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Akl EA, Khabsa J, Iannizzi C, Piechotta V, Kahale LA, Barker JM, McKenzie JE, Page MJ, Skoetz N. Extension of the PRISMA 2020 statement for living systematic reviews (PRISMA-LSR): checklist and explanation. BMJ 2024; 387:e079183. [PMID: 39562017 DOI: 10.1136/bmj-2024-079183] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/21/2024]
Affiliation(s)
- Elie A Akl
- Department of Internal Medicine, American University of Beirut, Beirut, Lebanon
- Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada
| | - Joanne Khabsa
- Clinical Research Institute, American University of Beirut Medical Center, Beirut, Lebanon
| | - Claire Iannizzi
- Institute of Public Health, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Vanessa Piechotta
- Immunization Unit, Department of Infectious Disease Epidemiology, Robert Koch-Institut, Berlin, Germany
| | - Lara A Kahale
- Infectious Disease Society of America, Arlington, VA, USA
| | | | - Joanne E McKenzie
- Methods in Evidence Synthesis Unit, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
| | - Matthew J Page
- Methods in Evidence Synthesis Unit, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
| | - Nicole Skoetz
- Institute of Public Health, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
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Gustavson AM, Morrow CD, Brown RJ, Kaka AS, Sowerby C, Wilt TJ, Diem SJ. Reimagining How We Synthesize Information to Impact Clinical Care, Policy, and Research Priorities in Real Time: Examples and Lessons Learned from COVID-19. J Gen Intern Med 2024; 39:2554-2559. [PMID: 38926318 PMCID: PMC11436695 DOI: 10.1007/s11606-024-08855-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2023] [Accepted: 06/03/2024] [Indexed: 06/28/2024]
Abstract
Real-time clinical care, policy, and research decisions need real-time evidence synthesis. However, as we found during the COVID-19 pandemic, it is challenging to rapidly address key clinical and policy questions through rigorous, relevant, and usable evidence. Our objective is to present three exemplar cases of rapid evidence synthesis products from the Veterans Healthcare Administration Evidence Synthesis Program (ESP) and, in the context of these examples, outline ESP products, challenges, and lessons learned. We faced challenges in (1) balancing scientific rigor with the speed in which evidence synthesis was needed, (2) sorting through rapidly evolving large bodies of evidence, and (3) assessing the impact of evidence synthesis products on clinical care, policy, and research. We found solutions in (1) engaging stakeholders early, (2) utilizing artificial intelligence capabilities, (3) building infrastructure to establish living reviews, and (4) planning for dissemination to maximize impact.
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Affiliation(s)
- Allison M Gustavson
- Veterans Affairs Health Services Research and Development Center for Care Delivery and Outcomes Research, Minneapolis Veterans Affairs Healthcare System, Minneapolis, MN, USA.
- Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
| | | | - Rebecca Jl Brown
- Veterans Affairs Health Services Research and Development Center for Care Delivery and Outcomes Research, Minneapolis Veterans Affairs Healthcare System, Minneapolis, MN, USA
- School of Nursing, University of Minnesota, Minneapolis, MN, USA
| | - Anjum S Kaka
- Veterans Affairs Health Services Research and Development Center for Care Delivery and Outcomes Research, Minneapolis Veterans Affairs Healthcare System, Minneapolis, MN, USA
- Department of Medicine, University of Minnesota, Minneapolis, MN, USA
| | - Catherine Sowerby
- Veterans Affairs Health Services Research and Development Center for Care Delivery and Outcomes Research, Minneapolis Veterans Affairs Healthcare System, Minneapolis, MN, USA
| | - Timothy J Wilt
- Veterans Affairs Health Services Research and Development Center for Care Delivery and Outcomes Research, Minneapolis Veterans Affairs Healthcare System, Minneapolis, MN, USA
- Department of Medicine, University of Minnesota, Minneapolis, MN, USA
- Division of Health Policy and Management, School of Public Health, University of Minnesota, Minneapolis, MN, USA
| | - Susan J Diem
- Veterans Affairs Health Services Research and Development Center for Care Delivery and Outcomes Research, Minneapolis Veterans Affairs Healthcare System, Minneapolis, MN, USA
- Department of Medicine, University of Minnesota, Minneapolis, MN, USA
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Pourhoseingholi MA, Looha MA, Ilkhani S, Hatamabadi H, Sadeghi A, Safavi-Naini SAA, Heidari K, Taraghikhah N, Fallah MM, Kalantar R, Naderi N, Esbati R, Ebrahimi N, Solhpour A, Jamialahmadi T, Sahebkar A. Assessing the effect of remdesivir alone and in combination with corticosteroids on time to death in COVID-19: A propensity score-matched analysis. JOURNAL OF CLINICAL VIROLOGY PLUS 2024; 4:100180. [DOI: 10.1016/j.jcvp.2024.100180] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2024] Open
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Arbabzadeh T, Masoumi Shahrbabak M, Pooransari P, Khatuni M, Mirzamoradi M, Saleh Gargari S, Naeiji Z, Rahmati N, Omidi S, Ebrahimi Meimand F. Remdesivir in pregnant women with moderate to severe coronavirus disease 2019 (COVID-19): a retrospective cohort study. Clin Exp Med 2023; 23:3709-3717. [PMID: 37277553 PMCID: PMC10241383 DOI: 10.1007/s10238-023-01095-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Accepted: 05/16/2023] [Indexed: 06/07/2023]
Abstract
Data on the efficacy of remdesivir in Coronavirus Disease 2019 (COVID-19) are limited in pregnant patients since they have been excluded from clinical trials. We aimed to investigate some clinical outcomes following remdesivir administration in pregnancy. This was a retrospective cohort study conducted on pregnant women with moderate to severe COVID-19. The enrolled patients were divided into two groups with and without remdesivir treatment. The primary outcomes of this study were the length of hospital and intensive care unit stay; respiratory parameters of hospital day 7 including respiratory rate, oxygen saturation, and mode of oxygen support; discharge until days 7 and 14, and need for home oxygen therapy. Secondary outcomes included some maternal and neonatal consequences. Eighty-one pregnant women (57 in the remdesivir group and 24 in the non-remdesivir group) were included. The two study groups were comparable according to the baseline demographic and clinical characteristics. Of the respiratory outcomes, remdesivir was significantly associated with a reduced length of hospital stay (p = 0.021) and also with a lower level of oxygen requirement in patients on low-flow oxygen [odds ratio (OR) 3.669]. Among the maternal consequences, no patients in the remdesivir group developed preeclampsia but three patients (12.5%) experienced this complication in the non-remdesivir group (p = 0.024). Furthermore, in patients with moderate COVID-19, the percentage of emergency termination was significantly lower in remdesivir group (OR 2.46). Our results demonstrated some probable benefits of remdesivir in respiratory and also maternal outcomes. Further investigations with a larger sample size should confirm these results.
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Affiliation(s)
- Taraneh Arbabzadeh
- Department of Gynecology and Obstetrics, Shohada-e Tajrish Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Maryam Masoumi Shahrbabak
- Department of Gynecology and Obstetrics, Shohada-e Tajrish Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Parichehr Pooransari
- Department of Gynecology and Obstetrics, Shohada-e Tajrish Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mahdi Khatuni
- Department of Pulmonology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Masoumeh Mirzamoradi
- Department of Gynecology and Obstetrics, Shohada-e Tajrish Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Soraya Saleh Gargari
- Department of Gynecology and Obstetrics, Mahdiyeh Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Zahra Naeiji
- Department of Gynecology and Obstetrics, Mahdiyeh Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Nayereh Rahmati
- Department of Gynecology and Obstetrics, Mahdiyeh Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Samaneh Omidi
- Department of Gynecology and Obstetrics, Shohada-e Tajrish Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Faridadin Ebrahimi Meimand
- Department of Surgery, Minimally Invasive Surgery Research Center, Rasool-e Akram Hospital, Iran University of Medical Sciences, Tehran, Iran
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Abstract
Remdesivir (Veklury®), a nucleotide analogue prodrug with broad-spectrum antiviral activity, is approved for the treatment of coronavirus disease 2019 (COVID-19), the illness caused by severe acute respiratory syndrome coronavirus 2 infection. Unlike some antivirals, remdesivir has a low potential for drug-drug interactions. In the pivotal ACTT-1 trial in hospitalized patients with COVID-19, daily intravenous infusions of remdesivir significantly reduced time to recovery relative to placebo. Subsequent trials provided additional support for the efficacy of remdesivir in hospitalized patients with moderate or severe COVID-19, with a greater benefit seen in patients with minimal oxygen requirements at baseline. Clinical trials also demonstrated the efficacy of remdesivir in other patient populations, including outpatients at high risk for progression to severe COVID-19, as well as hospitalized paediatric patients. In terms of mortality, results were equivocal. However, remdesivir appeared to have a small mortality benefit in hospitalized patients who were not already being ventilated at baseline. Remdesivir was generally well tolerated in clinical trials, but pharmacovigilance data found an increased risk of hepatic, renal and cardiovascular adverse drug reactions in the real-world setting. In conclusion, remdesivir represents a useful treatment option for patients with COVID-19, particularly those who require supplemental oxygen.
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Affiliation(s)
- Hannah A Blair
- Springer Nature, Private Bag 65901, Mairangi Bay, Auckland, 0754, New Zealand.
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Luo J, Chen Z, Liu D, Li H, He S, Zeng L, Yang M, Liu Z, Xiao X, Zhang L. Methodological quality and reporting quality of COVID-19 living systematic review: a cross-sectional study. BMC Med Res Methodol 2023; 23:175. [PMID: 37525117 PMCID: PMC10388517 DOI: 10.1186/s12874-023-01980-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2022] [Accepted: 06/18/2023] [Indexed: 08/02/2023] Open
Abstract
OBJECTIVES The main objective of this study is to evaluate the methodological quality and reporting quality of living systematic reviews (LSRs) on Coronavirus disease 2019 (COVID-19), while the secondary objective is to investigate potential factors that may influence the overall quality of COVID-19 LSRs. METHODS Six representative databases, including Medline, Excerpta Medica Database (Embase), Cochrane Library, China national knowledge infrastructure (CNKI), Wanfang Database, and China Science, Technology Journal Database (VIP) were systematically searched for COVID-19 LSRs. Two authors independently screened articles, extracted data, and then assessed the methodological and reporting quality of COVID-19 LSRs using the "A Measurement Tool to Assess systematic Reviews-2" (AMSTAR-2) tool and "Preferred Reporting Items for Systematic reviews and Meta-Analyses" (PRISMA) 2020 statement, respectively. Univariate linear regression and multivariate linear regression were used to explore eight potential factors that might affect the methodological quality and reporting quality of COVID-19 LSRs. RESULTS A total of 64 COVID-19 LSRs were included. The AMSTAR-2 evaluation results revealed that the number of "yes" responses for each COVID-19 LSR was 13 ± 2.68 (mean ± standard deviation). Among them, 21.9% COVID-19 LSRs were rated as "high", 4.7% as "moderate", 23.4% as "low", and 50% as "critically low". The evaluation results of the PRISMA 2020 statement showed that the sections with poor adherence were methods, results and other information. The number of "yes" responses for each COVID-19 LSR was 21 ± 4.18 (mean ± standard deviation). The number of included studies and registration are associated with better methodological quality; the number of included studies and funding are associated with better reporting quality. CONCLUSIONS Improvement is needed in the methodological and reporting quality of COVID-19 LSRs. Researchers conducting COVID-19 LSRs should take note of the quality-related factors identified in this study to generate evidence-based evidence of higher quality.
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Affiliation(s)
- Jiefeng Luo
- Department of Pharmacy, West China Second University Hospital, Sichuan University, Chengdu, China
- Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, China
- NMPA Key Laboratory for Technical Research On Drug Products In Vitro and In Vivo Correlation, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, Chengdu, China
- West China School of Pharmacy, Sichuan University, Chengdu, China
| | - Zhe Chen
- Department of Pharmacy, West China Second University Hospital, Sichuan University, Chengdu, China
- Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, China
- NMPA Key Laboratory for Technical Research On Drug Products In Vitro and In Vivo Correlation, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, Chengdu, China
- West China School of Pharmacy, Sichuan University, Chengdu, China
| | - Dan Liu
- Department of Pharmacy, West China Second University Hospital, Sichuan University, Chengdu, China
- Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, China
- NMPA Key Laboratory for Technical Research On Drug Products In Vitro and In Vivo Correlation, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, Chengdu, China
- West China School of Pharmacy, Sichuan University, Chengdu, China
| | - Hailong Li
- Department of Pharmacy, West China Second University Hospital, Sichuan University, Chengdu, China
- Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, China
- NMPA Key Laboratory for Technical Research On Drug Products In Vitro and In Vivo Correlation, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, Chengdu, China
| | - Siyi He
- Department of Pharmacy, West China Second University Hospital, Sichuan University, Chengdu, China
- Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, China
- NMPA Key Laboratory for Technical Research On Drug Products In Vitro and In Vivo Correlation, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, Chengdu, China
- West China School of Pharmacy, Sichuan University, Chengdu, China
| | - Linan Zeng
- Department of Pharmacy, West China Second University Hospital, Sichuan University, Chengdu, China
- Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, China
- NMPA Key Laboratory for Technical Research On Drug Products In Vitro and In Vivo Correlation, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, Chengdu, China
| | - Mengting Yang
- Department of Pharmacy, West China Second University Hospital, Sichuan University, Chengdu, China
- Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, China
- NMPA Key Laboratory for Technical Research On Drug Products In Vitro and In Vivo Correlation, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, Chengdu, China
- West China School of Medicine, Sichuan University, Chengdu, China
| | - Zheng Liu
- Department of Pharmacy, West China Second University Hospital, Sichuan University, Chengdu, China
- Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, China
- NMPA Key Laboratory for Technical Research On Drug Products In Vitro and In Vivo Correlation, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, Chengdu, China
- West China School of Medicine, Sichuan University, Chengdu, China
| | - Xue Xiao
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, Chengdu, China.
- Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Chengdu, China.
| | - Lingli Zhang
- Department of Pharmacy, West China Second University Hospital, Sichuan University, Chengdu, China.
- Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, China.
- NMPA Key Laboratory for Technical Research On Drug Products In Vitro and In Vivo Correlation, Chengdu, China.
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, Chengdu, China.
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Gonçalves J, Santos CD, Fresco P, Fernandez-Llimos F. Potential use of renin-angiotensin-aldosterone system inhibitors to reduce COVID-19 severity. Rev Port Cardiol 2023; 42:373-383. [PMID: 36893838 PMCID: PMC9999244 DOI: 10.1016/j.repc.2022.02.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Revised: 01/21/2022] [Accepted: 02/03/2022] [Indexed: 03/09/2023] Open
Abstract
SARS-CoV-2 infection and its clinical manifestations (COVID-19) quickly evolved to a pandemic and a global public health emergency. The limited effectivity of available treatments aimed at reducing virus replication and the lessons learned from other coronavirus infections (SARS-CoV-1 or NL63) that share the internalization process of SARS-CoV-2, led us to revisit the COVID-19 pathogenesis and potential treatments. Virus protein S binds to the angiotensin-converting enzyme 2 (ACE2) initiating the internalization process. Endosome formation removes ACE2 from the cellular membrane preventing its counter-regulative effect mediated by the metabolism of angiotensin II to angiotensin (1-7). Internalized virus-ACE2 complexes have been identified for these coronaviruses. SARS-CoV-2 presents the highest affinity for ACE2 and produces the most severe symptoms. Assuming ACE2 internalization is the trigger for COVID-19 pathogenesis, accumulation of angiotensin II can be viewed as the potential cause of symptoms. Angiotensin II is a strong vasoconstrictor, but has also important roles in hypertrophy, inflammation, remodeling, and apoptosis. Higher levels of ACE2 in the lungs explain the acute respiratory distress syndrome as primary symptoms. Most of the described findings and clinical manifestations of COVID-19, including increased interleukin levels, endothelial inflammation, hypercoagulability, myocarditis, dysgeusia, inflammatory neuropathies, epileptic seizures and memory disorders can be explained by excessive angiotensin II levels. Several meta-analyses have demonstrated that previous use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers were associated with better prognosis for COVID-19. Therefore, pragmatic trials to assess the potential therapeutic benefits of renin-angiotensin-aldosterone system inhibitors should be urgently promoted by health authorities to widen the therapeutic options for COVID-19.
