratory for Health Security, Eötvös Loránd University, 1117 Budapest, Hungary
| | - Viktor Müller
- Institute of Biology, Eötvös Loránd University, 1117 Budapest, Hungary
- National Laboratory for Health Security, Eötvös Loránd University, 1117 Budapest, Hungary
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15
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Das U, Gangisetty O, Chaudhary S, Tarale P, Rousseau B, Price J, Frazier I, Sarkar DK. Epigenetic insight into effects of prenatal alcohol exposure on stress axis development: Systematic review with meta-analytic approaches. ALCOHOL, CLINICAL & EXPERIMENTAL RESEARCH 2023; 47:18-35. [PMID: 36341762 DOI: 10.1111/acer.14972] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Revised: 10/26/2022] [Accepted: 11/02/2022] [Indexed: 11/09/2022]
Abstract
We conducted a systematic review with meta-analytic elements using publicly available Gene Expression Omnibus (GEO) datasets to determine the role of epigenetic mechanisms in prenatal alcohol exposure (PAE)-induced hypothalamic-pituitary-adrenal (HPA) axis dysfunctions in offspring. Several studies have demonstrated that PAE has long-term consequences on HPA axis functions in offspring. Some studies determined that alcohol-induced epigenetic alterations during fetal development persist in adulthood. However, additional research is needed to understand the major epigenetic events leading to alcohol-induced teratogenesis of the HPA axis. Our network analysis of GEO datasets identified key pathways relevant to alcohol-mediated histone modifications, DNA methylation, and miRNA involvement associated with PAE-induced alterations of the HPA axis. Our analysis indicated that PAE perturbated the epigenetic machinery to activate corticotrophin-releasing hormone, while it suppressed opioid, glucocorticoid receptor, and circadian clock genes. These results help to further our understanding of the epigenetic basis of alcohol's effects on HPA axis development.
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Affiliation(s)
- Ujjal Das
- Endocrinology Program, Rutgers, The State University of New Jersey, New Brunswick, New Jersey, USA
- Department of Animal Sciences, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
| | - Omkaram Gangisetty
- Endocrinology Program, Rutgers, The State University of New Jersey, New Brunswick, New Jersey, USA
- Department of Animal Sciences, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
| | - Shaista Chaudhary
- Endocrinology Program, Rutgers, The State University of New Jersey, New Brunswick, New Jersey, USA
- Department of Animal Sciences, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
| | - Prashant Tarale
- Endocrinology Program, Rutgers, The State University of New Jersey, New Brunswick, New Jersey, USA
- Department of Animal Sciences, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
| | - Bénédicte Rousseau
- Endocrinology Program, Rutgers, The State University of New Jersey, New Brunswick, New Jersey, USA
- Department of Animal Sciences, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
| | - Julianne Price
- Molecular Neuroscience of Alcohol and Drug Abuse Research Training, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
- Center of Alcohol & Substance Use Studies, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
- Department of Kinesiology & Health, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
| | - Ian Frazier
- Molecular Neuroscience of Alcohol and Drug Abuse Research Training, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
- Center of Alcohol & Substance Use Studies, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
- Department of Kinesiology & Health, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
| | - Dipak K Sarkar
- Endocrinology Program, Rutgers, The State University of New Jersey, New Brunswick, New Jersey, USA
- Department of Animal Sciences, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
- Molecular Neuroscience of Alcohol and Drug Abuse Research Training, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
- Center of Alcohol & Substance Use Studies, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA
- Rutgers Endocrinology Program, Department of Animal Sciences, Rutgers, The State University of New Jersey, New Brunswick, New Jersey, USA
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16
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Chang SL, Bishir M. Commentary on "Alcohol use disorder as a potential risk factor for COVID-19 severity: A narrative review". ALCOHOL, CLINICAL & EXPERIMENTAL RESEARCH 2023; 47:45-49. [PMID: 36404612 DOI: 10.1111/acer.14978] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/12/2022] [Revised: 11/08/2022] [Accepted: 11/15/2022] [Indexed: 11/22/2022]
Affiliation(s)
- Sulie L Chang
- Institute of NeuroImmune Pharmacology, South Orange, New Jersey, USA
- Department of Biological Sciences, Seton Hall University, South Orange, New Jersey, USA
| | - Muhammed Bishir
- Institute of NeuroImmune Pharmacology, South Orange, New Jersey, USA
- Department of Biological Sciences, Seton Hall University, South Orange, New Jersey, USA
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17
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Liu YB, Chen MK. Epidemiology of liver cirrhosis and associated complications: Current knowledge and future directions. World J Gastroenterol 2022; 28:5910-5930. [PMID: 36405106 PMCID: PMC9669831 DOI: 10.3748/wjg.v28.i41.5910] [Citation(s) in RCA: 62] [Impact Index Per Article: 20.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2022] [Revised: 09/30/2022] [Accepted: 10/20/2022] [Indexed: 02/06/2023] Open
Abstract
Cirrhosis causes a heavy global burden. In this review, we summarized up-to-date epidemiological features of cirrhosis and its complications. Recent epidemiological studies reported an increase in the prevalence of cirrhosis in 2017 compared to in 1990 in both men and women, with 5.2 million cases of cirrhosis and chronic liver disease occurring in 2017. Cirrhosis caused 1.48 million deaths in 2019, an increase of 8.1% compared to 2017. Disability-adjusted life-years due to cirrhosis ranked 16th among all diseases and 7th in people aged 50-74 years in 2019. The global burden of hepatitis B virus and hepatitis C virus-associated cirrhosis is decreasing, while the burden of cirrhosis due to alcohol and nonalcoholic fatty liver disease (NAFLD) is increasing rapidly. We described the current epidemiology of the major complications of cirrhosis, including ascites, variceal bleeding, hepatic encephalopathy, renal disorders, and infections. We also summarized the epidemiology of hepatocellular carcinoma in patients with cirrhosis. In the future, NAFLD-related cirrhosis will likely become more common due to the prevalence of metabolic diseases such as obesity and diabetes, and the prevalence of alcohol-induced cirrhosis is increasing. This altered epidemiology should be clinically noted, and relevant interventions should be undertaken.
