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1
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Silveira AF, Santos MB, Collange NZ, Hayashi CY, Vilela GHF, Almeida SLSD, Andrade JBCD, Rojas S, Moraes FMD, Veiga VC, Flato UAP, Russo TL, Silva GS. Intracranial compliance in patients with COVID-19: a multicenter observational study. ARQUIVOS DE NEURO-PSIQUIATRIA 2024; 82:1-8. [PMID: 39121935 DOI: 10.1055/s-0044-1788669] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/12/2024]
Abstract
BACKGROUND Patients with severe coronavirus disease-19 (COVID-19) may require the use of invasive mechanical ventilation (MV) for prolonged periods. Aggressive MV parameters have been associated with changes in intracranial pressure (ICP) in patients with acute intracranial disorders. Significant ICP elevation could compromise intracranial compliance (ICC) and cerebrovascular hemodynamics (CVH). However, the effects of these parameters in individuals without neurological disorders have not yet been evaluated. OBJECTIVE To evaluate ICC in patients on MV with COVID-19 infection compared to other diagnoses, to better characterize the effects of MV and COVID-19 upon ICC. We also compared between the ICC in patients with COVID-19 who did not require MV and healthy volunteers, to assess the isolated effect of COVID-19 upon ICC. METHODS This was an exploratory, observational study with a convenience sample. The ICC was evaluated with a noninvasive ICP monitoring device. The P2/P1 ratio was calculated by dividing the amplitude of these two points, being defined as "abnormal" when P2 > P1. The statistical analysis was performed using a mixed linear model with random effects to compare the P2/P1 ratio in all four groups on the first monitoring day. RESULTS A convenience sample of 78 subjects (15 MV-COVID-19, 15 MV non-COVID-19, 24 non-MV-COVID-19, and 24 healthy participants) was prospectively enrolled. There was no difference in P2/P1 ratios between MV patients with and without COVID-19, nor between non-MV patients with COVID-19 and healthy volunteers. However, the P2/P1 ratio was higher in COVID-19 patients with MV use than in those without it. CONCLUSION This exploratory analysis suggests that COVID-19 does not impair ICC.
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Affiliation(s)
- Ana Flávia Silveira
- Universidade Federal de São Carlos, Departamento de Fisioterapia, São Carlos SP, Brazil
| | - Marcella Barreto Santos
- Universidade Federal de São Paulo, Departamento de Neurologia e Neurocirurgia, São Paulo SP, Brazil
| | - Nelci Zanon Collange
- Universidade Federal de São Paulo, Departamento de Neurologia e Neurocirurgia, São Paulo SP, Brazil
- Centro de Neurocirurgia Pediátrica (CENEPE), São Paulo SP, Brazil
| | | | | | | | - João Brainer Clares de Andrade
- Universidade Federal de São Paulo, Departamento de Neurologia e Neurocirurgia, São Paulo SP, Brazil
- Centro Universitário São Camilo, São Paulo SP, Brazil
| | - Salómon Rojas
- Beneficência Portuguesa Hospital, Divisão da Unidade de Terapia Intensiva Neurológica, São Paulo SP, Brazil
| | - Fabiano Moulin de Moraes
- Universidade Federal de São Paulo, Departamento de Neurologia e Neurocirurgia, São Paulo SP, Brazil
| | - Viviane Cordeiro Veiga
- Beneficência Portuguesa Hospital, Divisão da Unidade de Terapia Intensiva Neurológica, São Paulo SP, Brazil
| | - Uri Adrian Prync Flato
- Hospital Samaritano, Américas Serviços Médicos, Unidade de Terapia Intensiva Geral, São Paulo SP, Brazil
| | - Thiago Luiz Russo
- Universidade Federal de São Carlos, Departamento de Fisioterapia, São Carlos SP, Brazil
| | - Gisele Sampaio Silva
- Universidade Federal de São Paulo, Departamento de Neurologia e Neurocirurgia, São Paulo SP, Brazil
- Hospital Israelita Albert Einstein, Departamento de Neurologia, São Paulo SP, Brazil
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2
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Fadlallah MM, Salman SM, Fadlallah MM, Rahal H. Hemophagocytic Syndrome and COVID-19: A Comprehensive Review. Cureus 2023; 15:e36140. [PMID: 37065291 PMCID: PMC10101193 DOI: 10.7759/cureus.36140] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/14/2023] [Indexed: 03/17/2023] Open
Abstract
Hemophagocytic lymphohistiocytosis (HLH), a hyperinflammatory hyperferritinemic syndrome, is triggered by various etiologies and diseases and can lead to multiorgan dysfunction and death. There are two types of HLH: primary and secondary. Primary HLH (pHLH) is caused by a genetic mutation resulting in dysfunction in cytotoxic T lymphocytes (CTLs), natural killer (NK) cells, hyperactivated immune cells, and hypercytokinemia. In secondary HLH (sHLH), an underlying etiology is the cause of the disease. Infections, malignancy, and autoimmune diseases are well-known triggers for sHLH. Infectious triggers for sHLH are most frequently viruses, where different mechanisms, including dysregulated CTLs and NK cell activity and persistent immune system stimulation, have been reported. Similarly, in severe coronavirus disease 2019 (COVID-19) patients, a hyperinflammatory mechanism leading to hypercytokinemia and hyperferritinemia has been demonstrated. A similar dysfunction in CTLs and NK cells, persistent immune system stimulation with increased cytokines production, and severe end-organ damage have been reported. Therefore, a significant overlap is present between the clinical and laboratory features seen in COVID-19 and sHLH. However, SARS-CoV-2, similar to other viruses, can trigger sHLH. Hence, a diagnostic approach is needed in severe COVID-19 patients presenting with multiorgan failure, in whom sHLH should be considered.
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Affiliation(s)
- Mahdi M Fadlallah
- Department of Laboratory Medicine, Faculty of Medical Sciences, Lebanese University, Beirut, LBN
| | - Sarah M Salman
- Department of Laboratory Medicine, Al-Zahraa Hospital University Medical Center, Beirut, LBN
- Department of Laboratory Medicine, Faculty of Medical Sciences, Lebanese University, Beirut, LBN
| | | | - Hassan Rahal
- Department of Infectious Diseases, Bahman Hospital, Beirut, LBN
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Trivanović D, Peršurić Ž, Agaj A, Jakopović M, Samaržija M, Bitar L, Pavelić K. The Interplay of Lung Cancer, COVID-19, and Vaccines. Int J Mol Sci 2022; 23:15067. [PMID: 36499394 PMCID: PMC9738445 DOI: 10.3390/ijms232315067] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2022] [Revised: 11/21/2022] [Accepted: 11/29/2022] [Indexed: 12/03/2022] Open
Abstract
Patients with cancer are more susceptible to a higher risk of coronavirus infection and its severe complications than the general population. In addition, these patients were not included in the pivotal clinical trials for COVID-19 vaccines. Therefore, considerable uncertainty remains regarding the management of cancer patients during the COVID-19 pandemic and the safety of COVID-19 vaccinations in cancer patients. In this review, we summarize the current knowledge generated from the beginning of the COVID-19 pandemic on the vulnerability of cancer patients to the coronavirus disease, as well as the effectiveness of COVID-19 vaccines in this population. We also discuss the available data on the effects of anticancer treatment with immune checkpoint inhibitors on the immune responses to SARS-CoV-2 in cancer patients. Special attention in this review will be given to patients with lung cancer, as such patients are at an increased risk for severe effects from COVID-19.
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Affiliation(s)
- Dragan Trivanović
- Department of Oncology and Hematology, General Hospital Pula, Santorijeva 24a, 52100 Pula, Croatia
- Faculty of Medicine, Juraj Dobrila University of Pula, Zagrebačka 30, 52100 Pula, Croatia
| | - Željka Peršurić
- Faculty of Chemical Engineering and Technology, University of Zagreb, Trg Marka Marulića 19, 10000 Zagreb, Croatia
| | - Andrea Agaj
- Faculty of Medicine, Juraj Dobrila University of Pula, Zagrebačka 30, 52100 Pula, Croatia
| | - Marko Jakopović
- Department for Respiratory Diseases Jordanovac, KBC Zagreb-Jordanovac Clinic for Lung Diseases, 10000 Zagreb, Croatia
| | - Miroslav Samaržija
- Department for Respiratory Diseases Jordanovac, KBC Zagreb-Jordanovac Clinic for Lung Diseases, 10000 Zagreb, Croatia
| | - Lela Bitar
- Department for Respiratory Diseases Jordanovac, KBC Zagreb-Jordanovac Clinic for Lung Diseases, 10000 Zagreb, Croatia
| | - Krešimir Pavelić
- Faculty of Medicine, Juraj Dobrila University of Pula, Zagrebačka 30, 52100 Pula, Croatia
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Sung PS, Peng YC, Yang SP, Chiu CH, Hsieh SL. CLEC5A is critical in Pseudomonas aeruginosa-induced acute lung injury. JCI Insight 2022; 7:156613. [PMID: 36048544 PMCID: PMC9676025 DOI: 10.1172/jci.insight.156613] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Accepted: 08/10/2022] [Indexed: 11/30/2022] Open
Abstract
Pseudomonas aeruginosa is one of the most common nosocomial infections worldwide, and it frequently causes ventilator-associated acute pneumonia in immunocompromised patients. Abundant neutrophil extracellular traps (NETs) contribute to acute lung injury, thereby aggravating ventilator-induced lung damage. While pattern recognition receptors (PRRs) TLR4 and TLR5 are required for host defense against P. aeruginosa invasion, the PRR responsible for P. aeruginosa–induced NET formation, proinflammatory cytokine release, and acute lung injury remains unclear. We found that myeloid C-type lectin domain family 5 member A (CLEC5A) interacts with LPS of P. aeruginosa and is responsible for P. aeruginosa–induced NET formation and lung inflammation. P. aeruginosa activates CLEC5A to induce caspase-1–dependent NET formation, but it neither causes gasdermin D (GSDMD) cleavage nor contributes to P. aeruginosa–induced neutrophil death. Blockade of CLEC5A attenuates P. aeruginosa–induced NETosis and lung injury, and simultaneous administration of anti-CLEC5A mAb with ciprofloxacin increases survival rate and decreases collagen deposition in the lungs of mice challenged with a lethal dose of P. aeruginosa. Thus, CLEC5A is a promising therapeutic target to reduce ventilator-associated lung injury and fibrosis in P. aeruginosa–induced pneumonia.
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Affiliation(s)
- Pei-Shan Sung
- Genomics Research Center, Academia Sinica, Taipei, Taiwan
| | - Yu-Chun Peng
- Genomics Research Center, Academia Sinica, Taipei, Taiwan
| | - Shao-Ping Yang
- Genomics Research Center, Academia Sinica, Taipei, Taiwan
| | - Cheng-Hsun Chiu
- Department of Pediatrics, Chang Gung Children's Hospital, Taoyuan, Taiwan
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Wang R, Wu Z, Huang C, Hashimoto K, Yang L, Yang C. Deleterious effects of nervous system in the offspring following maternal SARS-CoV-2 infection during the COVID-19 pandemic. Transl Psychiatry 2022; 12:232. [PMID: 35668063 PMCID: PMC9169439 DOI: 10.1038/s41398-022-01985-z] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2022] [Revised: 05/17/2022] [Accepted: 05/25/2022] [Indexed: 12/11/2022] Open
Abstract
During the Coronavirus disease 2019 (COVID-19) pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is universally susceptible to all types of populations. In addition to the elderly and children becoming the groups of great concern, pregnant women carrying new lives need to be even more alert to SARS-CoV-2 infection. Studies have shown that pregnant women infected with SARS-CoV-2 can lead to brain damage and post-birth psychiatric disorders in offspring. It has been widely recognized that SARS-CoV-2 can affect the development of the fetal nervous system directly or indirectly. Pregnant women are recommended to mitigate the effects of COVID-19 on the fetus through vaccination, nutritional supplements, and psychological support. This review summarizes the possible mechanisms of the nervous system effects of SARS-CoV-2 infection on their offspring during the pregnancy and analyzes the available prophylactic and treatment strategies to improve the prognosis of fetal-related neuropsychiatric diseases after birth.
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Affiliation(s)
- Ruting Wang
- grid.452253.70000 0004 1804 524XDepartment of Cardiology, The Third Affiliated Hospital of Soochow University, Changzhou, 213003 China
| | - Zifeng Wu
- grid.412676.00000 0004 1799 0784Department of Anesthesiology and Perioperative Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029 China
| | - Chaoli Huang
- grid.412676.00000 0004 1799 0784Department of Anesthesiology and Perioperative Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029 China
| | - Kenji Hashimoto
- grid.411500.1Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, 260-8670 Japan
| | - Ling Yang
- Department of Cardiology, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, China.
| | - Chun Yang
- Department of Anesthesiology and Perioperative Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
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Rajendran R, Chathambath A, Al-Sehemi AG, Pannipara M, Unnikrishnan MK, Aleya L, Raghavan RP, Mathew B. Critical role of nitric oxide in impeding COVID-19 transmission and prevention: a promising possibility. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2022; 29:38657-38672. [PMID: 35258738 PMCID: PMC8902850 DOI: 10.1007/s11356-022-19148-4] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/08/2021] [Accepted: 02/06/2022] [Indexed: 05/06/2023]
Abstract
COVID-19 is a serious respiratory infection caused by a beta-coronavirus that is closely linked to SARS. Hypoxemia is a symptom of infection, which is accompanied by acute respiratory distress syndrome (ARDS). Augmenting supplementary oxygen may not always improve oxygen saturation; reversing hypoxemia in COVID-19 necessitates sophisticated means to promote oxygen transfer from alveoli to blood. Inhaled nitric oxide (iNO) has been shown to inhibit the multiplication of the respiratory coronavirus, a property that distinguishes it from other vasodilators. These findings imply that NO may have a crucial role in the therapy of COVID-19, indicating research into optimal methods to restore pulmonary physiology. According to clinical and experimental data, NO is a selective vasodilator proven to restore oxygenation by helping to normalize shunts and ventilation/perfusion mismatches. This study examines the role of NO in COVID-19 in terms of its specific physiological and biochemical properties, as well as the possibility of using inhaled NO as a standard therapy. We have also discussed how NO could be used to prevent and cure COVID-19, in addition to the limitations of NO.