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Affiliation(s)
- Jorge Gonçalves
- Laboratório de Farmacologia, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal; I(3)S: Instituto de Investigação e Inovação em Saúde da Universidade do Porto, Porto, Portugal.
| | - Catarina D Santos
- Laboratório de Farmacologia, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal
| | - Paula Fresco
- Laboratório de Farmacologia, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal; I(3)S: Instituto de Investigação e Inovação em Saúde da Universidade do Porto, Porto, Portugal
| | - Fernando Fernandez-Llimos
- Laboratório de Farmacologia, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal; CINTESIS - Centro de Investigação em Tecnologias e Serviços de Saúde, Porto, Portugal
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Zhang J, Zou M, Tian Q, Sun Z, Chu W. N-Cyano-2,2'-biphenyldicarboimide as a Cyanation Reagent for Co(III)-Catalyzed C-H Cyanation of Indoles in Ionic Liquids. Org Lett 2023; 25:1436-1440. [PMID: 36856532 DOI: 10.1021/acs.orglett.3c00164] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/02/2023]
Abstract
A mild strategy for Co(III)-catalyzed C(sp2)-H cyanation of indoles was developed by using NCBLD as an electrophilic cyanation reagent and 1-butyl-3-acetylimidazole ditrifluoromethylsulfonimide ([BAIM]NTf2) as an environmentally friendly and recyclable solvent, and a series of 2-cyano products were obtained at room temperature. Adopting this strategy, the unnatural nucleotide fragment precursor of Remdesivir, which was a drug for COVID-19, was synthesized through cyano transformation, further proving the practicability of this cyanation method.
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Affiliation(s)
- Jingchao Zhang
- School of Chemistry and Materials Science, Heilongjiang University, Harbin, Heilongjiang 150080, P.R. China
| | - MengQi Zou
- School of Chemistry and Materials Science, Heilongjiang University, Harbin, Heilongjiang 150080, P.R. China
| | - QinYe Tian
- School of Chemistry and Materials Science, Heilongjiang University, Harbin, Heilongjiang 150080, P.R. China
| | - Zhizhong Sun
- School of Chemistry and Materials Science, Heilongjiang University, Harbin, Heilongjiang 150080, P.R. China
| | - Wenyi Chu
- School of Chemistry and Materials Science, Heilongjiang University, Harbin, Heilongjiang 150080, P.R. China
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Panahi Y, Gorabi AM, Talaei S, Beiraghdar F, Akbarzadeh A, Tarhriz V, Mellatyar H. An overview on the treatments and prevention against COVID-19. Virol J 2023; 20:23. [PMID: 36755327 PMCID: PMC9906607 DOI: 10.1186/s12985-023-01973-9] [Citation(s) in RCA: 35] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Accepted: 01/14/2023] [Indexed: 02/10/2023] Open
Abstract
BACKGROUND The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to plague the world. While COVID-19 is asymptomatic in most individuals, it can cause symptoms like pneumonia, ARDS (acute respiratory distress syndrome), and death in others. Although humans are currently being vaccinated with several COVID-19 candidate vaccines in many countries, however, the world still is relying on hygiene measures, social distancing, and approved drugs. RESULT There are many potential therapeutic agents to pharmacologically fight COVID-19: antiviral molecules, recombinant soluble angiotensin-converting enzyme 2 (ACE2), monoclonal antibodies, vaccines, corticosteroids, interferon therapies, and herbal agents. By an understanding of the SARS-CoV-2 structure and its infection mechanisms, several vaccine candidates are under development and some are currently in various phases of clinical trials. CONCLUSION This review describes potential therapeutic agents, including antiviral agents, biologic agents, anti-inflammatory agents, and herbal agents in the treatment of COVID-19 patients. In addition to reviewing the vaccine candidates that entered phases 4, 3, and 2/3 clinical trials, this review also discusses the various platforms that are used to develop the vaccine COVID-19.
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Affiliation(s)
- Yunes Panahi
- Pharmacotherapy Department, Faculty of Pharmacy, Bagyattallah University of Medical Sciences, Tehran, Iran
| | - Armita Mahdavi Gorabi
- Chronic Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Sona Talaei
- Department of Basic Sciences, Maragheh University of Medical Sciences, Maragheh, Iran
| | - Fatemeh Beiraghdar
- Nephrology and Urology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Abolfazl Akbarzadeh
- Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Vahideh Tarhriz
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hassan Mellatyar
- Pharmacotherapy Department, Faculty of Pharmacy, Bagyattallah University of Medical Sciences, Tehran, Iran
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Campagna R, Mazzuti L, Guerrizio G, Nonne C, Migliara G, De Vito C, Mezzaroma I, Chiaretti S, Fimiani C, Pistolesi V, Morabito S, Turriziani O. Humoral and T-cell mediated response after administration of mRNA vaccine BNT162b2 in frail populations. Vaccine X 2022; 12:100246. [PMID: 36506461 PMCID: PMC9721197 DOI: 10.1016/j.jvacx.2022.100246] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Revised: 12/01/2022] [Accepted: 12/02/2022] [Indexed: 12/12/2022] Open
Abstract
Patients with frailty are considered to be at greater risk to get severe infection from SARS-CoV-2. One of the most effective strategies is vaccination. In our study we evaluated both the humoral immune response elicited by the vaccination at different time points, and the T-cell response in terms of interferon (IFN)-γ production in frail patients and healthy donors. Fifty-seven patients (31 patients undergoing hemodialysis and 26 HIV positive subjects) and 39 healthcare workers were enrolled. All participants received two doses of the mRNA vaccine BNT162b2. Healthcare workers showed a significantly higher antibody titer than patients twenty-one days after the first dose (p < 0.001). From the same time point we observed for both groups a decay of the antibody levels with a steeper slope of decline in the patients group. Regarding T-cell response the only significant difference between non-reactive and reactive subjects was found in median antibody levels, higher in the responders group than in non-responders. The healthcare workers seem to better respond to the vaccination in terms of antibodies production; the lack of T-cell response in about 50% of the participants seems to suggest that in our study population both humoral and cell-mediated response decline over time remarking the importance of the booster doses, particularly for frail patients.
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Affiliation(s)
- Roberta Campagna
- Department of Molecular Medicine Sapienza University of Rome, Viale dell’Università, 33, 000185 Rome, Italy,Corresponding author
| | - Laura Mazzuti
- Department of Molecular Medicine Sapienza University of Rome, Viale dell’Università, 33, 000185 Rome, Italy
| | - Giuliana Guerrizio
- Department of Molecular Medicine Sapienza University of Rome, Viale dell’Università, 33, 000185 Rome, Italy
| | - Chiara Nonne
- Department of Molecular Medicine Sapienza University of Rome, Viale dell’Università, 33, 000185 Rome, Italy
| | - Giuseppe Migliara
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, Piazzale Aldo Moro, 5, 00185 Rome, Italy
| | - Corrado De Vito
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, Piazzale Aldo Moro, 5, 00185 Rome, Italy
| | - Ivano Mezzaroma
- Department of Translational and Precision Medicine, Sapienza University of Rome, Viale dell'Università, 37, 00185 Rome, Italy
| | - Sabina Chiaretti
- Department of Translational and Precision Medicine, Sapienza University of Rome, Viale dell'Università, 37, 00185 Rome, Italy
| | - Caterina Fimiani
- Department of Internal Medicine, Endocrine-Metabolic Sciences and Infectious Disease, Policlinico Umberto I, 155, 00161, Italy
| | - Valentina Pistolesi
- Department of Internal Medicine and Medical Specialties Sapienza University of Rome, Policlinico, 155, 00161 Rome, Italy
| | - Santo Morabito
- Department of Internal Medicine and Medical Specialties Sapienza University of Rome, Policlinico, 155, 00161 Rome, Italy
| | - Ombretta Turriziani
- Department of Molecular Medicine Sapienza University of Rome, Viale dell’Università, 33, 000185 Rome, Italy
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Mohseni M, Ameri H, Arab-Zozani M. Potential limitations in systematic review studies assessing the effect of the main intervention for treatment/therapy of COVID-19 patients: An overview. Front Med (Lausanne) 2022; 9:966632. [PMID: 36203750 PMCID: PMC9531544 DOI: 10.3389/fmed.2022.966632] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2022] [Accepted: 08/30/2022] [Indexed: 01/09/2023] Open
Abstract
Background Although several studies have assessed the safety, efficacy, and effectiveness of interventions in treating the COVID-19, many of them have limitations that can have an immense impact on their results. This study aims to assess the potential limitations in systematic reviews (SRs) that evaluate the effect of interventions on the treatment of the COVID-19. Methods PubMed, Scopus, and Web of Sciences (WOS) databases were searched from inception to January 1, 2022. All systematic reviews investigated the effectiveness, efficacy, safety, and outcome of the main intervention (Favipiravir, Remdesivir, Hydroxychloroquine, Ivermectin, Lopinavir/Ritonavir, or Tocilizumab) for the treatment of COVID-19 patients and reported the potential limitations of the included studies. We assessed the quality of the included studies using the Quality Assessment Tool (QAT) for review articles. We conducted a content analysis and prepared a narrative summary of the limitations. Results Forty-six studies were included in this review. Ninety one percent of the included studies scored as strong quality and the remaining (9%) as moderate quality. Only 29.7% of the included systematic reviews have a registered protocol. 26% of the included studies mentioned a funding statement. The main limitations of the included studies were categorized in 10 domains: sample size, heterogeneity, follow-up, treatment, including studies, design, definitions, synthesis, quality, and search. Conclusion Various limitations have been reported in all the included studies. Indeed, the existence of limitations in studies can affect their results, therefore, identifying these limitations can help researchers design better studies. As a result, stronger studies with more reliable results will be reported and disseminated. Further research on COVID-19 SRs is essential to improve research quality and also, efficiency among scientists across the world.
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Affiliation(s)
- Mahsa Mohseni
- Knowledge Utilization Research Centre, Tehran University of Medical Sciences, Tehran, Iran
| | - Hosein Ameri
- Health Policy and Management Research Center, Department of Health Management and Economics, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Morteza Arab-Zozani
- Social Determinants of Health Research Center, Birjand University of Medical Sciences, Birjand, Iran
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Natesan Pushparaj P, Damiati LA, Denetiu I, Bakhashab S, Asif M, Hussain A, Ahmed S, Hamdard MH, Rasool M. Deciphering SARS CoV-2-associated pathways from RNA sequencing data of COVID-19-infected A549 cells and potential therapeutics using in silico methods. Medicine (Baltimore) 2022; 101:e29554. [PMID: 36107502 PMCID: PMC9439635 DOI: 10.1097/md.0000000000029554] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Coronavirus (CoV) disease (COVID-19) identified in Wuhan, China, in 2019, is mainly characterized by atypical pneumonia and severe acute respiratory syndrome (SARS) and is caused by SARS CoV-2, which belongs to the Coronaviridae family. Determining the underlying disease mechanisms is central to the identification and development of COVID-19-specific drugs for effective treatment and prevention of human-to-human transmission, disease complications, and deaths. METHODS Here, next-generation RNA sequencing (RNA Seq) data were obtained using Illumina Next Seq 500 from SARS CoV-infected A549 cells and mock-treated A549 cells from the Gene Expression Omnibus (GEO) (GSE147507), and quality control (QC) was assessed before RNA Seq analysis using CLC Genomics Workbench 20.0. Differentially expressed genes (DEGs) were imported into BioJupies to decipher COVID-19 induced signaling pathways and small molecules derived from chemical synthesis or natural sources to mimic or reverse COVID -19 specific gene signatures. In addition, iPathwayGuide was used to identify COVID-19-specific signaling pathways, as well as drugs and natural products with anti-COVID-19 potential. RESULTS Here, we identified the potential activation of upstream regulators such as signal transducer and activator of transcription 2 (STAT2), interferon regulatory factor 9 (IRF9), and interferon beta (IFNβ), interleukin-1 beta (IL-1β), and interferon regulatory factor 3 (IRF3). COVID-19 infection activated key infectious disease-specific immune-related signaling pathways such as influenza A, viral protein interaction with cytokine and cytokine receptors, measles, Epstein-Barr virus infection, and IL-17 signaling pathway. Besides, we identified drugs such as prednisolone, methylprednisolone, diclofenac, compound JQ1, and natural products such as Withaferin-A and JinFuKang as candidates for further experimental validation of COVID-19 therapy. CONCLUSIONS In conclusion, we have used the in silico next-generation knowledge discovery (NGKD) methods to discover COVID-19-associated pathways and specific therapeutics that have the potential to ameliorate the disease pathologies associated with COVID-19.
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Affiliation(s)
- Peter Natesan Pushparaj
- Center of Excellence in Genomic Medicine Research, Department of Medical Laboratory Technology Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
- Centre for Transdisciplinary Research, Department of Pharmacology, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Chennai, India
- * Correspondence: Peter Natesan Pushparaj, Department of Medical Laboratory Technology, Center of Excellence in Genomic Medicine Research, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia (e-mail: )
| | | | - Iuliana Denetiu
- King Fahad Medical Research Center, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Sherin Bakhashab
- Department of Biochemistry, Faculty of Biological Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Muhammad Asif
- Department of Biotechnology, BUITEMS, Quetta, Pakistan
- Office of Research Innovation and Commercialization, BUITEMS, Quetta, Pakistan
| | - Abrar Hussain
- Department of Biotechnology, BUITEMS, Quetta, Pakistan
| | - Sagheer Ahmed
- Shifa College of Pharmaceutical Sciences, Shifa Tameer-e-Millat University Islamabad, Pakistan
| | | | - Mahmood Rasool
- Center of Excellence in Genomic Medicine Research, Department of Medical Laboratory Technology Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
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13
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Babayigit C, Kokturk N, Kul S, Cetinkaya PD, Atis Nayci S, Argun Baris S, Karcioglu O, Aysert P, Irmak I, Akbas Yuksel A, Sekibag Y, Baydar Toprak O, Azak E, Mulamahmutoglu S, Cuhadaroglu C, Demirel A, Kerget B, Baran Ketencioglu B, Ozger HS, Ozkan G, Ture Z, Ergan B, Avkan Oguz V, Kilinc O, Ercelik M, Ulukavak Ciftci T, Alici O, Nurlu Temel E, Ataoglu O, Aydin A, Cetiner Bahcetepe D, Gullu YT, Fakili F, Deveci F, Kose N, Tor MM, Gunluoglu G, Altin S, Turgut T, Tuna T, Ozturk O, Dikensoy O, Yildiz Gulhan P, Basyigit I, Boyaci H, Oguzulgen IK, Borekci S, Gemicioglu B, Bayraktar F, Elbek O, Hanta I, Kuzu Okur H, Sagcan G, Uzun O, Akgun M, Altinisik G, Dursun B, Cakir Edis E, Gulhan E, Oner Eyuboglu F, Gultekin O, Havlucu Y, Ozkan M, Sakar Coskun A, Sayiner A, Kalyoncu AF, Itil O, Bayram H. The association of antiviral drugs with COVID-19 morbidity: The retrospective analysis of a nationwide COVID-19 cohort. Front Med (Lausanne) 2022; 9:894126. [PMID: 36117966 PMCID: PMC9471091 DOI: 10.3389/fmed.2022.894126] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Accepted: 08/11/2022] [Indexed: 11/29/2022] Open
Abstract
Background and objectives Although several repurposed antiviral drugs have been used for the treatment of COVID-19, only a few such as remdesivir and molnupiravir have shown promising effects. The objectives of our study were to investigate the association of repurposed antiviral drugs with COVID-19 morbidity. Methods Patients admitted to 26 different hospitals located in 16 different provinces between March 11–July 18, 2020, were enrolled. Case definition was based on WHO criteria. Patients were managed according to the guidelines by Scientific Board of Ministry of Health of Turkey. Primary outcomes were length of hospitalization, intensive care unit (ICU) requirement, and intubation. Results We retrospectively evaluated 1,472 COVID-19 adult patients; 57.1% were men (mean age = 51.9 ± 17.7years). A total of 210 (14.3%) had severe pneumonia, 115 (7.8%) were admitted to ICUs, and 69 (4.7%) were intubated during hospitalization. The median (interquartile range) of duration of hospitalization, including ICU admission, was 7 (5–12) days. Favipiravir (n = 328), lopinavir/ritonavir (n = 55), and oseltamivir (n = 761) were administered as antiviral agents, and hydroxychloroquine (HCQ, n = 1,382) and azithromycin (n = 738) were used for their immunomodulatory activity. Lopinavir/ritonavir (β [95% CI]: 4.71 [2.31–7.11]; p = 0.001), favipiravir (β [95% CI]: 3.55 [2.56–4.55]; p = 0.001) and HCQ (β [95% CI]: 0.84 [0.02–1.67]; p = 0.046) were associated with increased risk of lengthy hospital stays. Furthermore, favipiravir was associated with increased risks of ICU admission (OR [95% CI]: 3.02 [1.70–5.35]; p = 0.001) and invasive mechanical ventilation requirement (OR [95% CI]: 2.94 [1.28–6.75]; p = 0.011). Conclusion Our findings demonstrated that antiviral drugs including lopinavir, ritonavir, and favipiravir were associated with negative clinical outcomes such as increased risks for lengthy hospital stay, ICU admission, and invasive mechanical ventilation requirement. Therefore, repurposing such agents without proven clinical evidence might not be the best approach for COVID-19 treatment.