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Affiliation(s)
- Yuan-Bin Liu
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430000, Hubei Province, China
| | - Ming-Kai Chen
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430000, Hubei Province, China
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18
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Forsyth CB, Voigt RM, Swanson GR, Bishehsari F, Shaikh M, Zhang L, Engen P, Keshavarzian A. Alcohol use disorder as a potential risk factor for COVID-19 severity: A narrative review. Alcohol Clin Exp Res 2022; 46:1930-1943. [PMID: 36394508 PMCID: PMC9722573 DOI: 10.1111/acer.14936] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Revised: 07/25/2022] [Accepted: 08/31/2022] [Indexed: 11/19/2022]
Abstract
In Dec. 2019-January 2020, a pneumonia illness originating in Wuhan, China, designated as coronavirus disease 2019 (COVID-19) was shown to be caused by a novel RNA coronavirus designated as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). People with advanced age, male sex, and/or underlying health conditions (obesity, type 2 diabetes, cardiovascular disease, hypertension, chronic kidney disease, and chronic lung disease) are especially vulnerable to severe COVID-19 symptoms and death. These risk factors impact the immune system and are also associated with poor health, chronic illness, and shortened longevity. However, a large percent of patients without these known risk factors also develops severe COVID-19 disease that can result in death. Thus, there must exist risk factors that promote exaggerated inflammatory and immune response to the SARS-CoV-2 virus leading to death. One such risk factor may be alcohol misuse and alcohol use disorder because these can exacerbate viral lung infections like SARS, influenza, and pneumonia. Thus, it is highly plausible that alcohol misuse is a risk factor for either increased infection rate when individuals are exposed to SARS-CoV-2 virus and/or more severe COVID-19 in infected patients. Alcohol use is a well-known risk factor for lung diseases and ARDS in SARS patients. We propose that alcohol has three key pathogenic elements in common with other COVID-19 severity risk factors: namely, inflammatory microbiota dysbiosis, leaky gut, and systemic activation of the NLRP3 inflammasome. We also propose that these three elements represent targets for therapy for severe COVID-19.