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Affiliation(s)
- Rajalakshmi Rajendran
- Department of Pharmacy Practice, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, Kochi, 682041, Kerala, India
| | - Anjana Chathambath
- Department of Pharmacy Practice, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, Kochi, 682041, Kerala, India
| | - Abdullah G Al-Sehemi
- Research Center for Advanced Materials Science, King Khalid University, Abha, 61413, Saudi Arabia
- Department of Chemistry, King Khalid University, Abha, 61413, Saudi Arabia
| | - Mehboobali Pannipara
- Research Center for Advanced Materials Science, King Khalid University, Abha, 61413, Saudi Arabia
- Department of Chemistry, King Khalid University, Abha, 61413, Saudi Arabia
| | | | - Lotfi Aleya
- Laboratoire Chrono-Environment, Universite de Bourgogne Franche-Comte, CNRS6249, Besancon, France
| | - Roshni Pushpa Raghavan
- Department of Pharmacy Practice, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, Kochi, 682041, Kerala, India.
| | - Bijo Mathew
- Department of Pharmaceutical Chemistry, Amrita School of Pharmacy, AIMS Health Sciences Campus, Amrita Vishwa Vidyapeetham, Kochi, 682 041, India
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7
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Hasanvand A. COVID-19 and the role of cytokines in this disease. Inflammopharmacology 2022; 30:789-798. [PMID: 35505267 PMCID: PMC9064717 DOI: 10.1007/s10787-022-00992-2] [Citation(s) in RCA: 55] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2022] [Accepted: 04/05/2022] [Indexed: 12/13/2022]
Abstract
Studies have shown that SARS-CoV-2 has the ability to activate and mature proinflammatory cytokines in the body. Cytokine markers are a group of polypeptide signalling molecules that can induce and regulate many cellular biological processes by stimulating cell receptors at the surface. SARS-CoV-2 has been shown to be associated with activation of innate immunity, and an increase in neutrophils, mononuclear phagocytes, and natural killer cells has been observed, as well as a decrease in T cells including CD4+ and CD8. It is noteworthy that during the SARS-CoV-2 infection, an increase in the secretion or production of IL-6 and IL-8 is seen in COVID-19 patients along with a decrease in CD4+ and CD8+ and T cells in general. SARS-CoV-2 has been shown to significantly increase Th2, Th1/Th17 cells and antibody production in the body of patients with COVID-19. Specific immune profiles of SARS-CoV-2 infection can lead to secondary infections and dysfunction of various organs in the body. It has been shown that Interleukins (such as IL-1, IL-4, IL-6, IL-7, IL-10, IL-12, IL-17, and IL-18), IFN-γ, TNF-α,TGF-β and NF-κB play major roles in the body's inflammatory response to SARS-CoV-2 infection. The most important goal of this review is to study the role of inflammatory cytokines in COVID-19.
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Affiliation(s)
- Amin Hasanvand
- Department of Physiology and Pharmacology, Faculty of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran.
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8
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Anushiravani A, Saberzadeh-Ardestani B, Vahedi H, Fakheri H, Mansour-Ghanaei F, Maleki I, Nasseri-Moghaddam S, Vosoghinia H, Ghadir MR, Hormati A, Kasaeian A, Radmard AR, Khosravi B, Malekzadeh M, Alatab S, Sadeghi A, Aminisani N, Poustchi H, Sima AR, Malekzadeh R. Susceptibility of Patients with Inflammatory Bowel Disease to COVID-19 Compared with Their Households. Middle East J Dig Dis 2022; 14:182-191. [PMID: 36619152 PMCID: PMC9489316 DOI: 10.34172/mejdd.2022.271] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2021] [Accepted: 01/11/2022] [Indexed: 01/11/2023] Open
Abstract
BACKGROUND: Immunosuppressive agents used in the treatment of inflammatory bowel diseases (IBDs) could potentially increase the risk of coronavirus disease 2019 (COVID-19). We aimed to compare COVID-19 frequency in patients with IBD with their households and identify the related risk factors. METHODS: Firstly, a multi-centered, observational study on 2110 patients with IBD and 2110 age-matched household members was conducted to compare COVID-19 frequency. Secondly, the data of patients with IBD and COVID-19 who had called the COVID-19 hotline were added. Multivariable logistic regression was used to evaluate the effect of age, type and severity of IBD, the number of comorbidities, and medications on the frequency of COVID-19 among the patients with IBD. RESULTS: The prevalence of COVID-19 in patients with IBD and household groups was similar (34 [1.61%] versus 35 [1.65%]; P = 0.995). The prevalence of COVID-19 increased from 2.1% to 7.1% in those with three or more comorbidities (P = 0.015) and it was significantly higher in those with severe IBD (P = 0.026). The multivariable analysis only showed a significant association with anti-TNF monotherapy (OR: 2.5, CI: 0.97-6.71, P = 0.05), and other medications were not associated with COVID-19. CONCLUSION: The prevalence of COVID-19 in patients with IBD was similar to the household members. Only patients with IBD receiving anti-TNF monotherapy had a higher risk of COVID-19 susceptibility. This finding could be attributed to the higher exposure to the virus during administration in health care facilities.
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Affiliation(s)
- Amir Anushiravani
- Digestive Disease Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Bahar Saberzadeh-Ardestani
- Digestive Disease Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Homayoon Vahedi
- Digestive Disease Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Hafez Fakheri
- Gut and Liver Research Center, Mazandaran University of Medical Sciences, Sari, Iran
| | - Fariborz Mansour-Ghanaei
- Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran
| | - Iraj Maleki
- Gut and Liver Research Center, Mazandaran University of Medical Sciences, Sari, Iran
| | - Siavosh Nasseri-Moghaddam
- Digestive Disease Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Hasan Vosoghinia
- Gastroenterology and Hematology Department, Faculty of Medicine, Ghaem Hospital, Mashhad, Iran
| | - Mohammad Reza Ghadir
- Gastroenterology and Hepatology Diseases Research Center, Qom University of Medical Science, Iran
| | - Ahmad Hormati
- Gastroenterology and Hepatology Diseases Research Center, Qom University of Medical Science, Iran,Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Amir Kasaeian
- Digestive Disease Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran,Hematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Amir Reza Radmard
- Department of Radiology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Bardia Khosravi
- Digestive Disease Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Masoud Malekzadeh
- Digestive Disease Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Sudabeh Alatab
- Digestive Disease Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Anahita Sadeghi
- Digestive Disease Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Nayyereh Aminisani
- Department of Epidemiology and Statistics, Faculty of Health Sciences, Neyshabur University of Medical Sciences, Neyshabur, Iran
| | - Hossein Poustchi
- Digestive Disease Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Ali Reza Sima
- Digestive Disease Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran,Corresponding Author: Ali Reza Sima, MD Digestive Diseases Research Institute, Tehran University of Medical Sciences, Shariati Hospital, Kargar Shomali Avenue, Tehran, Iran Tel: + 98 21 82415000 Fax: + 98 21 82415400
| | - Reza Malekzadeh
- Digestive Disease Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
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Bhola S, Trisal J, Thakur V, Kaur P, Kulshrestha S, Bhatia SK, Kumar P. Neurological toll of COVID-19. Neurol Sci 2022; 43:2171-2186. [PMID: 35034236 PMCID: PMC8761097 DOI: 10.1007/s10072-022-05875-6] [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: 11/10/2021] [Accepted: 01/04/2022] [Indexed: 02/08/2023]
Abstract
The first case of coronavirus illness was discovered in Wuhan, China, in January 2020 and quickly spread worldwide within the next couple of months. The condition was initially only linked with respiratory disorders. After the evolution of various variants of the SARS-CoV-2, the critical impact of the virus spread to multiple organs and soon, neurological disorder manifestations started to appear in the infected patients. The review is focused on the manifestation of various neurological disorders linked with both the central nervous system and peripheral nervous system. Disorders such as cytokine release syndrome, encephalitis, acute stroke, and Bell's palsy are given specific attention and psychological manifestations are also investigated. For a clear conclusion, cognitive impairment, drug addiction disorders, mood and anxiety disorders, and post-traumatic stress disorder are all fully examined. The association of the SARS-CoV-2 with neurological disorders and pathway is yet to be clear. For better understanding, the explanation of the possible mechanism of viral infection influencing the nervous system is also attempted in the review. While several vaccines and drugs are already involved in treating the SARS-CoV-2 condition, the disease is still considered fatal and more likely to leave permanent neurological damage, which leads to an essential requirement for more research to explore the neurological toll of the COVID-19 disease.
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Affiliation(s)
- Shivam Bhola
- Faculty of Applied Sciences and Biotechnology, Shoolini University of Biotechnology and Management Sciences, Solan, Himachal Pradesh, India
| | - Jhillika Trisal
- Faculty of Applied Sciences and Biotechnology, Shoolini University of Biotechnology and Management Sciences, Solan, Himachal Pradesh, India
| | - Vikram Thakur
- Department of Virology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, Pin-160012, India
| | - Parneet Kaur
- Faculty of Applied Sciences and Biotechnology, Shoolini University of Biotechnology and Management Sciences, Solan, Himachal Pradesh, India
| | - Saurabh Kulshrestha
- Faculty of Applied Sciences and Biotechnology, Shoolini University of Biotechnology and Management Sciences, Solan, Himachal Pradesh, India
| | - Shashi Kant Bhatia
- Department of Biological Engineering, Konkuk University, Seoul, 05029, Republic of Korea
| | - Pradeep Kumar
- Faculty of Applied Sciences and Biotechnology, Shoolini University of Biotechnology and Management Sciences, Solan, Himachal Pradesh, India.
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Saeed SA, Pastis IS, Santos MG. COVID-19 and its impact on the brain and Mind- A conceptual model and supporting evidence. Psychiatr Q 2022; 93:271-284. [PMID: 35303244 PMCID: PMC8931572 DOI: 10.1007/s11126-022-09980-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2021] [Revised: 02/11/2022] [Accepted: 02/20/2022] [Indexed: 12/13/2022]
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the novel coronavirus that is causing the ongoing coronavirus disease 2019 (COVID-19) pandemic, was first reported in late 2019. Since then, an unprecedented amount of new knowledge has emerged about this virus and its treatment. Although the reported symptoms of COVID-19 are primarily respiratory with acute respiratory distress syndrome, SARS-CoV-2 has also been shown to affect other organs, including brain, and there are growing reports of neuropsychiatric symptoms due to COVID-19. There are two suggested pathways for how COVID-19 can affect the brain and mind: the direct impact on the brain and impact mediated via stress. Direct impact on the brain is manifested as encephalitis/encephalopathy with altered mental status (AMS) and delirium. In this paper, we summarize evidence from studies of previous outbreaks and current data from the COVID-19 pandemic that describe how COVID-19 is associated with an increased prevalence of anxiety, stress, poor sleep quality, obsessive-compulsive symptoms, and depression among the general population during the pandemic. In addition, we summarize the current evidence that supports how COVID-19 can also impact the CNS directly and result in delirium, cerebrovascular events, encephalitis, unspecified encephalopathy, AMS, or peripheral neurologic disorders.
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Affiliation(s)
- Sy Atezaz Saeed
- Department of Psychiatry and Behavioral Medicine, Brody School of Medicine at East Carolina University, 600 Moye Blvd, 27834, Greenville, NC, United States.
| | - Irene S Pastis
- Department of Psychiatry and Behavioral Medicine, Brody School of Medicine at East Carolina University, 600 Moye Blvd, 27834, Greenville, NC, United States
| | - Melody Grace Santos
- Department of Psychiatry and Behavioral Medicine, Brody School of Medicine at East Carolina University, 600 Moye Blvd, 27834, Greenville, NC, United States
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Rais N, Ahmad R, Ved A, Parveen K, Ishrat T, Prakash O, Shadab M, Bari DG, Siddiqui NA. Diabetes Mellitus during the Pandemic Covid-19: Prevalence, Pathophysiology, Mechanism, and Management: An updated overview. Curr Diabetes Rev 2022; 18:e120721194712. [PMID: 34931983 DOI: 10.2174/1573399817666210712160651] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2021] [Revised: 04/27/2021] [Accepted: 05/23/2021] [Indexed: 01/08/2023]
Abstract
BACKGROUND Diabetes mellitus (DM) is among the most frequently reported comorbidities in patients tainted with the pandemic coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). With a high pervasiveness of diabetes mellitus, there is an urgency to understand the special aspects of COVID-19 in hyperglycemic patients. Diabetic patients are at higher risk than the general population of viral or bacterial infections, thus require special attention since diabetes is linked with severe, critical, and lethal modes of COVID-19. OBJECTIVE The objective of this study was to focus on epidemiology, pathophysiology, mechanism, and management of DM with COVID-19. METHODS The search was carried out on databases portals such as Pubmed, EMBASE, Google Scholar, and CINAHL with the keywords, i.e., COVID-19, coronavirus, SARS-CoV-2, diabetes, covid-19, etc. Result: DM and COVID-19 disease conditions can impact each other in terms of clinical progression and outcome. Available laboratory/clinical observations suggest that hyperglycemia-induced immune dysfunction, inflated lactate grades, and cytokines storm may play critical roles in the seriousness of COVID-19 in patients with diabetes; however, the exact mechanisms linking diabetes and COVID-19 remain to be further clarified. CONCLUSION Standards to constrain the disease spread at the individual and community level are the key to extenuate the speedily rising pandemic, while definitive treatment, like plasma therapy, chemoprophylaxis, or vaccine for COVID-19, has yet to be discovered.
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Affiliation(s)
- Nadeem Rais
- Department of Pharmacy, Bhagwant University, Ajmer, Rajasthan, 305004, India
| | - Rizwan Ahmad
- Department of Pharmacy, Vivek College of Technical Education, Bijnor, Uttar Pradesh, 246701, India
| | - Akash Ved
- Goel Institute of Pharmaceutical Sciences, Lucknow, Uttar Pradesh, 226028, India
| | - Kehkashan Parveen
- Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, Uttar Pradesh, 202002, India
| | - Tauheed Ishrat
- Department of Anatomy and Neurobiology, The University of Tennessee Health Science Center, TN, 38163, USA
| | - Om Prakash
- Goel Institute of Pharmacy and Sciences, Faizabad Road, Lucknow, Uttar Pradesh, 226028, India
| | - Mohd Shadab
- Arabian Gulf University, Manama, 26671, Bahrain
| | | | - Nasir Ali Siddiqui
- Department of Pharmacognosy, King Saud University, Riyadh, 2457-11451, KSA
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12
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Vaz de Paula CB, Nagashima S, Liberalesso V, Collete M, da Silva FPG, Oricil AGG, Barbosa GS, da Silva GVC, Wiedmer DB, da Silva Dezidério F, Noronha L. COVID-19: Immunohistochemical Analysis of TGF-β Signaling Pathways in Pulmonary Fibrosis. Int J Mol Sci 2021; 23:ijms23010168. [PMID: 35008594 PMCID: PMC8745764 DOI: 10.3390/ijms23010168] [Citation(s) in RCA: 54] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Revised: 12/13/2021] [Accepted: 12/21/2021] [Indexed: 02/07/2023] Open
Abstract
Acute respiratory distress syndrome (ARDS) followed by repair with lung remodeling is observed in COVID-19. These findings can lead to pulmonary terminal fibrosis, a form of irreversible sequelae. There is evidence that TGF-β is intimately involved in the fibrogenic process. When activated, TGF-β promotes the differentiation of fibroblasts into myofibroblasts and regulates the remodeling of the extracellular matrix (ECM). In this sense, the present study evaluated the histopathological features and immunohistochemical biomarkers (ACE-2, AKT-1, Caveolin-1, CD44v6, IL-4, MMP-9, α-SMA, Sphingosine-1, and TGF-β1 tissue expression) involved in the TGF-β1 signaling pathways and pulmonary fibrosis. The study consisted of 24 paraffin lung samples from patients who died of COVID-19 (COVID-19 group), compared to 10 lung samples from patients who died of H1N1pdm09 (H1N1 group) and 11 lung samples from patients who died of different causes, with no lung injury (CONTROL group). In addition to the presence of alveolar septal fibrosis, diffuse alveolar damage (DAD) was found to be significantly increased in the COVID-19 group, associated with a higher density of Collagen I (mature) and III (immature). There was also a significant increase observed in the immunoexpression of tissue biomarkers ACE-2, AKT-1, CD44v6, IL-4, MMP-9, α-SMA, Sphingosine-1, and TGF-β1 in the COVID-19 group. A significantly lower expression of Caveolin-1 was also found in this group. The results suggest the participation of TGF-β pathways in the development process of pulmonary fibrosis. Thus, it would be plausible to consider therapy with TGF-β inhibitors in those patients recovered from COVID-19 to mitigate a possible development of pulmonary fibrosis and its consequences for post-COVID-19 life quality.