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Affiliation(s)
- Cenk Babayigit
- Department of Pulmonary Medicine, Faculty of Medicine, Mustafa Kemal University, Antakya, Turkey
| | - Nurdan Kokturk
- Department of Pulmonary Medicine, Faculty of Medicine, Gazi University, Ankara, Turkey
| | - Seval Kul
- Department of Biostatistics, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey
| | - Pelin Duru Cetinkaya
- Department of Pulmonary Medicine, Adana City Training and Research Hospital, University of Health Sciences, Adana, Turkey
- Department of Pulmonary Medicine, Faculty of Medicine, Çukurova University, Adana, Turkey
| | - Sibel Atis Nayci
- Department of Pulmonary Medicine, Faculty of Medicine, Mersin University, Yenişehir, Turkey
| | - Serap Argun Baris
- Department of Pulmonary Medicine, Faculty of Medicine, Kocaeli University, İzmit, Turkey
| | - Oguz Karcioglu
- Department of Pulmonary Medicine, Halil Şıvgın Cubuk State Hospital, Ankara, Turkey
| | - Pinar Aysert
- Department of Infectious Disease, Faculty of Medicine, Gazi University, Ankara, Turkey
| | - Ilim Irmak
- Department of Pulmonary Medicine, Faculty of Medicine, Hacettepe University, Ankara, Turkey
| | - Aycan Akbas Yuksel
- Department of Pulmonary Medicine, Faculty of Medicine, Ufuk University, Ankara, Turkey
| | - Yonca Sekibag
- Department of Pulmonary Disease, Cerrahpaşa Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Oya Baydar Toprak
- Department of Pulmonary Medicine, Faculty of Medicine, Çukurova University, Adana, Turkey
| | - Emel Azak
- Department of Infectious Disease and Clinical Microbiology, Faculty of Medicine, Kocaeli University, İzmit, Turkey
| | - Sait Mulamahmutoglu
- Department of Pulmonary Disease, Cerrahpaşa Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Caglar Cuhadaroglu
- Department of Pulmonary Medicine, Faculty of Medicine, Altunizade Acibadem Hospital, Acibadem University, Istanbul, Turkey
| | - Aslihan Demirel
- Department of Infectious Disease, Kadıköy Florence Nightingale Hospital, Istanbul, Turkey
| | - Bugra Kerget
- Department of Pulmonary Medicine, Faculty of Medicine, Ataturk University, Erzurum, Turkey
| | | | - Hasan Selcuk Ozger
- Department of Infectious Disease, Faculty of Medicine, Gazi University, Ankara, Turkey
| | - Gulcihan Ozkan
- Department of Pulmonary Medicine, Acibadem Maslak Hospital, Istanbul, Turkey
- Operating Room Services Department, Vocational School, Nişantaşı University, Istanbul, Turkey
| | - Zeynep Ture
- Department of Infectious Disease and Clinical Microbiology, Faculty of Medicine, Erciyes University, Kayseri, Turkey
| | - Begum Ergan
- Department of Pulmonary Medicine, Faculty of Medicine, Dokuz Eylul University, Izmir, Turkey
| | - Vildan Avkan Oguz
- Department of Infectious Disease and Clinical Microbiology, Faculty of Medicine, Dokuz Eylul University, Izmir, Turkey
| | - Oguz Kilinc
- Department of Pulmonary Medicine, Faculty of Medicine, Dokuz Eylul University, Izmir, Turkey
| | - Merve Ercelik
- Department of Pulmonary Medicine, Faculty of Medicine, Düzce University, Düzce, Turkey
| | - Tansu Ulukavak Ciftci
- Department of Pulmonary Medicine, Faculty of Medicine, Gazi University, Ankara, Turkey
| | - Ozlem Alici
- Department of Infectious Disease, Turkiye Gazetesi Private Hospital, Istanbul, Turkey
| | - Esra Nurlu Temel
- Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Suleyman Demirel University, Isparta, Turkey
| | - Ozlem Ataoglu
- Department of Pulmonary Medicine, Faculty of Medicine, Düzce University, Düzce, Turkey
| | - Asena Aydin
- Department of Pulmonary Medicine, Kestel State Hospital, Bursa, Turkey
| | | | - Yusuf Taha Gullu
- Department of Pulmonary Medicine, Faculty of Medicine, Ondokuz Mayıs University, Samsun, Turkey
| | - Fusun Fakili
- Department of Pulmonary Medicine, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey
| | - Figen Deveci
- Department of Pulmonary Medicine, Faculty of Medicine, Firat University, Elazıg˘, Turkey
| | - Neslihan Kose
- Department of Pulmonary Medicine, Bilecik Training and Research Hospital, Bilecik, Turkey
| | - Muge Meltem Tor
- Department of Pulmonary Medicine, Faculty of Medicine, Zonguldak Bülent Ecevit University, Zonguldak, Turkey
| | - Gulsah Gunluoglu
- Department of Pulmonary Medicine, Yedikule Chest Diseases and Chest Surgery Training and Research Hospital, University of Health Science, Istanbul, Turkey
| | - Sedat Altin
- Department of Pulmonary Medicine, Yedikule Chest Diseases and Chest Surgery Training and Research Hospital, University of Health Science, Istanbul, Turkey
| | - Teyfik Turgut
- Department of Pulmonary Medicine, Faculty of Medicine, Firat University, Elazıg˘, Turkey
| | - Tibel Tuna
- Department of Pulmonary Medicine, Faculty of Medicine, Ondokuz Mayıs University, Samsun, Turkey
| | - Onder Ozturk
- Department of Pulmonary Medicine, Faculty of Medicine, Suleyman Demirel University, Isparta, Turkey
| | - Oner Dikensoy
- Department of Pulmonary Medicine, Faculty of Medicine, Taksim, Acibadem University, Istanbul, Turkey
| | - Pinar Yildiz Gulhan
- Department of Pulmonary Medicine, Faculty of Medicine, Düzce University, Düzce, Turkey
| | - Ilknur Basyigit
- Department of Pulmonary Medicine, Faculty of Medicine, Kocaeli University, İzmit, Turkey
| | - Hasim Boyaci
- Department of Pulmonary Medicine, Faculty of Medicine, Kocaeli University, İzmit, Turkey
| | | | - Sermin Borekci
- Department of Pulmonary Disease, Cerrahpaşa Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Bilun Gemicioglu
- Department of Pulmonary Disease, Cerrahpaşa Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Firat Bayraktar
- Department of Internal Medicine, Faculty of Medicine, Dokuz Eylul University, Izmir, Turkey
| | - Osman Elbek
- Department of Pulmonary Medicine, Kadıköy Florence Nightingale Hospital, Istanbul, Turkey
| | - Ismail Hanta
- Department of Pulmonary Medicine, Faculty of Medicine, Çukurova University, Adana, Turkey
| | - Hacer Kuzu Okur
- Department of Pulmonary Medicine, Faculty of Medicine, Altunizade Acibadem Hospital, Acibadem University, Istanbul, Turkey
| | - Gulseren Sagcan
- Department of Pulmonary Medicine, Faculty of Medicine, Altunizade Acibadem Hospital, Acibadem University, Istanbul, Turkey
| | - Oguz Uzun
- Department of Pulmonary Medicine, Faculty of Medicine, Ondokuz Mayıs University, Samsun, Turkey
| | - Metin Akgun
- Department of Pulmonary Medicine, Faculty of Medicine, Ataturk University, Erzurum, Turkey
| | - Goksel Altinisik
- Department of Pulmonary Medicine, Faculty of Medicine, Pamukkale University, Denizli, Turkey
| | - Berna Dursun
- Department of Pulmonary Medicine, Ankara Memorial Hospital, Ankara, Turkey
| | - Ebru Cakir Edis
- Department of Pulmonary Medicine, Faculty of Medicine, Trakya University, Edirne, Turkey
| | - Erkmen Gulhan
- Department of Thoracic Surgery, Atatürk Chest Diseases and Thoracic Surgery Training and Research Hospital, Ankara, Turkey
| | - Fusun Oner Eyuboglu
- Department of Pulmonary Medicine, School of Medicine, Başkent University, Ankara, Turkey
| | - Okkes Gultekin
- Department of Pulmonary Medicine, Faculty of Medicine, Celal Bayar University, Manisa, Turkey
| | - Yavuz Havlucu
- Department of Pulmonary Medicine, Faculty of Medicine, Celal Bayar University, Manisa, Turkey
| | - Metin Ozkan
- Department of Pulmonary Medicine, Ankara Memorial Hospital, Ankara, Turkey
| | - Aysin Sakar Coskun
- Department of Pulmonary Medicine, Faculty of Medicine, Celal Bayar University, Manisa, Turkey
| | - Abdullah Sayiner
- Department of Pulmonary Medicine, Faculty of Medicine, Ege University, Izmir, Turkey
| | - A. Fuat Kalyoncu
- Department of Pulmonary Medicine, Faculty of Medicine, Hacettepe University, Ankara, Turkey
| | - Oya Itil
- Department of Pulmonary Medicine, Faculty of Medicine, Dokuz Eylul University, Izmir, Turkey
| | - Hasan Bayram
- Department of Pulmonary Medicine, Koç University School of Medicine, Istanbul, Turkey
- Koç University Research Center for Translational Medicine (KUTTAM), Koç University School of Medicine, Istanbul, Turkey
- *Correspondence: Hasan Bayram,
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Wang S, Gelfand JM, Calabrese C. Outpatient Management of COVID-19: A Primer for the Dermatologist. CURRENT DERMATOLOGY REPORTS 2022; 11:318-327. [PMID: 36035078 PMCID: PMC9391204 DOI: 10.1007/s13671-022-00368-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/04/2022] [Indexed: 12/15/2022]
Abstract
Purpose of Review To summarize diagnostic and therapeutic management of COVID-19 in the outpatient setting for dermatologists. Recent Findings Paxlovid (nirmatrelvir-ritonavir) is the preferred treatment in patients with mild symptoms at high risk of progression to severe SARS-CoV2 infection. Additional options include monoclonal antibodies (bebtelovimab), remdesivir, and molnupiravir. Summary Dermatologists need to be aware of recent developments in diagnostic and therapeutic management of COVID-19 in the outpatient setting, as their patients may rely on dermatologists to provide advice, particularly in cases where treatments for dermatological disease may impact the risk of COVID-19 and/or vaccine efficacy. Supplementary Information The online version contains supplementary material available at 10.1007/s13671-022-00368-3.
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Affiliation(s)
- Sonia Wang
- University of Pennsylvania, Perelman School of Medicine, PA 19104 Philadelphia, USA
| | - Joel M. Gelfand
- University of Pennsylvania, Perelman School of Medicine, PA 19104 Philadelphia, USA
- Department of Dermatology, Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia, PA 19104 USA
| | - Cassandra Calabrese
- Department of Rheumatologic and Immunologic Disease, Cleveland Clinic, Cleveland, OH 44195 USA
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15
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Sedighi M, Amanollahi A, Moradi Moghaddam O, Basir Ghafouri H, Hoseini SE, Tavakoli N. Linear mixed model analysis to evaluate correlations between remdesivir adverse effects with age and gender of patients with mild Covid-19 pneumonia. J Med Virol 2022; 94:3783-3790. [PMID: 35491957 PMCID: PMC9348259 DOI: 10.1002/jmv.27800] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Revised: 04/06/2022] [Accepted: 04/19/2022] [Indexed: 11/14/2022]
Abstract
We aimed to assess longitudinal changes in clinical indexes of corona disease 2019 (Covid-19) patients with mild pulmonary infection during 5 days of remdesivir therapy and determine the effect of age and gender on remdesivir adverse effects (AE). Patients' clinical data including inflammatory markers, liver and renal function tests, and heart rate (HR) were extracted from medical records. Linear mixed model (LMM) was used to analyze longitudinal changes in patients' clinical indexes. Gender and age were inserted in LMM as covariates to find their correlation with AE and clinical indexes. Of 84 patients, 35 patients met our criteria for the study. There were significant increases in mean levels of white blood cell (WBC; p = 0.005), alanine aminotransferase (ALT; p = 0.001), aspartate aminotransferase (p = 0.001), blood urea nitrogen (BUN; p = 0.001), and creatinine (p = 0.006), whereas mean levels of erythrocyte sedimentation rate (p = 0.005), C-reactive protein (p = 0.001), alkaline phosphatase (p = 0.001), and potassium (p = 0.003) decreased significantly. Estimated glomerular filtration rate (p = 0.001) and HR (p = 0.001) showed a notable decline over the course of treatment. LMM analysis showed that mean changes in WBC (β = 0.94, p = 0.029), creatinine (β = 0.12, p = 0.020), and HR (β = 6.47, p = 0.008) were greater in males than in females. Also, age of patients had a significant effect on the mean changes of WBC (β = -0.02, p = 0.023), sodium (β = -0.06, p = 0.010), BUN (β = 0.23, p = 0.001), and HR (β = -0.29, p = 0.001). Despite no renal and liver dysfunction, Covid-19 patients with mild pulmonary infection may develop some remdesivir AE and attributed side effects might be affected by gender and age of patients.
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Affiliation(s)
- Mohsen Sedighi
- Trauma and Injury Research CenterIran University of Medical SciencesTehranIran
| | - Alireza Amanollahi
- Department of Epidemiology, School of Public Health and SafetyShahid Beheshti University of Medical SciencesTehranIran
| | | | | | | | - Nader Tavakoli
- Trauma and Injury Research CenterIran University of Medical SciencesTehranIran
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16
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Chen Z, Luo J, Li S, Xu P, Zeng L, Yu Q, Zhang L. Characteristics of Living Systematic Review for COVID-19. Clin Epidemiol 2022; 14:925-935. [PMID: 35958161 PMCID: PMC9359410 DOI: 10.2147/clep.s367339] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2022] [Accepted: 07/28/2022] [Indexed: 11/24/2022] Open
Abstract
Purpose The systematic review aims to analyze and summarize the characteristics of living systematic review (LSR) for coronavirus disease 2019 (COVID-19). Methods Six databases including Medline, Excerpta Medica (Embase), Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Database and China Science, and Technology Journal Database (VIP), were searched as the source of basic information and methodology of LSR. Descriptive analytical methods were used to analyze the included COVID-19 LSRs, and the study characteristics of COVID-19 LSRs were further assessed. Results Sixty-four COVID-19 LSRs were included. Eighty-nine point one percent of LSRs were published on Science Citation Index (SCI) journals, and 64.1% publication with an impact factor (IF) >5 and 17.2% with an IF >15 among SCI journals. The first unit of the published LSRs for COVID-19 came from 19 countries, with the largest contribution from the UK (17.2%, 11/64). Forty point six percent of LSRs for COVID-19 were related to therapeutics topic which was considered the most concerned perspective for LSRs for COVID-19. Seventy-six point six percent of LSRs focused on the general population, with less attention to children, pregnant women and the elderly. However, the LSR for COVID-19 was reported incomplete on “living” process, including 40.6% of studies without search frequency, 79.7% of studies without screening frequency, 20.3% of studies without update frequency, and 65.6% of studies without the timing or criteria of transitioning LSR out of living mode. Conclusion Although researchers in many countries have applied LSRs to COVID-19, most of the LSRs for COVID-19 were incomplete in reporting on the “living” process and less focused on special populations. This could reduce the confidence of health-care providers and policy makers in the results of COVID-19 LSR, thereby hindering the translation of evidence on COVID-19 LSR into clinical practice. It was necessary to explicitly enact preferred reporting items for systematic reviews and meta-analyses (PRISMA) to improve the reporting quality of LSR and support ongoing efforts of therapeutics research for special patients with COVID-19.