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Affiliation(s)
- Christopher B. Forsyth
- Department of Internal Medicine, Section of Gastroenterology, Rush University Medical Center, Chicago, IL 60612
- Rush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, IL 60612
- Department of Anatomy and Cell Biology, Rush University Medical Center, Chicago, IL 60612
- Rush University Graduate College, Rush University Medical Center, Chicago, IL 60612
| | - Robin M. Voigt
- Department of Internal Medicine, Section of Gastroenterology, Rush University Medical Center, Chicago, IL 60612
- Rush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, IL 60612
- Department of Anatomy and Cell Biology, Rush University Medical Center, Chicago, IL 60612
- Rush University Graduate College, Rush University Medical Center, Chicago, IL 60612
| | - Garth R. Swanson
- Department of Internal Medicine, Section of Gastroenterology, Rush University Medical Center, Chicago, IL 60612
- Rush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, IL 60612
- Department of Anatomy and Cell Biology, Rush University Medical Center, Chicago, IL 60612
- Rush University Graduate College, Rush University Medical Center, Chicago, IL 60612
| | - Faraz Bishehsari
- Department of Internal Medicine, Section of Gastroenterology, Rush University Medical Center, Chicago, IL 60612
- Rush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, IL 60612
- Department of Anatomy and Cell Biology, Rush University Medical Center, Chicago, IL 60612
- Rush University Graduate College, Rush University Medical Center, Chicago, IL 60612
| | - Maliha Shaikh
- Rush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, IL 60612
| | - Lijuan Zhang
- Rush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, IL 60612
| | - Phillip Engen
- Rush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, IL 60612
| | - Ali Keshavarzian
- Department of Internal Medicine, Section of Gastroenterology, Rush University Medical Center, Chicago, IL 60612
- Rush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, IL 60612
- Department of Anatomy and Cell Biology, Rush University Medical Center, Chicago, IL 60612
- Rush University Graduate College, Rush University Medical Center, Chicago, IL 60612
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19
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Deutsch-Link S, Curtis B, Singal AK. Covid-19 and alcohol associated liver disease. Dig Liver Dis 2022; 54:1459-1468. [PMID: 35933291 PMCID: PMC9349236 DOI: 10.1016/j.dld.2022.07.007] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2022] [Accepted: 07/11/2022] [Indexed: 02/07/2023]
Abstract
The COVID-19 pandemic is having substantial impacts on the health status of individuals with alcohol use disorder (AUD) and alcohol-associated liver disease (ALD). AUD and ALD have both been impacted throughout the pandemic, with increases in alcohol use during the early stages of the pandemic, reduced access to treatment during the mid-pandemic, and challenges in managing the downstream effects in the post-COVID era. This review will focus on how the COVID-19 pandemic has impacted AUD and ALD epidemiology and access to treatment, and will discuss to address this rising AUD and ALD disease burden.
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Affiliation(s)
- Sasha Deutsch-Link
- Division of Gastroenterology & Hepatology, University of North Carolina School of Medicine, Chapel Hill, NC, United States
| | - Brenda Curtis
- National Institute on Drug Abuse, Baltimore, MD, United States
| | - Ashwani K Singal
- Division of Gastroenterology & Hepatology, University of South Dakota Sanford School of Medicine, Sioux Falls, SD, United States.
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20
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Solopov PA, Colunga Biancatelli RML, Catravas JD. Alcohol Increases Lung Angiotensin-Converting Enzyme 2 Expression and Exacerbates Severe Acute Respiratory Syndrome Coronavirus 2 Spike Protein Subunit 1-Induced Acute Lung Injury in K18-hACE2 Transgenic Mice. THE AMERICAN JOURNAL OF PATHOLOGY 2022; 192:990-1000. [PMID: 35483427 PMCID: PMC9040477 DOI: 10.1016/j.ajpath.2022.03.012] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Revised: 03/14/2022] [Accepted: 03/31/2022] [Indexed: 12/18/2022]
Abstract
During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, alcohol consumption increased markedly. Nearly one in four adults reported drinking more alcohol to cope with stress. Chronic alcohol abuse is now recognized as a factor complicating the course of acute respiratory distress syndrome and increasing mortality. To investigate the mechanisms behind this interaction, a combined acute respiratory distress syndrome and chronic alcohol abuse mouse model was developed by intratracheally instilling the subunit 1 (S1) of SARS-CoV-2 spike protein (S1SP) in K18-human angiotensin-converting enzyme 2 (ACE2) transgenic mice that express the human ACE2 receptor for SARS-CoV-2 and were kept on an ethanol diet. Seventy-two hours after S1SP instillation, mice on an ethanol diet showed a strong decrease in body weight, a dramatic increase in white blood cell content of bronchoalveolar lavage fluid, and an augmented cytokine storm, compared with S1SP-treated mice on a control diet. Histologic examination of lung tissue showed abnormal recruitment of immune cells in the alveolar space, abnormal parenchymal architecture, and worsening Ashcroft score in S1SP- and alcohol-treated animals. Along with the activation of proinflammatory biomarkers [NF-κB, STAT3, NLR family pyrin domain-containing protein 3 (NLRP3) inflammasome], lung tissue homogenates from mice on an alcohol diet showed overexpression of ACE2 compared with mice on a control diet. This model could be useful for the development of therapeutic approaches against alcohol-exacerbated coronavirus disease 2019.
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Affiliation(s)
- Pavel A Solopov
- Frank Reidy Research Center for Bioelectrics, Old Dominion University, Norfolk, Virginia.
