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Liu Y, Lu T, Li C, Wang X, Chen F, Yue L, Jiang C. Comparative transcriptome analysis of SARS-CoV-2, SARS-CoV, MERS-CoV, and HCoV-229E identifying potential IFN/ISGs targets for inhibiting virus replication. Front Med (Lausanne) 2023; 10:1267903. [PMID: 38143441 PMCID: PMC10739311 DOI: 10.3389/fmed.2023.1267903] [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: 07/27/2023] [Accepted: 11/13/2023] [Indexed: 12/26/2023] Open
Abstract
Introduction Since its outbreak in December 2019, SARS-CoV-2 has spread rapidly across the world, posing significant threats and challenges to global public health. SARS-CoV-2, together with SARS-CoV and MERS-CoV, is a highly pathogenic coronavirus that contributes to fatal pneumonia. Understanding the similarities and differences at the transcriptome level between SARS-CoV-2, SARS-CoV, as well as MERS-CoV is critical for developing effective strategies against these viruses. Methods In this article, we comparatively analyzed publicly available transcriptome data of human cell lines infected with highly pathogenic SARS-CoV-2, SARS-CoV, MERS-CoV, and lowly pathogenic HCoV-229E. The host gene expression profiles during human coronavirus (HCoV) infections were generated, and the pathways and biological functions involved in immune responses, antiviral efficacy, and organ damage were intensively elucidated. Results Our results indicated that SARS-CoV-2 induced a stronger immune response versus the other two highly pathogenic HCoVs. Specifically, SARS-CoV-2 induced robust type I and type III IFN responses, marked by higher upregulation of type I and type III IFNs, as well as numerous interferon-stimulated genes (ISGs). Further Ingenuity Pathway Analysis (IPA) revealed the important role of ISGs for impeding SARS-CoV-2 infection, and the interferon/ISGs could be potential targets for therapeutic interventions. Moreover, our results uncovered that SARS-CoV-2 infection was linked to an enhanced risk of multi-organ toxicity in contrast to the other two highly pathogenic HCoVs. Discussion These findings provided valuable insights into the pathogenic mechanism of SARS-CoV-2, which showed a similar pathological feature but a lower fatality rate compared to SARS-CoV and MERS-CoV.
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Affiliation(s)
- Yuzhuang Liu
- National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, China
| | - Tianyi Lu
- CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing, China
- Beijing Institute of Genomics, University of Chinese Academy of Sciences, Beijing, China
| | - Cuidan Li
- CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing, China
| | - Xiaotong Wang
- CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing, China
| | - Fei Chen
- CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing, China
- Beijing Institute of Genomics, University of Chinese Academy of Sciences, Beijing, China
- Beijing Key Laboratory of Genome and Precision Medicine Technologies, Beijing, China
| | - Liya Yue
- CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing, China
| | - Chunlai Jiang
- National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, China
- Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, School of Life Sciences, Jilin University, Changchun, China
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2
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Zhang C, Liu J, Sui Y, Liu S, Yang M. In silico drug repurposing carvedilol and its metabolites against SARS-CoV-2 infection using molecular docking and molecular dynamic simulation approaches. Sci Rep 2023; 13:21404. [PMID: 38049492 PMCID: PMC10696093 DOI: 10.1038/s41598-023-48398-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2023] [Accepted: 11/26/2023] [Indexed: 12/06/2023] Open
Abstract
The pandemic of coronavirus disease 2019 (COVID-19) caused by the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a significant impact on the economy and public health worldwide. Therapeutic options such as drugs and vaccines for this newly emerged disease are eagerly desired due to the high mortality. Using the U.S. Food and Drug Administration (FDA) approved drugs to treat a new disease or entirely different diseases, in terms of drug repurposing, minimizes the time and cost of drug development compared to the de novo design of a new drug. Drug repurposing also has some other advantages such as reducing safety evaluation to accelerate drug application on time. Carvedilol, a non-selective beta-adrenergic blocker originally designed to treat high blood pressure and manage heart disease, has been shown to impact SARS-CoV-2 infection in clinical observation and basic studies. Here, we applied computer-aided approaches to investigate the possibility of repurposing carvedilol to combat SARS-CoV-2 infection. The molecular mechanisms and potential molecular targets of carvedilol were identified by evaluating the interactions of carvedilol with viral proteins. Additionally, the binding affinities of in vivo metabolites of carvedilol with selected targets were evaluated. The docking scores for carvedilol and its metabolites with RdRp were - 10.0 kcal/mol, - 9.8 kcal/mol (1-hydroxyl carvedilol), - 9.7 kcal/mol (3-hydroxyl carvedilol), - 9.8 kcal/mol (4-hydroxyl carvedilol), - 9.7 kcal/mol (5-hydroxyl carvedilol), - 10.0 kcal/mol (8-hydroxyl carvedilol), and - 10.1 kcal/mol (O-desmethyl carvedilol), respectively. Using the molecular dynamics simulation (100 ns) method, we further confirmed the stability of formed complexes of RNA-dependent RNA polymerase (RdRp) and carvedilol or its metabolites. Finally, the drug-target interaction mechanisms that contribute to the complex were investigated. Overall, this study provides the molecular targets and mechanisms of carvedilol and its metabolites as repurposed drugs to fight against SARS-CoV-2 infection.
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Affiliation(s)
- Chunye Zhang
- Christopher S. Bond Life Sciences Center, University of Missouri, Columbia, MO, 65212, USA
| | - Jiazheng Liu
- State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Taipa, Macau, 999078, China
| | - Yuxiang Sui
- School of Life Science, Shanxi Normal University, Linfen, 041004, Shanxi, China
| | - Shuai Liu
- The First Affiliated Hospital, Zhejiang University, Hangzhou, 310006, Zhejiang, China
| | - Ming Yang
- Department of Surgery, University of Missouri, Columbia, MO, 65212, USA.
- NextGen Precision Health Institution, University of Missouri, Columbia, MO, 65212, USA.
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3
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Zhao SW, Li YM, Li YL, Su C. Liver injury in COVID-19: Clinical features, potential mechanisms, risk factors and clinical treatments. World J Gastroenterol 2023; 29:241-256. [PMID: 36687127 PMCID: PMC9846943 DOI: 10.3748/wjg.v29.i2.241] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Revised: 11/11/2022] [Accepted: 12/08/2022] [Indexed: 01/06/2023] Open
Abstract
The coronavirus disease 2019 (COVID-19) pandemic has been a serious threat to global health for nearly 3 years. In addition to pulmonary complications, liver injury is not uncommon in patients with novel COVID-19. Although the prevalence of liver injury varies widely among COVID-19 patients, its incidence is significantly increased in severe cases. Hence, there is an urgent need to understand liver injury caused by COVID-19. Clinical features of liver injury include detectable liver function abnormalities and liver imaging changes. Liver function tests, computed tomography scans, and ultrasound can help evaluate liver injury. Risk factors for liver injury in patients with COVID-19 include male sex, preexisting liver disease including liver transplantation and chronic liver disease, diabetes, obesity, and hypertension. To date, the mechanism of COVID-19-related liver injury is not fully understood. Its pathophysiological basis can generally be explained by systemic inflammatory response, hypoxic damage, ischemia-reperfusion injury, and drug side effects. In this review, we systematically summarize the existing literature on liver injury caused by COVID-19, including clinical features, underlying mechanisms, and potential risk factors. Finally, we discuss clinical management and provide recommendations for the care of patients with liver injury.
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Affiliation(s)
- Shu-Wu Zhao
- Department of Anesthesiology, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Changsha 410013, Hunan Province, China
| | - Yi-Ming Li
- School of Basic Medical Science, Naval Medical University/Second Military University, Shanghai 200433, China
| | - Yi-Lin Li
- Department of Pathology, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Changsha 410013, Hunan Province, China
| | - Chen Su
- Department of Anesthesiology and Pain, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Changsha 410013, Hunan Province, China
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4
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Manna PR, Gray ZC, Sikdar M, Reddy H. COVID-19 and its genomic variants: Molecular pathogenesis and therapeutic interventions. EXCLI JOURNAL 2022; 21:1196-1221. [PMID: 36381644 PMCID: PMC9650701 DOI: 10.17179/excli2022-5315] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/10/2022] [Accepted: 09/05/2022] [Indexed: 11/25/2022]
Abstract
Coronavirus disease-19 (COVID-19), caused by a β-coronavirus and its genomic variants, is associated with substantial morbidities and mortalities globally. The COVID-19 virus and its genomic variants enter host cells upon binding to the angiotensin converting enzyme 2 receptors that are expressed in a variety of tissues, but predominantly in the lungs, heart, and blood vessels. Patients afflicted with COVID-19 may be asymptomatic or present with critical symptoms possibly due to diverse lifestyles, immune responses, aging, and underlying medical conditions. Geriatric populations, especially men in comparison to women, with immunocompromised conditions, are most vulnerable to severe COVID-19 associated infections, complications, and mortalities. Notably, whereas immunomodulation, involving nutritional consumption, is essential to protecting an individual from COVID-19, immunosuppression is detrimental to a person with this aggressive disease. As such, immune health is inversely correlated to COVID-19 severity and resulting consequences. Advances in genomic and proteomic technologies have helped us to understand the molecular events underlying symptomatology, transmission and, pathogenesis of COVID-19 and its genomic variants. Accordingly, there has been development of a variety of therapeutic interventions, ranging from mask wearing to vaccination to medication. This review summarizes the current understanding of molecular pathogenesis of COVID-19, effects of comorbidities on COVID-19, and prospective therapeutic strategies for the prevention and treatment of this contagious disease.