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13
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Post COVID-19 longitudinally extensive transverse myelitis (LETM)-a case report. Acta Neurol Belg 2021; 121:1875-1876. [PMID: 32948995 PMCID: PMC7500496 DOI: 10.1007/s13760-020-01497-x] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2020] [Accepted: 09/07/2020] [Indexed: 12/27/2022]
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14
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Campione E, Lanna C, Cosio T, Rosa L, Conte MP, Iacovelli F, Romeo A, Falconi M, Del Vecchio C, Franchin E, Lia MS, Minieri M, Chiaramonte C, Ciotti M, Nuccetelli M, Terrinoni A, Iannuzzi I, Coppeta L, Magrini A, Bernardini S, Sabatini S, Rosapepe F, Bartoletti PL, Moricca N, Di Lorenzo A, Andreoni M, Sarmati L, Miani A, Piscitelli P, Squillaci E, Valenti P, Bianchi L. Lactoferrin as Antiviral Treatment in COVID-19 Management: Preliminary Evidence. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:ijerph182010985. [PMID: 34682731 PMCID: PMC8535893 DOI: 10.3390/ijerph182010985] [Citation(s) in RCA: 47] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Revised: 10/04/2021] [Accepted: 10/13/2021] [Indexed: 01/08/2023]
Abstract
Lactoferrin (Lf), a multifunctional cationic glycoprotein synthesized by exocrine glands and neutrophils, possesses an in vitro antiviral activity against SARS-CoV-2. Thus, we conducted an in vivo preliminary study to investigate the antiviral effect of oral and intranasal liposomal bovine Lf (bLf) in asymptomatic and mild-to-moderate COVID-19 patients. From April 2020 to June 2020, a total of 92 mild-to-moderate (67/92) and asymptomatic (25/92) COVID-19 patients were recruited and divided into three groups. Thirty-two patients (14 hospitalized and 18 in home-based isolation) received only oral and intranasal liposomal bLf; 32 hospitalized patients were treated only with standard of care (SOC) treatment; and 28, in home-based isolation, did not take any medication. Furthermore, 32 COVID-19 negative, untreated, healthy subjects were added for ancillary analysis. Liposomal bLf-treated COVID-19 patients obtained an earlier and significant (p < 0.0001) SARS-CoV-2 RNA negative conversion compared to the SOC-treated and untreated COVID-19 patients (14.25 vs. 27.13 vs. 32.61 days, respectively). Liposomal bLf-treated COVID-19 patients showed fast clinical symptoms recovery compared to the SOC-treated COVID-19 patients. In bLf-treated patients, a significant decrease in serum ferritin, IL-6, and D-dimers levels was observed. No adverse events were reported. These observations led us to speculate a potential role of bLf in the management of mild-to-moderate and asymptomatic COVID-19 patients.
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Affiliation(s)
- Elena Campione
- Dermatology Unit, Department of Systems Medicine, Tor Vergata University Hospital, 00133 Rome, Italy; (C.L.); (T.C.); (L.B.)
- Correspondence:
| | - Caterina Lanna
- Dermatology Unit, Department of Systems Medicine, Tor Vergata University Hospital, 00133 Rome, Italy; (C.L.); (T.C.); (L.B.)
| | - Terenzio Cosio
- Dermatology Unit, Department of Systems Medicine, Tor Vergata University Hospital, 00133 Rome, Italy; (C.L.); (T.C.); (L.B.)
| | - Luigi Rosa
- Department of Public Health and Infectious Diseases, University of Rome “La Sapienza”, 00185 Rome, Italy; (L.R.); (M.P.C.); (P.V.)
| | - Maria Pia Conte
- Department of Public Health and Infectious Diseases, University of Rome “La Sapienza”, 00185 Rome, Italy; (L.R.); (M.P.C.); (P.V.)
| | - Federico Iacovelli
- Structural Bioinformatics Group, Department of Biology, University of Rome “Tor Vergata”, 00133 Rome, Italy; (F.I.); (A.R.); (M.F.)
| | - Alice Romeo
- Structural Bioinformatics Group, Department of Biology, University of Rome “Tor Vergata”, 00133 Rome, Italy; (F.I.); (A.R.); (M.F.)
| | - Mattia Falconi
- Structural Bioinformatics Group, Department of Biology, University of Rome “Tor Vergata”, 00133 Rome, Italy; (F.I.); (A.R.); (M.F.)
| | - Claudia Del Vecchio
- Department of Molecular Medicine, University of Padova, 35122 Padova, Italy; (C.D.V.); (E.F.)
| | - Elisa Franchin
- Department of Molecular Medicine, University of Padova, 35122 Padova, Italy; (C.D.V.); (E.F.)
| | - Maria Stella Lia
- Department of Experimental Medicine, Tor Vergata University Hospital, 00133 Rome, Italy; (M.S.L.); (M.M.); (A.T.)
| | - Marilena Minieri
- Department of Experimental Medicine, Tor Vergata University Hospital, 00133 Rome, Italy; (M.S.L.); (M.M.); (A.T.)
| | - Carlo Chiaramonte
- Department of Statistics, University of Rome Tor Vergata, 00133 Rome, Italy;
| | - Marco Ciotti
- Virology Unit, Tor Vergata University Hospital, 00133 Rome, Italy;
| | - Marzia Nuccetelli
- Laboratory Medicine, Department of Experimental Medicine and Surgery, Tor Vergata University Hospital, 00133 Rome, Italy; (M.N.); (S.B.)
| | - Alessandro Terrinoni
- Department of Experimental Medicine, Tor Vergata University Hospital, 00133 Rome, Italy; (M.S.L.); (M.M.); (A.T.)
| | - Ilaria Iannuzzi
- Occupational Medicine Department, University of Rome “Tor Vergata”, 00133 Rome, Italy; (I.I.); (L.C.); (A.M.)
| | - Luca Coppeta
- Occupational Medicine Department, University of Rome “Tor Vergata”, 00133 Rome, Italy; (I.I.); (L.C.); (A.M.)
| | - Andrea Magrini
- Occupational Medicine Department, University of Rome “Tor Vergata”, 00133 Rome, Italy; (I.I.); (L.C.); (A.M.)
| | - Sergio Bernardini
- Laboratory Medicine, Department of Experimental Medicine and Surgery, Tor Vergata University Hospital, 00133 Rome, Italy; (M.N.); (S.B.)
| | | | | | | | - Nicola Moricca
- Villa dei Pini Hospital, 00042 Anzio, Italy; (S.S.); (N.M.)
| | - Andrea Di Lorenzo
- Infectious Disease Unit, Tor Vergata University Hospital, 00133 Rome, Italy; (A.D.L.); (M.A.); (L.S.)
| | - Massimo Andreoni
- Infectious Disease Unit, Tor Vergata University Hospital, 00133 Rome, Italy; (A.D.L.); (M.A.); (L.S.)
| | - Loredana Sarmati
- Infectious Disease Unit, Tor Vergata University Hospital, 00133 Rome, Italy; (A.D.L.); (M.A.); (L.S.)
| | - Alessandro Miani
- Department of Environmental Sciences and Policy, University of Milan, 20133 Milan, Italy;
| | - Prisco Piscitelli
- UNESCO Chair on Health Education and Sustainable Development, University of Naples Federico II, 80131 Naples, Italy;
| | - Ettore Squillaci
- Department of Diagnostic and Molecular Imaging, Radiation Therapy and Interventional Radiology, University Hospital Tor Vergata, 00133 Rome, Italy;
| | - Piera Valenti
- Department of Public Health and Infectious Diseases, University of Rome “La Sapienza”, 00185 Rome, Italy; (L.R.); (M.P.C.); (P.V.)
| | - Luca Bianchi
- Dermatology Unit, Department of Systems Medicine, Tor Vergata University Hospital, 00133 Rome, Italy; (C.L.); (T.C.); (L.B.)
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15
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Targeting Ferroptosis for Lung Diseases: Exploring Novel Strategies in Ferroptosis-Associated Mechanisms. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2021; 2021:1098970. [PMID: 34630843 PMCID: PMC8494591 DOI: 10.1155/2021/1098970] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Revised: 09/04/2021] [Accepted: 09/22/2021] [Indexed: 02/07/2023]
Abstract
Ferroptosis is an iron-dependent regulated necrosis characterized by the peroxidation damage of lipid molecular containing unsaturated fatty acid long chain on the cell membrane or organelle membrane after cellular deactivation restitution system, resulting in the cell membrane rupture. Ferroptosis is biochemically and morphologically distinct and disparate from other forms of regulated cell death. Recently, mounting studies have investigated the mechanism of ferroptosis, and numerous proteins play vital roles in regulating ferroptosis. With detailed studies, emerging evidence indicates that ferroptosis is found in multiple lung diseases, demonstrating that ferroptosis appears to be particularly important for lung diseases. The mounting interest in ferroptosis drugs specifically targeting the ferroptosis mechanism holds substantial therapeutic promise in lung diseases. The present review emphatically summarizes the functions and integrated molecular mechanisms of ferroptosis in various lung diseases, proposing that multiangle regulation of ferroptosis might be a promising strategy for the clinical treatment of lung diseases.
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16
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Kgatle MM, Lawal IO, Mashabela G, Boshomane TMG, Koatale PC, Mahasha PW, Ndlovu H, Vorster M, Rodrigues HG, Zeevaart JR, Gordon S, Moura-Alves P, Sathekge MM. COVID-19 Is a Multi-Organ Aggressor: Epigenetic and Clinical Marks. Front Immunol 2021; 12:752380. [PMID: 34691068 PMCID: PMC8531724 DOI: 10.3389/fimmu.2021.752380] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Accepted: 09/21/2021] [Indexed: 12/19/2022] Open
Abstract
The progression of coronavirus disease 2019 (COVID-19), resulting from a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, may be influenced by both genetic and environmental factors. Several viruses hijack the host genome machinery for their own advantage and survival, and similar phenomena might occur upon SARS-CoV-2 infection. Severe cases of COVID-19 may be driven by metabolic and epigenetic driven mechanisms, including DNA methylation and histone/chromatin alterations. These epigenetic phenomena may respond to enhanced viral replication and mediate persistent long-term infection and clinical phenotypes associated with severe COVID-19 cases and fatalities. Understanding the epigenetic events involved, and their clinical significance, may provide novel insights valuable for the therapeutic control and management of the COVID-19 pandemic. This review highlights different epigenetic marks potentially associated with COVID-19 development, clinical manifestation, and progression.
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Affiliation(s)
- Mankgopo Magdeline Kgatle
- Nuclear Medicine Research Infrastructure (NuMeRI), Steve Biko Academic Hospital, Pretoria, South Africa
- Department of Nuclear Medicine, University of Pretoria & Steve Biko Academic Hospital, Pretoria, South Africa
| | - Ismaheel Opeyemi Lawal
- Nuclear Medicine Research Infrastructure (NuMeRI), Steve Biko Academic Hospital, Pretoria, South Africa
- Department of Nuclear Medicine, University of Pretoria & Steve Biko Academic Hospital, Pretoria, South Africa
- Department of Nuclear Medicine, Steve Biko Academic Hospital, Pretoria, South Africa
| | - Gabriel Mashabela
- SAMRC/NHLS/UCT Molecular Mycobacteriology Research Unit, DSI/NRF Centre of Excellence for Biomedical TB Research, Department of Pathology and Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
| | - Tebatso Moshoeu Gillian Boshomane
- Nuclear Medicine Research Infrastructure (NuMeRI), Steve Biko Academic Hospital, Pretoria, South Africa
- Department of Nuclear Medicine, University of Pretoria & Steve Biko Academic Hospital, Pretoria, South Africa
- Department of Nuclear Medicine, Steve Biko Academic Hospital, Pretoria, South Africa
- Nuclear and Oncology Division, AXIM Medical (Pty), Midrand
| | - Palesa Caroline Koatale
- Nuclear Medicine Research Infrastructure (NuMeRI), Steve Biko Academic Hospital, Pretoria, South Africa
- Department of Nuclear Medicine, University of Pretoria & Steve Biko Academic Hospital, Pretoria, South Africa
| | - Phetole Walter Mahasha
- Precision Medicine and SAMRC Genomic Centre, Grants, Innovation, and Product Development (GIPD) Unit, South African Medical Research Council, Pretoria, South Africa
| | - Honest Ndlovu
- Department of Nuclear Medicine, University of Pretoria & Steve Biko Academic Hospital, Pretoria, South Africa
| | - Mariza Vorster
- Department of Nuclear Medicine, University of Pretoria & Steve Biko Academic Hospital, Pretoria, South Africa
| | - Hosana Gomes Rodrigues
- Laboratory of Nutrients and Tissue Repair, School of Applied Sciences, University of Campinas, Campinas, Brazil
| | - Jan Rijn Zeevaart
- Nuclear Medicine Research Infrastructure (NuMeRI), Steve Biko Academic Hospital, Pretoria, South Africa
- South African Nuclear Energy Corporation, Radiochemistry and NuMeRI PreClinical Imaging Facility, Mahikeng, South Africa
- Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan City, Taiwan
| | - Siamon Gordon
- Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan City, Taiwan
- Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom
| | - Pedro Moura-Alves
- Ludwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
| | - Mike Machaba Sathekge
- Nuclear Medicine Research Infrastructure (NuMeRI), Steve Biko Academic Hospital, Pretoria, South Africa
- Department of Nuclear Medicine, University of Pretoria & Steve Biko Academic Hospital, Pretoria, South Africa
- SAMRC/NHLS/UCT Molecular Mycobacteriology Research Unit, DSI/NRF Centre of Excellence for Biomedical TB Research, Department of Pathology and Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
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17
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Varela AA, Cheng S, Werren JH. Novel ACE2 protein interactions relevant to COVID-19 predicted by evolutionary rate correlations. PeerJ 2021; 9:e12159. [PMID: 34616619 PMCID: PMC8449537 DOI: 10.7717/peerj.12159] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2021] [Accepted: 08/24/2021] [Indexed: 12/13/2022] Open
Abstract
Angiotensin-converting enzyme 2 (ACE2) is the cell receptor that the coronavirus SARS-CoV-2 binds to and uses to enter and infect human cells. COVID-19, the pandemic disease caused by the coronavirus, involves diverse pathologies beyond those of a respiratory disease, including micro-thrombosis (micro-clotting), cytokine storms, and inflammatory responses affecting many organ systems. Longer-term chronic illness can persist for many months, often well after the pathogen is no longer detected. A better understanding of the proteins that ACE2 interacts with can reveal information relevant to these disease manifestations and possible avenues for treatment. We have undertaken an approach to predict candidate ACE2 interacting proteins which uses evolutionary inference to identify a set of mammalian proteins that “coevolve” with ACE2. The approach, called evolutionary rate correlation (ERC), detects proteins that show highly correlated evolutionary rates during mammalian evolution. Such proteins are candidates for biological interactions with the ACE2 receptor. The approach has uncovered a number of key ACE2 protein interactions of potential relevance to COVID-19 pathologies. Some proteins have previously been reported to be associated with severe COVID-19, but are not currently known to interact with ACE2, while additional predicted novel ACE2 interactors are of potential relevance to the disease. Using reciprocal rankings of protein ERCs, we have identified strongly interconnected ACE2 associated protein networks relevant to COVID-19 pathologies. ACE2 has clear connections to coagulation pathway proteins, such as Coagulation Factor V and fibrinogen components FGA, FGB, and FGG, the latter possibly mediated through ACE2 connections to Clusterin (which clears misfolded extracellular proteins) and GPR141 (whose functions are relatively unknown). ACE2 also connects to proteins involved in cytokine signaling and immune response (e.g. XCR1, IFNAR2 and TLR8), and to Androgen Receptor (AR). The ERC prescreening approach has elucidated possible functions for relatively uncharacterized proteins and possible new functions for well-characterized ones. Suggestions are made for the validation of ERC-predicted ACE2 protein interactions. We propose that ACE2 has novel protein interactions that are disrupted during SARS-CoV-2 infection, contributing to the spectrum of COVID-19 pathologies.