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Affiliation(s)
- Zhe Chen
- Department of Pharmacy, West China Second University Hospital, Sichuan University, Chengdu, People’s Republic of China
- Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, People’s Republic of China
- NMPA Key Laboratory for Technical Research on Drug Products in Vitro and in Vivo Correlation, Chengdu, People’s Republic of China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, People’s Republic of China
- West China School of Pharmacy, Sichuan University, Chengdu, People’s Republic of China
| | - Jiefeng Luo
- Department of Pharmacy, West China Second University Hospital, Sichuan University, Chengdu, People’s Republic of China
- Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, People’s Republic of China
- NMPA Key Laboratory for Technical Research on Drug Products in Vitro and in Vivo Correlation, Chengdu, People’s Republic of China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, People’s Republic of China
- West China School of Pharmacy, Sichuan University, Chengdu, People’s Republic of China
| | - Siyu Li
- Department of Pharmacy, West China Second University Hospital, Sichuan University, Chengdu, People’s Republic of China
- Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, People’s Republic of China
- NMPA Key Laboratory for Technical Research on Drug Products in Vitro and in Vivo Correlation, Chengdu, People’s Republic of China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, People’s Republic of China
- West China School of Medicine, Sichuan University, Chengdu, People’s Republic of China
| | - Peipei Xu
- Department of Pharmacy, West China Second University Hospital, Sichuan University, Chengdu, People’s Republic of China
- Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, People’s Republic of China
- NMPA Key Laboratory for Technical Research on Drug Products in Vitro and in Vivo Correlation, Chengdu, People’s Republic of China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, People’s Republic of China
- West China School of Medicine, Sichuan University, Chengdu, People’s Republic of China
| | - Linan Zeng
- Department of Pharmacy, West China Second University Hospital, Sichuan University, Chengdu, People’s Republic of China
- Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, People’s Republic of China
- NMPA Key Laboratory for Technical Research on Drug Products in Vitro and in Vivo Correlation, Chengdu, People’s Republic of China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, People’s Republic of China
| | - Qin Yu
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, People’s Republic of China
- National Drug Clinical Trial Institute, West China Second University Hospital, Sichuan University, Chengdu, People’s Republic of China
- Qin Yu, Email
| | - Lingli Zhang
- Department of Pharmacy, West China Second University Hospital, Sichuan University, Chengdu, People’s Republic of China
- Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, People’s Republic of China
- NMPA Key Laboratory for Technical Research on Drug Products in Vitro and in Vivo Correlation, Chengdu, People’s Republic of China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, People’s Republic of China
- Correspondence: Lingli Zhang, Email
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17
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Kaka AS, Wilt TJ. Major Update 2: Remdesivir for Adults With COVID-19. Ann Intern Med 2022; 175:W81-W82. [PMID: 35969873 DOI: 10.7326/l22-0212] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Affiliation(s)
- Anjum S Kaka
- Minneapolis VA Section of Infectious Diseases and University of Minnesota School of Medicine, Minneapolis, Minnesota
| | - Timothy J Wilt
- Minneapolis VA Evidence Synthesis Program, Center for Care Delivery and Outcomes Research, and University of Minnesota School of Medicine, Minneapolis, Minnesota
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18
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Ruan X, Yu J, Miao H, Li R, Tong Z. Remdesivir Powders Manufactured by Jet Milling for Potential Pulmonary Treatment of COVID-19. Pharm Dev Technol 2022; 27:635-645. [PMID: 35787731 DOI: 10.1080/10837450.2022.2098975] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
Abstract
Remdesivir is one of the effective drugs proposed for the treatment of coronavirus disease 2019 (COVID-19). However, the study on inhalable regimen is currently limited though COVID-19 is respiratory diseases and infects lung area. This work aims to prepare inhalable remdesivir formulations and verify their effectiveness through in vitro evaluations.Formulations containing different ratios of jet-milled inhalable remdesivir (5%, 10%, 20%,40%,70%) with excipients were produced and characterized in terms of the particle size distribution, particle morphology, flowability, water content, crystallinity, the water sorption and desorption capabilities and the aerodynamic performance.Results indicating that drug loading is a vital factor in facilitating the dispersion of remdesivir dry powder, and the ternary excipient plays a negligible role in improving aerosol performance. Besides, the 70% remdesivir with lactose carrier (70%RD-Lac) was physically stable and retain high aerosol performance after conditioned at 40 °C and 75% RH for a month. Therefore, formulation 70% RD-Lac might be recommended as a candidate product for the potential treatment of COVID-19.
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Affiliation(s)
- Xiaoying Ruan
- Southeast University - Sipailou Campus, School of Energy and Environment, Nanjing, 210096 China
| | - Jiaqi Yu
- Institute for Process Modelling and Optimization, suzhou, China
| | - Hao Miao
- Monash University, Clayton, 3800 Australia
| | - Renjie Li
- Monash University, Clayton, 3800 Australia
| | - Zhenbo Tong
- Southeast University, School of Energy and Environment, Nanjing, 210096 China
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19
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Franczyk B, Rysz J, Miłoński J, Konecki T, Rysz-Górzyńska M, Gluba-Brzózka A. Will the Use of Pharmacogenetics Improve Treatment Efficiency in COVID-19? Pharmaceuticals (Basel) 2022; 15:739. [PMID: 35745658 PMCID: PMC9230944 DOI: 10.3390/ph15060739] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Revised: 05/31/2022] [Accepted: 05/31/2022] [Indexed: 12/13/2022] Open
Abstract
The COVID-19 pandemic is associated with a global health crisis and the greatest challenge for scientists and doctors. The virus causes severe acute respiratory syndrome with an outcome that is fatal in more vulnerable populations. Due to the need to find an efficient treatment in a short time, there were several drugs that were repurposed or repositioned for COVID-19. There are many types of available COVID-19 therapies, including antiviral agents (remdesivir, lopinavir/ritonavir, oseltamivir), antibiotics (azithromycin), antiparasitics (chloroquine, hydroxychloroquine, ivermectin), and corticosteroids (dexamethasone). A combination of antivirals with various mechanisms of action may be more efficient. However, the use of some of these medicines can be related to the occurrence of adverse effects. Some promising drug candidates have been found to be ineffective in clinical trials. The knowledge of pharmacogenetic issues, which translate into variability in drug conversion from prodrug into drug, metabolism as well as transport, could help to predict treatment efficiency and the occurrence of adverse effects in patients. However, many drugs used for the treatment of COVID-19 have not undergone pharmacogenetic studies, perhaps as a result of the lack of time.
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Affiliation(s)
- Beata Franczyk
- Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, 90-549 Lodz, Poland; (B.F.); (J.R.)
| | - Jacek Rysz
- Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, 90-549 Lodz, Poland; (B.F.); (J.R.)
| | - Jarosław Miłoński
- Department of Otolaryngology, Laryngological Oncology, Audiology and Phoniatrics, Medical University of Lodz, 90-549 Lodz, Poland;
| | - Tomasz Konecki
- Department of Urology, Medical University of Lodz, 90-549 Lodz, Poland;
| | - Magdalena Rysz-Górzyńska
- Department of Ophthalmology and Visual Rehabilitation, Medical University of Lodz, 90-549 Lodz, Poland;
| | - Anna Gluba-Brzózka
- Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, 90-549 Lodz, Poland; (B.F.); (J.R.)
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20
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Apiyo M, Olum R, Kabuye A, Khainza B, Amate AM, Byabashaija V, Nomujuni D, Sebbaale K, Senfuka P, Kazibwe S, Sharma G, Davidson L, Bongomin F. Clinical Characteristics and Outcomes of Patients Hospitalized with COVID-19 at Case Hospital, Uganda. Interdiscip Perspect Infect Dis 2022; 2022:5477790. [PMID: 35698593 PMCID: PMC9188300 DOI: 10.1155/2022/5477790] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2022] [Revised: 05/01/2022] [Accepted: 05/10/2022] [Indexed: 01/18/2023] Open
Abstract
Data on clinical outcomes of patients hospitalized with coronavirus disease 2019 (COVID-19) in private health facilities in Uganda is scarce. We conducted a retrospective cohort study of patients hospitalized with COVID-19 at Case Hospital, Kampala, Uganda, between June 2020 and September 2021. Data of 160 participants (median age 45 years (interquartile range [IQR]: 37-57) and 63.5% male) was analyzed. Seventy-seven (48.1%) participants had non-severe, 18 (11.3%) severe, and 83 (51.9%) critical COVID-19 illness. In 62 participants with chest computed tomography findings, 54 (87%) had bilateral disease, with 22 (35%) having ground-glass opacities. The median duration of hospitalization was 5 days (IQR: 3-9 days). Overall, 18 (11.3%) participants died. Survival at 14 and 28 days was 89% and 72%, respectively. Factors strongly associated with all-cause mortality were as follows: age >50 years (odds ratio [OR]: 8.6, 95% confidence interval [CI]: 1.1-69.2, and p=0.042), having at least 1 comorbidity (OR: 3.2, 95% CI: 1.1-8.9, and p=0.029), hypertension (OR: 3.2, 95% CI: 1.2-8.6, and p=0.024), diabetes mellitus (OR: 2.9, 95% CI: 1.0-8.5, andp=0.056), and oxygen saturation <92% (OR: 5.1, 95% CI: 1.8-14.4, and p=0.002). In this private health facility, mortality was about 1 in 10 patients, and more people presented with critical illness in the second wave of the pandemic, and most deaths occurred after 2 weeks of hospitalization.
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Affiliation(s)
| | - Ronald Olum
- Department of Internal Medicine, St. Francis Hospital Nsambya, Kampala, Uganda
| | | | | | | | | | | | | | | | | | | | | | - Felix Bongomin
- Department of Medical Microbiology & Immunology, Faculty of Medicine, Gulu University, Gulu, Uganda
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21
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Luo W, Ding R, Guo X, Zhan T, Tang T, Fan R, Wang Y. Clinical data mining reveals Gancao-Banxia as a potential herbal pair against moderate COVID-19 by dual binding to IL-6/STAT3. Comput Biol Med 2022; 145:105457. [PMID: 35366469 PMCID: PMC8957363 DOI: 10.1016/j.compbiomed.2022.105457] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2022] [Revised: 03/15/2022] [Accepted: 03/23/2022] [Indexed: 01/08/2023]
Abstract
BACKGROUND Coronavirus disease 2019 (COVID-19) keeps spreading globally. Chinese medicine (CM) exerts a critical role for the prevention or therapy of COVID-19 in an integrative and holistic way. However, mining and development of early, efficient, multisite binding CMs that inhibit the cytokine storm are imminent. METHODS The formulae were extracted retrospectively from clinical records in Hunan Province. Clinical data mining analysis and association rule analysis were employed for mining the high-frequency herbal pairs and groups from formulae. Network pharmacology methods were applied to initially explore the most critical pair's hub targets, active ingredients, and potential mechanisms. The binding power of active ingredients to the hub targets was verified by molecular docking. RESULTS Eight hundred sixty-two prescriptions were obtained from 320 moderate COVID-19 through the Hunan Provincial Health Commission. Glycyrrhizae Radix et Rhizoma (Gancao) and Pinelliae Rhizoma (Banxia) were used with the highest frequency and support. There were 49 potential genes associated with Gancao-Banxia pair against moderate COVID-19 patients. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) indicated that Gancao-Banxia might act via inflammatory response, viral defense, and immune responses signaling pathways. IL-6 and STAT3 were the two most hub targets in the protein-protein interaction (PPI) network. The binding of five active ingredients originated from Gancao-Banxia to IL-6-STAT3 was verified by molecular docking, namely quercetin, coniferin, licochalcone a, Licoagrocarpin and (3S,6S)-3-(benzyl)-6-(4-hydroxybenzyl)piperazine-2,5-quinone, maximizing therapeutic efficacy. CONCLUSIONS This work provided some potential candidate Chinese medicine formulas for moderate COVID-19. Among them, Gancao-Banxia was considered the most potential herbal pair. Bioinformatic data demonstrated that Gancao-Banxia pair may achieve dual inhibition of IL-6-STAT3 via directly interacting with IL-6 and STAT3, suppressing the IL-6 amplifier. SARS-CoV-2 models will be needed to validate this possibility in the future.
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Affiliation(s)
- Weikang Luo
- Institute of Integrative Medicine, Department of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, Changsha, 410008, PR China,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, PR China
| | - Ruoqi Ding
- Institute of Integrative Medicine, Department of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, Changsha, 410008, PR China,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, PR China
| | - Xiaohang Guo
- Hunan University of Chinese Medicine, Changsha, 410008, PR China
| | - Tao Zhan
- Department of Integrated TCM and Western Medicine, The First Hospital of Changsha, Changsha, 410005, PR China
| | - Tao Tang
- Institute of Integrative Medicine, Department of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, Changsha, 410008, PR China,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, PR China
| | - Rong Fan
- Institute of Integrative Medicine, Department of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, Changsha, 410008, PR China,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, PR China,Corresponding author. Institute of Integrative Medicine, Department of Integrated Chinese and Western Medicine, Xiangya Hospital, Central South University, Changsha, 410008, PR China
| | - Yang Wang
- Institute of Integrative Medicine, Department of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, Changsha, 410008, PR China,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, PR China,Corresponding author. Institute of Integrative Medicine, Department of Integrated Chinese and Western Medicine, Xiangya Hospital, Central South University, Changsha, 410008, PR China
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22
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Colaneri M, Amarasinghe N, Rezzonico L, Pieri TC, Segalini E, Sambo M, Roda S, Meloni F, Gregorini M, Rampino T, Pelenghi S, Ricciardi A, Bruno R. Early remdesivir to prevent severe COVID-19 in recipients of solid organ transplant: a real-life study from Northern Italy. Int J Infect Dis 2022; 121:157-160. [PMID: 35533831 PMCID: PMC9076039 DOI: 10.1016/j.ijid.2022.05.001] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Revised: 04/28/2022] [Accepted: 05/01/2022] [Indexed: 12/20/2022] Open
Abstract
Objectives The effectiveness of a 3-day course of remdesivir to prevent severe disease in patients with COVID-19 who received solid organ transplant (SOT) is unknown. We wanted to study the efficacy of this therapeutic option in patients with COVID-19 who received SOT in preventing both hospitalizations for outpatients and clinical worsening due to COVID-19 for those already hospitalized for other reasons. Methods This is a single-center, retrospective, observational study conducted in the Fondazione IRCSS Policlinico San Matteo of Pavia, Northern Italy. We extracted all the data of patients with COVID-19 receiving SOT who received and did not receive pre-emptive remdesivir between December 23, 2021, and February 26, 2022. We used a Cox proportional hazard model to assess whether receiving pre-emptive remdesivir was associated with lower rates of hospitalization. Results A total of 24 patients who received SOT were identified. Among these, seven patients (29, 1%) received pre-emptive remdesivir, whereas 17 (70, 9%) patients did not. Receiving remdesivir significantly reduced the hospitalization rate in outpatients who received SOT and the clinical worsening of the condition of already hospitalized patients who received SOT (hazard ratio 0.05; confidence interval [0.00–0.65], P-value = 0.01). Conclusion In our cohort of patients infected with SARS-CoV-2 who received SOT, pre-emptive remdesivir was effective in reducing the hospitalization rate due to COVID-19 and in preventing the clinical worsening of the condition of patients who received SOT who were hospitalized for reasons other than COVID-19.
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Affiliation(s)
- Marta Colaneri
- Division of Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
| | - Nicolò Amarasinghe
- Division of Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Leonardo Rezzonico
- Division of Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Teresa Chiara Pieri
- Division of Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Emilio Segalini
- Division of Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Margherita Sambo
- Division of Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Silvia Roda
- Division of Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Federica Meloni
- Division of Pneumology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Marilena Gregorini
- Division of Nefrology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Teresa Rampino
- Division of Nefrology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Stefano Pelenghi
- Division of Cardiac Surgery, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Alessandra Ricciardi
- Division of Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Raffaele Bruno
- Department of Medical, Surgical, Diagnostic and Paediatric Science, University of Pavia, Italy
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23
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Shukla AK, Misra S. Antimicrobials in COVID-19: strategies for treating a COVID-19 pandemic. J Basic Clin Physiol Pharmacol 2022:jbcpp-2022-0061. [PMID: 35503307 DOI: 10.1515/jbcpp-2022-0061] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2022] [Accepted: 03/28/2022] [Indexed: 11/15/2022]
Abstract
The COVID-19 pandemic continues to pose a serious global challenge, with the world engulfed in fighting second, third and fourth waves of the disease, which is reaching scary proportions in terms of cases and mortality in countries like India. Despite the urgent need of proven management protocols, there is still confusion about the best practices for treating COVID-19 with different pharmaceutical interventions. Antimicrobials are empirically used in COVID-19 patients. During the initial phase of this pandemic, hydroxychloroquine, ivermectin, azithromycin and doxycycline were widely suggested for possible prophylaxis or treatment for COVID-19 in outpatient as well as hospitalized settings. Various national and international guidelines recommended its use. However, cumulative evidence from subsequent clinical trials has revealed no significant clinical benefits in any setting, with the risk of adverse effects being high particularly in combination with azithromycin. Yet, there is continued use of antimicrobials particularly in outpatient settings which should be avoided because there is no justifiable rationale for doing so. Antimicrobial resistance (AMR) was one of the top problems for global public health before the coronavirus 2019 (COVID-19) pandemic began. AMR, which is already a difficult problem, must now be handled in the context of a changing healthcare sector.