| | | | - John D Catravas
- Frank Reidy Research Center for Bioelectrics, Old Dominion University, Norfolk, Virginia; School of Medical Diagnostic and Translational Sciences, College of Health Sciences, Old Dominion University, Norfolk, Virginia
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21
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Alcohol Consumption and Smoking During Covid-19 Pandemic: Association with Sociodemographic, Behavioral, and Mental Health Characteristics. J Community Health 2022; 47:588-597. [PMID: 35334032 PMCID: PMC8951656 DOI: 10.1007/s10900-022-01085-5] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/12/2022] [Indexed: 12/23/2022]
Abstract
The Covid-19 pandemic is related to increased alcohol consumption and smoking. These behaviors may be related to several sociodemographic, behavioral and mental health factors. Thus, the aim of this study was to assess the association between alcohol consumption and cigarette smoking with sociodemographic, behavioral and mental health characteristics. This study used data from two population-based studies conducted in two cities from Southern Brazil amid the Covid-19 pandemic. Individuals aged 18 years or older were included and selected using a multistage sampling procedure. Alcohol consumption and smoking and changes in such consumption during the Covid-19 pandemic were evaluated. Sociodemographic, behavioral, pandemic-related, and mental health variables were also included. A hierarchical model was used to conduct the adjusted analyses, and Poisson regression with robust adjustment was used for variance. A total of 2170 individuals were studied. The prevalence of alcohol consumption and smoking were 9.3% and 14.2%, respectively. The rates of increase in alcohol consumption and smoking during the Covid-pandemic were about 20% and 30%, respectively. They were higher among those with depressive symptoms, feeling of sadness and self-reported stress. Those with poor diet quality had higher prevalence of alcohol consumption (PR: 1.82) and were 1.58 times more likely to smoke. The findings may help stakeholders in health and political systems to better understand the consequences of the Covid-19 pandemic and develop strategies to mitigate these consequences in Brazil and elsewhere.
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22
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Liu A, Raja xavier J, Singh Y, Brucker SY, Salker MS. Molecular and Physiological Aspects of SARS-CoV-2 Infection in Women and Pregnancy. Front Glob Womens Health 2022; 3:756362. [PMID: 35284910 PMCID: PMC8908006 DOI: 10.3389/fgwh.2022.756362] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Accepted: 02/01/2022] [Indexed: 01/08/2023] Open
Abstract
Whilst scientific knowledge about SARS-CoV-2 and COVID-19 is rapidly increasing, much of the effects on pregnant women is still unknown. To accommodate pregnancy, the human endometrium must undergo a physiological transformation called decidualization. These changes encompass the remodeling of endometrial immune cells leading to immunotolerance of the semi-allogenic conceptus as well as defense against pathogens. The angiotensin converting enzyme 2 (ACE2) plays an important regulatory role in the renin-angiotensin-system (RAS) and has been shown to be protective against comorbidities known to worsen COVID-19 outcomes. Furthermore, ACE2 is also crucial for decidualization and thus for early gestation. An astounding gender difference has been found in COVID-19 with male patients presenting with more severe cases and higher mortality rates. This could be attributed to differences in sex chromosomes, hormone levels and behavior patterns. Despite profound changes in the female body during pregnancy, expectant mothers do not face worse outcomes compared with non-pregnant women. Whereas mother-to-child transmission through respiratory droplets during labor or in the postnatal period is known, another question of in utero transmission remains unanswered. Evidence of placental SARS-CoV-2 infection and expression of viral entry receptors at the maternal-fetal interface suggests the possibility of in utero transmission. SARS-CoV-2 can cause further harm through placental damage, maternal systemic inflammation, and hindered access to health care during the pandemic. More research on the effects of COVID-19 during early pregnancy as well as vaccination and treatment options for gravid patients is urgently needed.
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Affiliation(s)
- Anna Liu
- Research Institute of Women's Health, Eberhard Karls University, Tübingen, Germany
| | - Janet Raja xavier
- Research Institute of Women's Health, Eberhard Karls University, Tübingen, Germany
| | - Yogesh Singh
- Research Institute of Women's Health, Eberhard Karls University, Tübingen, Germany
- Institute of Medical Genetics and Applied Genomics, Eberhard Karls University, Tübingen, Germany
| | - Sara Y. Brucker
- Research Institute of Women's Health, Eberhard Karls University, Tübingen, Germany
| | - Madhuri S. Salker
- Research Institute of Women's Health, Eberhard Karls University, Tübingen, Germany
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23
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Morales JS, Valenzuela PL, Castillo-García A, Butragueño J, Jiménez-Pavón D, Carrera-Bastos P, Lucia A. The Exposome and Immune Health in Times of the COVID-19 Pandemic. Nutrients 2021; 14:24. [PMID: 35010900 PMCID: PMC8746533 DOI: 10.3390/nu14010024] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Revised: 12/17/2021] [Accepted: 12/19/2021] [Indexed: 02/07/2023] Open
Abstract
Growing evidence supports the importance of lifestyle and environmental exposures-collectively referred to as the 'exposome'-for ensuring immune health. In this narrative review, we summarize and discuss the effects of the different exposome components (physical activity, body weight management, diet, sun exposure, stress, sleep and circadian rhythms, pollution, smoking, and gut microbiome) on immune function and inflammation, particularly in the context of the current coronavirus disease 2019 (COVID-19) pandemic. We highlight the potential role of 'exposome improvements' in the prevention-or amelioration, once established-of this disease as well as their effect on the response to vaccination. In light of the existing evidence, the promotion of a healthy exposome should be a cornerstone in the prevention and management of the COVID-19 pandemic and other eventual pandemics.