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Affiliation(s)
- Pulak R. Manna
- Department of Internal Medicine, Texas Tech University Health Sciences Center, School of Medicine, Lubbock, TX 79430, USA,*To whom correspondence should be addressed: Pulak R. Manna, Department of Internal Medicine, Texas Tech University Health Sciences Center, School of Medicine, Lubbock, TX 79430, USA; Tel: +1-806-743-3573, Fax: +1-806-743-3143, E-mail:
| | - Zackery C. Gray
- Department of Internal Medicine, Texas Tech University Health Sciences Center, School of Medicine, Lubbock, TX 79430, USA
| | - Malabika Sikdar
- Department of Zoology, Dr. Hari Singh Gour Vishwavidyalaya, Sagar, MP 470003, India
| | - Hemachandra Reddy
- Department of Internal Medicine, Texas Tech University Health Sciences Center, School of Medicine, Lubbock, TX 79430, USA,Department of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA,Neurology, Departments of School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA,Public Health Department of the Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA,Department of Speech, Language and Hearing Sciences, School Health Professions, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA,Nutritional Sciences Department, College of Human Sciences, Texas Tech University, Lubbock, TX 79409, USA
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5
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Elahi R, Karami P, Heidary AH, Esmaeilzadeh A. An updated overview of recent advances, challenges, and clinical considerations of IL-6 signaling blockade in severe coronavirus disease 2019 (COVID-19). Int Immunopharmacol 2022; 105:108536. [PMID: 35074571 PMCID: PMC8747952 DOI: 10.1016/j.intimp.2022.108536] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2021] [Revised: 01/01/2022] [Accepted: 01/07/2022] [Indexed: 02/07/2023]
Abstract
Since 2019, COVID-19 has become the most important health dilemma around the world. The dysregulated immune response which results in ARDS and cytokine storm has an outstanding role in the progression of pulmonary damage in COVID-19. IL-6, through induction of pro-inflammatory chemokines and cytokines, is the pioneer of the hyperinflammatory condition and cytokine storm in severe COVID-19. Therefore, IL-6 pathway blockade is considered an emerging approach with high efficacy to reduce lung damage in COVID-19. This article aims to review the pleiotropic roles of the IL-6 pathway in lung damage and ARDS in severe COVID-19, and the rationale for IL-6 signaling blockade at different levels, including IL-6 soluble and membrane receptor pathways, IL-6 downstream signaling (such as JAK-STAT) inhibition, and non-specific anti-inflammatory therapeutic approaches. Recent clinical data of each method, with specific concentration on tocilizumab, along with other new drugs, such as sarilumab and siltuximab, have been discussed. Challenges of IL-6 signaling inhibition, such as the risk of superinfection and hepatic injury, and possible solutions have also been explained. Moreover, to achieve the highest efficacy, ongoing clinical trials and special clinical considerations of using different IL-6 inhibitors have been discussed in detail. Special considerations, including the appropriate timing and dosage, monotherapy or combination therapy, and proper side effect managment must be noticed regarding the clinical administration of these drugs. Future studies are still necessary to improve the productivity and unknown aspects of IL-6 signaling blockade for personalized treatment of severe COVID-19.
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Affiliation(s)
- Reza Elahi
- Zanjan University of Medical Sciences, Zanjan, Iran
| | - Parsa Karami
- School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | | | - Abdolreza Esmaeilzadeh
- Department of Immunology, Zanjan University of Medical Sciences, Zanjan, Iran; Cancer Gene Therapy Research Center (CGRC), Zanjan University of Medical Sciences, Zanjan, Iran.
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6
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Chandra A, Johri A. A Peek into Pandora’s Box: COVID-19 and Neurodegeneration. Brain Sci 2022; 12:brainsci12020190. [PMID: 35203953 PMCID: PMC8870638 DOI: 10.3390/brainsci12020190] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Revised: 01/27/2022] [Accepted: 01/28/2022] [Indexed: 02/07/2023] Open
Abstract
Ever since it was first reported in Wuhan, China, the coronavirus-induced disease of 2019 (COVID-19) has become an enigma of sorts with ever expanding reports of direct and indirect effects of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on almost all the vital organ systems. Along with inciting acute pulmonary complications, the virus attacks the cardiac, renal, hepatic, and gastrointestinal systems as well as the central nervous system (CNS). The person-to-person variability in susceptibility of individuals to disease severity still remains a puzzle, although the comorbidities and the age/gender of a person are believed to play a key role. SARS-CoV-2 needs angiotensin-converting enzyme 2 (ACE2) receptor for its infectivity, and the association between SARS-CoV-2 and ACE2 leads to a decline in ACE2 activity and its neuroprotective effects. Acute respiratory distress may also induce hypoxia, leading to increased oxidative stress and neurodegeneration. Infection of the neurons along with peripheral leukocytes’ activation results in proinflammatory cytokine release, rendering the brain more susceptible to neurodegenerative changes. Due to the advancement in molecular biology techniques and vaccine development programs, the world now has hope to relatively quickly study and combat the deadly virus. On the other side, however, the virus seems to be still evolving with new variants being discovered periodically. In keeping up with the pace of this virus, there has been an avalanche of studies. This review provides an update on the recent progress in adjudicating the CNS-related mechanisms of SARS-CoV-2 infection and its potential to incite or accelerate neurodegeneration in surviving patients. Current as well as emerging therapeutic opportunities and biomarker development are highlighted.
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7
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Akbarzadehlaleh P, Farjami A, Montazersaheb S, Soofiyani S, Salatin S. Biopharmaceuticals for prevention of COVID-19: A scoping review. ASIAN PAC J TROP MED 2022. [DOI: 10.4103/1995-7645.348158] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
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8
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Zhang J, Zhang H, Sun L. Therapeutic antibodies for COVID-19: is a new age of IgM, IgA and bispecific antibodies coming? MAbs 2022; 14:2031483. [PMID: 35220888 PMCID: PMC8890389 DOI: 10.1080/19420862.2022.2031483] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Revised: 01/13/2022] [Accepted: 01/16/2022] [Indexed: 12/23/2022] Open
Abstract
Early humoral immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are dominated by IgM and IgA antibodies, which greatly contribute to virus neutralization at mucosal sites. Given the essential roles of IgM and IgA in the control and elimination of SARS-CoV-2 infection, the mucosal immunity could be exploited for therapeutic and prophylactic purposes. However, almost all neutralizing antibodies that are authorized for emergency use and under clinical development are IgG antibodies, and no vaccine has been developed to boost mucosal immunity for SARS-CoV-2 infection. In addition to IgM and IgA, bispecific antibodies (bsAbs) combine specificities of two antibodies in one molecule, representing an important alternative to monoclonal antibody cocktails. Here, we summarize the latest advances in studies on IgM, IgA and bsAbs against SARS-CoV-2. The current challenges and future directions in vaccine design and antibody-based therapeutics are also discussed.
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Affiliation(s)
- Jingjing Zhang
- Department of Pathogens and Infectious Disease Prevention and Control, School of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen, 518107China
| | - Han Zhang
- Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, Yunnan, China, 650118
| | - Litao Sun
- Department of Pathogens and Infectious Disease Prevention and Control, School of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen, 518107China
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9
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Allegretti M, Cesta MC, Zippoli M, Beccari A, Talarico C, Mantelli F, Bucci EM, Scorzolini L, Nicastri E. Repurposing the estrogen receptor modulator raloxifene to treat SARS-CoV-2 infection. Cell Death Differ 2022; 29:156-166. [PMID: 34404919 PMCID: PMC8370058 DOI: 10.1038/s41418-021-00844-6] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Revised: 07/09/2021] [Accepted: 07/25/2021] [Indexed: 12/15/2022] Open
Abstract
The ongoing coronavirus disease 2019 (COVID-19) pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) necessitates strategies to identify prophylactic and therapeutic drug candidates to enter rapid clinical development. This is particularly true, given the uncertainty about the endurance of the immune memory induced by both previous infections or vaccines, and given the fact that the eradication of SARS-CoV-2 might be challenging to reach, given the attack rate of the virus, which would require unusually high protection by a vaccine. Here, we show how raloxifene, a selective estrogen receptor modulator with anti-inflammatory and antiviral properties, emerges as an attractive candidate entering clinical trials to test its efficacy in early-stage treatment COVID-19 patients.