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Affiliation(s)
| | - Saurav Misra
- Department of Pharmacology, Kalpana Chawla Government Medical College, Karnal, India
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24
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Kaka AS, MacDonald R, Linskens EJ, Langsetmo L, Vela K, Duan-Porter W, Wilt TJ. Major Update 2: Remdesivir for Adults With COVID-19: A Living Systematic Review and Meta-analysis for the American College of Physicians Practice Points. Ann Intern Med 2022; 175:701-709. [PMID: 35226522 PMCID: PMC8924790 DOI: 10.7326/m21-4784] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND Remdesivir is approved for the treatment of adults hospitalized with COVID-19. PURPOSE To update a living review of remdesivir for adults with COVID-19. DATA SOURCES Several electronic U.S. Food and Drug Administration, company, and journal websites from 1 January 2020 through 19 October 2021. STUDY SELECTION English-language, randomized controlled trials (RCTs) of remdesivir for COVID-19. DATA EXTRACTION One reviewer abstracted, and a second reviewer verified data. The Cochrane Risk of Bias Tool and GRADE (Grading of Recommendations Assessment, Development and Evaluation) method were used. DATA SYNTHESIS Since the last update (search date 9 August 2021), 1 new RCT and 1 new subtrial comparing a 10-day course of remdesivir with control (placebo or standard care) were identified. This review summarizes and updates the evidence on the cumulative 5 RCTs and 2 subtrials for this comparison. Our updated results confirm a 10-day course of remdesivir, compared with control, probably results in little to no mortality reduction (5 RCTs). Updated results also confirm that remdesivir probably results in a moderate increase in the proportion of patients recovered by day 29 (4 RCTs) and may reduce time to clinical improvement (2 RCTs) and hospital length of stay (4 RCTs). New RCTs, by increasing the strength of evidence, lead to an updated conclusion that remdesivir probably results in a small reduction in the proportion of patients receiving ventilation or extracorporeal membrane oxygenation at specific follow-up times (4 RCTs). New RCTs also alter the conclusions for harms-remdesivir, compared with control, may lead to a small reduction in serious adverse events but may lead to a small increase in any adverse event. LIMITATION The RCTs differed in definitions of COVID-19 severity and outcomes reported. CONCLUSION In hospitalized adults with COVID-19, the findings confirm that remdesivir probably results in little to no difference in mortality and increases the proportion of patients recovered. Remdesivir may reduce time to clinical improvement and may lead to small reductions in serious adverse events but may result in a small increase in any adverse event. PRIMARY FUNDING SOURCE U.S. Department of Veterans Affairs.
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Affiliation(s)
- Anjum S Kaka
- Minneapolis VA Section of Infectious Diseases and University of Minnesota School of Medicine, Minneapolis, Minnesota (A.S.K.)
| | - Roderick MacDonald
- Minneapolis VA Evidence Synthesis Program, Center for Care Delivery and Outcomes Research, Minneapolis, Minnesota (R.M., E.J.L., L.L.)
| | - Eric J Linskens
- Minneapolis VA Evidence Synthesis Program, Center for Care Delivery and Outcomes Research, Minneapolis, Minnesota (R.M., E.J.L., L.L.)
| | - Lisa Langsetmo
- Minneapolis VA Evidence Synthesis Program, Center for Care Delivery and Outcomes Research, Minneapolis, Minnesota (R.M., E.J.L., L.L.)
| | - Kathryn Vela
- Portland VA Health Care System, Portland, Oregon (K.V.)
| | - Wei Duan-Porter
- Minneapolis VA Evidence Synthesis Program, Center for Care Delivery and Outcomes Research, and University of Minnesota School of Medicine, Minneapolis, Minnesota (W.D., T.J.W.)
| | - Timothy J Wilt
- Minneapolis VA Evidence Synthesis Program, Center for Care Delivery and Outcomes Research, and University of Minnesota School of Medicine, Minneapolis, Minnesota (W.D., T.J.W.)
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25
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Qaseem A, Yost J, Etxeandia-Ikobaltzeta I, Abraham GM, Jokela JA, Forciea MA, Miller MC, Humphrey LL. Should Remdesivir Be Used for the Treatment of Patients With COVID-19? Rapid, Living Practice Points From the American College of Physicians (Version 2, Update Alert 3). Ann Intern Med 2022; 175:W55-W57. [PMID: 35226518 PMCID: PMC8900283 DOI: 10.7326/m21-4810] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Affiliation(s)
- Amir Qaseem
- American College of Physicians, Philadelphia, Pennsylvania
| | - Jennifer Yost
- American College of Physicians, Philadelphia, Pennsylvania, and Villanova University, Villanova, Pennsylvania
| | | | - George M Abraham
- University of Massachusetts Medical School and Saint Vincent Hospital, Worcester, Massachusetts
| | - Janet A Jokela
- University of Illinois College of Medicine at Urbana-Champaign, Champaign, Illinois
| | | | | | - Linda L Humphrey
- Portland Veterans Affairs Medical Center and Oregon Health & Science University, Portland, Oregon
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26
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Dutta A. Optimizing antiviral therapy for COVID-19 with learned pathogenic model. Sci Rep 2022; 12:6873. [PMID: 35477965 PMCID: PMC9044392 DOI: 10.1038/s41598-022-10929-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Accepted: 04/15/2022] [Indexed: 01/08/2023] Open
Abstract
COVID-19 together with variants have caused an unprecedented amount of mental and economic turmoil with ever increasing fatality and no proven therapies in sight. The healthcare industry is racing to find a cure with multitude of clinical trials underway to access the efficacy of repurposed antivirals, however the much needed insights into the dynamics of pathogenesis of SARS-CoV-2 and corresponding pharmacology of antivirals are lacking. This paper introduces systematic pathological model learning of COVID-19 dynamics followed by derivative free optimization based multi objective drug rescheduling. The pathological model learnt from clinical data of severe COVID-19 patients treated with remdesivir could additionally predict immune T cells response and resulted in a dramatic reduction in remdesivir dose and schedule leading to lower toxicities, however maintaining a high virological efficacy.
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Affiliation(s)
- Abhishek Dutta
- Department of Electrical & Computer Engineering, Storrs, 06269, USA.
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27
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Huang J, Ding Y, Yao J, Zhang M, Zhang Y, Xie Z, Zuo J. Nasal Nanovaccines for SARS-CoV-2 to Address COVID-19. Vaccines (Basel) 2022; 10:vaccines10030405. [PMID: 35335037 PMCID: PMC8952855 DOI: 10.3390/vaccines10030405] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2021] [Revised: 03/04/2022] [Accepted: 03/04/2022] [Indexed: 02/06/2023] Open
Abstract
COVID-19 is still prevalent around the globe. Although some SARS-CoV-2 vaccines have been distributed to the population, the shortcomings of vaccines and the continuous emergence of SARS-CoV-2 mutant virus strains are a cause for concern. Thus, it is vital to continue to improve vaccines and vaccine delivery methods. One option is nasal vaccination, which is more convenient than injections and does not require a syringe. Additionally, stronger mucosal immunity is produced under nasal vaccination. The easy accessibility of the intranasal route is more advantageous than injection in the context of the COVID-19 pandemic. Nanoparticles have been proven to be suitable delivery vehicles and adjuvants, and different NPs have different advantages. The shortcomings of the SARS-CoV-2 vaccine may be compensated by selecting or modifying different nanoparticles. It travels along the digestive tract to the intestine, where it is presented by GALT, tissue-resident immune cells, and gastrointestinal lymph nodes. Nasal nanovaccines are easy to use, safe, multifunctional, and can be distributed quickly, demonstrating strong prospects as a vaccination method for SARS-CoV-2, SARS-CoV-2 variants, or SARS-CoV-n.
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Affiliation(s)
- Jialu Huang
- The Laboratory of Translational Medicine, Hengyang Medical School, University of South China, Hengyang 421001, China; (J.H.); (M.Z.); (Y.Z.); (Z.X.)
| | - Yubo Ding
- Nanhua Hospital Affiliated to University of South China, Hengyang Medical School, University of South China, Hengyang 421002, China; (Y.D.); (J.Y.)
| | - Jingwei Yao
- Nanhua Hospital Affiliated to University of South China, Hengyang Medical School, University of South China, Hengyang 421002, China; (Y.D.); (J.Y.)
| | - Minghui Zhang
- The Laboratory of Translational Medicine, Hengyang Medical School, University of South China, Hengyang 421001, China; (J.H.); (M.Z.); (Y.Z.); (Z.X.)
| | - Yu Zhang
- The Laboratory of Translational Medicine, Hengyang Medical School, University of South China, Hengyang 421001, China; (J.H.); (M.Z.); (Y.Z.); (Z.X.)
| | - Zhuoyi Xie
- The Laboratory of Translational Medicine, Hengyang Medical School, University of South China, Hengyang 421001, China; (J.H.); (M.Z.); (Y.Z.); (Z.X.)
| | - Jianhong Zuo
- The Laboratory of Translational Medicine, Hengyang Medical School, University of South China, Hengyang 421001, China; (J.H.); (M.Z.); (Y.Z.); (Z.X.)
- Nanhua Hospital Affiliated to University of South China, Hengyang Medical School, University of South China, Hengyang 421002, China; (Y.D.); (J.Y.)
- The Third Affiliated Hospital of University of South China, Hengyang Medical School, University of South China, Hengyang 421900, China
- Correspondence: ; Tel.: +86-7345-675219
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28
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Beyersmann J, Friede T, Schmoor C. Design aspects of COVID-19 treatment trials: Improving probability and time of favorable events. Biom J 2022; 64:440-460. [PMID: 34677829 PMCID: PMC8653377 DOI: 10.1002/bimj.202000359] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2020] [Revised: 08/13/2021] [Accepted: 09/04/2021] [Indexed: 12/24/2022]
Abstract
As a reaction to the pandemic of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a multitude of clinical trials for the treatment of SARS-CoV-2 or the resulting corona disease 2019 (COVID-19) are globally at various stages from planning to completion. Although some attempts were made to standardize study designs, this was hindered by the ferocity of the pandemic and the need to set up clinical trials quickly. We take the view that a successful treatment of COVID-19 patients (i) increases the probability of a recovery or improvement within a certain time interval, say 28 days; (ii) aims to expedite favorable events within this time frame; and (iii) does not increase mortality over this time period. On this background, we discuss the choice of endpoint and its analysis. Furthermore, we consider consequences of this choice for other design aspects including sample size and power and provide some guidance on the application of adaptive designs in this particular context.
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Affiliation(s)
| | - Tim Friede
- Institut für Medizinische StatistikUniversitätsmedizin GöttingenGöttingenGermany
- Deutsches Zentrum für Herz‐Kreislaufforschung (DZHK)Standort GöttingenGöttingenGermany
| | - Claudia Schmoor
- Zentrum Klinische Studien, Universitätsklinikum Freiburg, Medizinische FakultätAlbert‐Ludwigs Universität FreiburgFreiburg im BreisgauGermany
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Arikawa S, Fukuoka K, Nakamoto K, Kunitomo R, Matsuno Y, Shimazaki T, Saraya T, Kawakami T, Kishimoto M, Komagata Y, Kurai D, Ishi H, Kaname S. Effectiveness of neutralizing antibody cocktail in hemodialysis patients: a case series of 20 patients treated with or without REGN-COV2. Clin Exp Nephrol 2022; 26:476-485. [PMID: 35182277 PMCID: PMC8856930 DOI: 10.1007/s10157-021-02151-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Accepted: 10/17/2021] [Indexed: 12/03/2022]
Abstract
The number of patients with SARS-CoV-2 infection continues to increase, and it has become a global pandemic. Although there is an urgent need to establish an effective treatment, the medication available for dialysis patients has been limited. An antibody cocktail containing two SARS-CoV-2-neutrarizing antibodies, REGN-COV2 has been granted special approval for COVID-19 in Japan, since July 2021, and this intravenous preparation can be used for dialysis patients. At our hospital, we had 22 hemodialysis patients with COVID-19, and five of them were treated with REGN-COV2. On admission, four of the five patients had moderate disease (pneumonia but O2 inhalation) and one patient had mild disease (not having pneumonia). The mean duration of hospitalization treated with REGN-COV2 was 10.2 ± 2.86 days (mean ± SD), which was less than half, compared to patients untreated of similar severity on admission (22.12 ± 15.5). The time to fever resolution was average 7 days, and no cases progressed to severe illness or death. Among these patients, no obvious adverse reactions were shown. Although more studies with a larger number of patients could be needed for a rigorous evaluation of the effect, our result suggests that REGN-COV2 may be safe and having the possibilities in preventing severe disease in hemodialysis patients. Given the difficulty in securing inpatient beds tend to be in short supply, the strategy combined with neutralizing antibody could be beneficial for end-stage kidney disease (ESKD) patients with hemodialysis who are at high risk of severe disease.
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Affiliation(s)
- Shigehisa Arikawa
- Department of Nephrology and Rheumatology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-shi, PO 181-8611, Tokyo, Japan
| | - Kazuhito Fukuoka
- Department of Nephrology and Rheumatology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-shi, PO 181-8611, Tokyo, Japan.
| | - Keitaro Nakamoto
- Department of Respiratory Disease, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-shi, Tokyo, Japan
| | - Rie Kunitomo
- Department of Nephrology and Rheumatology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-shi, PO 181-8611, Tokyo, Japan
| | - Yuki Matsuno
- Department of Nephrology and Rheumatology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-shi, PO 181-8611, Tokyo, Japan
| | - Teppei Shimazaki
- Department of General Medicine, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-shi, Tokyo, Japan
| | - Takeshi Saraya
- Department of Respiratory Disease, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-shi, Tokyo, Japan
| | - Takahisa Kawakami
- Department of Nephrology and Rheumatology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-shi, PO 181-8611, Tokyo, Japan
| | - Mitsumasa Kishimoto
- Department of Nephrology and Rheumatology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-shi, PO 181-8611, Tokyo, Japan
| | - Yoshinori Komagata
- Department of Nephrology and Rheumatology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-shi, PO 181-8611, Tokyo, Japan
| | - Daisuke Kurai
- Department of General Medicine, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-shi, Tokyo, Japan
| | - Haruyuki Ishi
- Department of Respiratory Disease, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-shi, Tokyo, Japan
| | - Shinya Kaname
- Department of Nephrology and Rheumatology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-shi, PO 181-8611, Tokyo, Japan
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Gressens SB, Esnault V, De Castro N, Sellier P, Sene D, Chantelot L, Hervier B, Delaugerre C, Chevret S, Molina JM. Remdesivir in combination with dexamethasone for patients hospitalized with COVID-19: A retrospective multicenter study. PLoS One 2022; 17:e0262564. [PMID: 35176057 PMCID: PMC8853490 DOI: 10.1371/journal.pone.0262564] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2021] [Accepted: 12/30/2021] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Dexamethasone is standard of care for the treatment of patients with COVID-19 requiring oxygen. The objective is to assess the clinical benefit of adding remdesivir to dexamethasone. PATIENTS AND METHODS A retrospective cohort study of hospitalized patients with COVID-19 pneumonia requesting low-flow oxygen who received dexamethasone. Patients admitted to infectious diseases wards also received remdesivir. Primary outcome was duration of hospitalization after oxygen initiation. Secondary outcomes were in-hospital death, and death and/or transfer to the intensive care unit. To handle potential confounding by indication bias, outcome comparison was performed on propensity score-matched populations. Propensity score was estimated by a multivariable logistic model including prognostic covariates; then 1:1 matching was performed without replacement, using the nearest neighbor algorithm with a caliper of 0.10 fold the standard deviation of the propensity score as the maximal distance. Balance after matching was checked on standardized mean differences. RESULTS From August 15th 2020, to February 28th, 2021, 325 patients were included, 101 of whom received remdesivir. At admission median time from symptoms onset was 7 days, median age: 68 years, male sex; 61%, >1 comorbidity: 58.5%. Overall 180 patients matched on propensity score were analyzed, 90 each received remdesivir plus dexamethasone or dexamethasone alone. Median duration of hospitalization was 9 (IQR: 7-13) and 9 (IQR: 5-18) days with and without remdesivir, respectively (p = 0.37). In-hospital death rates and rates of transfer to the intensive care unit or death were 8.9 and 17.8% (HR: 0.46, 95% CI: 0.21-1.02, p = 0.06) and 20.0 and 35.6% with and without remdesivir, respectively (HR: 0.45, 95% CI: 0.23-0.89, p = 0.015). CONCLUSION In hospitalized patients with COVID-19 pneumonia receiving low-flow oxygen and dexamethasone, the addition of remdesivir was not associated with shorter hospitalization or lower in-hospital mortality but may have reduced the combined outcome of death and transfer to the intensive care unit.