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Affiliation(s)
- Javier S. Morales
- MOVE-IT Research Group, Department of Physical Education, Faculty of Education Sciences, Universidad de Cádiz, 11519 Cadiz, Spain;
- Biomedical Research and Innovation Institute of Cádiz (INiBICA) Research Unit, Puerta del Mar University Hospital, University of Cádiz, 11009 Cadiz, Spain
| | - Pedro L. Valenzuela
- Faculty of Sport Sciences, Universidad Europea de Madrid, 28670 Madrid, Spain; (P.L.V.); (A.L.)
- Physical Activity and Health Research Group (‘PaHerg’), Research Institute of the Hospital 12 de Octubre (‘imas12′), 28041 Madrid, Spain
| | | | - Javier Butragueño
- LFE Research Group, Department of Health and Human Performance, Faculty of Physical Activity and Sport Sciences, Polytechnic University of Madrid (UPM), 28040 Madrid, Spain;
| | - David Jiménez-Pavón
- MOVE-IT Research Group, Department of Physical Education, Faculty of Education Sciences, Universidad de Cádiz, 11519 Cadiz, Spain;
- Biomedical Research and Innovation Institute of Cádiz (INiBICA) Research Unit, Puerta del Mar University Hospital, University of Cádiz, 11009 Cadiz, Spain
- CIBER of Frailty and Healthy Aging (CIBERFES), 28029 Madrid, Spain
| | - Pedro Carrera-Bastos
- Centre for Primary Health Care Research, Lund University, Skane University Hospital, 205 02 Malmö, Sweden;
- Faculty of Biomedical and Health Sciences, Universidad Europea de Madrid, 28670 Madrid, Spain
| | - Alejandro Lucia
- Faculty of Sport Sciences, Universidad Europea de Madrid, 28670 Madrid, Spain; (P.L.V.); (A.L.)
- Physical Activity and Health Research Group (‘PaHerg’), Research Institute of the Hospital 12 de Octubre (‘imas12′), 28041 Madrid, Spain
- CIBER of Frailty and Healthy Aging (CIBERFES), 28029 Madrid, Spain
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24
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Almutairi MM, Sivandzade F, Albekairi TH, Alqahtani F, Cucullo L. Neuroinflammation and Its Impact on the Pathogenesis of COVID-19. Front Med (Lausanne) 2021; 8:745789. [PMID: 34901061 PMCID: PMC8652056 DOI: 10.3389/fmed.2021.745789] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Accepted: 10/15/2021] [Indexed: 12/14/2022] Open
Abstract
Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The clinical manifestations of COVID-19 include dry cough, difficult breathing, fever, fatigue, and may lead to pneumonia and respiratory failure. There are significant gaps in the current understanding of whether SARS-CoV-2 attacks the CNS directly or through activation of the peripheral immune system and immune cell infiltration. Although the modality of neurological impairments associated with COVID-19 has not been thoroughly investigated, the latest studies have observed that SARS-CoV-2 induces neuroinflammation and may have severe long-term consequences. Here we review the literature on possible cellular and molecular mechanisms of SARS-CoV-2 induced-neuroinflammation. Activation of the innate immune system is associated with increased cytokine levels, chemokines, and free radicals in the SARS-CoV-2-induced pathogenic response at the blood-brain barrier (BBB). BBB disruption allows immune/inflammatory cell infiltration into the CNS activating immune resident cells (such as microglia and astrocytes). This review highlights the molecular and cellular mechanisms involved in COVID-19-induced neuroinflammation, which may lead to neuronal death. A better understanding of these mechanisms will help gain substantial knowledge about the potential role of SARS-CoV-2 in neurological changes and plan possible therapeutic intervention strategies.