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Affiliation(s)
| | | | | | | | | | | | - Enrico M Bucci
- Sbarro Health Research Organization, Biology Department CFT, Temple University, Philadelphia, PA, USA
| | - Laura Scorzolini
- Lazzaro Spallanzani National Institute for Infectious Diseases, IRCCS, Rome, Italy
| | - Emanuele Nicastri
- Lazzaro Spallanzani National Institute for Infectious Diseases, IRCCS, Rome, Italy
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Kunnumakkara AB, Rana V, Parama D, Banik K, Girisa S, Henamayee S, Thakur KK, Dutta U, Garodia P, Gupta SC, Aggarwal BB. COVID-19, cytokines, inflammation, and spices: How are they related? Life Sci 2021; 284:119201. [PMID: 33607159 PMCID: PMC7884924 DOI: 10.1016/j.lfs.2021.119201] [Citation(s) in RCA: 55] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2020] [Revised: 01/20/2021] [Accepted: 01/30/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND Cytokine storm is the exaggerated immune response often observed in viral infections. It is also intimately linked with the progression of COVID-19 disease as well as associated complications and mortality. Therefore, targeting the cytokine storm might help in reducing COVID-19-associated health complications. The number of COVID-19 associated deaths (as of January 15, 2021; https://www.worldometers.info/coronavirus/) in the USA is high (1199/million) as compared to countries like India (110/million). Although the reason behind this is not clear, spices may have some role in explaining this difference. Spices and herbs are used in different traditional medicines, especially in countries such as India to treat various chronic diseases due to their potent antioxidant and anti-inflammatory properties. AIM To evaluate the literature available on the anti-inflammatory properties of spices which might prove beneficial in the prevention and treatment of COVID-19 associated cytokine storm. METHOD A detailed literature search has been conducted on PubMed for collecting information pertaining to the COVID-19; the history, origin, key structural features, and mechanism of infection of SARS-CoV-2; the repurposed drugs in use for the management of COVID-19, and the anti-inflammatory role of spices to combat COVID-19 associated cytokine storm. KEY FINDINGS The literature search resulted in numerous in vitro, in vivo and clinical trials that have reported the potency of spices to exert anti-inflammatory effects by regulating crucial molecular targets for inflammation. SIGNIFICANCE As spices are derived from Mother Nature and are inexpensive, they are relatively safer to consume. Therefore, their anti-inflammatory property can be exploited to combat the cytokine storm in COVID-19 patients. This review thus focuses on the current knowledge on the role of spices for the treatment of COVID-19 through suppression of inflammation-linked cytokine storm.
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Affiliation(s)
- Ajaikumar B Kunnumakkara
- Cancer Biology Laboratory and DBT-AIST International Center for Translational and Environmental Research (DAICENTER), Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam 781039, India.
| | - Varsha Rana
- Cancer Biology Laboratory and DBT-AIST International Center for Translational and Environmental Research (DAICENTER), Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam 781039, India
| | - Dey Parama
- Cancer Biology Laboratory and DBT-AIST International Center for Translational and Environmental Research (DAICENTER), Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam 781039, India
| | - Kishore Banik
- Cancer Biology Laboratory and DBT-AIST International Center for Translational and Environmental Research (DAICENTER), Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam 781039, India
| | - Sosmitha Girisa
- Cancer Biology Laboratory and DBT-AIST International Center for Translational and Environmental Research (DAICENTER), Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam 781039, India
| | - Sahu Henamayee
- Cancer Biology Laboratory and DBT-AIST International Center for Translational and Environmental Research (DAICENTER), Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam 781039, India
| | - Krishan Kumar Thakur
- Cancer Biology Laboratory and DBT-AIST International Center for Translational and Environmental Research (DAICENTER), Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam 781039, India
| | - Uma Dutta
- Cell and Molecular Biology Lab, Department of Zoology, Cotton University, Guwahati, Assam 781001, India
| | | | - Subash C Gupta
- Department of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi 221005, India
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11
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Sonzogni-Desautels K, Ndao M. Will Auranofin Become a Golden New Treatment Against COVID-19? Front Immunol 2021; 12:683694. [PMID: 34630379 PMCID: PMC8492993 DOI: 10.3389/fimmu.2021.683694] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Accepted: 09/06/2021] [Indexed: 12/15/2022] Open
Abstract
Auranofin is an FDA-approved disease-modifying anti-rheumatic drug that has been used for decades for treatment of rheumatoid arthritis. This gold(I) compound has anti-inflammatory properties because it reduces IL-6 expression via inhibition of the NF-κB-IL-6-STAT3 signaling pathway. Also, by inhibiting redox enzymes such as thioredoxin reductase, auranofin increases cellular oxidative stress and promotes apoptosis. Auranofin also possesses antiviral properties. Recently, it was reported that auranofin reduced by 95% SARS-CoV-2 RNA in infected human cells in vitro and decreased SARS-CoV-2-induced cytokine expression, including IL-6. During SARS-CoV-2 infection, a cytokine storm involving IL-6 increases severity of illness and worsens prognosis. Therefore, auranofin could, in our point of view, reduce pathology due to SARS-CoV-2-induced IL-6. COVID-19 is a rapidly-evolving respiratory disease now distributed worldwide. Strikingly high numbers of new COVID-19 cases are reported daily. We have begun a race to vaccinate people, but due to the complex logistics of this effort, the virus will continue to spread before all humans can be immunized, and new variants that may be less well contained by current vaccines are of concern. The COVID-19 pandemic has overwhelmed health care systems and new treatments to reduce mortality are urgently needed. We encourage to further evaluate the potential of auranofin in the treatment of COVID-19 in vitro and in animal models of SARS-CoV-2 infection and, if preliminary data are promising, in clinical trials with COVID-19 patients. In our opinion, auranofin has the potential to become a valuable addition to available therapies in this pandemic.
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Affiliation(s)
- Karine Sonzogni-Desautels
- Infectious Diseases and Immunity in Global Health Program, Research Institute of the McGill University Health Centre, Montreal, QC, Canada.,Department of Microbiology and Immunology, Faculty of Medicine and Health Sciences, McGill University, Montreal, QC, Canada
| | - Momar Ndao
- Infectious Diseases and Immunity in Global Health Program, Research Institute of the McGill University Health Centre, Montreal, QC, Canada.,Department of Microbiology and Immunology, Faculty of Medicine and Health Sciences, McGill University, Montreal, QC, Canada.,National Reference Centre for Parasitology, Research Institute of the McGill University Health Centre, Montreal, QC, Canada
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12
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Esmaeilzadeh A, Rostami S, Yeganeh PM, Tahmasebi S, Ahmadi M. Recent advances in antibody-based immunotherapy strategies for COVID-19. J Cell Biochem 2021; 122:1389-1412. [PMID: 34160093 PMCID: PMC8427040 DOI: 10.1002/jcb.30017] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2021] [Revised: 05/12/2021] [Accepted: 05/17/2021] [Indexed: 01/09/2023]
Abstract
The emergence of a new acute respiratory syndrome Coronavirus 2 (SARS-CoV-2), the cause of the 2019-nCOV disease (COVID-19), has caused a pandemic and a global health crisis. Rapid human-to-human transmission, even from asymptomatic individuals, has led to the quick spread of the virus worldwide, causing a wide range of clinical manifestations from cold-like symptoms to severe pneumonia, acute respiratory distress syndrome (ARDS), multiorgan injury, and even death. Therefore, using rapid and accurate diagnostic methods to identify the virus and subsequently select appropriate and effective treatments can help improvement of patients and control the pandemic. So far, various treatment regimens along with prophylactic vaccines have been developed to manage COVID-19-infected patients. Among these, antibody-based therapies, including neutralizing antibodies (against different parts of the virus), polyclonal and monoclonal antibodies, plasma therapy, and high-dose intravenous immunoglobulin (IVIG) have shown promising outcomes in accelerating and improving the treatment process of patients, avoiding the viral spreading widely, and managing the pandemic. In the current review paper, different types and applications of therapeutic antibodies in the COVID-19 treatment are comprehensively discussed.
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Affiliation(s)
- Abdolreza Esmaeilzadeh
- Department of Immunology, School of MedicineZanjan University of Medical SciencesZanjanIran
- Immunotherapy Research and Technology GroupZanjan University of Medical SciencesZanjanIran
| | - Samaneh Rostami
- Department of immunology, School of medicineZanjan University of Medical SciencesZanjanIran
| | - Pegah M. Yeganeh
- Department of immunology, School of medicineZanjan University of Medical SciencesZanjanIran
| | - Safa Tahmasebi
- Department of Immunology, School of Public HealthTehran University of Medical SciencesTehranIran
| | - Majid Ahmadi
- Stem Cell Research CenterTabriz University of Medical SciencesTabrizIran
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13
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Guo Z, Zhang Z, Prajapati M, Li Y. Lymphopenia Caused by Virus Infections and the Mechanisms Beyond. Viruses 2021; 13:v13091876. [PMID: 34578457 PMCID: PMC8473169 DOI: 10.3390/v13091876] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2021] [Revised: 09/14/2021] [Accepted: 09/18/2021] [Indexed: 02/07/2023] Open
Abstract
Viral infections can give rise to a systemic decrease in the total number of lymphocytes in the blood, referred to as lymphopenia. Lymphopenia may affect the host adaptive immune responses and impact the clinical course of acute viral infections. Detailed knowledge on how viruses induce lymphopenia would provide valuable information into the pathogenesis of viral infections and potential therapeutic targeting. In this review, the current progress of viruses-induced lymphopenia is summarized and the potential mechanisms and factors involved are discussed.
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Affiliation(s)
- Zijing Guo
- State Key Laboratory on Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730030, China;
- College of Animal Husbandry and Veterinary Medicine, Southwest Minzu University, Chengdu 610041, China; (Z.Z.); (M.P.)
| | - Zhidong Zhang
- College of Animal Husbandry and Veterinary Medicine, Southwest Minzu University, Chengdu 610041, China; (Z.Z.); (M.P.)
| | - Meera Prajapati
- College of Animal Husbandry and Veterinary Medicine, Southwest Minzu University, Chengdu 610041, China; (Z.Z.); (M.P.)