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Affiliation(s)
- Simon B. Gressens
- Département des Maladies Infectieuses, Hôpitaux Saint Louis-Lariboisière, Université de Paris, AP-HP, Paris, France
| | - Violaine Esnault
- Département des Maladies Infectieuses, Hôpitaux Saint Louis-Lariboisière, Université de Paris, AP-HP, Paris, France
| | - Nathalie De Castro
- Département des Maladies Infectieuses, Hôpitaux Saint Louis-Lariboisière, Université de Paris, AP-HP, Paris, France
| | - Pierre Sellier
- Département des Maladies Infectieuses, Hôpitaux Saint Louis-Lariboisière, Université de Paris, AP-HP, Paris, France
| | - Damien Sene
- Département de Médecine Interne, AP-HP Hôpital Lariboisière, Paris, France
| | - Louise Chantelot
- Service de Pneumologie, AP-HP Hôpital Saint Louis, Paris, France
| | - Baptiste Hervier
- UF de Médecine Interne, AP-HP Hôpital Saint Louis, Paris, France
| | | | - Sylvie Chevret
- Service de Biostatistique et Information Médicale, AP-HP Hôpital Saint Louis, Paris, France
| | - Jean-Michel Molina
- Département des Maladies Infectieuses, Hôpitaux Saint Louis-Lariboisière, Université de Paris, AP-HP, Paris, France
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Tanni SE, Silvinato A, Floriano I, Bacha HA, Barbosa AN, Bernardo WM. Use of remdesivir in patients with COVID-19: a systematic review and meta-analysis. J Bras Pneumol 2022; 48:e20210393. [PMID: 35137874 PMCID: PMC8836613 DOI: 10.36416/1806-3756/e20210393] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2021] [Accepted: 11/02/2021] [Indexed: 02/06/2023] Open
Abstract
Objective: Studies in the literature regarding the use of remdesivir to treat COVID-19 patients have shown conflicting results. This study sought to answer questions related to the use of remdesivir for the treatment of patients hospitalized with moderate to severe COVID-19. Methods: This was a systematic review and meta-analysis including phase 3 randomized clinical trials (RCTs) and observational cohort studies selected from various databases, comparing patients hospitalized with moderate to severe COVID-19 receiving remdesivir and controls. Results: A total of 207 studies were retrieved, 9 of which met the eligibility criteria and were included in the study. The meta-analysis using RCTs alone showed no statistically significant differences regarding mortality or use of mechanical ventilation/extracorporeal membrane oxygenation between remdesivir and control groups, and the quality of evidence was moderate and low, respectively. The use of remdesivir increased the recovery rate by 6% (95% CI, 3-9); p = 0.004) and the clinical improvement rate by 7% (95% CI, 1-14); p = 0.02). Additionally, no significant differences in mortality were found between remdesivir and control groups when the meta-analysis used observational cohort studies alone (risk difference = −0.01 (95% CI, −0.02 to 0.01; p = 0.32), the quality of evidence being moderate, and the risk of adverse events was 4% ([95% CI, −0.08 to 0.01]; p = 0.09). Conclusions: The use of remdesivir for the treatment of patients with moderate to severe COVID-19 had no significant impact on clinically important outcomes.
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Affiliation(s)
- Suzana E Tanni
- . Disciplina de Pneumologia, Departamento de Clínica Médica, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista - UNESP - Botucatu (SP) Brasil
| | - Antonio Silvinato
- . Medicina Baseada em Evidências, Associação Médica Brasileira, São Paulo (SP) Brasil
| | - Idevaldo Floriano
- . Medicina Baseada em Evidências, Cooperativa Baixa Mogiana, Mogi-Guaçu (SP) Brasil
| | - Hélio A Bacha
- . Hospital Israelita Albert Einstein, São Paulo (SP) Brasil
| | - Alexandre Naime Barbosa
- . Departamento de Infectologia, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista - UNESP - Botucatu (SP) Brasil
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Most published systematic reviews of remdesivir for COVID-19 were redundant and lacked currency. J Clin Epidemiol 2022; 146:22-31. [PMID: 35192923 PMCID: PMC8858007 DOI: 10.1016/j.jclinepi.2022.02.006] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Revised: 02/08/2022] [Accepted: 02/16/2022] [Indexed: 12/12/2022]
Abstract
Objective To investigate the completeness and currency of published systematic reviews of remdesivir for COVID-19 and to compare this with a living guidelines approach. Study Design and Setting In this cross-sectional study, we searched Europe PMC on May 20, 2021 for systematic reviews of remdesivir (including preprints, living review updates). Completeness and currency were based on the inclusion of four major randomized trials of remdesivir available at the time of publication of the review (including as preliminary results and preprints). Results We included 38 reviews (45 reports), equivalent to a new publication every 9 days. 23 (51%) reports were out of date at the time of publication. Eleven reviews that were current on publication had a median survival time of 10 days (range 4–57). A third of reviews cited other systematic reviews, but only four provided justifications for why another review was necessary. Eight (21%) of the reviews were registered in PROSPERO. The Australian COVID-19 Clinical Evidence Taskforce living guidelines were updated within 14 days for three of the remdesivir trials, and within 28 days for the fourth. Conclusion There was considerable duplication of systematic reviews of remdesivir, and half were already out of date at the time of publication.
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Angamo MT, Mohammed MA, Peterson GM. Efficacy and safety of remdesivir in hospitalised COVID-19 patients: a systematic review and meta-analysis. Infection 2022; 50:27-41. [PMID: 34331674 PMCID: PMC8325414 DOI: 10.1007/s15010-021-01671-0] [Citation(s) in RCA: 38] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Accepted: 07/21/2021] [Indexed: 12/17/2022]
Abstract
PURPOSE This review was aimed to synthesise the best available evidence on the effectiveness and safety of remdesivir in the treatment of moderate to severe COVID-19. METHOD Randomised controlled trials (RCTs) and observational studies reporting the effectiveness and safety of remdesivir were searched via databases and other sources from December 2019 to December 2020. Two independent reviewers performed literature screening, data extraction and assessment of risk bias. Seven studies involving 3686 patients were included. RESULTS Treatment with remdesivir was associated with an increase in clinical recovery rate by 21% (RR 1.21; 95% CI 1.08-1.35) on day 7 and 29% (RR 1.29; 95% CI 1.22-1.37) on day 14. The likelihoods of requiring high-flow supplemental oxygen and invasive mechanical ventilation in the remdesivir group were lower than in the placebo group by 27% (RR 0.73; 95% CI 0.54-0.99) and 47% (RR 0.53; 95% CI 0.39-0.72), respectively. Remdesivir-treated patients showed a 39% (RR 0.61; 95% CI 0.46-0.79) reduction in the risk of mortality on day 14 compared to the control group; however, there was no significant difference on day 28. Serious adverse effects (SAEs) were significantly less common in patients treated with remdesivir, with an absolute risk difference of 6% (RD -0.06; 95% CI -0.09 to -0.03). CONCLUSION Despite conditional recommendation against its use, remdesivir could still be effective in early clinical improvement; reduction of early mortality and avoiding high-flow supplemental oxygen and invasive mechanical ventilation among hospitalised COVID-19 patients. Remdesivir was also well tolerated without significant SAEs compared to placebo, yet available evidence from clinical studies support the need to conduct close monitoring.
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Affiliation(s)
- Mulugeta T Angamo
- School of Pharmacy and Pharmacology, University of Tasmania, Hobart, Australia.
| | | | - Gregory M Peterson
- School of Pharmacy and Pharmacology, University of Tasmania, Hobart, Australia
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Gupte V, Hegde R, Sawant S, Kalathingal K, Jadhav S, Malabade R, Gogtay J. Safety and clinical outcomes of remdesivir in hospitalised COVID-19 patients: a retrospective analysis of active surveillance database. BMC Infect Dis 2022; 22:1. [PMID: 34983406 PMCID: PMC8724590 DOI: 10.1186/s12879-021-07004-8] [Citation(s) in RCA: 64] [Impact Index Per Article: 21.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2021] [Accepted: 12/22/2021] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Real-world data on safety and clinical outcomes of remdesivir in COVID-19 management is scant. We present findings of data analysis conducted for assessing the safety and clinical outcomes of remdesivir treatment for COVID-19 in India. METHODS This retrospective analysis used data from an active surveillance programme database of hospitalised patients with COVID-19 who were receiving remdesivir. RESULTS Of the 2329 patients included, 67.40% were men. Diabetes (29.69%) and hypertension (20.33%) were the most common comorbidities. At remdesivir initiation, 2272 (97.55%) patients were receiving oxygen therapy. Remdesivir was administered for 5 days in 65.38% of patients. Antibiotics (64.90%) and steroids (47.90%) were the most common concomitant medications. Remdesivir was overall well tolerated, and total 119 adverse events were reported; most common were nausea and vomiting in 45.40% and increased liver enzymes in 14.28% patients. 84% of patients were cured/improved, 6.77% died and 9.16% showed no improvement in their clinical status at data collection. Subgroup analyses showed that the mortality rate was significantly lower in patients < 60 years old than in those > 60 years old. Amongst patients on oxygen therapy, the cure/improvement rate was significantly higher in those receiving standard low-flow oxygen than in those receiving mechanical ventilation, non-invasive ventilation, or high-flow oxygen. Factors that were associated with higher mortality were age > 60 years, cardiac disease, diabetes high flow oxygen, non-invasive ventilation and mechanical ventilation. CONCLUSION Our analysis showed that remdesivir is well tolerated and has an acceptable safety profile. The clinical outcome of cure/improvement was 84%, with a higher improvement in patients < 60 years old and on standard low-flow oxygen.
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Affiliation(s)
| | | | | | | | - Sonali Jadhav
- Medical Services, Clinical Trial Group, Cipla Ltd., Mumbai, India
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Liu Y, Zhou X, Liu X, Jiang X. The immunology and immunotherapy for COVID-19. Expert Rev Mol Med 2021; 23:e24. [PMID: 34915958 PMCID: PMC8723987 DOI: 10.1017/erm.2021.30] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Revised: 10/26/2021] [Accepted: 12/13/2021] [Indexed: 12/15/2022]
Abstract
The ongoing global pandemic of coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and significantly impacts the world economy and daily life. Symptoms of COVID-19 range from asymptomatic to fever, dyspnoea, acute respiratory distress and multiple organ failure. Critical cases often occur in the elderly and patients with pre-existing conditions. By binding to the angiotensin-converting enzyme 2 receptor, SARS-CoV-2 can enter and replicate in the host cell, exerting a cytotoxic effect and causing local and systemic inflammation. Currently, there is no specific treatment for COVID-19, and immunotherapy has consistently attracted attention because of its essential role in boosting host immunity to the virus and reducing overwhelming inflammation. In this review, we summarise the immunopathogenic features of COVID-19 and highlight recent advances in immunotherapy to illuminate ideas for the development of new potential therapies.
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Affiliation(s)
- Yixin Liu
- Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
| | - Xinsheng Zhou
- Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Xuan Liu
- Department of Pediatrics, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Xiaotao Jiang
- Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
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Qaseem A, Yost J, Etxeandia-Ikobaltzeta I, Abraham GM, Jokela JA, Miller MC, Forciea MA, Humphrey LL. Update Alert 2: Should Remdesivir Be Used for the Treatment of Patients With COVID-19? Rapid, Living Practice Points From the American College of Physicians (Version 2). Ann Intern Med 2021; 174:W116-W117. [PMID: 34606308 PMCID: PMC8496689 DOI: 10.7326/l21-0607] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Affiliation(s)
- Amir Qaseem
- American College of Physicians, Philadelphia, Pennsylvania
| | | | | | - George M Abraham
- Saint Vincent Hospital-Worcester Medical Center, Worcester, Massachusetts
| | - Janet A Jokela
- University of Illinois College of Medicine at Urbana-Champaign, Champaign, Illinois
| | | | | | - Linda L Humphrey
- Portland Veterans Affairs Medical Center and Oregon Health & Science University, Portland, Oregon
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Kaka AS, MacDonald R, Linskens EJ, Wilt TJ. Update Alert 2: Remdesivir for Adults With COVID-19. Ann Intern Med 2021; 174:W114-W115. [PMID: 34606312 PMCID: PMC8496690 DOI: 10.7326/l21-0600] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Affiliation(s)
- Anjum S Kaka
- Minneapolis VA Health Care System and University of Minnesota School of Medicine, Minneapolis, Minnesota
| | | | | | - Timothy J Wilt
- Minneapolis VA Health Care System and University of Minnesota School of Medicine and School of Public Health, Minneapolis, Minnesota
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Davis J, Umeh U, Saba R. Treatment of SARS-CoV-2 (COVID-19): A safety perspective. World J Pharmacol 2021; 10:1-32. [DOI: 10.5497/wjp.v10.i1.1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Revised: 08/22/2021] [Accepted: 09/17/2021] [Indexed: 02/06/2023] Open
Abstract
The goal of this review is to report a balanced perspective of current evidence for efficacy of treatments for coronavirus disease 2019 (COVID-19) against the historical safety of these treatments as of May 2021. We preselected therapies of interest for COVID-19 based on national guidelines and modified over time. We searched PubMed and Medline for these specific COVID-19 treatments and data related to their efficacy. We also searched for prior randomized controlled trials of each therapy to assess adverse effects, and we obtained the Food and Drug Administration Approval label for this information. Several drugs have been approved for the treatment of COVID-19, and many more are under study. This includes dexamethasone, remdesivir, hydroxychloroquine/chloroquine, lopinvir/ritonavir, interferon or interleukin inhibitors, convalescent plasma and several vitamins and minerals. The strongest evidence for benefit is mortality benefit with dexamethasone in patients with COVID-19 and hypoxemia, although there is a signal of harm if this is started too early. There are several other promising therapies, like interleukin inhibitors and ivermectin. Hydroxychloroquine/chloroquine, lopinvir/ritonavir, and convalescent plasma do not have enough evidence of benefit to outweigh the known risks of these drugs.
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Affiliation(s)
- Joshua Davis
- Department of Emergency Medicine, Vituity, Wichita, KS 67214, United States
| | - Ugochukwu Umeh
- College of Medicine, Medical University of Lublin, Lublin 20-093, Poland
| | - Rand Saba
- Department of Surgery, Ascension Providence Hospital, Southfield, MI 48075, United States
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Rouamba T, Barry H, Ouédraogo E, Tahita MC, Yaméogo NV, Poda A, Diendéré AE, Ouedraogo AS, Valea I, Koné AM, Thiombiano C, Traoré I, Tarnagda Z, Sawadogo SA, Gansané Z, Kambiré Y, Sanou I, Barro-Traoré F, Drabo MK, Tinto H. Safety of Chloroquine or Hydroxychloroquine Plus Azithromycin for the Treatment of COVID-19 Patients in Burkina Faso: An Observational Prospective Cohort Study. Ther Clin Risk Manag 2021; 17:1187-1198. [PMID: 34815671 PMCID: PMC8604637 DOI: 10.2147/tcrm.s330813] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Accepted: 10/31/2021] [Indexed: 12/21/2022] Open
Abstract
INTRODUCTION Though chloroquine derivatives are used in the treatment of coronavirus disease 2019 (COVID-19) in many countries worldwide, doubts remain about the safety and efficacy of these drugs, especially in African communities where published data are scarce. METHODS We conducted an observational prospective cohort study from April 24 to September 03, 2020, in Burkina Faso to assess (as primary outcome) the clinical, biological, and cardiac (electrocardiographic) safety of chloroquine or hydroxychloroquine plus azithromycin administered to COVID-19 patients. The main secondary outcomes were all-cause mortality and median time of viral clearance. RESULTS A total of 153 patients were enrolled and followed for 21 days. Among patients who took at least one dose of chloroquine or hydroxychloroquine (90.1% [138/153]), few clinical adverse events were reported and were mainly rash/pruritus, diarrhea, chest pain, and palpitations. No statistically significant increase in hepatic, renal, and hematological parameters or electrolyte disorders were reported. However, there was a significant increase in the QTc value without exceeding 500ms, especially in those who received chloroquine phosphate. Three adverse events of special interest classified as serious (known from chloroquine derivatives) were recorded namely pruritus, paresthesia, and drowsiness. One case of death occurred. The average onset of SARS-CoV-2 PCR negativity was estimated at 7.0 (95% CI: 5.0-10.0) days. CONCLUSION Hydroxychloroquine appeared to be well tolerated in treated COVID-19 patients in Burkina Faso. In the absence of a robust methodological approach that could generate a high level of scientific evidence, our results could at least contribute to guide health decisions that should be made based on different sources of scientific evidence including those from our study.