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Affiliation(s)
- Austin A Varela
- Department of Biology, University of Rochester, Rochester, New York, United States
| | - Sammy Cheng
- Department of Biology, University of Rochester, Rochester, New York, United States
| | - John H Werren
- Department of Biology, University of Rochester, Rochester, New York, United States
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18
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Kim YS. COVID-19 and encephalitis. ENCEPHALITIS 2021; 1:98-102. [PMID: 37470052 PMCID: PMC10295891 DOI: 10.47936/encephalitis.2021.00122] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Revised: 09/20/2021] [Accepted: 09/22/2021] [Indexed: 07/21/2023] Open
Abstract
The current coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2. Due to the increasing number of confirmed cases and accumulating clinical data, in addition to the predominant respiratory symptoms, a significant proportion of patients with COVID-19 experience neurological complications. Presumedly, several mechanisms, such as direct viral effects on the brain parenchyma and endothelium, and activation of the inflammatory and thrombotic pathways, cause these neurological disorders. Herein, the literature focusing on encephalitis among the central nervous system disorders associated with COVID-19 was reviewed.
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Affiliation(s)
- Young-Soo Kim
- Department of Neurology, Gyeongsang National University Hospital, Jinju, Korea
- Department of Neurology and Institute of Health Science, Gyeongsang National University College of Medicine, Jinju, Korea
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19
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Samanta P, Ghosh AR. Environmental perspectives of COVID-19 outbreaks: A review. World J Gastroenterol 2021; 27:5822-5850. [PMID: 34629805 PMCID: PMC8475003 DOI: 10.3748/wjg.v27.i35.5822] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Revised: 01/10/2021] [Accepted: 08/12/2021] [Indexed: 02/06/2023] Open
Abstract
The coronavirus disease 2019 (COVID-19) pandemic, caused by the novel virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), began in December 2019 in China and has led to a global public health emergency. Previously, it was known as 2019-nCoV and caused disease mainly through respiratory pathways. The COVID-19 outbreak is ranked third globally as the most highly pathogenic disease of the twenty-first century, after the outbreak of SARS-CoV and Middle East respiratory syndrome in 2002 and 2012, respectively. Clinical, laboratory, and diagnostic methodology have been demonstrated in some observational studies. No systematic reviews on COVID-19 have been published regarding the integration of COVID-19 outbreaks (monitoring, fate and treatment) with environmental and human health perspectives. Accordingly, this review systematically addresses environmental aspects of COVID-19 outbreak such as the origin of SARS-CoV-2, epidemiological characteristics, diagnostic methodology, treatment options and technological advancement for the prevention of COVID-19 outbreaks. Finally, we integrate COVID-19 outbreaks (monitoring, fate and treatment) with environmental and human health perspectives. We believe that this review will help to understand the SARS-CoV-2 outbreak as a multipurpose document, not only for the scientific community but also for global citizens. Countries should adopt emergency preparedness such as prepare human resources, infrastructure and facilities to treat severe COVID-19 as the virus spreads rapidly globally.
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Affiliation(s)
- Palas Samanta
- Department of Environmental Science, Sukanta Mahavidyalaya, University of North Bengal, Dhupguri 735210, West Bengal, India
| | - Apurba Ratan Ghosh
- Department of Environmental Science, The University of Burdwan, Burdwan 713104, West Bengal, India
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20
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Kaundal RK, Kalvala AK, Kumar A. Neurological Implications of COVID-19: Role of Redox Imbalance and Mitochondrial Dysfunction. Mol Neurobiol 2021; 58:4575-4587. [PMID: 34110602 PMCID: PMC8190166 DOI: 10.1007/s12035-021-02412-y] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2021] [Accepted: 04/29/2021] [Indexed: 12/20/2022]
Abstract
Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 or COVID-19 has been declared as a pandemic disease by the World Health Organization (WHO). Globally, this disease affected 159 million of the population and reported ~ 3.3 million deaths to the current date (May 2021). There is no definitive treatment strategy that has been identified, although this disease has prevailed in its current form for the past 18 months. The main challenges in the (SARS-CoV)-2 infections are in identifying the heterogeneity in viral strains and the plausible mechanisms of viral infection to human tissues. In parallel to the investigations into the patho-mechanism of SARS-CoV-2 infection, understanding the fundamental processes underlying the clinical manifestations of COVID-19 is very crucial for designing effective therapies. Since neurological symptoms are very apparent in COVID-19 infected patients, here, we tried to emphasize the involvement of redox imbalance and subsequent mitochondrial dysfunction in the progression of the COVID-19 infection. It has been articulated that mitochondrial dysfunction is very apparent and also interlinked to neurological symptoms in COVID-19 infection. Overall, this article provides an in-depth overview of redox imbalance and mitochondrial dysfunction involvement in aggravating COVID-19 infection and its probable contribution to the neurological manifestation of the disease.
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Affiliation(s)
- Ravinder K Kaundal
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Raebareli, Lucknow, India
- Icahn School of Medicine At Mount Sinai, 1470 Madison Ave, New York, NY, USA
| | - Anil K Kalvala
- College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL, North America, USA
| | - Ashutosh Kumar
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Kolkata, Kolkata, India.
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21
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Uberti F, Ruga S, Farghali M, Galla R, Molinari C. A Combination of α-Lipoic Acid (ALA) and Palmitoylethanolamide (PEA) Blocks Endotoxin-Induced Oxidative Stress and Cytokine Storm: A Possible Intervention for COVID-19. J Diet Suppl 2021; 20:133-155. [PMID: 34405764 DOI: 10.1080/19390211.2021.1966152] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
The global scientific community is striving to understand the pathophysiological mechanisms and develop effective therapeutic strategies for COVID-19. Despite overwhelming data, there is limited knowledge about the molecular mechanisms involved in the prominent cytokine storm syndrome and multiple organ failure and fatality in COVID-19 cases. The aim of this work is to investigate the possible role of of α-lipoic acid (ALA) and palmitoylethanolamide (PEA), in countering the mechanisms in overproduction of reactive oxygen species (ROS), and inflammatory cytokines. An in vitro model of lipopolysaccharide (LPS)-stimulated human epithelial lung cells that mimics the pathogen-associated molecular pattern and reproduces the cell signaling pathways in cytokine storm syndrome has been used. In this model of acute lung injury, the combination effects of ALAPEA, administered before and after LPS injury, were investigated. Our data demonstrated that a combination of 50 µM ALA + 5 µM PEA can reduce ROS and nitric oxide (NO) levels modulating the major cytokines involved on COVID-19 infection when administered either before or after LPS-induced damage. The best outcome was observed when administered after LPS, thus reinforcing the hypothesis that ALA combined with PEA to modulate the key point of cytokine storm syndrome. This work supports for the first time that the combination of ALA with PEA may represent a novel intervention strategy to counteract inflammatory damage related to COVID-19 by restoring the cascade activation of the immune response and acting as a powerful antioxidant.
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Affiliation(s)
- Francesca Uberti
- Laboratory Physiology, Department of Translational Medicine, UPO, Novara, Italy
| | - Sara Ruga
- Laboratory Physiology, Department of Translational Medicine, UPO, Novara, Italy
| | - Mahitab Farghali
- Laboratory Physiology, Department of Translational Medicine, UPO, Novara, Italy
| | - Rebecca Galla
- Laboratory Physiology, Department of Translational Medicine, UPO, Novara, Italy
| | - Claudio Molinari
- Laboratory Physiology, Department of Translational Medicine, UPO, Novara, Italy
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Gurunathan S, Kang MH, Kim JH. Diverse Effects of Exosomes on COVID-19: A Perspective of Progress From Transmission to Therapeutic Developments. Front Immunol 2021; 12:716407. [PMID: 34394121 PMCID: PMC8355618 DOI: 10.3389/fimmu.2021.716407] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Accepted: 07/05/2021] [Indexed: 01/08/2023] Open
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new strain of coronavirus and the causative agent of the current global pandemic of coronavirus disease 2019 (COVID-19). There are currently no FDA-approved antiviral drugs for COVID-19 and there is an urgent need to develop treatment strategies that can effectively suppress SARS-CoV-2 infection. Numerous approaches have been researched so far, with one of them being the emerging exosome-based therapies. Exosomes are nano-sized, lipid bilayer-enclosed structures, share structural similarities with viruses secreted from all types of cells, including those lining the respiratory tract. Importantly, the interplay between exosomes and viruses could be potentially exploited for antiviral drug and vaccine development. Exosomes are produced by virus-infected cells and play crucial roles in mediating communication between infected and uninfected cells. SARS-CoV-2 modulates the production and composition of exosomes, and can exploit exosome formation, secretion, and release pathways to promote infection, transmission, and intercellular spread. Exosomes have been exploited for therapeutic benefits in patients afflicted with various diseases including COVID-19. Furthermore, the administration of exosomes loaded with immunomodulatory cargo in combination with antiviral drugs represents a novel intervention for the treatment of diseases such as COVID-19. In particular, exosomes derived from mesenchymal stem cells (MSCs) are used as cell-free therapeutic agents. Mesenchymal stem cell derived exosomes reduces the cytokine storm and reverse the inhibition of host anti-viral defenses associated with COVID-19 and also enhances mitochondrial function repair lung injuries. We discuss the role of exosomes in relation to transmission, infection, diagnosis, treatment, therapeutics, drug delivery, and vaccines, and present some future perspectives regarding their use for combating COVID-19.
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Affiliation(s)
- Sangiliyandi Gurunathan
- Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul, South Korea
| | - Min Hee Kang
- Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul, South Korea
| | - Jin-Hoi Kim
- Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul, South Korea
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23
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Simões JLB, de Araújo JB, Bagatini MD. Anti-inflammatory Therapy by Cholinergic and Purinergic Modulation in Multiple Sclerosis Associated with SARS-CoV-2 Infection. Mol Neurobiol 2021; 58:5090-5111. [PMID: 34247339 PMCID: PMC8272687 DOI: 10.1007/s12035-021-02464-0] [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: 05/12/2021] [Accepted: 06/17/2021] [Indexed: 02/07/2023]
Abstract
The virus "acute respiratory syndrome coronavirus 2" (SARS-CoV-2) is the etiologic agent of coronavirus disease 2019 (COVID-19), initially responsible for an outbreak of pneumonia in Wuhan, China, which, due to the high level of contagion and dissemination, has become a pandemic. The clinical picture varies from mild to critical cases; however, all of these signs already show neurological problems, from sensory loss to neurological diseases. Thus, patients with multiple sclerosis (MS) infected with the new coronavirus are more likely to develop severe conditions; in addition to worsening the disease, this is due to the high level of pro-inflammatory cytokines, which is closely associated with increased mortality both in COVID-19 and MS. This increase is uncontrolled and exaggerated, characterizing the cytokine storm, so a possible therapy for this neuronal inflammation is the modulation of the cholinergic anti-inflammatory pathway, since acetylcholine (ACh) acts to reduce pro-inflammatory cytokines and acts directly on the brain for being released by cholinergic neurons, as well as acting on other cells such as immune and blood cells. In addition, due to tissue damage, there is an exacerbated release of adenosine triphosphate (ATP), potentiating the inflammatory process and activating purinergic receptors which act directly on neuroinflammation and positively modulate the inflammatory cycle. Associated with this, in neurological pathologies, there is greater expression of P2X7 in the cells of the microglia, which positively activates the immune inflammatory response. Thus, the administration of blockers of this receptor can act in conjunction with the action of ACh in the anticholinergic inflammatory pathway. Finally, there will be a reduction in the cytokine storm and triggered hyperinflammation, as well as the level of mortality in patients with multiple sclerosis infected with SARS-CoV-2 and the development of possible neurological damage.
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Yang L, Xie X, Tu Z, Fu J, Xu D, Zhou Y. The signal pathways and treatment of cytokine storm in COVID-19. Signal Transduct Target Ther 2021; 6:255. [PMID: 34234112 PMCID: PMC8261820 DOI: 10.1038/s41392-021-00679-0] [Citation(s) in RCA: 353] [Impact Index Per Article: 88.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2021] [Revised: 05/22/2021] [Accepted: 06/12/2021] [Indexed: 02/07/2023] Open
Abstract
The Coronavirus Disease 2019 (COVID-19) pandemic has become a global crisis and is more devastating than any other previous infectious disease. It has affected a significant proportion of the global population both physically and mentally, and destroyed businesses and societies. Current evidence suggested that immunopathology may be responsible for COVID-19 pathogenesis, including lymphopenia, neutrophilia, dysregulation of monocytes and macrophages, reduced or delayed type I interferon (IFN-I) response, antibody-dependent enhancement, and especially, cytokine storm (CS). The CS is characterized by hyperproduction of an array of pro-inflammatory cytokines and is closely associated with poor prognosis. These excessively secreted pro-inflammatory cytokines initiate different inflammatory signaling pathways via their receptors on immune and tissue cells, resulting in complicated medical symptoms including fever, capillary leak syndrome, disseminated intravascular coagulation, acute respiratory distress syndrome, and multiorgan failure, ultimately leading to death in the most severe cases. Therefore, it is clinically important to understand the initiation and signaling pathways of CS to develop more effective treatment strategies for COVID-19. Herein, we discuss the latest developments in the immunopathological characteristics of COVID-19 and focus on CS including the current research status of the different cytokines involved. We also discuss the induction, function, downstream signaling, and existing and potential interventions for targeting these cytokines or related signal pathways. We believe that a comprehensive understanding of CS in COVID-19 will help to develop better strategies to effectively control immunopathology in this disease and other infectious and inflammatory diseases.
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Affiliation(s)
- Lan Yang
- Institute of Pediatrics, Children's Hospital of Fudan University, National Children's Medical Center, and the Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai, China
- National Health Commission (NHC) Key Laboratory of Neonatal Diseases, Fudan University, Shanghai, China
| | - Xueru Xie
- Institute of Pediatrics, Children's Hospital of Fudan University, National Children's Medical Center, and the Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai, China
- National Health Commission (NHC) Key Laboratory of Neonatal Diseases, Fudan University, Shanghai, China
| | - Zikun Tu
- Institute of Pediatrics, Children's Hospital of Fudan University, National Children's Medical Center, and the Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai, China
- National Health Commission (NHC) Key Laboratory of Neonatal Diseases, Fudan University, Shanghai, China
| | - Jinrong Fu
- General Department, Children's Hospital of Fudan University, Shanghai, China
| | - Damo Xu
- State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen Key Laboratory of Allergy and Immunology, Shenzhen University School of Medicine, Shenzhen, China.
- Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.
| | - Yufeng Zhou
- Institute of Pediatrics, Children's Hospital of Fudan University, National Children's Medical Center, and the Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
- National Health Commission (NHC) Key Laboratory of Neonatal Diseases, Fudan University, Shanghai, China.
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25
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Ma Q, Hao ZW, Wang YF. The effect of estrogen in coronavirus disease 2019. Am J Physiol Lung Cell Mol Physiol 2021; 321:L219-L227. [PMID: 33949212 PMCID: PMC8270516 DOI: 10.1152/ajplung.00332.2020] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Accepted: 04/30/2021] [Indexed: 12/24/2022] Open
Abstract
The outcomes of coronavirus disease 2019 (COVID-19) vary between men and women. Some statistical reports have shown that men have a higher risk of developing COVID-19 and suffer from worse outcomes than females. Although there are many factors that can explain the high prevalence of COVID-19 in men, such as lifestyle habits and the different profile of comorbidities among sexes, the distinctions between male and female immune systems cannot be ignored. It has been sufficiently shown that sex differences have a critical influence on the shaping of immune response, which then leads to different pathogenesis in infectious diseases. Compared with males, females typically have a more effective innate and adaptive immune response to viral infections in COVID-19. What's more, there is a growing body of evidence showing that estrogen exerts an effect on the regulation of immune response. This article examines the effect and mechanism of estrogen on COVID-19.
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Affiliation(s)
- Qing Ma
- Institute of Hepatobiliary Diseases of Wuhan University, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Zhuo-Wen Hao
- Institute of Hepatobiliary Diseases of Wuhan University, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Yan-Feng Wang
- Institute of Hepatobiliary Diseases of Wuhan University, Zhongnan Hospital of Wuhan University, Wuhan, China
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26
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Kumar R, Harilal S, Al-Sehemi AG, Mathew GE, Carradori S, Mathew B. The Chronicle of COVID-19 and Possible Strategies to Curb the Pandemic. Curr Med Chem 2021; 28:2852-2886. [PMID: 32614740 DOI: 10.2174/0929867327666200702151018] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Revised: 05/19/2020] [Accepted: 06/02/2020] [Indexed: 11/22/2022]
Abstract
COVID-19, a type of infection that emerged in Wuhan, has become a pandemic affecting people worldwide and is rapidly spreading and evolving. Day by day, the confirmed cases and deaths are increasing many folds. SARS-CoV-2 is a novel virus; therefore, limited data are available to curb the disease. Epidemiological approaches, such as isolation, quarantine, social distancing, lockdown, and curfew, are being employed to halt the spread of the disease. Individual and joint efforts all over the world are producing a wealth of data and information which are expected to produce therapeutic strategies against COVID-19. Current research focuses on the utilization of antiviral drugs, repurposing strategies, vaccine development, as well as basic to advanced research about the organism and the infection. The review focuses on its life cycle, targets, and possible therapeutic strategies, which can lead to further research and development of COVID-19 therapy.
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Affiliation(s)
- Rajesh Kumar
- Department of Pharmacy, Kerala University of Health Sciences, Thrissur, Kerala, India
| | - Seetha Harilal
- Department of Pharmacy, Kerala University of Health Sciences, Thrissur, Kerala, India
| | - Abdullah G Al-Sehemi
- Research center for Advanced Materials Science, King Khalid University, 61413 Abha, Saudi Arabia
| | | | - Simone Carradori
- Department of Pharmacy, "G. d'Annunzio" University of Chieti-Pescara, via dei Vestini 31, 66100 Chieti, Italy
| | - Bijo Mathew
- Department of Pharmaceutical Chemistry, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Sciences Campus, Kochi-682 041, India
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Richter K, Kellner S, Hillemacher T, Golubnitschaja O. Sleep quality and COVID-19 outcomes: the evidence-based lessons in the framework of predictive, preventive and personalised (3P) medicine. EPMA J 2021; 12:221-241. [PMID: 34122671 PMCID: PMC8185312 DOI: 10.1007/s13167-021-00245-2] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2021] [Accepted: 05/12/2021] [Indexed: 01/08/2023]
Abstract
Sleep quality and duration play a pivotal role in maintaining physical and mental health. In turn, sleep shortage, deprivation and disorders are per evidence the risk factors and facilitators of a broad spectrum of disorders, amongst others including depression, stroke, chronic inflammation, cancers, immune defence insufficiency and individual predisposition to infection diseases with poor outcomes, for example, related to the COVID-19 pandemic. Keeping in mind that COVID-19-related global infection distribution is neither the first nor the last pandemic severely affecting societies around the globe to the costs of human lives accompanied with enormous economic burden, lessons by predictive, preventive and personalised (3P) medical approach are essential to learn and to follow being better prepared to defend against global pandemics. To this end, under extreme conditions such as the current COVID-19 pandemic, the reciprocal interrelationship between the sleep quality and individual outcomes becomes evident, namely, at the levels of disease predisposition, severe versus mild disease progression, development of disease complications, poor outcomes and related mortality for both - population and healthcare givers. The latter is the prominent example clearly demonstrating the causality of severe outcomes, when the long-lasting work overload and shift work rhythm evidently lead to the sleep shortage and/or deprivation that in turn causes immune response insufficiency and strong predisposition to the acute infection with complications. This article highlights and provides an in-depth analysis of the concerted risk factors related to the sleep disturbances under the COVID-19 pandemic followed by the evidence-based recommendations in the framework of predictive, preventive and personalised medical approach.
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Affiliation(s)
- Kneginja Richter
- Outpatient Clinic for Sleep Disorders, University Clinic for Psychiatry and Psychotherapy, Paracelsus Medical University Nuremberg, 90419 Nuremberg, Germany
- Faculty for Social Work, Technical University of Applied Sciences Nuremberg Georg Simon Ohm, 90489 Nuremberg, Germany
- Faculty for Medical Sciences, University Goce Delcev Stip, 2000 Stip, North Macedonia
| | - Stefanie Kellner
- Faculty for Social Work, Technical University of Applied Sciences Nuremberg Georg Simon Ohm, 90489 Nuremberg, Germany
| | - Thomas Hillemacher
- Outpatient Clinic for Sleep Disorders, University Clinic for Psychiatry and Psychotherapy, Paracelsus Medical University Nuremberg, 90419 Nuremberg, Germany
| | - Olga Golubnitschaja
- Predictive, Preventive and Personalised (3P) Medicine, Department of Radiation Oncology, University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, 53127 Bonn, Germany
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28
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Sánchez-Arribas N, Martínez-Negro M, Aicart-Ramos C, Tros de Ilarduya C, Aicart E, Guerrero-Martínez A, Junquera E. Gemini Cationic Lipid-Type Nanovectors Suitable for the Transfection of Therapeutic Plasmid DNA Encoding for Pro-Inflammatory Cytokine Interleukin-12. Pharmaceutics 2021; 13:729. [PMID: 34063469 PMCID: PMC8156092 DOI: 10.3390/pharmaceutics13050729] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Revised: 04/26/2021] [Accepted: 05/13/2021] [Indexed: 12/12/2022] Open
Abstract
Ample evidence exists on the role of interleukin-12 (IL-12) in the response against many pathogens, as well as on its remarkable antitumor properties. However, the unexpected toxicity and disappointing results in some clinical trials are prompting the design of new strategies and/or vectors for IL-12 delivery. This study was conceived to further endorse the use of gemini cationic lipids (GCLs) in combination with zwitterionic helper lipid DOPE (1,2-dioleoyl-sn-glycero-3-phosphatidyl ethanol amine) as nanovectors for the insertion of plasmid DNA encoding for IL-12 (pCMV-IL12) into cells. Optimal GCL formulations previously reported by us were selected for IL-12-based biophysical experiments. In vitro studies demonstrated efficient pCMV-IL12 transfection by GCLs with comparable or superior cytokine levels than those obtained with commercial control Lipofectamine2000*. Furthermore, the nanovectors did not present significant toxicity, showing high cell viability values. The proteins adsorbed on the nanovector surface were found to be mostly lipoproteins and serum albumin, which are both beneficial to increase the blood circulation time. These outstanding results are accompanied by an initial physicochemical characterization to confirm DNA compaction and protection by the lipid mixture. Although further studies would be necessary, the present GCLs exhibit promising characteristics as candidates for pCMV-IL12 transfection in future in vivo applications.
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Affiliation(s)
- Natalia Sánchez-Arribas
- Departamento de Química Física, Facultad de Ciencias Químicas, Universidad Complutense de Madrid, 28040 Madrid, Spain; (N.S.-A.); (M.M.-N.); (E.A.); (A.G.-M.)
| | - María Martínez-Negro
- Departamento de Química Física, Facultad de Ciencias Químicas, Universidad Complutense de Madrid, 28040 Madrid, Spain; (N.S.-A.); (M.M.-N.); (E.A.); (A.G.-M.)
| | - Clara Aicart-Ramos
- Departamento de Estructura de Macromoléculas, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, 28049 Madrid, Spain;
| | - Conchita Tros de Ilarduya
- Departamento de Tecnología y Química Farmacéuticas, Facultad de Farmacia y Nutrición, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Universidad de Navarra, 31080 Pamplona, Spain;
| | - Emilio Aicart
- Departamento de Química Física, Facultad de Ciencias Químicas, Universidad Complutense de Madrid, 28040 Madrid, Spain; (N.S.-A.); (M.M.-N.); (E.A.); (A.G.-M.)
| | - Andrés Guerrero-Martínez
- Departamento de Química Física, Facultad de Ciencias Químicas, Universidad Complutense de Madrid, 28040 Madrid, Spain; (N.S.-A.); (M.M.-N.); (E.A.); (A.G.-M.)
| | - Elena Junquera
- Departamento de Química Física, Facultad de Ciencias Químicas, Universidad Complutense de Madrid, 28040 Madrid, Spain; (N.S.-A.); (M.M.-N.); (E.A.); (A.G.-M.)
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Zawawi A, Naser AY, Alwafi H, Minshawi F. Profile of Circulatory Cytokines and Chemokines in Human Coronaviruses: A Systematic Review and Meta-Analysis. Front Immunol 2021; 12:666223. [PMID: 34046036 PMCID: PMC8147689 DOI: 10.3389/fimmu.2021.666223] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Accepted: 04/09/2021] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND SARS, MERS, and COVID-19 share similar characteristics. For instance, the genetic homology of SARS-CoV-2 compared to SARS-CoV and MERS-CoV is 80% and 50%, respectively, which may cause similar clinical features. Moreover, uncontrolled release of proinflammatory mediators (also called a cytokine storm) by activated immune cells in SARS, MERS, and COVID-19 patients leads to severe phenotype development. AIM This systematic review and meta-analysis aimed to evaluate the inflammatory cytokine profile associated with three strains of severe human coronavirus diseases (MERS-CoV, SARS-CoV, and SARS-CoV-2). METHOD The PubMed, Embase, and Cochrane Library databases were searched for studies published until July 2020. Randomized and observational studies reporting the inflammatory cytokines associated with severe and non-severe human coronavirus diseases, including MERS-CoV, SARS-CoV, and SARS-CoV-2, were included. Two reviewers independently screened articles, extracted data, and assessed the quality of the included studies. Meta-analysis was performed using a random-effects model with a 95% confidence interval to estimate the pooled mean of inflammatory biomarkers. RESULTS A high level of circulating IL-6 could be associated with the severity of infection of the three coronavirus strains. TNF, IL-10, and IL-8 are associated with the severity of COVID-19. Increased circulating levels of CXCL10/IP10 and CCL2/MCP-1 might also be related to the severity of MERS. CONCLUSION This study suggests that the immune response and immunopathology in the three severe human coronavirus strains are somewhat similar. The findings highlight that nearly all studies reporting severe cases of SARS, MERS, and COVID-19 have been associated with elevated levels of IL-6. This could be used as a potential therapeutic target to improve patients' outcomes in severe cases. SYSTEMATIC REVIEW REGISTRATION PROSPERO registration 94 number: CRD42020209931.
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Affiliation(s)
- Ayat Zawawi
- Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
- Vaccines and Immunotherapy Unit, King Fahad Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Abdallah Y. Naser
- Department of Applied Pharmaceutical Sciences and Clinical Pharmacy, Faculty of Pharmacy, Isra University, Amman, Jordan
| | - Hassan Alwafi
- Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Faisal Minshawi
- Department of Laboratory Medicine, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi Arabia
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Verma HK. Radiological and clinical spectrum of COVID-19: A major concern for public health. World J Radiol 2021; 13:53-63. [PMID: 33815683 PMCID: PMC8006056 DOI: 10.4329/wjr.v13.i3.53] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2020] [Revised: 12/07/2020] [Accepted: 03/12/2021] [Indexed: 02/06/2023] Open
Abstract
The pandemic of novel coronavirus disease 2019 (COVID-19) is an infectious disease caused by +ve strand RNA virus (SARS-CoV-2, severe acute respiratory syndrome coronavirus 2) that belongs to the corona viridae family. In March, the World Health Organization declared the outbreak of novel coronavirus for the public health emergency. Although SARS-CoV-2 infection presents with respiratory symptoms, it affects other organs such as the kidneys, liver, heart and brain. Early-stage laboratory disease testing shows many false positive or negative outcomes such as less white blood cell count and a low number of lymphocyte count. However, radiological examination and diagnosis are among the main components of the diagnosis and treatment of COVID-19. In particular, for COVID-19, chest computed tomography developed vigorous initial diagnosis and disease progression assessment. However, the accuracy is limited. Although real-time reverse transcription-polymerase chain reaction is the gold standard method for the diagnosis of COVID-19, sometimes it may give false-negative results. Due to the consequences of the missing diagnosis. This resulted in a discrepancy between the two means of examination. Conversely, based on currently available evidence, we summarized the possible understanding of the various patho-physiology, radio diagnostic methods in severe COVID-19 patients. As the information on COVID-19 evolves rapidly, this review will provide vital information for scientists and clinicians to consider novel perceptions for the comprehensive knowledge of the diagnostic approaches based on current experience.
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Affiliation(s)
- Henu Kumar Verma
- Developmental and Stem Cell Biology Lab, Institute of Experimental Endocrinology and Oncology CNR, Naples 80131, Campania, Italy
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31
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Gilboa T, Maley AM, Ogata AF, Wu C, Walt DR. Sequential Protein Capture in Multiplex Single Molecule Arrays: A Strategy for Eliminating Assay Cross-Reactivity. Adv Healthc Mater 2021; 10:e2001111. [PMID: 32893488 PMCID: PMC8238389 DOI: 10.1002/adhm.202001111] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Revised: 08/12/2020] [Indexed: 12/31/2022]
Abstract
Measurements of multiple biomolecules within the same biological sample are important for many clinical applications to enable accurate disease diagnosis or classification. These disease-related biomarkers often exist at very low levels in biological fluids, necessitating ultrasensitive measurement methods. Single-molecule arrays (Simoa), a bead-based digital enzyme-linked immunosorbent assay, is the current state of the art for ultrasensitive protein detection and can detect sub-femtomolar protein concentrations, but its ability to achieve high-order multiplexing without cross-reactivity remains a challenge. Here, a sequential protein capture approach for multiplex Simoa assays is implemented to eliminate cross-reactivity between binding reagents by sequentially capturing each protein analyte and then incubating each capture bead with only its corresponding detection antibody. This strategy not only reduces cross-reactivity to background levels and significantly improves measurement accuracies, but also enables higher-order multiplexing. As a proof of concept, the sequential multiplex Simoa assay is used to measure five different cytokines in plasma samples from Coronavirus Disease 2019 (COVID-19) patients. The ultrasensitive sequential multiplex Simoa assays will enable the simultaneous measurements of multiple low-abundance analytes in a time- and cost-effective manner and will prove especially critical in many cases where sample volumes are limited.