- National Animal Health Research Centre, Nepal Agricultural Research Council, Lalitpur 44700, Nepal
| | - Yanmin Li
- College of Animal Husbandry and Veterinary Medicine, Southwest Minzu University, Chengdu 610041, China; (Z.Z.); (M.P.)
- Correspondence: ; Tel.: +28-85528276
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14
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Nezametdinova VZ, Yunes RA, Dukhinova MS, Alekseeva MG, Danilenko VN. The Role of the PFNA Operon of Bifidobacteria in the Recognition of Host's Immune Signals: Prospects for the Use of the FN3 Protein in the Treatment of COVID-19. Int J Mol Sci 2021; 22:ijms22179219. [PMID: 34502130 PMCID: PMC8430577 DOI: 10.3390/ijms22179219] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2021] [Revised: 08/21/2021] [Accepted: 08/24/2021] [Indexed: 12/11/2022] Open
Abstract
Bifidobacteria are some of the major agents that shaped the immune system of many members of the animal kingdom during their evolution. Over recent years, the question of concrete mechanisms underlying the immunomodulatory properties of bifidobacteria has been addressed in both animal and human studies. A possible candidate for this role has been discovered recently. The PFNA cluster, consisting of five core genes, pkb2, fn3, aaa-atp, duf58, tgm, has been found in all gut-dwelling autochthonous bifidobacterial species of humans. The sensory region of the species-specific serine-threonine protein kinase (PKB2), the transmembrane region of the microbial transglutaminase (TGM), and the type-III fibronectin domain-containing protein (FN3) encoded by the I gene imply that the PFNA cluster might be implicated in the interaction between bacteria and the host immune system. Moreover, the FN3 protein encoded by one of the genes making up the PFNA cluster, contains domains and motifs of cytokine receptors capable of selectively binding TNF-α. The PFNA cluster could play an important role for sensing signals of the immune system. Among the practical implications of this finding is the creation of anti-inflammatory drugs aimed at alleviating cytokine storms, one of the dire consequences resulting from SARS-CoV-2 infection.
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Affiliation(s)
- Venera Z. Nezametdinova
- Laboratory of Bacterial Genetics, The Vavilov Institute of General Genetics, 117971 Moscow, Russia; (V.Z.N.); (R.A.Y.); (M.G.A.)
| | - Roman A. Yunes
- Laboratory of Bacterial Genetics, The Vavilov Institute of General Genetics, 117971 Moscow, Russia; (V.Z.N.); (R.A.Y.); (M.G.A.)
| | - Marina S. Dukhinova
- International Institute ‘Solution Chemistry of Advanced Materials and Technologies’, ITMO University, 197101 Saint-Petersburg, Russia;
| | - Maria G. Alekseeva
- Laboratory of Bacterial Genetics, The Vavilov Institute of General Genetics, 117971 Moscow, Russia; (V.Z.N.); (R.A.Y.); (M.G.A.)
| | - Valery N. Danilenko
- Laboratory of Bacterial Genetics, The Vavilov Institute of General Genetics, 117971 Moscow, Russia; (V.Z.N.); (R.A.Y.); (M.G.A.)
- Correspondence:
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15
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Pinzon RT, Wijaya VO, Buana RB. Interleukin-6 (IL-6) inhibitors as therapeutic agents for coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis. J Infect Public Health 2021; 14:1001-1009. [PMID: 34153723 PMCID: PMC8204364 DOI: 10.1016/j.jiph.2021.06.004] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2021] [Revised: 05/29/2021] [Accepted: 06/01/2021] [Indexed: 02/08/2023] Open
Abstract
INTRODUCTION Preliminary studies showed that coronavirus disease 2019 (COVID-19) disrupts body immune system, including dysregulation of cytokine interleukin-6 (IL-6). IL-6 inhibitors agents have been used as treatment options for COVID-19, yet their benefit as therapeutic agents remains unclear. OBJECTIVE We performed a systematic review and meta-analysis to synthesize the available evidence on the potential therapeutic effect of IL-6 inhibitor agents for the treatment of COVID-19. METHODS Two authors initially screened and reviewed the relevant studies from available databases. The data extracted will be tabulated and analyzed for the outcomes. The primary outcome was mortality. Secondary outcomes included discharge from the hospital, length of stay, and requirement for mechanical ventilation. The quality of each study was assessed using OCEBM ratings. RESULTS We reviewed 18 studies with a total of 3303 subjects. Tocilizumab was the most commonly used in the studies (15 studies). Meta-analysis of included studies revealed significant reduction in mortality with tocilizumab and sarilumab (RR = 0.61, 95% CI 0.49-0.76). Other outcomes including hospital discharge (RR = 1.04, 95% CI 0.86-1.24), length of stay (mean difference -1.96 days, 95% CI -4.24 to 0.33) or requirement for mechanical ventilation (RR = 0.68, 95% CI 0.32-1.45) revealed no differences of IL-6 inhibitor agents compared to controls. CONCLUSIONS Available evidence suggests that IL-6 inhibitor agents reduce the risk of mortality in COVID-19, especially in severe conditions. Further well-designed trials are needed for assessing its efficacy and safety for COVID-19.
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Affiliation(s)
- Rizaldy Taslim Pinzon
- Faculty of Medicine, Duta Wacana Christian University, Yogyakarta, Indonesia; Bethesda Hospital, Yogyakarta, Indonesia.
| | - Vincent Ongko Wijaya
- Faculty of Medicine, Duta Wacana Christian University, Yogyakarta, Indonesia; Bethesda Hospital, Yogyakarta, Indonesia
| | - Ranbebasa Bijak Buana
- Faculty of Medicine, Duta Wacana Christian University, Yogyakarta, Indonesia; Bethesda Hospital, Yogyakarta, Indonesia
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16
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Goyal M, Tewatia N, Vashisht H, Jain R, Kumar S. Novel corona virus (COVID-19); Global efforts and effective investigational medicines: A review. J Infect Public Health 2021; 14:910-921. [PMID: 34119845 PMCID: PMC8088038 DOI: 10.1016/j.jiph.2021.04.011] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Revised: 04/05/2021] [Accepted: 04/25/2021] [Indexed: 12/23/2022] Open
Abstract
Coronavirus disease-2019 (COVID-19), associated with the outbreak of deadly virus originating in Wuhan, China, is now a global health emergency and a matter of serious concern. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is rapidly spreading worldwide, and WHO declared the outbreak of this disease a pandemic on March 11, 2020. Though some of the countries have succeeded in slowing down the rate of the spread of this pandemic, most the countries across the globe are still continuing to experience an increasing trend in the growth and spread of this deadly disease. Hence, in the current scenario, is has now become essential to control and finally irradicate this deadly disease using an effective vaccine. One can expect the prominent role of already available antivirals, antibodies and anti-inflammatory drugs in the market, in this pandemic. Immunomodulatory and biological therapeutics are also in the high expectations to combat COVID-19. RNA based vaccines might be more advantageous over traditional vaccines, to deal with the pandemic threat. Aiming towards this direction, clinical trials for SARS-CoV-2 vaccine are currently underway all across the globe. Currently, about 150 health related organizations and research labs are in the progress for the evolution of COVID-19 vaccines, globally. The initial aim of these clinical trials is to assess vaccine's safety, which is tested in Phase I/II/III studies where the primary outcomes typically examine the frequency of adverse effects. The vaccine is about to undergo phase III testing in several countries such as India, USA, South Africa, Brazil and England. US Government, under Operation Wrap Speed is even ready to sponsor three candidates, namely-The University of Oxford and AstraZeneca's AZD1222; Moderna's mRNA-1273; and Pfizer and BioNTech's BNT162 for Phase III trials.
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Affiliation(s)
- Madhusudan Goyal
- Department of Chemistry, Pt. J.L.N. Government College, Department of Higher Education, Faridabad 121002, Haryana, India.
| | - Nisha Tewatia
- Department of Chemistry, Pt. J.L.N. Government College, Department of Higher Education, Faridabad 121002, Haryana, India
| | - Hemlata Vashisht
- Department of Chemistry, Kirori Mal College, University of Delhi, Delhi 110007, India
| | - Reena Jain
- Department of Chemistry, Hindu College, University of Delhi, Delhi 110007,India
| | - Sudershan Kumar
- Department of Chemistry, Hindu College, University of Delhi, Delhi 110007,India
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17
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Jiang J, Wang J, Yao L, Lai S, Zhang X. What do we know about IL-6 in COVID-19 so far? BIOPHYSICS REPORTS 2021; 7:193-206. [PMID: 37287491 PMCID: PMC10244797 DOI: 10.52601/bpr.2021.200024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Accepted: 04/01/2021] [Indexed: 11/05/2022] Open
Abstract
Interleukin 6 (IL-6) is a cytokine with dual functions of pro-inflammation and anti-inflammation. It is mainly produced by mononuclear macrophages, Th2 cells, vascular endothelial cells and fibroblasts. IL-6 binds to glycoprotein 130 and one of these two receptors, membrane-bound IL-6R or soluble IL-6R, forming hexamer (IL-6/IL-6R/gp130), which then activates different signaling pathways (classical pathway, trans-signaling pathway) to exert dual immune-modulatory effects of anti-inflammation or pro-inflammation. Abnormal levels of IL-6 can cause multiple pathological reactions, including cytokine storm. Related clinical studies have found that IL-6 levels in severe COVID-19 patients were much higher than in healthy population. A large number of studies have shown that IL-6 can trigger a downstream cytokine storm in patients with COVID-19, resulting in lung damages, aggravating clinical symptoms and developing excessive inflammation and acute respiratory distress syndrome (ARDS). Monoclonal antibodies against IL-6 or IL-6R, such as tocilizumab, sarilumab, siltuximab and olokizumab may serve as therapeutic options for COVID-19 infection.