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Affiliation(s)
- Toussaint Rouamba
- Institut de Recherche en Sciences de la Santé (CNRST-IRSS), Nanoro, Burkina Faso
| | - Houreratou Barry
- Institut National de Santé Publique, Centre Muraz, Bobo-Dioulasso, Burkina Faso
| | - Esperance Ouédraogo
- Institut de Recherche en Sciences de la Santé (CNRST-IRSS), Nanoro, Burkina Faso
| | | | | | - Armel Poda
- Centre Hospitalier Universitaire Sourou Sanon, Bobo-Dioulasso, Burkina Faso
| | | | | | - Innocent Valea
- Institut de Recherche en Sciences de la Santé (CNRST-IRSS), Nanoro, Burkina Faso
| | - Amariane M Koné
- Institut National de Santé Publique, Centre Muraz, Bobo-Dioulasso, Burkina Faso
| | | | - Isidore Traoré
- Institut National de Santé Publique, Centre Muraz, Bobo-Dioulasso, Burkina Faso
| | - Zekiba Tarnagda
- Institut de Recherche en Sciences de la Santé (CNRST-IRSS), Nanoro, Burkina Faso
| | - Serge A Sawadogo
- Centre PrïmO Nelson Mandela (Promotion de la Recherche et de l’Innovation en Immunologie Médicale de Ouagadougou), Ouagadougou, Burkina Faso
| | - Zakaria Gansané
- Clinical Monitoring in Africa-Clinical Research Organization, Ouagadougou, Burkina Faso
| | - Yibar Kambiré
- Centre Hospitalier Universitaire de Tengandogo, Ouagadougou, Burkina Faso
| | - Idrissa Sanou
- Centre Hospitalier Universitaire de Tengandogo, Ouagadougou, Burkina Faso
| | - Fatou Barro-Traoré
- Centre Hospitalier Universitaire de Tengandogo, Ouagadougou, Burkina Faso
| | - Maxime K Drabo
- Institut de Recherche en Sciences de la Santé (CNRST-IRSS), Nanoro, Burkina Faso
| | - Halidou Tinto
- Institut de Recherche en Sciences de la Santé (CNRST-IRSS), Nanoro, Burkina Faso
| | - On behalf of the CHLORAZ Study Group
- Institut de Recherche en Sciences de la Santé (CNRST-IRSS), Nanoro, Burkina Faso
- Institut National de Santé Publique, Centre Muraz, Bobo-Dioulasso, Burkina Faso
- Centre Hospitalier Universitaire Yalgado Ouédraogo, Ouagadougou, Burkina Faso
- Centre Hospitalier Universitaire Sourou Sanon, Bobo-Dioulasso, Burkina Faso
- Centre Hospitalier Universitaire de Bogodogo, Ouagadougou, Burkina Faso
- Centre PrïmO Nelson Mandela (Promotion de la Recherche et de l’Innovation en Immunologie Médicale de Ouagadougou), Ouagadougou, Burkina Faso
- Clinical Monitoring in Africa-Clinical Research Organization, Ouagadougou, Burkina Faso
- Centre Hospitalier Universitaire de Tengandogo, Ouagadougou, Burkina Faso
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Human carboxylesterase 1A plays a predominant role in the hydrolytic activation of remdesivir in humans. Chem Biol Interact 2021; 351:109744. [PMID: 34774545 DOI: 10.1016/j.cbi.2021.109744] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2021] [Revised: 10/12/2021] [Accepted: 11/09/2021] [Indexed: 11/23/2022]
Abstract
Remdesivir, an intravenous nucleotide prodrug, has been approved for treating COVID-19 in hospitalized adults and pediatric patients. Upon administration, remdesivir can be readily hydrolyzed to form its active form GS-441524, while the cleavage of the carboxylic ester into GS-704277 is the first step for remdesivir activation. This study aims to assign the key enzymes responsible for remdesivir hydrolysis in humans, as well as to investigate the kinetics of remdesivir hydrolysis in various enzyme sources. The results showed that remdesivir could be hydrolyzed to form GS-704277 in human plasma and the microsomes from human liver (HLMs), lung (HLuMs) and kidney (HKMs), while the hydrolytic rate of remdesivir in HLMs was the fastest. Chemical inhibition and reaction phenotyping assays suggested that human carboxylesterase 1 (hCES1A) played a predominant role in remdesivir hydrolysis, while cathepsin A (CTSA), acetylcholinesterase (AchE) and butyrylcholinesterase (BchE) contributed to a lesser extent. Enzymatic kinetic analyses demonstrated that remdesivir hydrolysis in hCES1A (SHUTCM) and HLMs showed similar kinetic plots and much closed Km values to each other. Meanwhile, GS-704277 formation rates were strongly correlated with the CES1A activities in HLM samples from different individual donors. Further investigation revealed that simvastatin (a therapeutic agent for adjuvant treating COVID-19) strongly inhibited remdesivir hydrolysis in both recombinant hCES1A and HLMs. Collectively, our findings reveal that hCES1A plays a predominant role in remdesivir hydrolysis in humans, which are very helpful for predicting inter-individual variability in response to remdesivir and for guiding the rational use of this anti-COVID-19 agent in clinical settings.
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Masiá M, Padilla S, García JA, García-Abellán J, Navarro A, Guillén L, Telenti G, Mascarell P, Botella Á, Gutiérrez F. Impact of the Addition of Baricitinib to Standard of Care Including Tocilizumab and Corticosteroids on Mortality and Safety in Severe COVID-19. Front Med (Lausanne) 2021; 8:749657. [PMID: 34820393 PMCID: PMC8606519 DOI: 10.3389/fmed.2021.749657] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Accepted: 10/04/2021] [Indexed: 12/15/2022] Open
Abstract
Background: Baricitinib is a Janus kinase (JAK) inhibitor with a broader anti-inflammatory activity than tocilizumab and an antiviral potential although no head-to-head trials are available. The benefits of adding baricitinib to patients with COVID-19 experiencing clinical progression despite the standard of care (SOC), including corticosteroids and tocilizumab, are also unknown. Methods: A cohort study included microbiologically confirmed COVID-19 hospitalizations. The primary outcome was 28-day mortality. Secondary outcomes were 60- and 90-day mortality, the composite outcome "28-day invasive mechanical ventilation (IMV) or death" and the safety of the combination. Propensity score (PS) matching was used to identify the association between baricitinib use and the outcomes of interest. Results: Of 1,709 admissions, 994 patients received corticosteroids and tocilizumab and 110 of them received baricitinib after tocilizumab. PS matched 190 (95:95) patients with baricitinib + SOC vs. SOC, of whom 69.5% received remdesivir. No significant effect of baricitinib was observed on 28-day [39 events; adjusted hazard ratio (aHR), 0.76; 95% CI, 0.31-1.86], 60-day (49 events, aHR, 1.17; 95% CI, 0.55-2.52), or 90-day mortality (49 events; aHR, 1.14; 95% CI, 0.53-2.47), or on the composite outcome 28-day IMV/death (aHR, 0.88; 95% CI, 0.45-1.72). Secondary infections during hospitalization were not different between groups (17.9 vs. 10.5%, respectively; p = 0.212) and thromboembolic events were higher with baricitinib (11.6% vs. 3.2%; p = 0.048), but differences vanished after the adjustment [aHR 1.89 (0.31-11.57), p = 0.490]. Conclusion: The addition of baricitinib did not substantially reduce mortality in hospitalized patients with COVID-19 having clinical progression despite the therapy with tocilizumab and corticosteroids. The combination of baricitinib and tocilizumab was not associated with an increased risk of secondary infections or thromboembolic events.
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Affiliation(s)
- Mar Masiá
- Infectious Diseases Unit, Hospital General Universitario de Elche, Universidad Miguel Hernández, Elche, Spain
| | - Sergio Padilla
- Infectious Diseases Unit, Hospital General Universitario de Elche, Universidad Miguel Hernández, Elche, Spain
| | - José Alberto García
- Infectious Diseases Unit, Hospital General Universitario de Elche, Elche, Spain
| | | | - Andrés Navarro
- Department of Clinical Pharmacy, Hospital General Universitario de Elche, Elche, Spain
| | - Lucía Guillén
- Infectious Diseases Unit, Hospital General Universitario de Elche, Elche, Spain
| | - Guillermo Telenti
- Infectious Diseases Unit, Hospital General Universitario de Elche, Elche, Spain
| | - Paula Mascarell
- Infectious Diseases Unit, Hospital General Universitario de Elche, Elche, Spain
| | - Ángela Botella
- Infectious Diseases Unit, Hospital General Universitario de Elche, Elche, Spain
| | - Félix Gutiérrez
- Infectious Diseases Unit, Hospital General Universitario de Elche, Universidad Miguel Hernández, Elche, Spain
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Watson ME, Inagaki K, Weinberg JB. Severe Acute Respiratory Syndrome Coronavirus 2: Manifestations of Disease and Approaches to Treatment and Prevention in Humans. Comp Med 2021; 71:342-358. [PMID: 34535198 PMCID: PMC8594263 DOI: 10.30802/aalas-cm-21-000011] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Revised: 04/08/2021] [Accepted: 06/14/2021] [Indexed: 12/15/2022]
Abstract
The coronavirus disease 2019 (COVID-19) pandemic was caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This virus has challenged civilization and modern science in ways that few infectious diseases and natural disasters have previously, causing globally significant human morbidity and mortality and triggering economic downturns across financial markets that will be dealt with for generations. Despite this, the pandemic has also brought an opportunity for humanity to come together and participate in a shared scientific investigation. Clinically, SARS-CoV-2 is associated with lower mortality rates than other recently emerged coronaviruses, such as SARS-CoV and the Middle East respiratory syndrome coronavirus (MERS-CoV). However, SARS-CoV-2 exhibits efficient human-to-human spread, with transmission often occurring before symptom recognition; this feature averts containment strategies that had worked previ- ously for SARS-CoV and MERS-CoV. Severe COVID-19 disease is characterized by dysregulated inflammatory responses associated with pulmonary congestion and intravascular coagulopathy leading to pneumonia, vascular insults, and multiorgan disease. Approaches to treatment have combined supportive care with antivirals, such as remdesivir, with immunomodulatory medications, including corticosteroids and cytokine-blocking antibody therapies; these treatments have advanced rapidly through clinical trials. Innovative approaches to vaccine development have facilitated rapid advances in design, testing, and distribution. Much remains to be learned about SARS-CoV-2 and COVID-19, and further biomedical research is necessary, including comparative medicine studies in animal models. This overview of COVID-19 in humans will highlight important aspects of disease, relevant pathophysiology, underlying immunology, and therapeutics that have been developed to date.
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Key Words
- ards, acute respiratory distress syndrome
- ace2, angiotensin-converting enzyme 2
- covid-19, coronavirus disease 2019
- hcov, human coronavirus
- ifn, interferon
- mers, middle east respiratory syndrome
- mis-c, multisystem inflammatory syndrome in children
- rbd, receptor binding domain
- sars, severe acute respiratory syndrome
- sars-cov-2, severe acute respiratory syndrome coronavirus 2
- s, spike
- tmprss2, type 2 transmembrane serine protease
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Affiliation(s)
- Michael E Watson
- Division of Pediatric Infectious Diseases, Department of Pediatrics, University of Michigan, Ann Arbor, Michigan
| | - Kengo Inagaki
- Division of Pediatric Infectious Diseases, Department of Pediatrics, University of Michigan, Ann Arbor, Michigan
| | - Jason B Weinberg
- Division of Pediatric Infectious Diseases, Department of Pediatrics, University of Michigan, Ann Arbor, Michigan
- Department of Microbiology & Immunology, University of Michigan, Ann Arbor, Michigan
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Iturricastillo G, Ávalos Pérez-Urría E, Couñago F, Landete P. Scientific evidence in the COVID-19 treatment: A comprehensive review. World J Virol 2021; 10:217-228. [PMID: 34631473 PMCID: PMC8474978 DOI: 10.5501/wjv.v10.i5.217] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 05/12/2021] [Accepted: 08/09/2021] [Indexed: 02/06/2023] Open
Abstract
In December 2019, cases of unknown origin pneumonia appeared in Wuhan, China; the causal agent of this pneumonia was a new virus of the coronaviridae family called severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). According to the clinical severity, symptoms and response to the different treatments, the evolution of the disease is divided in three phases. We analysed the most used treatments for coronavirus disease 2019 and the phase in which they are supposed to be effective. In the viral phase, remdesivir has demonstrated reduction in recovery time but no mortality reduction. Other drugs proposed for viral phase such as convalescent plasma and lopinavir/ritonavir did not demonstrate to be effective. In the inflammatory phase, corticosteroids demonstrated reduction of 28-d mortality in patients who needed oxygen, establishing that a corticosteroid regimen should be part of the standard treatment of critically ill patients. There are other immunosuppressive and immunomodulatory treatments such as anakinra, sarilumab, tocilizumab, colchicine or baricitinib that are being studied. Other treatments that were proposed at the beginning, like hydroxichloroquine or azithromycin, demonstrated no efficacy and increased mortality when combined.
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Affiliation(s)
- Gorane Iturricastillo
- Department of Pulmonology, Hospital Universitario de La Princesa, Madrid 28006, Spain
| | | | - Felipe Couñago
- Department of Radiation Oncology, Hospital Universitario Quirónsalud Madrid, Pozuelo de Alarcón 28223, Spain
- Department of Radiation Oncology, Hospital La Luz, Madrid 28003, Spain
- Department of Radiation Oncology Universidad Europea de Madrid, Madrid 28670, Spain
| | - Pedro Landete
- Department of Pulmonology, Hospital Universitario de La Princesa, Madrid 28006, Spain
- Department of Pulmonology, Universidad Autónoma de Madrid, Madrid 28049, Spain
- Department of Pulmonology, Instituto Investigación Princesa, Madrid 28006, Spain
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Qaseem A, Yost J, Etxeandia-Ikobaltzeta I, Abraham GM, Jokela JA, Miller MC, Forciea MA, Humphrey LL, Dunn A, Andrews R, Haeme R, Tschanz MP. Update Alert: Should Remdesivir Be Used for the Treatment of Patients With COVID-19? Rapid, Living Practice Points From the American College of Physicians (Version 2). Ann Intern Med 2021; 174:W66-W67. [PMID: 34251904 PMCID: PMC8297419 DOI: 10.7326/l21-0389] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Affiliation(s)
- Amir Qaseem
- American College of Physicians, Philadelphia, Pennsylvania
| | | | | | - George M Abraham
- Saint Vincent Hospital-Worcester Medical Center, Worcester, Massachusetts
| | - Janet A Jokela
- University of Illinois College of Medicine at Urbana-Champaign, Champaign, Illinois
| | | | | | - Linda L Humphrey
- Portland Veterans Affairs Medical Center and Oregon Health & Science University, Portland, Oregon
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Efficacy of Remdesivir-Containing Therapy in Hospitalized COVID-19 Patients: A Prospective Clinical Experience. J Clin Med 2021; 10:jcm10173784. [PMID: 34501233 PMCID: PMC8432083 DOI: 10.3390/jcm10173784] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Revised: 08/17/2021] [Accepted: 08/23/2021] [Indexed: 02/06/2023] Open
Abstract
Objectives: Remdesivir is currently approved for the treatment of COVID-19. The recommendation for using remdesivir in patients with COVID-19 was based on the in vitro and in vivo activity of this drug against SARS-CoV-2. Methods: This was a prospective observational study conducted on a population of patients hospitalized for COVID-19. The primary endpoint of this study was the impact of remdesivir-containing therapy on 30-day mortality; the secondary endpoint was the impact of remdesivir-containing therapy on the need for high-flow oxygen therapy (HFNC), non-invasive ventilation (NIV), or mechanical ventilation. The data were analyzed after propensity score matching. Results: A total of 407 patients with SARS-CoV-2 pneumonia were consecutively enrolled. Out of these, 294 (72.2%) were treated with remdesivir and 113 (27.8%) were not. Overall, 61 patients (14.9%) were treated during hospitalization with HFNC, NIV, or mechanical ventilation, while 30-day mortality was observed in 21 patients (5.2%). Univariate analysis of patients treated with remdesivir or not showed no differences in 30-day mortality (4% vs. 6%, p = 0.411) in the two study groups. Cox regression analysis, after propensity score matching, showed that therapies, including remdesivir-containing therapy, were not statistically associated with 30-day survival or mortality. The Kaplan–Meier curves of 30-day survival in patients treated with remdesivir or not before (p = 0.24) and after (p = 0.88) propensity score matching showed no differences between the two study groups. Finally, patients treated with remdesivir or not showed the same need for HFNC/NIV or mechanical ventilation. Conclusions: This real-life experience of remdesivir use in hospitalized patients with COVID-19 was not associated with significant increases in rates of survival or reduced use of HFNC/NIV or mechanical ventilation compared with patients treated with other therapies not including remdesivir.