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Affiliation(s)
- Tal Gilboa
- Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, 02115, USA
| | - Adam M Maley
- Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, 02115, USA
| | - Alana F Ogata
- Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, 02115, USA
| | - Connie Wu
- Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, 02115, USA
| | - David R Walt
- Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, 02115, USA
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Ratre YK, Kahar N, Bhaskar LVKS, Bhattacharya A, Verma HK. Molecular mechanism, diagnosis, and potential treatment for novel coronavirus (COVID-19): a current literature review and perspective. 3 Biotech 2021; 11:94. [PMID: 33520580 PMCID: PMC7832422 DOI: 10.1007/s13205-021-02657-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2020] [Accepted: 01/12/2021] [Indexed: 12/12/2022] Open
Abstract
Novel coronavirus disease 2019 (COVID-19) is a positive-sense single-stranded RNA virus which belongs to the Coronaviridae family. COVID-19 outbreak became evident after the severe acute respiratory syndrome coronavirus and the Middle East respiratory syndrome coronavirus in the twenty-first century as the start of the third deadly coronavirus. Currently, research is at an early stage, and the exact etiological dimensions of COVID-19 are unknown. Several candidate drugs and plasma therapy have been considered and evaluated for the treatment of severe COVID-19 patients. These include clinically available drugs such as chloroquine, hydroxychloroquine, and lopinavir/ritonavir. However, understanding the pathogenic mechanisms of this virus is critical for predicting interaction with humans. Based on recent evidence, we have summarized the current virus biology in terms of the possible understanding of the various pathophysiologies, molecular mechanisms, recent efficient diagnostics, and therapeutic approaches to control the disease. In addition, we briefly reviewed the biochemistry of leading candidates for novel therapies and their current status in clinical trials. As information from COVID-19 is evolving rapidly, this review will help the researcher to consider new insights and potential therapeutic approaches based on up-to-date knowledge. Finally, this review illustrates a list of alternative therapeutic solutions for a viral infection.
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Affiliation(s)
| | - Namrata Kahar
- Department of Zoology, Guru Ghasidas Vishwavidyalaya, Bilaspur, India
| | | | - Antaripa Bhattacharya
- Department of Molecular Medicine and Medical Biotechnology, University of Naples “Federico II”, Naples, Italy
| | - Henu Kumar Verma
- Developmental and Stem Cell Biology Lab, Institute of Experimental Endocrinology and Oncology CNR, Naples, Italy
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Földvári-Nagy L, Schnabel T, Dörnyei G, Korcsmáros T, Lenti K. On the role of bacterial metalloproteases in COVID-19 associated cytokine storm. Cell Commun Signal 2021; 19:7. [PMID: 33441142 PMCID: PMC7805260 DOI: 10.1186/s12964-020-00699-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2020] [Accepted: 12/23/2020] [Indexed: 12/15/2022] Open
Abstract
The cytokine release syndrome or cytokine storm, which is the hyper-induction of inflammatory responses has a central role in the mortality rate of COVID-19 and some other viral infections. Interleukin-6 (IL-6) is a key player in the development of cytokine storms. Shedding of interleukin-6 receptor (IL-6Rα) results in the accumulation of soluble interleukin-6 receptors (sIL-6R). Only relatively few cells express membrane-bound IL-6Rα. However, sIL-6R can act on potentially all cells and organs through the ubiquitously expressed gp130, the coreceptor of IL-6Rα. Through this, so-called trans-signaling, IL-6-sIL-6R is a powerful factor in the development of cytokine storms and multiorgan involvement. Some bacteria (e.g., Serratia marcescens, Staphylococcus aureus, Pseudomonas aeruginosa, Listeria monocytogenes), commonly considered to cause co-infections during viral pneumonia, can directly induce the shedding of membrane receptors, including IL-6Rα, or enhance endogenous shedding mechanisms causing the increase of sIL-6R level. Here we hypothesise that bacteria promoting shedding and increase the sIL-6R level can be an important contributing factor for the development of cytokine storms. Therefore, inhibition of IL-6Rα shedding by drastically reducing the number of relevant bacteria may be a critical element in reducing the chance of a cytokine storm. Validation of this hypothesis can support the consideration of the prophylactic use of antibiotics more widely and at an earlier stage of infection to decrease the mortality rate of COVID-19. Video abstract.
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Affiliation(s)
- László Földvári-Nagy
- Department of Morphology and Physiology, Faculty of Health Sciences, Semmelweis University, 17. Vas str., Budapest, 1088 Hungary
| | - Tamás Schnabel
- I. Department of Internal Medicine and Gastroenterology, Department of Orthopaedics - COVID Quarantine, ÉKC New Saint John’s Hospital, 1-3. Diós árok, Budapest, 1125 Hungary
| | - Gabriella Dörnyei
- Department of Morphology and Physiology, Faculty of Health Sciences, Semmelweis University, 17. Vas str., Budapest, 1088 Hungary
| | - Tamás Korcsmáros
- Earlham Institute, Norwich Research Park, Norwich, NR4 7UZ UK
- Quadram Institute Bioscience, Norwich Research Park, Norwich, NR4 7UQ UK
| | - Katalin Lenti
- Department of Morphology and Physiology, Faculty of Health Sciences, Semmelweis University, 17. Vas str., Budapest, 1088 Hungary
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Anwar MM. Immunotherapies and COVID-19 related Neurological manifestations: A Comprehensive Review Article. J Immunoassay Immunochem 2021; 41:960-975. [PMID: 33393415 DOI: 10.1080/15321819.2020.1865400] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
In December 2019, an outbreak of pandemic severe respiratory distress syndrome coronavirus disease 2019 (COVID-19) initially occurred in China, has spread the world resulted in serious threats to human public health. Uncommon neurological manifestations with pathophysiological symptoms were observed in infected patients including headache, seizures, and neuroimmunological disorders. Regardless of whether these neurological symptoms are direct or indirect casual infection relationship, this novel viral infection has a relevant impact on the neuroimmune system that requires a neurologist's careful assessment. Recently, the use of immunotherapy has been emerged in fighting against COVID-19 infection despite the uncertain efficiency in managing COVID-19 related disorders or even its proven failure by increasing its severity. Herein, the author is addressing the first approaches in using immunotherapies in controlling COVID-19 viral impact on the brain by highlighting their role in decreasing or increasing infection risks among subjects. This point of view review article supports the use of immunotherapies in managing COVID-19 neurological disorders but in optimal timing and duration to ensure the maximum therapeutic outcome by reducing morbidity and mortality rate. Based on recently published data, the current review article highlights the beneficial effects and drawbacks of using immunotherapies to combat COVID-19 and its neurological symptoms.
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Affiliation(s)
- Mai M Anwar
- Department of Biochemistry, National Organization for Drug Control and Research (Nodcar)/egyptian Drug Authority , Cairo, Egypt
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35
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Widyadharma IPE, Sari NNSP, Pradnyaswari KE, Yuwana KT, Adikarya IPGD, Tertia C, Wijayanti IAS, Indrayani IAS, Utami DKI. Pain as clinical manifestations of COVID-19 infection and its management in the pandemic era: a literature review. THE EGYPTIAN JOURNAL OF NEUROLOGY, PSYCHIATRY AND NEUROSURGERY 2020; 56:121. [PMID: 33390724 PMCID: PMC7767578 DOI: 10.1186/s41983-020-00258-0] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2020] [Accepted: 12/09/2020] [Indexed: 12/25/2022] Open
Abstract
Coronavirus disease 2019 (COVID-19) is a current global pandemic. The case number has increased since December 31, 2019. It has been reported that COVID-19 patients have been giving pain complaints, one of which is muscular pain. Other types of pain that have also been reported by COVID-19 patients are joint pain, stomach pain, and testicular pain. Neuropathic pain is the rarest case among others. COVID-19 mechanisms in the nerve and musculoskeletal damage are believed to be caused by the expression and distribution of angiotensin-converting enzyme 2 (ACE-2). Patients with pain, especially neuropathic pain, normally do not respond well to various therapies, and experience psychiatric disorders such as depression, which leads to a decrease in the patient's quality of life. Important considerations for health professionals in terms of pain management during this pandemic include ensuring treatment continuity, painkillers, utilization of telemedicine, biopsychosocial management approach, and modifying therapy needs to reduce the risks of COVID-19 complications.
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Affiliation(s)
- I. Putu Eka Widyadharma
- Department of Neurology, Faculty of Medicine, Udayana University/Sanglah Hospital, Bali, Indonesia
| | | | | | - Kadek Tresna Yuwana
- Medical Student, Faculty of Medicine, Udayana University/Sanglah Hospital, Bali, Indonesia
| | | | - Clarissa Tertia
- Department of Neurology, Faculty of Medicine, Udayana University/Sanglah Hospital, Bali, Indonesia
| | - I. A. Sri Wijayanti
- Department of Neurology, Faculty of Medicine, Udayana University/Sanglah Hospital, Bali, Indonesia
| | - I. A. Sri Indrayani
- Department of Neurology, Faculty of Medicine, Udayana University/Sanglah Hospital, Bali, Indonesia
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Nasir N, Mahmood F, Habib K, Khanum I, Jamil B. Tocilizumab for COVID-19 Acute Respiratory Distress Syndrome: Outcomes Assessment Using the WHO Ordinal Scale. Cureus 2020; 12:e12290. [PMID: 33510989 PMCID: PMC7829612 DOI: 10.7759/cureus.12290] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/24/2020] [Indexed: 12/14/2022] Open
Abstract
Introduction Cytokine release syndrome in COVID-19 is characterized by hyperinflammation, which manifests as acute respiratory distress syndrome (ARDS), multiorgan failure, and high inflammatory parameters. Tocilizumab, an interleukin 6 (IL-6) antagonist has been used in COVID-19 ARDS with conflicting results from different parts of the world. Objective To study the treatment outcomes with tocilizumab in patients with COVID-19 ARDS and hyperinflammation using the World Health Organization (WHO) COVID-19 ordinal scale. Methods An observational study was conducted from Feb 2020 to May 2020 on COVID-19 ARDS patients with hyperinflammation. Results A total of 244 patients with COVID-19 were admitted, out of which 107 had ARDS. Thirty patients had both ARDS and hyperinflammation and received tocilizumab. The mean age was 62.5 years (SD: 13.5) and the majority were male (83%). The mean CRP pre-treatment was 217.5 mg/L and post 48 to 72 hours of tocilizumab treatment was 98.5 mg/L. Twenty-one patients (70%) also received concomitant intravenous (IV) methylprednisolone. Of the 30 patients, seven died and 20 recovered. Ten patients required intensive care unit admission and nine developed nosocomial infections. COVID-19-associated aspergillosis was diagnosed in three patients post tocilizumab treatment. Mortality was significantly higher in patients who developed a nosocomial infection and who required intermittent positive pressure ventilation (IPPV). Post-treatment, clinical improvement was observed in patients who had a median score of 5 on the WHO ordinal scale. Conclusion Our study supports the use of tocilizumab in COVID-19 ARDS patients with a pre-treatment median WHO ordinal severity score of 5 and recommends the monitoring of nosocomial infections and opportunistic infections.
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Affiliation(s)
- Nosheen Nasir
- Internal Medicine, Aga Khan University, Karachi, PAK
| | - Faisal Mahmood
- Internal Medicine, Aga Khan University Hospital, Karachi, PAK
| | | | | | - Bushra Jamil
- Medicine/Infectious Diseases, Aga Khan University Hospital, Karachi, PAK
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Tsatsakis A, Calina D, Falzone L, Petrakis D, Mitrut R, Siokas V, Pennisi M, Lanza G, Libra M, Doukas SG, Doukas PG, Kavali L, Bukhari A, Gadiparthi C, Vageli DP, Kofteridis DP, Spandidos DA, Paoliello MMB, Aschner M, Docea AO. SARS-CoV-2 pathophysiology and its clinical implications: An integrative overview of the pharmacotherapeutic management of COVID-19. Food Chem Toxicol 2020; 146:111769. [PMID: 32979398 PMCID: PMC7833750 DOI: 10.1016/j.fct.2020.111769] [Citation(s) in RCA: 117] [Impact Index Per Article: 23.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2020] [Revised: 09/16/2020] [Accepted: 09/18/2020] [Indexed: 02/06/2023]
Abstract
Common manifestations of COVID-19 are respiratory and can extend from mild symptoms to severe acute respiratory distress. The severity of the illness can also extend from mild disease to life-threatening acute respiratory distress syndrome (ARDS). SARS-CoV-2 infection can also affect the gastrointestinal tract, liver and pancreatic functions, leading to gastrointestinal symptoms. Moreover, SARS-CoV-2 can cause central and peripheral neurological manifestations, affect the cardiovascular system and promote renal dysfunction. Epidemiological data have indicated that cancer patients are at a higher risk of contracting the SARS-CoV-2 virus. Considering the multitude of clinical symptoms of COVID-19, the objective of the present review was to summarize their pathophysiology in previously healthy patients, as well as in those with comorbidities. The present review summarizes the current, though admittedly fluid knowledge on the pathophysiology and symptoms of COVID-19 infection. Although unclear issues still remain, the present study contributes to a more complete understanding of the disease, and may drive the direction of new research. The recognition of the severity of the clinical symptoms of COVID-19 is crucial for the specific therapeutic management of affected patients.