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Affiliation(s)
- Mohammed M. Almutairi
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - Farzane Sivandzade
- Department of Biological Sciences, Oakland University, Rochester, MI, United States
- Department of Foundation Medical Studies, Oakland University William Beaumont School of Medicine, Rochester, MI, United States
| | - Thamer H. Albekairi
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - Faleh Alqahtani
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - Luca Cucullo
- Department of Foundation Medical Studies, Oakland University William Beaumont School of Medicine, Rochester, MI, United States
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25
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Network Meta-analysis on the Changes of Amyloid Precursor Protein Expression Following SARS-CoV-2 Infection. J Neuroimmune Pharmacol 2021; 16:756-769. [PMID: 34757528 PMCID: PMC8579188 DOI: 10.1007/s11481-021-10012-9] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Accepted: 08/19/2021] [Indexed: 12/31/2022]
Abstract
SARS-CoV-2 infection begins with the attachment of its spike (S) protein to angiotensin-converting enzyme-2 (ACE2) followed by complex host immune responses with cardiovascular and neurological implications. Our meta-analyses used QIAGEN Ingenuity Pathway Analysis (IPA) and Knowledge Base (QKB) to investigate how the expression of amyloid precursor protein (APP) was modulated by attachment of SARS-CoV-2 S protein in the brain microvascular endothelial cells (BMVECs) and during COVID-19 in progress. Published 80 host response genes reported to be modulated in BMVECs following SARS-CoV-2 S protein binding were used to identify key canonical pathways and intermediate molecules mediating the regulation of APP production following the attachment of S protein to endothelial cells. This revealed that the attachment of SARS-CoV-2 S protein may inhibit APP expression in the BMVECs. Our results shed light on the molecular mechanisms by which SARS-CoV-2 infection may potentiate the incidence of stroke by inhibiting the production of APP in the BMVECs. We also analyzed molecules associated with COVID-19, which revealed six upstream regulators, TNF, IFNG, STAT1, IL1β, IL6, and STAT3. The upstream regulators mediate the increased production of APP via intermediators, with eleven regulated by all six upstream regulators. These COVID-19 upstream regulators increased APP expression with a statistically significant Z-score of 3.705 (p value = 0.000211). These findings have revealed molecular mechanisms by which COVID-19 disease may lead to long-term neurological manifestations resulting from the elevated APP expression in line with immune response in the host. Altogether, our study revealed two distinct scenarios which may have differential impact on APP expression.
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26
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Bhalla S, Sharma B, Smith D, Boley R, McCluskey C, Ilyas Y, Afshar M, Balk R, Karnik N, Keshavarzian A. Investigating Unhealthy Alcohol Use As an Independent Risk Factor for Increased COVID-19 Disease Severity: Observational Cross-sectional Study. JMIR Public Health Surveill 2021; 7:e33022. [PMID: 34665758 PMCID: PMC8575002 DOI: 10.2196/33022] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2021] [Revised: 10/11/2021] [Accepted: 10/14/2021] [Indexed: 01/10/2023] Open
Abstract
BACKGROUND Unhealthy alcohol use (UAU) is known to disrupt pulmonary immune mechanisms and increase the risk of acute respiratory distress syndrome in patients with pneumonia; however, little is known about the effects of UAU on outcomes in patients with COVID-19 pneumonia. To our knowledge, this is the first observational cross-sectional study that aims to understand the effect of UAU on the severity of COVID-19. OBJECTIVE We aim to determine if UAU is associated with more severe clinical presentation and worse health outcomes related to COVID-19 and if socioeconomic status, smoking, age, BMI, race/ethnicity, and pattern of alcohol use modify the risk. METHODS In this observational cross-sectional study that took place between January 1, 2020, and December 31, 2020, we ran a digital machine learning classifier on the electronic health record of patients who tested positive for SARS-CoV-2 via nasopharyngeal swab or had two COVID-19 International Classification of Disease, 10th Revision (ICD-10) codes to identify patients with UAU. After controlling for age, sex, ethnicity, BMI, smoking status, insurance status, and presence of ICD-10 codes for cancer, cardiovascular disease, and diabetes, we then performed a multivariable regression to examine the relationship between UAU and COVID-19 severity as measured by hospital care level (ie, emergency department admission, emergency department admission with ventilator, or death). We used a predefined cutoff with optimal sensitivity and specificity on the digital classifier to compare disease severity in patients with and without UAU. Models were adjusted for age, sex, race/ethnicity, BMI, smoking status, and insurance status. RESULTS Each incremental increase in the predicted probability from the digital alcohol classifier was associated with a greater odds risk for more severe COVID-19 disease (odds ratio 1.15, 95% CI 1.10-1.20). We found that patients in the unhealthy alcohol group had a greater odds risk to develop more severe disease (odds ratio 1.89, 95% CI 1.17-3.06), suggesting that UAU was associated with an 89% increase in the odds of being in a higher severity category. CONCLUSIONS In patients infected with SARS-CoV-2, UAU is an independent risk factor associated with greater disease severity and/or death.