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Affiliation(s)
- Jingrui Jiang
- Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- Department of Biomedicine and Biopharmacology, Hubei University of Technology, Wuhan 430068, China
| | - Jun Wang
- Department of Biomedicine and Biopharmacology, Hubei University of Technology, Wuhan 430068, China
- National 111 Center for Cellular Regulation and Molecular Pharmaceutics, Wuhan 430068, China
| | - Lulu Yao
- Department of Biomedicine and Biopharmacology, Hubei University of Technology, Wuhan 430068, China
- National 111 Center for Cellular Regulation and Molecular Pharmaceutics, Wuhan 430068, China
| | - Shenghan Lai
- Department of Pathology, Johns Hopkins University School of Medicine, MD 21287, USA
| | - Xueji Zhang
- Guangdong Laboratory of Artificial Intelligence and Digital Economy (SZ), School of Biomedical Engineering, Shenzhen University, Shenzhen 518037, Guangdong, China
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18
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Bakhshandeh B, Sorboni SG, Javanmard AR, Mottaghi SS, Mehrabi MR, Sorouri F, Abbasi A, Jahanafrooz Z. Variants in ACE2; potential influences on virus infection and COVID-19 severity. INFECTION, GENETICS AND EVOLUTION : JOURNAL OF MOLECULAR EPIDEMIOLOGY AND EVOLUTIONARY GENETICS IN INFECTIOUS DISEASES 2021; 90:104773. [PMID: 33607284 PMCID: PMC7886638 DOI: 10.1016/j.meegid.2021.104773] [Citation(s) in RCA: 64] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/14/2020] [Revised: 02/08/2021] [Accepted: 02/12/2021] [Indexed: 02/07/2023]
Abstract
The third pandemic of coronavirus infection, called COVID-19 disease, was first detected in November 2019th. Various determinants of disease progression such as age, sex, virus mutations, comorbidity, lifestyle, host immune response, and genetic background variation have caused clinical variability of COVID-19. The causative agent of COVID-19 is an enveloped coronavirus named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that invades host cells using an endocytic pathway. The SARS-CoV-2 spike protein is the main viral protein that contributes to the fusion of the virus particle to the host cell through angiotensin-converting enzyme 2 (ACE2). The highly conserved expression of ACE2 is found in various animals, which indicates its pivotal physiological function. The ACE2 has a crucial role in vascular, renal, and myocardial physiology. Genetic factors contributing to the outcome of SARS-CoV-2 infection are unknown; however, variants in the specific sites of ACE2 gene could be regarded as a main genetic risk factor for COVID-19. Given that ACE2 is the main site for virus landing on host cells, the effect of amino acid sequences of ACE2 on host susceptibility to COVID-19 seems reasonable. It would likely have a substantial role in the occurrence of a wide range of clinical symptoms. Several ACE2 variants can affect the protein stability, influencing the interaction between spike protein and ACE2 through imposing conformational changes while some other variants are known to cause a decrease or an increase in the ligand-receptor affinity. The other variations are located at the proteolytic cleavage site, which can influence virus infection; because soluble ACE2 can act as a decoy receptor for virus and decrease virus intake by cell surface ACE2. Notably, polymorphisms of regulatory and non-coding regions such as promoter in ACE2, can play crucial role in different expression levels of ACE2 among different individuals. Many studies should be performed to investigate the involvement of ACE2 polymorphism with susceptibility to COVID-19. Herein, we discuss some reported associations between variants of ACE2 and COVID-19 in details. In addition, the mode of action of ACE2 and its role in SARS-CoV-2 infection are highlighted which is followed by addressing the effects of several ACE2 variants on its protein stability, viral tropism or ligand-receptor affinity, secondary and tertiary structure or protein conformation, proteolytic cleavage site, and finally inter-individual clinical variability in COVID-19. The polymorphisms of regulatory regions of ACE2 and their effect on expression levels of ACE2 are also provided in this review. Such studies can improve the prediction of the affinity of mutant ACE2 variations with spike protein, and help the biopharmaceutical industry to design effective approaches for recombinant hACE2 therapy and vaccination of COVID-19 disease.
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Affiliation(s)
- Behnaz Bakhshandeh
- Department of Biotechnology, College of Science, University of Tehran, Tehran, Iran; Department of Microbiology, School of Biology, College of Science, University of Tehran, Tehran, Iran.
| | | | - Amir-Reza Javanmard
- Molecular Genetics Department, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
| | - Seyed Saeed Mottaghi
- Department of Biotechnology, College of Science, University of Tehran, Tehran, Iran
| | - Mohammad-Reza Mehrabi
- Department of Microbial Biotechnology, School of Biology, College of Science, University of Tehran, Tehran, Iran
| | - Farzaneh Sorouri
- Department of Pharmaceutical Biomaterials, Faculty of Pharmacy, Tehran University of Medical Science, Tehran, Iran
| | - Ardeshir Abbasi
- Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Zohreh Jahanafrooz
- Department of Biology, Faculty of Sciences, University of Maragheh, Maragheh, Iran
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19
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Xu K, Wei Y, Giunta S, Zhou M, Xia S. Do inflammaging and coagul-aging play a role as conditions contributing to the co-occurrence of the severe hyper-inflammatory state and deadly coagulopathy during COVID-19 in older people? Exp Gerontol 2021; 151:111423. [PMID: 34048906 PMCID: PMC8149167 DOI: 10.1016/j.exger.2021.111423] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2020] [Revised: 05/22/2021] [Accepted: 05/24/2021] [Indexed: 12/19/2022]
Abstract
The coronavirus disease 2019 (COVID-19) is a new infectious respiratory disease, which has caused a pandemic that has become the world's leading public health emergency, threatening people of all ages worldwide, especially the elderly. Complications of COVID-19 are closely related to an upregulation of the inflammatory response revealed by the pro-inflammatory profile of plasma cytokines (to the point of causing a cytokine storm), which is also a contributing cause of the associated coagulation disorders with venous and arterial thromboembolisms, causing multiple organ dysfunction and failure. In severe fulminant cases of COVID-19, there is an activation of coagulation and consumption of clotting factors leading to a deadly disseminated intravascular coagulation (DIC). It is well established that human immune response changes with age, and also that the pro-inflammatory profile of plasma cytokines is upregulated in both healthy and diseased elderly people. In fact, normal aging is known to be associated with a subclinical, sterile, low-grade, systemic pro-inflammatory state linked to the chronic activation of the innate immune system, a phenomenon known as “inflammaging”. Inflammaging may play a role as a condition contributing to the co-occurrence of the severe hyper-inflammatory state (cytokine storm) during COVID-19, and also in other severe infections (sepsis) in older people. Moreover, we must consider the impact of inflammation on coagulation due to the crosstalk between inflammation and coagulation. The systemic inflammatory state and coagulation disorders are closely related, a phenomenon that here we call “coagul-aging” (Giunta S.). In this review, we discuss the various degrees of inflammation in older adults after being infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the adverse effects of aging on the inflammatory response and coagulation system. It is important to note that although there is no gender difference in susceptibility to COVID-19 infection, however, due to differences in angiotensin-converting enzyme 2 (ACE2) expression, innate immunity, and comorbidities, older men exhibit more severe disease and higher mortality than older women. There are currently no FDA-approved specific antiviral drugs that can be used against the virus. Therapies used in patients with COVID-19 consist of remdesivir, dexamethasone, low-molecular-weight heparin, in addition to monoclonal antibodies against the spike protein of SARS-CoV-2 in the early phase of the disease. Future pharmacological research should also consider targeting the possible role of the underlying scenario of inflammaging in healthy older people to prevent or mitigate disease complications. It is worth mentioning that some specific cytokine antagonists and traditional Chinese medicine preparations can reduce the elderly's inflammatory state.
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Affiliation(s)
- Kangqiao Xu
- Department of Geriatrics, Shanghai Institute of Geriatrics, Huadong Hospital, Fudan University, Shanghai, PR China.
| | - Yaqin Wei
- Department of Geriatrics, Shanghai Institute of Geriatrics, Huadong Hospital, Fudan University, Shanghai, PR China; School of Clinical Medicine, Bengbu Medical College, Bengbu, PR China
| | - Sergio Giunta
- Casa di Cura Prof. Nobili-GHC Garofalo Health Care, Bologna, Italy
| | - Min Zhou
- Department of Respiratory Diseases, Jinshan Branch of the Sixth People's Hospital of Shanghai, Shanghai Jiaotong University, Shanghai, PR China.
| | - Shijin Xia
- Department of Geriatrics, Shanghai Institute of Geriatrics, Huadong Hospital, Fudan University, Shanghai, PR China.