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Affiliation(s)
- Aristides Tsatsakis
- Department of Forensic Sciences and Toxicology, Faculty of Medicine, University of Crete, 71003, Heraklion, Greece; I.M. Sechenov First Moscow State Medical University (Sechenov University), 119146, Moscow, Russia.
| | - Daniela Calina
- Department of Clinical Pharmacy, University of Medicine and Pharmacy of Craiova, 200349, Craiova, Romania.
| | - Luca Falzone
- Epidemiology Unit, IRCCS Istituto Nazionale Tumori "Fondazione G. Pascale", 80131, Naples, Italy.
| | - Dimitrios Petrakis
- Department of Forensic Sciences and Toxicology, Faculty of Medicine, University of Crete, 71003, Heraklion, Greece.
| | - Radu Mitrut
- Department of Cardiology, University and Emergency Hospital, 050098, Bucharest, Romania.
| | - Vasileios Siokas
- Department of Neurology, University of Thessaly, University Hospital of Larissa, 41221, Larissa, Greece.
| | - Manuela Pennisi
- Department of Biomedical and Biotechnological Sciences, University of Catania, 95123, Catania, Italy.
| | - Giuseppe Lanza
- Department of Surgery and Medical-Surgical Specialties, University of Catania, 95123, Catania, Italy; Department of Neurology IC, Oasi Research Institute-IRCCS, 94018, Troina, Italy.
| | - Massimo Libra
- Department of Biomedical and Biotechnological Sciences, University of Catania, 95123, Catania, Italy; Research Center for Prevention, Diagnosis and Treatment of Cancer, University of Catania, 95123, Catania, Italy.
| | - Sotirios G Doukas
- Department of Forensic Sciences and Toxicology, Faculty of Medicine, University of Crete, 71003, Heraklion, Greece; Department of Internal Medicine, Saint Peter's University Hospital, 254 Easton Ave, New Brunswick, NJ, 08901, USA.
| | - Panagiotis G Doukas
- University of Pavol Josef Safarik University, Faculty of Medicine, Kosice, Slovakia.
| | - Leena Kavali
- Department of Internal Medicine, Saint Peter's University Hospital, 254 Easton Ave, New Brunswick, NJ, 08901, USA.
| | - Amar Bukhari
- Department of Medicine, Division of Pulmonary and Critical Care 240 Easton Ave, Adult Ambulatory at Cares Building 4th Floor, New Brunswick, NJ, 08901, USA.
| | - Chiranjeevi Gadiparthi
- Division of Gastroenterology, Hepatology and Clinical Nutrition, Saint Peter's University Hospital, New Brunswick, NJ, USA.
| | - Dimitra P Vageli
- Department of Surgery, The Yale Larynx Laboratory, New Haven, CT, 06510, USA.
| | - Diamantis P Kofteridis
- Department of Internal Medicine, University Hospital of Heraklion, 71110, Heraklion, Crete, Greece.
| | - Demetrios A Spandidos
- Laboratory of Clinical Virology, Medical School, University of Crete, Heraklion, 71003, Greece.
| | - Monica M B Paoliello
- Department of Molecular Pharmacology, Albert Eisntein College of Medicine, 1300 Morris Park Avenue Bronx, NY, 10461, USA.
| | - Michael Aschner
- I.M. Sechenov First Moscow State Medical University (Sechenov University), 119146, Moscow, Russia; Department of Molecular Pharmacology, Albert Eisntein College of Medicine, 1300 Morris Park Avenue Bronx, NY, 10461, USA.
| | - Anca Oana Docea
- Department of Toxicology, University of Medicine and Pharmacy of Craiova, 200349, Craiova, Romania.
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Randhawa PK, Scanlon K, Rappaport J, Gupta MK. Modulation of Autophagy by SARS-CoV-2: A Potential Threat for Cardiovascular System. Front Physiol 2020; 11:611275. [PMID: 33329064 PMCID: PMC7734100 DOI: 10.3389/fphys.2020.611275] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2020] [Accepted: 11/09/2020] [Indexed: 12/15/2022] Open
Abstract
Recently, we have witnessed an unprecedented increase in the number of patients suffering from respiratory tract illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The COVID-19 virus is a single-stranded positive-sense RNA virus with a genome size of ~29.9 kb. It is believed that the viral spike (S) protein attaches to angiotensin converting enzyme 2 cell surface receptors and, eventually, the virus gains access into the host cell with the help of intracellular/extracellular proteases or by the endosomal pathway. Once, the virus enters the host cell, it can either be degraded via autophagy or evade autophagic degradation and replicate using the virus encoded RNA dependent RNA polymerase. The virus is highly contagious and can impair the respiratory system of the host causing dyspnea, cough, fever, and tightness in the chest. This disease is also characterized by an abrupt upsurge in the levels of proinflammatory/inflammatory cytokines and chemotactic factors in a process known as cytokine storm. Certain reports have suggested that COVID-19 infection can aggravate cardiovascular complications, in fact, the individuals with underlying co-morbidities are more prone to the disease. In this review, we shall discuss the pathogenesis, clinical manifestations, potential drug candidates, the interaction between virus and autophagy, and the role of coronavirus in exaggerating cardiovascular complications.
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Affiliation(s)
- Puneet Kaur Randhawa
- Division of Metabolic and Cardiovascular Sciences, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL, United States
| | - Kaylyn Scanlon
- Division of Metabolic and Cardiovascular Sciences, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL, United States
| | - Jay Rappaport
- Division of Comparative Pathology, Tulane National Primate Research Center, Covington, LA, United States
| | - Manish K. Gupta
- Division of Metabolic and Cardiovascular Sciences, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL, United States
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Kushwaha S, Seth V, Bapat P, R K, Chaturvedi M, Gupta R, Bhattar S, Maheshwari S, Anthony A. Neurological Associations of COVID-19-Do We Know Enough: A Tertiary Care Hospital Based Study. Front Neurol 2020; 11:588879. [PMID: 33329335 PMCID: PMC7732434 DOI: 10.3389/fneur.2020.588879] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2020] [Accepted: 09/30/2020] [Indexed: 01/08/2023] Open
Abstract
The neurotrophic potential of SARS-CoV-2 virus is manifesting as various neurological disorders in the present pandemic. Nervous system involvement can be due to the direct action of the virus on the brain tissue or due to an indirect action through the activation of immune-mediated mechanisms. This study will discuss the detailed systematically evaluated clinical profile and relevant investigations and outcome of 14 laboratory confirmed SARS-CoV-2 positive patients presenting with neurological signs and symptoms. The patients were further categorized into confirmed, probable, and possible neurological associations. The probable association was found in meningoencephalitis (n = 4), stroke (n = 2), Guillain-Barré syndrome (n = 1), and anosmia (n = 1). The other six patients had coexisting neurological diseases with SARS-CoV-2. One patient with a large artery stroke succumbed to the illness due to respiratory complication. Memory impairment as a sequela is present during follow up of one encephalitis patient. Presently the early recognition and diagnosis of neurological manifestations remains a challenge for clinicians as the SARS-CoV-2 related neurological manifestations are in evolution. A long-term correlation study of clinical profile, radiological and laboratory investigations, along with neuropathological studies is needed to further understand the pathophysiology behind the SARS-CoV-2 neurological manifestations. Further understanding will facilitate timely recognition, therapeutic intervention, and possible prevention of long-term sequalae.
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Affiliation(s)
- Suman Kushwaha
- Department of Neurology, Institute of Human Behaviour and Allied Sciences, New Delhi, India
| | - Vaibhav Seth
- Department of Neurology, Institute of Human Behaviour and Allied Sciences, New Delhi, India
| | - Prateek Bapat
- Department of Neurology, Institute of Human Behaviour and Allied Sciences, New Delhi, India
| | - KiranGowda R
- Department of Neurology, Institute of Human Behaviour and Allied Sciences, New Delhi, India
| | - Monali Chaturvedi
- Department of Neuroradiology, Institute of Human Behaviour and Allied Sciences, New Delhi, India
| | - Renu Gupta
- Department of Microbiology, Institute of Human Behaviour and Allied Sciences, New Delhi, India
| | - Sonali Bhattar
- Department of Microbiology, Rajiv Gandhi Super Speciality Hospital, New Delhi, India
| | - Siddharth Maheshwari
- Department of Neurology, Institute of Human Behaviour and Allied Sciences, New Delhi, India
| | - Aldrin Anthony
- Department of Neurology, Institute of Human Behaviour and Allied Sciences, New Delhi, India
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Çetin İ, Topçul M. Can mesenchymal stem cells be used to treat COVID-19-induced pneumonia? (Review). Biomed Rep 2020; 13:62. [PMID: 33194191 DOI: 10.3892/br.2020.1369] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Accepted: 09/08/2020] [Indexed: 12/13/2022] Open
Abstract
The novel severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) which has resulted in the COVID-19 pandemic, infection by which is commonly characterized by a sore throat, fever and cough, was first reported in Wuhan, China on 31st December 2019. This novel disease is mild in certain individuals, usually younger healthy individuals, whereas the elder and those with underlying health conditions develop severe symptoms and may die as a result of the disease or associated complications. Along with pneumonia, hypercytokinemia, also termed a cytokine storm, is one of the most common pathologies observed in patients with COVID-19. As patients react to the infection with the virus differently; in certain individuals, a cytokine storm may result in death. At present, there is no cure or widely available vaccine for the novel coronavirus. However, it has been hypothesized that mesenchymal stem cells may assist in the treatment/management of the cytokine storm due to their immunomodulating properties.
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Affiliation(s)
- İdil Çetin
- Department of Biology, Faculty of Science, Istanbul University, Istanbul 34459, Turkey
| | - Mehmet Topçul
- Department of Biology, Faculty of Science, Istanbul University, Istanbul 34459, Turkey
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Seth S, Batra J, Srinivasan S. COVID-19: Targeting Proteases in Viral Invasion and Host Immune Response. Front Mol Biosci 2020; 7:215. [PMID: 33195400 PMCID: PMC7581869 DOI: 10.3389/fmolb.2020.00215] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2020] [Accepted: 08/04/2020] [Indexed: 12/28/2022] Open
Abstract
An acute respiratory disorder (COVID-19) that accelerated across the globe has been found to be caused by a novel strain of coronaviruses (SARS-CoV-2). The absence of a specific antiviral drug or vaccination has promoted the development of immediate therapeutic responses against SARS-CoV-2. As increased levels of plasma chemokines and, cytokines and an uncontrolled influx of inflammatory cells were observed in lethal cases, it was concluded that the severity of the infection corresponded with the imbalanced host immunity against the virus. Tracing back the knowledge acquired from SERS and MERS infections, clinical evidence suggested similar host immune reactions and host ACE2 receptor-derived invasion by SARS-CoV-2. Further studies revealed the integral role of proteases (TMPRSS2, cathepsins, plasmin, etc.) in viral entry and the immune system. This review aims to provide a brief review on the latest research progress in identifying the potential role of proteases in SARS-CoV-2 viral spread and infection and combines it with already known information on the role of different proteases in providing an immune response. It further proposes a multidisciplinary clinical approach to target proteases specifically, through a combinatorial administration of protease inhibitors. This predictive review may help in providing a perspective to gain deeper insights of the proteolytic web involved in SARS-CoV-2 viral invasion and host immune response.
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Affiliation(s)
- Sanchit Seth
- School of Biomedical Sciences, Faculty of Health, Translational Research Institute, Queensland University of Technology, Brisbane, QLD, Australia
| | - Jyotsna Batra
- School of Biomedical Sciences, Faculty of Health, Translational Research Institute, Queensland University of Technology, Brisbane, QLD, Australia
| | - Srilakshmi Srinivasan
- School of Biomedical Sciences, Faculty of Health, Translational Research Institute, Queensland University of Technology, Brisbane, QLD, Australia
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Fernandes ACL, Vale AJM, Guzen FP, Pinheiro FI, Cobucci RN, de Azevedo EP. Therapeutic Options Against the New Coronavirus: Updated Clinical and Laboratory Evidences. Front Med (Lausanne) 2020; 7:546. [PMID: 33043030 PMCID: PMC7522372 DOI: 10.3389/fmed.2020.00546] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2020] [Accepted: 07/31/2020] [Indexed: 12/15/2022] Open
Abstract
The pandemic caused by the new coronavirus (SARS-Cov-2) has encouraged numerous in vitro studies and clinical trials around the world, with research groups testing existing drugs, novel drug candidates and vaccines that can prevent or treat infection caused by this virus. The urgency for an effective therapy is justified by the easy and fast viral transmission and the high number of patients with severe respiratory distress syndrome who have increasingly occupied intensive care hospital beds, leading to a collapse in health systems in several countries. However, to date, there is no sufficient evidence of the effectiveness of any researched therapy. The off-label or compassionate use of some drugs by health professionals is a reality in all continents, whose permission by regulatory agencies has been based on the results of some clinical trials. In order to guide decision-making for the treatment of COVID-19, this review aims to present studies and guidelines on the main therapies that have been and are currently being tested against SARS-CoV-2 and to critically analyze the reported evidences.
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Affiliation(s)
| | - Adson José Martins Vale
- Tocogynecology Department, Medical School, Universidade Federal do Rio Grande do Norte (UFRN), Natal, Brazil
- Graduate Program of Biotechnology, Laureate International Universities - Universidade Potiguar (UnP), Natal, Brazil
| | - Fausto Pierdoná Guzen
- Graduate Program of Biotechnology, Laureate International Universities - Universidade Potiguar (UnP), Natal, Brazil
| | - Francisco Irochima Pinheiro
- Graduate Program of Biotechnology, Laureate International Universities - Universidade Potiguar (UnP), Natal, Brazil
- Medical School, Laureate International Universities - Universidade Potiguar (UnP), Natal, Brazil
| | - Ricardo Ney Cobucci
- Graduate Program of Biotechnology, Laureate International Universities - Universidade Potiguar (UnP), Natal, Brazil
- Medical School, Laureate International Universities - Universidade Potiguar (UnP), Natal, Brazil
| | - Eduardo Pereira de Azevedo
- Graduate Program of Biotechnology, Laureate International Universities - Universidade Potiguar (UnP), Natal, Brazil
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Patel M, Dominguez E, Sacher D, Desai P, Chandar A, Bromberg M, Caricchio R, Criner GJ. Etoposide as Salvage Therapy for Cytokine Storm Due to Coronavirus Disease 2019. Chest 2020; 159:e7-e11. [PMID: 32931823 PMCID: PMC7486855 DOI: 10.1016/j.chest.2020.09.077] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Revised: 08/21/2020] [Accepted: 09/07/2020] [Indexed: 01/17/2023] Open
Abstract
Coronavirus disease 2019 (COVID-19) has resulted in significant morbidity and mortality because of a lack of effective therapies. Therapeutic strategies under investigation target the overactive cytokine response with anti-cytokine or immunomodulators therapies. We present a unique case of severe cytokine storm resistant to multiple anti-cytokine therapies, but eventually responsive to etoposide. Thus, etoposide may have a role as salvage therapy in treatment of cytokine storm in COVID-19. To our knowledge, this is the first reported case of use of etoposide in COVID-19.
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Affiliation(s)
- Maulin Patel
- Department of Thoracic Medicine and Surgery, Lewis Katz School of Medicine at Temple University, Philadelphia, PA.
| | - Eduardo Dominguez
- Department of Thoracic Medicine and Surgery, Lewis Katz School of Medicine at Temple University, Philadelphia, PA
| | - Daniel Sacher
- Department of Thoracic Medicine and Surgery, Lewis Katz School of Medicine at Temple University, Philadelphia, PA
| | - Parag Desai
- Department of Thoracic Medicine and Surgery, Lewis Katz School of Medicine at Temple University, Philadelphia, PA
| | - Ashwin Chandar
- Department of Hematology and Oncology, Temple University Hospital, Philadelphia, PA
| | - Michael Bromberg
- Department of Hematology and Oncology, Temple University Hospital, Philadelphia, PA
| | - Roberto Caricchio
- Department of Rheumatology, Temple University Hospital, Philadelphia, PA
| | - Gerard J Criner
- Department of Thoracic Medicine and Surgery, Lewis Katz School of Medicine at Temple University, Philadelphia, PA
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44
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Mishra R, Banerjea AC. Neurological Damage by Coronaviruses: A Catastrophe in the Queue! Front Immunol 2020; 11:565521. [PMID: 33013930 PMCID: PMC7511585 DOI: 10.3389/fimmu.2020.565521] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Accepted: 08/12/2020] [Indexed: 12/19/2022] Open
Abstract
Neurological disorders caused by neuroviral infections are an obvious pathogenic manifestation. However, non-neurotropic viruses or peripheral viral infections pose a considerable challenge as their neuropathological manifestations do not emerge because of primary infection. Their secondary or bystander pathologies develop much later, like a syndrome, during and after the recovery of patients from the primary disease. Massive inflammation caused by peripheral viral infections can trigger multiple neurological anomalies. These neurological damages may range from a general cognitive and motor dysfunction up to a wide spectrum of CNS anomalies, such as Acute Necrotizing Hemorrhagic Encephalopathy, Guillain-Barré syndrome, Encephalitis, Meningitis, anxiety, and other audio-visual disabilities. Peripheral viruses like Measles virus, Enteroviruses, Influenza viruses (HIN1 series), SARS-CoV-1, MERS-CoV, and, recently, SARS-CoV-2 are reported to cause various neurological manifestations in patients and are proven to be neuropathogenic even in cellular and animal model systems. This review presents a comprehensive picture of CNS susceptibilities toward these peripheral viral infections and explains some common underlying themes of their neuropathology in the human brain.