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Affiliation(s)
- Sameer Bhalla
- Department of Internal Medicine, Rush University Medical Center, Chicago, IL, United States
| | - Brihat Sharma
- Addiction Data Science Laboratory, Department of Psychiatry & Behavioral Sciences, Rush University Medical Center, Chicago, IL, United States
| | - Dale Smith
- Addiction Data Science Laboratory, Department of Psychiatry & Behavioral Sciences, Rush University Medical Center, Chicago, IL, United States
| | - Randy Boley
- Addiction Data Science Laboratory, Department of Psychiatry & Behavioral Sciences, Rush University Medical Center, Chicago, IL, United States
| | - Connor McCluskey
- Addiction Data Science Laboratory, Department of Psychiatry & Behavioral Sciences, Rush University Medical Center, Chicago, IL, United States
| | - Yousaf Ilyas
- Addiction Data Science Laboratory, Department of Psychiatry & Behavioral Sciences, Rush University Medical Center, Chicago, IL, United States
| | - Majid Afshar
- Department of Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, WI, United States
| | - Robert Balk
- Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, IL, United States
| | - Niranjan Karnik
- Addiction Data Science Laboratory, Department of Psychiatry & Behavioral Sciences, Rush University Medical Center, Chicago, IL, United States
| | - Ali Keshavarzian
- Center for Circadian Rhythm and Alcohol-Induced Tissue Injury, Rush University Medical Center, Chicago, IL, United States
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27
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Morojele NK, Shenoi SV, Shuper PA, Braithwaite RS, Rehm J. Alcohol Use and the Risk of Communicable Diseases. Nutrients 2021; 13:3317. [PMID: 34684318 PMCID: PMC8540096 DOI: 10.3390/nu13103317] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Revised: 09/13/2021] [Accepted: 09/14/2021] [Indexed: 01/12/2023] Open
Abstract
The body of knowledge on alcohol use and communicable diseases has been growing in recent years. Using a narrative review approach, this paper discusses alcohol's role in the acquisition of and treatment outcomes from four different communicable diseases: these include three conditions included in comparative risk assessments to date-Human Immunodeficiency Virus (HIV)/AIDS, tuberculosis (TB), and lower respiratory infections/pneumonia-as well as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) because of its recent and rapid ascension as a global health concern. Alcohol-attributable TB, HIV, and pneumonia combined were responsible for approximately 360,000 deaths and 13 million disability-adjusted life years lost (DALYs) in 2016, with alcohol-attributable TB deaths and DALYs predominating. There is strong evidence that alcohol is associated with increased incidence of and poorer treatment outcomes from HIV, TB, and pneumonia, via both behavioral and biological mechanisms. Preliminary studies suggest that heavy drinkers and those with alcohol use disorders are at increased risk of COVID-19 infection and severe illness. Aside from HIV research, limited research exists that can guide interventions for addressing alcohol-attributable TB and pneumonia or COVID-19. Implementation of effective individual-level interventions and alcohol control policies as a means of reducing the burden of communicable diseases is recommended.
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Affiliation(s)
- Neo K. Morojele
- Department of Psychology, University of Johannesburg, Johannesburg 2006, South Africa
| | - Sheela V. Shenoi
- Section of Infectious Diseases, Department of Medicine, Yale University School of Medicine, New Haven, CT 06510, USA;
- Yale Institute for Global Health, Yale University, New Haven, CT 06520, USA
| | - Paul A. Shuper
- Centre for Addiction and Mental Health, Institute for Mental Health Policy Research and Campbell Family Mental Health Research Institute, Toronto, ON M5S 2S1, Canada; (P.A.S.); (J.R.)
- Dalla Lana School of Public Health, University of Toronto, Toronto, ON M5T 3M7, Canada
- Institute for Collaboration on Health, Intervention, and Policy, University of Connecticut, Storrs, CT 06269, USA
- Alcohol, Tobacco and Other Drug Research Unit, South African Medical Research Council, Pretoria 0001, South Africa
| | - Ronald Scott Braithwaite
- Division of Comparative Effectiveness and Decision Science, Department of Population Health, NYU Grossman School of Medicine, New York University, New York, NY 10013, USA;
| | - Jürgen Rehm
- Centre for Addiction and Mental Health, Institute for Mental Health Policy Research and Campbell Family Mental Health Research Institute, Toronto, ON M5S 2S1, Canada; (P.A.S.); (J.R.)
- Dalla Lana School of Public Health, University of Toronto, Toronto, ON M5T 3M7, Canada
- Department of Psychiatry, University of Toronto, Toronto, ON M5T 1R8, Canada
- Center for Interdisciplinary Addiction Research (ZIS), Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf (UKE), 20246 Hamburg, Germany
- Institute of Clinical Psychology and Psychotherapy, Technische Universität Dresden, 01187 Dresden, Germany
- Faculty of Medicine, Institute of Medical Science, University of Toronto, Toronto, ON M5S 1A8, Canada
- Program on Substance Abuse, Public Health Agency of Catalonia, 08005 Barcelona, Spain
- Department of International Health Projects, Institute for Leadership and Health Management, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia
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28
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Joshi C, Jadeja V, Zhou H. Molecular Mechanisms of Palmitic Acid Augmentation in COVID-19 Pathologies. Int J Mol Sci 2021; 22:7127. [PMID: 34281182 PMCID: PMC8269364 DOI: 10.3390/ijms22137127] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Revised: 06/25/2021] [Accepted: 06/26/2021] [Indexed: 02/06/2023] Open
Abstract
The coronavirus disease 2019 (COVID-19) pandemic has claimed over 2.7 million lives globally. Obesity has been associated with increased severity and mortality of COVID-19. However, the molecular mechanisms by which obesity exacerbates COVID-19 pathologies are not well-defined. The levels of free fatty acids (FFAs) are elevated in obese subjects. This study was therefore designed to examine how excess levels of different FFAs may affect the progression of COVID-19. Biological molecules associated with palmitic acid (PA) and COVID-19 were retrieved from QIAGEN Knowledge Base, and Ingenuity Pathway Analysis tools were used to analyze these datasets and explore the potential pathways affected by different FFAs. Our study found that one of the top 10 canonical pathways affected by PA was the coronavirus pathogenesis pathway, mediated by key inflammatory mediators, including PTGS2; cytokines, including IL1β and IL6; chemokines, including CCL2 and CCL5; transcription factors, including NFκB; translation regulators, including EEF1A1; and apoptotic mediators, including BAX. In contrast, n-3 fatty acids may attenuate PA's activation of the coronavirus pathogenesis pathway by inhibiting the activity of such mediators as IL1β, CCL2, PTGS2, and BAX. Furthermore, PA may modulate the expression of ACE2, the main cell surface receptor for the SARS-CoV-2 spike protein.