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20
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Deng ML, Chen YJ, Yang ML, Liu YW, Chen H, Tang XQ, Yang XF. COVID-19 combined with liver injury: Current challenges and management. World J Clin Cases 2021; 9:3487-3497. [PMID: 34046449 PMCID: PMC8130088 DOI: 10.12998/wjcc.v9.i15.3487] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Revised: 03/07/2021] [Accepted: 03/29/2021] [Indexed: 02/06/2023] Open
Abstract
Coronavirus disease 2019 (COVID-19) combined with liver injury has become a very prominent clinical problem. Due to the lack of a clear definition of liver injury in patients with COVID-19, the different selection of evaluation parameters and statistical time points, there are the conflicting conclusions about the incidence rate in different studies. The mechanism of COVID-19 combined with liver injury is complicated, including the direct injury of liver cells caused by severe acute respiratory syndrome coronavirus 2 replication and liver injury caused by cytokines, ischemia and hypoxia, and drugs. In addition, underlying diseases, especially chronic liver disease, can aggravate COVID-19 liver injury. In the treatment of COVID-19 combined with liver injury, the primary and basic treatment is to treat the etiology and pathogenesis, followed by support, liver protection, and symptomatic treatment according to the clinical classification and severity of liver injury. This article evaluates the incidence, pathogenesis and prevention and treatment of COVID-19 combined with liver injury, and aims to provide countermeasures for the prevention and treatment of COVID-19 combined with liver injury.
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Affiliation(s)
- Man-Ling Deng
- Department of Gastroenterology, The Affiliated Nanhua Hospital, Hengyang Medical College, University of South China, Hengyang 421002, Hunan Province, China
| | - Yong-Jun Chen
- Department of Neurology, The Affiliated Nanhua Hospital, Hengyang Medical College, University of South China, Hengyang 421002, Hunan Province, China
| | - Mei-Ling Yang
- Department of Oncology, The Affiliated Nanhua Hospital, Hengyang Medical College, University of South China, Hengyang 421002, Hunan Province, China
| | - Yi-Wen Liu
- Department of Gastroenterology, The Affiliated Nanhua Hospital, Hengyang Medical College, University of South China, Hengyang 421002, Hunan Province, China
| | - Hui Chen
- Department of Gastroenterology, The Affiliated Nanhua Hospital, Hengyang Medical College, University of South China, Hengyang 421002, Hunan Province, China
| | - Xiao-Qing Tang
- Institute of Clinical Medicine, The First Affiliated Hospital, Hengyang Medical College, University of South China, Hengyang 421001, Hunan Province, China
| | - Xue-Feng Yang
- Department of Gastroenterology, The Affiliated Nanhua Hospital, Hengyang Medical College, University of South China, Hengyang 421002, Hunan Province, China
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21
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Trovato M, Sciacchitano S, Facciolà A, Valenti A, Visalli G, Di Pietro A. Interleukin‑6 signalling as a valuable cornerstone for molecular medicine (Review). Int J Mol Med 2021; 47:107. [PMID: 33907833 PMCID: PMC8057292 DOI: 10.3892/ijmm.2021.4940] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Accepted: 03/23/2021] [Indexed: 12/14/2022] Open
Abstract
The biological abilities of interleukin-6 (IL-6) have been under investigation for nearly 40 years. IL-6 works through an interaction with the complex peptide IL-6 receptor (IL-6R). IL-6 is built with four α-chain nanostructures, while two different chains, IL-6Rα (gp80) and gp130/IL6β (gp130), are included in IL-6R. The three-dimensional shapes of the six chains composing the IL-6/IL-6R complex are the basis for the nanomolecular roles of IL-6 signalling. Genes, pseudogenes and competitive endogenous RNAs of IL-6 have been identified. In the present review, the roles played by miRNA in the post-transcriptional regulation of IL-6 expression are evaluated. mRNAs are absorbed via the 'sponge' effect to dynamically balance mRNA levels and this has been assessed with regard to IL-6 transcription efficiency. According to current knowledge on molecular and nanomolecular structures involved in active IL-6 signalling, two different IL-6 models have been proposed. IL-6 mainly has functions in inflammatory processes, as well as in cognitive activities. Furthermore, the abnormal production of IL-6 has been found in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; also known as COVID-19). In the present review, both inflammatory and cognitive IL-6 models were analysed by evaluating the cytological and histological locations of IL-6 signalling. The goal of this review was to illustrate the roles of the classic and trans-signalling IL-6 pathways in endocrine glands such as the thyroid and in the central nervous system. Specifically, autoimmune thyroid diseases, disorders of cognitive processes and SARS-CoV-2 virus infection have been examined to determine the contribution of IL-6 to these disease states.
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Affiliation(s)
- Maria Trovato
- Department of Clinical and Experimental Medicine, University Hospital, I‑98125 Messina, Italy
| | | | - Alessio Facciolà
- Department of Clinical and Experimental Medicine, University Hospital, I‑98125 Messina, Italy
| | - Andrea Valenti
- Department of Clinical and Experimental Medicine, University Hospital, I‑98125 Messina, Italy
| | - Giuseppa Visalli
- Department of Biomedical and Dental Sciences and Morphofunctional Imaging, Policlinico Universitario, I‑98125 Messina, Italy
| | - Angela Di Pietro
- Department of Biomedical and Dental Sciences and Morphofunctional Imaging, Policlinico Universitario, I‑98125 Messina, Italy
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22
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Savla SR, Prabhavalkar KS, Bhatt LK. Cytokine storm associated coagulation complications in COVID-19 patients: Pathogenesis and Management. Expert Rev Anti Infect Ther 2021; 19:1397-1413. [PMID: 33832398 PMCID: PMC8074652 DOI: 10.1080/14787210.2021.1915129] [Citation(s) in RCA: 46] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Introduction SARS-CoV-2, the causative agent of COVID-19, attacks the immune system causing an exaggerated and uncontrolled release of pro-inflammatory mediators (cytokine storm). Recent studies propose an active role of coagulation disorders in disease progression. This hypercoagulability has been displayed by marked increase in D-dimer in hospitalized patients. Areas Covered This review summarizes the pathogenesis of SARS-CoV-2 infection, generation of cytokine storm, the interdependence between inflammation and coagulation, its consequences and the possible management options for coagulation complications like venous thromboembolism (VTE), microthrombosis, disseminated intravascular coagulation (DIC), and systemic and local coagulopathy. We searched PubMed, Scopus, and Google Scholar for relevant reports using COVID-19, cytokine storm, and coagulation as keywords. Expert Opinion A prophylactic dose of 5000–7500 units of low molecular weight heparin (LMWH) has been recommended for hospitalized COVID-19 patients in order to prevent VTE. Treatment dose of LMWH, based on disease severity, is being contemplated for patients showing a marked rise in levels of D-dimer due to possible pulmonary thrombi. Additionally, targeting PAR-1, thrombin, coagulation factor Xa and the complement system may be potentially useful in reducing SARS-CoV-2 infection induced lung injury, microvascular thrombosis, VTE and related outcomes like DIC and multi-organ failure.
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Affiliation(s)
- Shreya R Savla
- Department of Pharmacology, Dr. Bhanuben Nanavati College of Pharmacy, Vile Parle (West), Mumbai, 400056, India
| | - Kedar S Prabhavalkar
- Department of Pharmacology, Dr. Bhanuben Nanavati College of Pharmacy, Vile Parle (West), Mumbai, 400056, India
| | - Lokesh K Bhatt
- Department of Pharmacology, Dr. Bhanuben Nanavati College of Pharmacy, Vile Parle (West), Mumbai, 400056, India
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23
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Valenzuela-Almada MO, Putman MS, Duarte-García A. The protective effect of rheumatic disease agents in COVID-19. Best Pract Res Clin Rheumatol 2021; 35:101659. [PMID: 33526326 PMCID: PMC7833968 DOI: 10.1016/j.berh.2021.101659] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Several immunosuppressive therapies have been investigated as potential treatments for patients with severe and critical coronavirus disease 2019 (COVID-19). Notable examples include corticosteroids, interleukin 6 (IL-6), interleukin 1 (IL-1), Janus kinase (JAK), and tumor necrosis factor alpha (TNF-α) inhibitors. The aim of this narrative review is to analyze the mechanistic rationale and available evidence for these selected anti-rheumatic drugs for the treatment of COVID-19. Currently, only corticosteroids have consistently proven to be effective in decreasing mortality and are recommended in clinical guidelines for the treatment of severe and critical COVID-19. Multiple randomized controlled trials (RCTs) are ongoing to determine the role of other immunosuppressants.
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Affiliation(s)
| | - Michael S Putman
- Division of Rheumatology, Medical College of Wisconsin, Milwaukee, WI, USA
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24
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Khorramdelazad H, Kazemi MH, Najafi A, Keykhaee M, Zolfaghari Emameh R, Falak R. Immunopathological similarities between COVID-19 and influenza: Investigating the consequences of Co-infection. Microb Pathog 2021; 152:104554. [PMID: 33157216 PMCID: PMC7607235 DOI: 10.1016/j.micpath.2020.104554] [Citation(s) in RCA: 71] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2020] [Revised: 09/25/2020] [Accepted: 09/29/2020] [Indexed: 02/06/2023]
Abstract
Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a global public health emergency since December 2019, and so far, more than 980,000 people (until September 24, 2020) around the world have died. SARS-CoV-2 mimics the influenza virus regarding methods and modes of transmission, clinical features, related immune responses, and seasonal coincidence. Accordingly, co-infection by these viruses is imaginable because some studies have reported several cases with SARS-CoV-2 and influenza virus co-infection. Given the importance of the mentioned co-infection and the coming influenza season, it is essential to recognize the similarities and differences between the symptoms, immunopathogenesis and treatment of SARS-CoV-2 and influenza virus. Therefore, we reviewed the virology, clinical features, and immunopathogenesis of both influenza virus and SARS-CoV-2 and evaluated outcomes in cases with SARS-CoV-2 and influenza virus co-infection.