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Affiliation(s)
- Ritu Mishra
- Laboratory of Virology, National Institute of Immunology, New Delhi, India
| | - Akhil C. Banerjea
- Laboratory of Virology, National Institute of Immunology, New Delhi, India
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45
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HIV and Human Coronavirus Coinfections: A Historical Perspective. Viruses 2020; 12:v12090937. [PMID: 32858801 PMCID: PMC7552070 DOI: 10.3390/v12090937] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2020] [Revised: 07/31/2020] [Accepted: 08/02/2020] [Indexed: 02/06/2023] Open
Abstract
Seven human coronaviruses (hCoVs) are known to infect humans. The most recent one, SARS-CoV-2, was isolated and identified in January 2020 from a patient presenting with severe respiratory illness in Wuhan, China. Even though viral coinfections have the potential to influence the resultant disease pattern in the host, very few studies have looked at the disease outcomes in patients infected with both HIV and hCoVs. Groups are now reporting that even though HIV-positive patients can be infected with hCoVs, the likelihood of developing severe CoV-related diseases in these patients is often similar to what is seen in the general population. This review aimed to summarize the current knowledge of coinfections reported for HIV and hCoVs. Moreover, based on the available data, this review aimed to theorize why HIV-positive patients do not frequently develop severe CoV-related diseases.
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46
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Gozzo L, Viale P, Longo L, Vitale DC, Drago F. The Potential Role of Heparin in Patients With COVID-19: Beyond the Anticoagulant Effect. A Review. Front Pharmacol 2020; 11:1307. [PMID: 32973526 PMCID: PMC7472559 DOI: 10.3389/fphar.2020.01307] [Citation(s) in RCA: 61] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2020] [Accepted: 08/07/2020] [Indexed: 12/20/2022] Open
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is responsible of variable clinical manifestations, ranging from no symptoms to severe pneumonia with acute respiratory distress syndrome, septic shock, and multi-organ failure resulting in death. To date no specific antiviral drug have been approved for COVID-19, so the treatment of the disease is mainly focused on symptomatic treatment and supportive care. Moreover, there are no treatments of proven efficacy to reduce the progression of the disease from mild/moderate to severe/critical. An activation of the coagulation cascade leading to severe hypercoagulability has been detected in these patients, therefore early anticoagulation may reduce coagulopathy, microthrombus formation, and the risk of organ damages. The role of heparin in COVID-19 is supported by a lot of studies describing its pleiotropic activity but it must be proven in clinical trials. Several protocols have been designed to assess the risk-benefit profile of heparin (low-molecular-weight or unfractionated heparin) in hospitalized subjects. Although prophylactic doses may be adequate in most patients, it is important to wait the results of clinical trials in order to define the appropriate effective dose able to improve disease outcome.
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Affiliation(s)
- Lucia Gozzo
- Clinical Pharmacology Unit/Regional Pharmacovigilance Centre, University Hospital of Catania, Catania, Italy
| | - Pierluigi Viale
- Infectious Diseases Unit, Department of Medical and Surgical Sciences, Policlinico Sant’Orsola, University of Bologna, Bologna, Italy
| | - Laura Longo
- Clinical Pharmacology Unit/Regional Pharmacovigilance Centre, University Hospital of Catania, Catania, Italy
| | - Daniela Cristina Vitale
- Clinical Pharmacology Unit/Regional Pharmacovigilance Centre, University Hospital of Catania, Catania, Italy
| | - Filippo Drago
- Clinical Pharmacology Unit/Regional Pharmacovigilance Centre, University Hospital of Catania, Catania, Italy
- Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
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47
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Gong Y, Ma TC, Xu YY, Yang R, Gao LJ, Wu SH, Li J, Yue ML, Liang HG, He X, Yun T. Early Research on COVID-19: A Bibliometric Analysis. ACTA ACUST UNITED AC 2020; 1:100027. [PMID: 32914141 PMCID: PMC7403001 DOI: 10.1016/j.xinn.2020.100027] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2020] [Accepted: 07/21/2020] [Indexed: 12/13/2022]
Abstract
In December 2019, an outbreak of pneumonia, which was named COVID-2019, emerged as a global health crisis. Scientists worldwide are engaged in attempts to elucidate the transmission and pathogenic mechanisms of the causative coronavirus. COVID-19 was declared a pandemic by the World Health Organization in March 2020, making it critical to track and review the state of research on COVID-19 to provide guidance for further investigations. Here, bibliometric and knowledge mapping analyses of studies on COVID-19 were performed, including more than 1,500 papers on COVID-19 available in the PubMed and China National Knowledge Infrastructure databases from January 1, 2020 to March 8, 2020. In this review, we found that because of the rapid response of researchers worldwide, the number of COVID-19-related publications showed a high growth trend in the first 10 days of February; among these, the largest number of studies originated in China, the country most affected by pandemic in its early stages. Our findings revealed that the epidemic situation and data accessibility of different research teams have caused obvious difference in emphases of the publications. Besides, there was an unprecedented level of close cooperation and information sharing within the global scientific community relative to previous coronavirus research. We combed and drew the knowledge map of the SARS-CoV-2 literature, explored early status of research on etiology, pathology, epidemiology, treatment, prevention, and control, and discussed knowledge gaps that remain to be urgently addressed. Future perspectives on treatment, prevention, and control are also presented to provide fundamental references for current and future coronavirus research.
China initiated COVID-19-related research in considerable scope and depth at the early stage of the outbreak Researchers all over the world have rapidly launched unprecedented joint research efforts The knowledge map of SARS-CoV-2 is becoming increasingly comprehensive, and knowledge gaps to be filled have been identified The next step is to consider other factors conducive to research innovation, such as public and private's cooperation, equitable health system
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Affiliation(s)
- Yue Gong
- National Science Library, Chinese Academy of Sciences, Beijing 100190, China
| | - Ting-Can Ma
- Wuhan Library, Chinese Academy of Science, Wuhan 430071, China.,Department of Library, Information and Archives Management, University of Chinese Academy of Sciences, Beijing 100190, China
| | - Yang-Yang Xu
- China Center for Information Industry Development, Beijing 100036, China
| | - Rui Yang
- Key Laboratory of Plant Resources and Beijing Botanical Garden, Institute of Botany, Chinese Academy of Sciences, Beijing 100093, China.,University of Chinese Academy of Sciences, Beijing 100049, China
| | - Lan-Jun Gao
- Dongfang Hospital, Beijing University of Chinese Medicine, Beijing 100078, China
| | - Si-Hua Wu
- Clinical Medical College, Yangzhou University, Yangzhou, 225001, China
| | - Jing Li
- University of Chinese Academy of Sciences, Beijing 100049, China.,CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
| | - Ming-Liang Yue
- Wuhan Library, Chinese Academy of Science, Wuhan 430071, China
| | - Hui-Gang Liang
- Wuhan Library, Chinese Academy of Science, Wuhan 430071, China
| | - Xiao He
- National Science Library, Chinese Academy of Sciences, Beijing 100190, China
| | - Tao Yun
- China Science and Technology Exchange Center, Beijing 100045, China
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48
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Cao YL, Han YJ, Chen P, Liu ZM, Mutar M, Gao Y, Shao ZW, Tong W, Liu Y. Surgical treatment of thoracolumbar fracture with incomplete lower limb paralysis in a patient with COVID-19. Chin J Traumatol 2020; 23:211-215. [PMID: 32571532 PMCID: PMC7241380 DOI: 10.1016/j.cjtee.2020.05.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2020] [Revised: 03/31/2020] [Accepted: 04/04/2020] [Indexed: 02/04/2023] Open
Abstract
Since December 2019, COVID-19, an acute infectious disease, has gradually become a global threat. We report a case of thoracolumbar fractures (T12 and L1) and incomplete lower limb paralysis in a patient with COVID-19. After a series of conservative treatment which did not work at all, posterior open reduction and pedicle screw internal fixation of the thoracolumbar fracture were performed in Wuhan Union Hospital. Three weeks later, the patient could stand up and the pneumonia is almost cured. We successfully performed a surgery in a COVID-19 patient, and to our knowledge it is the first operation for a COVID-19 patient ever reported.
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Affiliation(s)
- Yu-Lin Cao
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Yan-Jiu Han
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Peng Chen
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Ze-Ming Liu
- Department of Plastic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China
| | - Muradil Mutar
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China,Department of Orthopedics, Silk Road Hospital, Kashgar, Xinjiang, 844000, China
| | - Yong Gao
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Zeng-Wu Shao
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Wei Tong
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Yong Liu
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China,Corresponding author.
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49
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Chauhan G, Madou MJ, Kalra S, Chopra V, Ghosh D, Martinez-Chapa SO. Nanotechnology for COVID-19: Therapeutics and Vaccine Research. ACS NANO 2020; 14:7760-7782. [PMID: 32571007 PMCID: PMC7325519 DOI: 10.1021/acsnano.0c04006] [Citation(s) in RCA: 207] [Impact Index Per Article: 41.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/13/2020] [Accepted: 06/22/2020] [Indexed: 05/04/2023]
Abstract
The current global health threat by the novel coronavirus disease 2019 (COVID-19) requires an urgent deployment of advanced therapeutic options available. The role of nanotechnology is highly relevant to counter this "virus" nano enemy. Nano intervention is discussed in terms of designing effective nanocarriers to counter the conventional limitations of antiviral and biological therapeutics. This strategy directs the safe and effective delivery of available therapeutic options using engineered nanocarriers, blocking the initial interactions of viral spike glycoprotein with host cell surface receptors, and disruption of virion construction. Controlling and eliminating the spread and reoccurrence of this pandemic demands a safe and effective vaccine strategy. Nanocarriers have potential to design risk-free and effective immunization strategies for severe acute respiratory syndrome coronavirus 2 vaccine candidates such as protein constructs and nucleic acids. We discuss recent as well as ongoing nanotechnology-based therapeutic and prophylactic strategies to fight against this pandemic, outlining the key areas for nanoscientists to step in.
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Affiliation(s)
- Gaurav Chauhan
- School of Engineering and Sciences,
Tecnologico de Monterrey, Av. Eugenio
Garza Sada 2501 Sur, 64849 Monterrey, Nuevo León,
Mexico
| | - Marc J. Madou
- School of Engineering and Sciences,
Tecnologico de Monterrey, Av. Eugenio
Garza Sada 2501 Sur, 64849 Monterrey, Nuevo León,
Mexico
- Department of Mechanical and Aerospace
Engineering, University of California
Irvine, Engineering Gateway 4200, Irvine,
California 92697, United States
| | - Sourav Kalra
- Department of Pharmaceutical Technology
(Process Chemistry), National Institute of Pharmaceutical
Education and Research, Sector 67, S.A.S. Nagar,
Punjab 160062, India
| | - Vianni Chopra
- Institute of Nano Science
and Technology, Habitat Centre, Phase 10 Mohali,
160062 Punjab, India
| | - Deepa Ghosh
- Institute of Nano Science
and Technology, Habitat Centre, Phase 10 Mohali,
160062 Punjab, India
| | - Sergio O. Martinez-Chapa
- School of Engineering and Sciences,
Tecnologico de Monterrey, Av. Eugenio
Garza Sada 2501 Sur, 64849 Monterrey, Nuevo León,
Mexico
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50
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Kihira S, Schefflein J, Chung M, Mahmoudi K, Rigney B, Delman BN, Mocco J, Doshi A, Belani P. Incidental COVID-19 related lung apical findings on stroke CTA during the COVID-19 pandemic. J Neurointerv Surg 2020; 12:669-672. [PMID: 32430481 PMCID: PMC7276243 DOI: 10.1136/neurintsurg-2020-016188] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Revised: 04/25/2020] [Accepted: 04/28/2020] [Indexed: 12/23/2022]
Abstract
BACKGROUND Authors have noticed an increase in lung apex abnormalities on CT angiography (CTA) of the head and neck performed for stroke workup during the coronavirus disease 2019 (COVID-19) pandemic. OBJECTIVE To evaluate the incidence of these CTA findings and their relation to COVID-19 infection. METHODS In this retrospective multicenter institutional review board-approved study, assessment was made of CTA findings of code patients who had a stroke between March 16 and April 5, 2020 at six hospitals across New York City. Demographic data, comorbidities, COVID-19 status, and neurological findings were collected. Assessment of COVID-19 related lung findings on CTA was made blinded to COVID-19 status. Incidence rates of COVID-19 related apical findings were assessed in all code patients who had a stroke and in patients with a stroke confirmed by imaging. RESULTS The cohort consisted of a total of 118 patients with mean±SD age of 64.9±15.7 years and 57.6% (68/118) were male. Among all code patients who had a stroke, 28% (33/118) had COVID-19 related lung findings. RT-PCR was positive for COVID-19 in 93.9% (31/33) of these patients with apical CTA findings.Among patients who had a stroke confirmed by imaging, 37.5% (18/48) had COVID-19 related apical findings. RT-PCR was positive for COVID-19 in all (18/18) of these patients with apical findings. CONCLUSION The incidence of COVID-19 related lung findings in stroke CTA scans was 28% in all code patients who had a stroke and 37.5% in patients with a stroke confirmed by imaging. Stroke teams should closely assess the lung apices during this COVID-19 pandemic as CTA findings may be the first indicator of COVID-19 infection.
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Affiliation(s)
- Shingo Kihira
- Diagnostic, Molecular and Interventional Radiology, Mount Sinai Health System, New York, New York, USA
| | - Javin Schefflein
- Diagnostic, Molecular and Interventional Radiology, Mount Sinai Health System, New York, New York, USA
| | - Michael Chung
- Diagnostic, Molecular and Interventional Radiology, Mount Sinai Health System, New York, New York, USA
| | - Keon Mahmoudi
- Diagnostic, Molecular and Interventional Radiology, Mount Sinai Health System, New York, New York, USA
| | - Brian Rigney
- Diagnostic, Molecular and Interventional Radiology, Mount Sinai Health System, New York, New York, USA
| | - Bradley N Delman
- Diagnostic, Molecular and Interventional Radiology, Mount Sinai Health System, New York, New York, USA
| | - J Mocco
- Department of Neurosurgery, The Mount Sinai Health System, New York, New York, USA
| | - Amish Doshi
- Diagnostic, Molecular and Interventional Radiology, Mount Sinai Health System, New York, New York, USA
| | - Puneet Belani
- Diagnostic, Molecular and Interventional Radiology, Mount Sinai Health System, New York, New York, USA
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