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Affiliation(s)
| | | | - Heping Zhou
- Department of Biological Sciences, Seton Hall University, South Orange, NJ 07079, USA; (C.J.); (V.J.)
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29
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Bidlack JM, Chang SL, Fitting S, Gendelman HE, Gorantla S, Kumar S, Marcondes MCG, Meigs DD, Melendez LM, Sariyer IK, Yelamanchili S. The COVID-19 Pandemic: Reflections of Science, Person, and Challenge in Academic Research Settings. J Neuroimmune Pharmacol 2021; 16:706-717. [PMID: 34826061 PMCID: PMC8616745 DOI: 10.1007/s11481-021-10035-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2021] [Accepted: 11/11/2021] [Indexed: 12/16/2022]
Abstract
In spring of 2021, the Society on NeuroImmune Pharmacology (SNIP) organized a virtual workshop on the coronavirus disease 2019 (COVID-19). The daylong event's fourth and final symposium, "Well-being and reflections," offered a glimpse at the pandemic's impact on the lives of our scientists and educators. This manuscript includes a brief summary of the symposium, a transcription of our incoming president Dr. Santosh Kumar's lecture, titled "Intervention and improved well-being of basic science researchers during the COVID-19 era: a case study," and the panel discussion that followed, "Reflection and sharing," featuring Drs. Jean M. Bidlack, Sylvia Fitting, Santhi Gorantla, Maria Cecilia G. Marcondes, Loyda M. Melendez, and Ilker K. Sariyer. The conclusion of this manuscript includes comments from SNIP's president Dr. Sulie L. Chang and our Chief Editor, Dr. Howard E. Gendelman. Drs. Sowmya Yelamanchili and Jeymohan Joseph co-chaired the symposium.
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Affiliation(s)
- Jean M. Bidlack
- grid.412750.50000 0004 1936 9166Department of Pharmacology and Physiology, School of Medicine and Dentistry, University of Rochester Medical Center, Rochester, NY USA
| | - Sulie L. Chang
- grid.263379.a0000 0001 2172 0072Department of Biological Sciences, Institute of Neuroimmune Pharmacology, Seton Hall University, South Orange, NJ USA
| | - Sylvia Fitting
- grid.10698.360000000122483208Department of Psychology and Neuroscience, University of North Carolina at Chapel Hill, Chapel Hill, NC USA
| | - Howard E. Gendelman
- grid.266813.80000 0001 0666 4105Department of Pharmacology and Experimental Neuroscience, College of Medicine, University of Nebraska Medical Center, Omaha, NE USA
| | - Santhi Gorantla
- grid.266813.80000 0001 0666 4105Department of Pharmacology and Experimental Neuroscience, College of Medicine, University of Nebraska Medical Center, Omaha, NE USA
| | - Santosh Kumar
- grid.267301.10000 0004 0386 9246Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN USA
| | | | - Douglas D. Meigs
- grid.266813.80000 0001 0666 4105Department of Pharmacology and Experimental Neuroscience, College of Medicine, University of Nebraska Medical Center, Omaha, NE USA
| | - Loyda M. Melendez
- grid.267034.40000 0001 0153 191XDepartment of Microbiology and Medical Zoology, University of Puerto Rico-Medical Sciences Campus, San Juan, Puerto Rico, USA
| | - Ilker K. Sariyer
- grid.264727.20000 0001 2248 3398Department of Neuroscience and Center for Neurovirology, Lewis Katz School of Medicine, Temple University, PA Philadelphia, USA
| | - Sowmya Yelamanchili
- grid.266813.80000 0001 0666 4105Department of Anesthesiology, College of Medicine, University of Nebraska Medical Center, Omaha, NE USA
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