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Affiliation(s)
- Hossein Khorramdelazad
- Department of Immunology, School of Medicine, Molecular Medicine Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran; Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Mohammad Hossein Kazemi
- Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran; Hematopoietic Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Alireza Najafi
- Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran; Immunology Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran
| | - Maryam Keykhaee
- Department of Pharmaceutical Biomaterials, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Reza Zolfaghari Emameh
- Department of Energy and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology (NIGEB), 14965/161, Tehran, Iran
| | - Reza Falak
- Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran; Immunology Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran.
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25
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Iluta S, Pasca S, Dima D, Mester G, Urian L, Bojan A, Zdrenghea M, Trifa A, Balacescu O, Tomuleasa C. Haematology patients infected with SARS-CoV-2, pretreated with eculizumab or siltuximab, develop oligosymptomatic disease. Eur J Hosp Pharm 2021; 29:e8. [PMID: 33541912 PMCID: PMC9614117 DOI: 10.1136/ejhpharm-2021-002694] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Affiliation(s)
- Sabina Iluta
- Department of Hematology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj Napoca, Romania
| | - Sergiu Pasca
- Medfuture Research Center for Advanced Medicine, Iuliu HaTieganu University of Medicine and Pharmacy Faculty of Medicine, Cluj Napoca, Romania
| | - Delia Dima
- Department of Hematology, Ion Chiricuta Oncology Institute, Cluj Napoca, Romania
| | - Gabriela Mester
- Department of Hematology, Ion Chiricuta Oncology Institute, Cluj Napoca, Romania
| | - Laura Urian
- Department of Hematology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj Napoca, Romania
| | - Anca Bojan
- Department of Hematology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj Napoca, Romania
| | - Mihnea Zdrenghea
- Department of Hematology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj Napoca, Romania
| | - Adrian Trifa
- Department of Hematology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj Napoca, Romania
| | - Ovidiu Balacescu
- Department of Genetics, Ion Chiricuta Oncology Institute, Cluj Napoca, Romania
| | - Ciprian Tomuleasa
- Department of Hematology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj Napoca, Romania .,Medfuture Research Center for Advanced Medicine, Iuliu HaTieganu University of Medicine and Pharmacy Faculty of Medicine, Cluj Napoca, Romania
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26
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Ni Y, Alu A, Lei H, Wang Y, Wu M, Wei X. Immunological perspectives on the pathogenesis, diagnosis, prevention and treatment of COVID-19. MOLECULAR BIOMEDICINE 2021; 2:1. [PMID: 34766001 PMCID: PMC7815329 DOI: 10.1186/s43556-020-00015-y] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2020] [Accepted: 10/21/2020] [Indexed: 02/08/2023] Open
Abstract
Coronavirus disease 2019 (COVID-19) is an acute respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-COV-2). COVID-19 can spread to the entire body and cause multiple organ failure. It is a daunting challenge to control the fast growing worldwide pandemic because effective prevention and treatment strategies are unavailable currently. Generally, the immune response of the human body triggered by viral infection is essential for the elimination of the virus. However, severe COVID-19 patients may manifest dysregulated immune responses, such as lymphopenia, lymphocyte exhaustion, exacerbated antibody response, cytokine release syndrome (CRS), etc. Understanding of these immunological characteristics may help identify better approaches for diagnosis, prognosis and treatment of COVID-19 patients. As specific anti-viral agents are notoriously difficult to develop, strategies for modulating the immune responses by either developing novel vaccines or using immunotherapy hold great promise to improve the management of SARS-CoV-2 infection.
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Affiliation(s)
- Yanghong Ni
- Laboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041 China
- Department of Gynecology and Obstetrics, Development and Related Disease of Women and Children Key Laboratory of Sichuan Province, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second Hospital, Sichuan University, Chengdu, 610041 P. R. China
| | - Aqu Alu
- Laboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041 China
| | - Hong Lei
- Laboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041 China
| | - Yang Wang
- Laboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041 China
| | - Min Wu
- Department of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND 58203 USA
| | - Xiawei Wei
- Laboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041 China
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27
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Li L, Li J, Gao M, Fan H, Wang Y, Xu X, Chen C, Liu J, Kim J, Aliyari R, Zhang J, Jin Y, Li X, Ma F, Shi M, Cheng G, Yang H. Interleukin-8 as a Biomarker for Disease Prognosis of Coronavirus Disease-2019 Patients. Front Immunol 2021; 11:602395. [PMID: 33488599 PMCID: PMC7820901 DOI: 10.3389/fimmu.2020.602395] [Citation(s) in RCA: 95] [Impact Index Per Article: 23.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Accepted: 11/26/2020] [Indexed: 12/21/2022] Open
Abstract
The widespread prevalence of coronavirus disease-2019 (COVID-19) which is caused by severe respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has resulted in a severe global public health emergency. However, there are no sensitive biomarkers to predict the disease prognosis of COVID-19 patients. Here, we have identified interleukin-8 (IL-8) as a biomarker candidate to predict different disease severity and prognosis of COVID-19 patients. While serum IL-6 become obviously elevated in severe COVID-19 patients, serum IL-8 was easily detectible in COVID-19 patients with mild syndromes. Furthermore, lL-8 levels correlated better than IL-6 levels with the overall clinical disease scores at different stages of the same COVID-19 patients. Thus, our studies suggest that IL-6 and IL-8 can be respectively used as biomarkers for severe COVID-19 patients and for COVID-19 disease prognosis.
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Affiliation(s)
- Lili Li
- Center for Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.,Cheng Lab, Suzhou Institute of Systems Medicine, Suzhou, China
| | - Jie Li
- Department of Laboratory Medicine, TaiHe Hospital, Hubei University of Medicine, Shiyan, China
| | - Meiling Gao
- Center for Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.,Cheng Lab, Suzhou Institute of Systems Medicine, Suzhou, China.,Department of Laboratory Medicine, TaiHe Hospital, Hubei University of Medicine, Shiyan, China
| | - Huimin Fan
- Center for Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.,Cheng Lab, Suzhou Institute of Systems Medicine, Suzhou, China
| | - Yanan Wang
- Department of Scientific Research, Suzhou Func Biotech Inc, Suzhou, China
| | - Xin Xu
- Center for Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.,Cheng Lab, Suzhou Institute of Systems Medicine, Suzhou, China
| | - Chunfeng Chen
- Department of Scientific Research, Suzhou Func Biotech Inc, Suzhou, China
| | - Junxiao Liu
- Center for Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.,Cheng Lab, Suzhou Institute of Systems Medicine, Suzhou, China
| | - Jocelyn Kim
- Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, United States
| | - Roghiyh Aliyari
- Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, United States
| | - Jicai Zhang
- Department of Laboratory Medicine, TaiHe Hospital, Hubei University of Medicine, Shiyan, China
| | - Yujie Jin
- Department of Laboratory Medicine, TaiHe Hospital, Hubei University of Medicine, Shiyan, China
| | - Xiaorong Li
- Center for Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.,Cheng Lab, Suzhou Institute of Systems Medicine, Suzhou, China
| | - Feng Ma
- Center for Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.,Cheng Lab, Suzhou Institute of Systems Medicine, Suzhou, China
| | - Minxin Shi
- Department of Surgery, Affiliated Tumor Hospital of Nantong University, Nantong, China
| | - Genhong Cheng
- Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, United States
| | - Heng Yang
- Center for Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.,Cheng Lab, Suzhou Institute of Systems Medicine, Suzhou, China
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28
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George JA, Mayne ES. The Novel Coronavirus and Inflammation. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2021; 1321:127-138. [PMID: 33656719 DOI: 10.1007/978-3-030-59261-5_11] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
The SARS-CoV-2 virus which causes COVID-19 disease was initially described in the Hubei Province of China and has since spread to more than 200 countries and territories of the world. Severe cases of the disease are characterised by release of high levels of pro-inflammatory cytokines and other inflammatory mediators in a process characterised as a cytokine storm. These inflammatory mediators are associated with pathological leukocyte activation states with tissue damage. Here, we review these effects with a focus on their potential use in diagnosis, patient stratification and prognosis, as well as new drug targets.
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Affiliation(s)
- J A George
- Department of Chemical Pathology, National Health Laboratory Services and Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - E S Mayne
- Department of Immunology, National Health Laboratory Services and Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
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29
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Grobler JA, Anderson AS, Fernandes P, Diamond MS, Colvis CM, Menetski JP, Alvarez RM, Young JAT, Carter KL. Accelerated Preclinical Paths to Support Rapid Development of COVID-19 Therapeutics. Cell Host Microbe 2020; 28:638-645. [PMID: 33152278 PMCID: PMC7528945 DOI: 10.1016/j.chom.2020.09.017] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2020] [Revised: 08/27/2020] [Accepted: 09/28/2020] [Indexed: 12/15/2022]
Abstract
When SARS-CoV-2 emerged at the end of 2019, no approved therapeutics or vaccines were available. An urgent need for countermeasures during this crisis challenges the current paradigm of traditional drug discovery and development, which usually takes years from start to finish. Approaches that accelerate this process need to be considered. Here we propose the minimum data package required to move a compound into clinical development safely. We further define the additional data that should be collected in parallel without impacting the rapid path to clinical development. Accelerated paths for antivirals, immunomodulators, anticoagulants, and other agents have been developed and can serve as "roadmaps" to support prioritization of compounds for clinical testing. These accelerated paths are fueled by a skewed risk-benefit ratio and are necessary to advance therapeutic agents into human trials rapidly and safely for COVID-19. Such paths are adaptable to other potential future pandemics.
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Affiliation(s)
| | | | | | - Michael S Diamond
- Departments of Medicine, Molecular Microbiology, Pathology & Immunology, Washington University School of Medicine, St Louis, MO 63110, USA
| | - Christine M Colvis
- National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892, USA
| | - Joseph P Menetski
- Foundation for the National Institutes of Health, 11400 Rockville Pike, Suite 600, North Bethesda, MD 20852, USA
| | - Rosa M Alvarez
- Deloitte Consulting LLP, 200 Berkeley Street, Boston, MA 02116, USA
| | - John A T Young
- Roche Pharma Research & Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Basel, Switzerland
| | - Kara L Carter
- Evotec ID Lyon, 40 Avenue Tony Garnier, 69007 Lyon, France.
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30
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Brábek J, Jakubek M, Vellieux F, Novotný J, Kolář M, Lacina L, Szabo P, Strnadová K, Rösel D, Dvořánková B, Smetana K. Interleukin-6: Molecule in the Intersection of Cancer, Ageing and COVID-19. Int J Mol Sci 2020; 21:ijms21217937. [PMID: 33114676 PMCID: PMC7662856 DOI: 10.3390/ijms21217937] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2020] [Revised: 10/19/2020] [Accepted: 10/21/2020] [Indexed: 12/12/2022] Open
Abstract
Interleukin-6 (IL-6) is a cytokine with multifaceted effects playing a remarkable role in the initiation of the immune response. The increased level of this cytokine in the elderly seems to be associated with the chronic inflammatory setting of the microenvironment in aged individuals. IL-6 also represents one of the main signals in communication between cancer cells and their non-malignant neighbours within the tumour niche. IL-6 also participates in the development of a premetastatic niche and in the adjustment of the metabolism in terminal-stage patients suffering from a malignant disease. IL-6 is a fundamental factor of the cytokine storm in patients with severe COVID-19, where it is responsible for the fatal outcome of the disease. A better understanding of the role of IL-6 under physiological as well as pathological conditions and the preparation of new strategies for the therapeutic control of the IL-6 axis may help to manage the problems associated with the elderly, cancer, and serious viral infections.
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Affiliation(s)
- Jan Brábek
- Department of Cell Biology, Faculty of Science, Charles University, 120 00 Prague 2, Czech Republic; (J.B.); (D.R.)
- BIOCEV, Faculty of Science, Charles University, 252 50 Vestec, Czech Republic
- Centre for Tumour Ecology, First Faculty of Medicine, Charles University, 120 00 Prague 2, Czech Republic; (M.J.); (F.V.); (J.N.); (M.K.); (L.L.); (K.S.); (B.D.)
| | - Milan Jakubek
- Centre for Tumour Ecology, First Faculty of Medicine, Charles University, 120 00 Prague 2, Czech Republic; (M.J.); (F.V.); (J.N.); (M.K.); (L.L.); (K.S.); (B.D.)
- Department of Paediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University and General University Hospital, 120 00 Prague, Czech Republic
- BIOCEV, First Faculty of Medicine, Charles University, 252 50 Vestec, Czech Republic
- Department of Analytical Chemistry, University of Chemistry and Technology Prague, 166 28 Praha 6, Czech Republic
| | - Fréderic Vellieux
- Centre for Tumour Ecology, First Faculty of Medicine, Charles University, 120 00 Prague 2, Czech Republic; (M.J.); (F.V.); (J.N.); (M.K.); (L.L.); (K.S.); (B.D.)
- BIOCEV, First Faculty of Medicine, Charles University, 252 50 Vestec, Czech Republic
| | - Jiří Novotný
- Centre for Tumour Ecology, First Faculty of Medicine, Charles University, 120 00 Prague 2, Czech Republic; (M.J.); (F.V.); (J.N.); (M.K.); (L.L.); (K.S.); (B.D.)
- Laboratory of Genomics and Bioinformatics, Institute of Molecular Genetics, Czech Academy of Sciences, 140 00 Prague 4, Czech Republic
| | - Michal Kolář
- Centre for Tumour Ecology, First Faculty of Medicine, Charles University, 120 00 Prague 2, Czech Republic; (M.J.); (F.V.); (J.N.); (M.K.); (L.L.); (K.S.); (B.D.)
- Laboratory of Genomics and Bioinformatics, Institute of Molecular Genetics, Czech Academy of Sciences, 140 00 Prague 4, Czech Republic
| | - Lukáš Lacina
- Centre for Tumour Ecology, First Faculty of Medicine, Charles University, 120 00 Prague 2, Czech Republic; (M.J.); (F.V.); (J.N.); (M.K.); (L.L.); (K.S.); (B.D.)
- BIOCEV, First Faculty of Medicine, Charles University, 252 50 Vestec, Czech Republic
- Institute of Anatomy, Fist Faculty of Medicine, Charles University, 120 00 Prague 2, Czech Republic;
- Department of Dermatovenereology, First Faculty of Medicine, Charles University and General University Hospital, 120 00 Prague 2, Czech Republic
| | - Pavol Szabo
- Institute of Anatomy, Fist Faculty of Medicine, Charles University, 120 00 Prague 2, Czech Republic;
| | - Karolína Strnadová
- Centre for Tumour Ecology, First Faculty of Medicine, Charles University, 120 00 Prague 2, Czech Republic; (M.J.); (F.V.); (J.N.); (M.K.); (L.L.); (K.S.); (B.D.)
- BIOCEV, First Faculty of Medicine, Charles University, 252 50 Vestec, Czech Republic
- Institute of Anatomy, Fist Faculty of Medicine, Charles University, 120 00 Prague 2, Czech Republic;
| | - Daniel Rösel
- Department of Cell Biology, Faculty of Science, Charles University, 120 00 Prague 2, Czech Republic; (J.B.); (D.R.)
- BIOCEV, Faculty of Science, Charles University, 252 50 Vestec, Czech Republic
- Centre for Tumour Ecology, First Faculty of Medicine, Charles University, 120 00 Prague 2, Czech Republic; (M.J.); (F.V.); (J.N.); (M.K.); (L.L.); (K.S.); (B.D.)
| | - Barbora Dvořánková
- Centre for Tumour Ecology, First Faculty of Medicine, Charles University, 120 00 Prague 2, Czech Republic; (M.J.); (F.V.); (J.N.); (M.K.); (L.L.); (K.S.); (B.D.)
- BIOCEV, First Faculty of Medicine, Charles University, 252 50 Vestec, Czech Republic
- Institute of Anatomy, Fist Faculty of Medicine, Charles University, 120 00 Prague 2, Czech Republic;
| | - Karel Smetana
- Centre for Tumour Ecology, First Faculty of Medicine, Charles University, 120 00 Prague 2, Czech Republic; (M.J.); (F.V.); (J.N.); (M.K.); (L.L.); (K.S.); (B.D.)
- BIOCEV, First Faculty of Medicine, Charles University, 252 50 Vestec, Czech Republic
- Institute of Anatomy, Fist Faculty of Medicine, Charles University, 120 00 Prague 2, Czech Republic;
- Correspondence: ; Tel.: +420-224-965-873
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31
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Abbasifard M, Khorramdelazad H. The bio-mission of interleukin-6 in the pathogenesis of COVID-19: A brief look at potential therapeutic tactics. Life Sci 2020; 257:118097. [PMID: 32679148 PMCID: PMC7361088 DOI: 10.1016/j.lfs.2020.118097] [Citation(s) in RCA: 60] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2020] [Revised: 07/09/2020] [Accepted: 07/10/2020] [Indexed: 01/08/2023]
Abstract
Interleukin-6 (IL-6), known as an inflammatory cytokine, can be involved in many innate and adaptive immune responses. The role of IL-6 in the pathogenesis of the novel coronavirus disease 2019 (COVID-19) has recently received much more attention due to the spread of the virus and its pandemic potential. Cytokine storm is among the most critical pathological events in patients affected with coronaviruses (CoVs), i.e., severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and COVID-19, causing inflammation-induced lung injury and also occurring as a result of dysregulation of immune responses to the mentioned viruses. IL-6, along with some other inflammatory cytokines, including IL-1 beta (β), IL-8, and tumor necrosis factor-alpha (TNF-α), as well as inflammatory chemokines, can significantly contribute to, fever, lymphopenia, coagulation, lung injury, and multi-organ failure (MOF). Therefore, researchers are to explore novel approaches to treat the disease through targeting of IL-6 and its receptors based on prior experience of other disorders. In this review article, the latest findings on the role of IL-6 in the pathogenesis of COVID-19, as well as therapeutic perspectives, were summarized and discussed.
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Affiliation(s)
- Mitra Abbasifard
- Molecular Medicine Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran; Department of Internal Medicine, Ali-Ibn-Abi-talib Hospital, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
| | - Hossein Khorramdelazad
- Molecular Medicine Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran; Department of Immunology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran; Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
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