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Ansems K, Grundeis F, Dahms K, Mikolajewska A, Thieme V, Piechotta V, Metzendorf MI, Stegemann M, Benstoem C, Fichtner F. Remdesivir for the treatment of COVID-19. Cochrane Database Syst Rev 2021; 8:CD014962. [PMID: 34350582 PMCID: PMC8406992 DOI: 10.1002/14651858.cd014962] [Citation(s) in RCA: 57] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
BACKGROUND Remdesivir is an antiviral medicine with properties to inhibit viral replication of SARS-CoV-2. Positive results from early studies attracted media attention and led to emergency use authorisation of remdesivir in COVID-19. A thorough understanding of the current evidence regarding the effects of remdesivir as a treatment for SARS-CoV-2 infection based on randomised controlled trials (RCTs) is required. OBJECTIVES To assess the effects of remdesivir compared to placebo or standard care alone on clinical outcomes in hospitalised patients with SARS-CoV-2 infection, and to maintain the currency of the evidence using a living systematic review approach. SEARCH METHODS We searched the Cochrane COVID-19 Study Register (which comprises the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, and medRxiv) as well as Web of Science (Science Citation Index Expanded and Emerging Sources Citation Index) and WHO COVID-19 Global literature on coronavirus disease to identify completed and ongoing studies without language restrictions. We conducted the searches on 16 April 2021. SELECTION CRITERIA We followed standard Cochrane methodology. We included RCTs evaluating remdesivir for the treatment of SARS-CoV-2 infection in hospitalised adults compared to placebo or standard care alone irrespective of disease severity, gender, ethnicity, or setting. We excluded studies that evaluated remdesivir for the treatment of other coronavirus diseases. DATA COLLECTION AND ANALYSIS We followed standard Cochrane methodology. To assess risk of bias in included studies, we used the Cochrane RoB 2 tool for RCTs. We rated the certainty of evidence using the GRADE approach for outcomes that were reported according to our prioritised categories: all-cause mortality at up to day 28, duration to liberation from invasive mechanical ventilation, duration to liberation from supplemental oxygen, new need for mechanical ventilation (high-flow oxygen or non-invasive or invasive mechanical ventilation), new need for invasive mechanical ventilation, new need for non-invasive mechanical ventilation or high-flow oxygen, new need for oxygen by mask or nasal prongs, quality of life, adverse events (any grade), and serious adverse events. MAIN RESULTS We included five RCTs with 7452 participants diagnosed with SARS-CoV-2 infection and a mean age of 59 years, of whom 3886 participants were randomised to receive remdesivir. Most participants required low-flow oxygen (n=4409) or mechanical ventilation (n=1025) at baseline. We identified two ongoing studies, one was suspended due to a lack of COVID-19 patients to recruit. Risk of bias was considered to be of some concerns or high risk for clinical status and safety outcomes because participants who had died did not contribute information to these outcomes. Without adjustment, this leads to an uncertain amount of missing values and the potential for bias due to missing data. Effects of remdesivir in hospitalised individuals Remdesivir probably makes little or no difference to all-cause mortality at up to day 28 (risk ratio (RR) 0.93, 95% confidence interval (CI) 0.81 to 1.06; risk difference (RD) 8 fewer per 1000, 95% CI 21 fewer to 7 more; 4 studies, 7142 participants; moderate-certainty evidence). Considering the initial severity of condition, only one study showed a beneficial effect of remdesivir in patients who received low-flow oxygen at baseline (RR 0.32, 95% CI 0.15 to 0.66, 435 participants), but conflicting results exists from another study, and we were unable to validly assess this observations due to limited availability of comparable data. Remdesivir may have little or no effect on the duration to liberation from invasive mechanical ventilation (2 studies, 1298 participants, data not pooled, low-certainty evidence). We are uncertain whether remdesivir increases or decreases the chance of clinical improvement in terms of duration to liberation from supplemental oxygen at up to day 28 (3 studies, 1691 participants, data not pooled, very low-certainty evidence). We are very uncertain whether remdesivir decreases or increases the risk of clinical worsening in terms of new need for mechanical ventilation at up to day 28 (high-flow oxygen or non-invasive ventilation or invasive mechanical ventilation) (RR 0.78, 95% CI 0.48 to 1.24; RD 29 fewer per 1000, 95% CI 68 fewer to 32 more; 3 studies, 6696 participants; very low-certainty evidence); new need for non-invasive mechanical ventilation or high-flow oxygen (RR 0.70, 95% CI 0.51 to 0.98; RD 72 fewer per 1000, 95% CI 118 fewer to 5 fewer; 1 study, 573 participants; very low-certainty evidence); and new need for oxygen by mask or nasal prongs (RR 0.81, 95% CI 0.54 to 1.22; RD 84 fewer per 1000, 95% CI 204 fewer to 98 more; 1 study, 138 participants; very low-certainty evidence). The evidence suggests that remdesivir may decrease the risk of clinical worsening in terms of new need for invasive mechanical ventilation (67 fewer participants amongst 1000 participants; RR 0.56, 95% CI 0.41 to 0.77; 2 studies, 1159 participants; low-certainty evidence). None of the included studies reported quality of life. Remdesivir probably decreases the serious adverse events rate at up to 28 days (RR 0.75, 95% CI 0.63 to 0.90; RD 63 fewer per 1000, 95% CI 94 fewer to 25 fewer; 3 studies, 1674 participants; moderate-certainty evidence). We are very uncertain whether remdesivir increases or decreases adverse events rate (any grade) (RR 1.05, 95% CI 0.86 to 1.27; RD 29 more per 1000, 95% CI 82 fewer to 158 more; 3 studies, 1674 participants; very low-certainty evidence). AUTHORS' CONCLUSIONS Based on the currently available evidence, we are moderately certain that remdesivir probably has little or no effect on all-cause mortality at up to day 28 in hospitalised adults with SARS-CoV-2 infection. We are uncertain about the effects of remdesivir on clinical improvement and worsening. There were insufficient data available to validly examine the effect of remdesivir on mortality in subgroups depending on the extent of respiratory support at baseline. Future studies should provide additional data on efficacy and safety of remdesivir for defined core outcomes in COVID-19 research, especially for different population subgroups. This could allow us to draw more reliable conclusions on the potential benefits and harms of remdesivir in future updates of this review. Due to the living approach of this work, we will update the review periodically.
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Affiliation(s)
- Kelly Ansems
- Department of Intensive Care Medicine, Medical Faculty, RWTH Aachen University, Aachen, Germany
| | - Felicitas Grundeis
- Department of Anesthesiology and Intensive Care, University of Leipzig, Leipzig, Germany
| | - Karolina Dahms
- Department of Intensive Care Medicine, Medical Faculty, RWTH Aachen University, Aachen, Germany
| | - Agata Mikolajewska
- Department of Infectious Diseases and Respiratory Medicine, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Volker Thieme
- Department of Anaesthesiology and Intensive Care, University of Leipzig Medical Center, Leipzig, Germany
| | - Vanessa Piechotta
- Cochrane Haematology, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Maria-Inti Metzendorf
- Cochrane Metabolic and Endocrine Disorders Group, Institute of General Practice, Medical Faculty of the Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
| | - Miriam Stegemann
- Department of Infectious Diseases and Respiratory Medicine, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Carina Benstoem
- Department of Intensive Care Medicine, Medical Faculty, RWTH Aachen University, Aachen, Germany
| | - Falk Fichtner
- Department of Anaesthesiology and Intensive Care, University of Leipzig Medical Center, Leipzig, Germany
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Abou Hassan OK, Sheng CC, Wang TKM, Cremer PC. SARS-CoV-2 Myocarditis: Insights Into Incidence, Prognosis, and Therapeutic Implications. Curr Cardiol Rep 2021; 23:129. [PMID: 34342728 PMCID: PMC8330199 DOI: 10.1007/s11886-021-01551-x] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/11/2021] [Indexed: 12/16/2022]
Abstract
PURPOSE OF REVIEW In coronavirus disease 2019 (COVID-19), myocardial injury occurs frequently in severe or critically ill hospitalized patients, yet myocarditis is much less common. In this context, revisiting the definition of myocarditis is appropriate with a specific focus on diagnostic and management considerations in patients infected with SARS-CoV-2. RECENT FINDINGS Pathologic cardiac specimens from patients with COVID-19 suggest a mixed inflammatory response involving lymphocytes and macrophages, and importantly, cellular injury occurs predominantly at the level of pericytes and endothelial cells, less often involving direct myocyte necrosis. In COVID-19, the diagnosis of myocarditis has understandably been based predominantly on clinical criteria, and the number of patients with clinically suspected myocarditis who would meet diagnostic histological criteria is unclear. Echocardiography and cardiac magnetic resonance are important diagnostic tools, although the prognostic implications of abnormalities are still being defined. Importantly, SARS-CoV2 myocarditis should be diagnosed within an appropriate clinical context and should not be based on isolated imaging findings. Therapies in COVID-19 have focused on the major clinical manifestation of pneumonia, but the promotion of viral clearance early in the disease could prevent the development of myocarditis, and further study of immunosuppressive therapies once myocarditis has developed are indicated. A strict and uniform approach is needed to diagnose myocarditis due to SARS-CoV-2 to better understand the natural history of this disease and to facilitate evaluation of potential therapeutic interventions. A methodological approach will also better inform the incidence of COVID-19 associated myocarditis and potential long-term health effects.
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Affiliation(s)
- Ossama K. Abou Hassan
- Section of Cardiovascular Imaging, Robert and Suzanne Tomsich Department of Cardiovascular Medicine, Sydell and Arnold Miller Family Heart and Vascular Institute, Cleveland Clinic, Cleveland, OH 44195 USA
| | - Calvin C. Sheng
- Section of Cardiovascular Imaging, Robert and Suzanne Tomsich Department of Cardiovascular Medicine, Sydell and Arnold Miller Family Heart and Vascular Institute, Cleveland Clinic, Cleveland, OH 44195 USA
| | - Tom Kai Ming Wang
- Section of Cardiovascular Imaging, Robert and Suzanne Tomsich Department of Cardiovascular Medicine, Sydell and Arnold Miller Family Heart and Vascular Institute, Cleveland Clinic, Cleveland, OH 44195 USA
| | - Paul C. Cremer
- Section of Cardiovascular Imaging, Robert and Suzanne Tomsich Department of Cardiovascular Medicine, Sydell and Arnold Miller Family Heart and Vascular Institute, Cleveland Clinic, Cleveland, OH 44195 USA
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Konwar M, Maurya M, Bose D. A Meta-Analysis of Safety of Different Regimens of Remdesivir in COVID-19 Patients. Curr Drug Saf 2021; 17:158-167. [PMID: 34323191 DOI: 10.2174/1574886316666210728110330] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2020] [Revised: 05/21/2021] [Accepted: 06/01/2021] [Indexed: 11/22/2022]
Abstract
Remdesivir is an adenosine analogue drug that targets RNA dependent RNA polymerase enzyme and inhibits the viral replication. As on 22nd of October 2020, US FDA fully approved drug Remdesivir for the treatment of COVID-19 patients who requires hospitalisation. Many clinical studies reported the derangement in hepatic and renal function tests which is alarming considering the health conditions of the COVID-19 patients. In view of these results, the present study was envisaged to review the safety of Remdesivir in COVID-19 patients. The PubMed, Embase and Cochrane databases was searched using 'Remdesivir', 'veklury', 'SARS' and 'COVID' till 1st of December 2020. The studies included in this meta-analysis were either randomised or non-randomised studies that evaluated Remdesivir for the treatment of COVID-19 against Placebo [standard of care]. The Adverse events [AEs], Serious adverse events [SAEs] and Treatment Discontinuation due to Adverse Events (TDAE) was used as primary outcome measures. The quality of studies was evaluated by using the Cochrane Collaboration's tool for assessment of RoB. Data analysis was performed by two authors (MK & DB) using statistical software Review manager [Revman] version 5.3. The pooled Risk Ratios (RR) and 95% Confidence Intervals (CI) were calculated by using a random-effects model for both primary and secondary outcomes. A total of four RCTs were included for the meta-analysis. Out of the four included clinical trials accepted for its methodological quality, three were of excellent quality and one study was of moderate quality. The pooled estimates of the three studies showed that Remdesivir had 24% lower risk of SAEs compared to placebo arm. However, the pooled estimates of two studies showed that 10 days of Remdesivir had 56% higher risk of SAEs compared to 5 days of Remdesivir regimen. Similarly, the 10 days of Remdesivir had two times higher risk of TDAEs compared to 5 days Remdesivir regimen. In conclusion, our meta-analysis demonstrated that Remdesivir is a safe therapeutic option. Our metanalysis revealed 5 days' regimen have better safety profile than 10 days' regimen of drug Remdesivir with respect to SAEs and TDAEs. For hospitalized patients, a 5-day course could be preferable with fewer safety concerns and lower drug costs.
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Affiliation(s)
- Mahanjit Konwar
- Department of Clinical Pharmacology, Seth GS Medical College & KEM Hospital, Parel-400 012, Mumbai, Maharashtra, India
| | - Miteshkumar Maurya
- Department of Clinical Pharmacology, Seth GS Medical College & KEM Hospital, Parel-400 012, Mumbai, Maharashtra, India
| | - Debdipta Bose
- Department of Clinical Pharmacology, Seth GS Medical College & KEM Hospital, Parel-400 012, Mumbai, Maharashtra, India
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Nassar M, Nso N, Alfishawy M, Novikov A, Yaghi S, Medina L, Toz B, Lakhdar S, Idrees Z, Kim Y, Gurung DO, Siddiqui RS, Zheng D, Agladze M, Sumbly V, Sandhu J, Castillo FC, Chowdhury N, Kondaveeti R, Bhuiyan S, Perez LG, Ranat R, Gonzalez C, Bhangoo H, Williams J, Osman AE, Kong J, Ariyaratnam J, Mohamed M, Omran I, Lopez M, Nyabera A, Landry I, Iqbal S, Gondal AZ, Hassan S, Daoud A, Baraka B, Trandafirescu T, Rizzo V. Current systematic reviews and meta-analyses of COVID-19. World J Virol 2021; 10:182-208. [PMID: 34367933 PMCID: PMC8316876 DOI: 10.5501/wjv.v10.i4.182] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Revised: 04/13/2021] [Accepted: 06/03/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Coronavirus disease 2019 (COVID-19) has left a significant impact on the world's health, economic and political systems; as of November 20, 2020, more than 57 million people have been infected worldwide, with over 1.3 million deaths. While the global spotlight is currently focused on combating this pandemic through means ranging from finding a treatment among existing therapeutic agents to inventing a vaccine that can aid in halting the further loss of life.
AIM To collect all systematic reviews and meta-analyses published related to COVID-19 to better identify available evidence, highlight gaps in knowledge, and elucidate further meta-analyses and umbrella reviews that are yet to be performed.
METHODS We explored studies based on systematic reviews and meta-analyses with the key-terms, including severe acute respiratory syndrome (SARS), SARS virus, coronavirus disease, COVID-19, and SARS coronavirus-2. The included studies were extracted from Embase, Medline, and Cochrane databases. The publication timeframe of included studies ranged between January 01, 2020, to October 30, 2020. Studies that were published in languages other than English were not considered for this systematic review. The finalized full-text articles are freely accessible in the public domain.
RESULTS Searching Embase, Medline, and Cochrane databases resulted in 1906, 669, and 19 results, respectively, that comprised 2594 studies. 515 duplicates were subsequently removed, leaving 2079 studies. The inclusion criteria were systematic reviews or meta-analyses. 860 results were excluded for being a review article, scope review, rapid review, panel review, or guideline that produced a total of 1219 studies. After screening articles were categorized, the included articles were put into main groups of clinical presentation, epidemiology, screening and diagnosis, severity assessment, special populations, and treatment. Subsequently, there was a second subclassification into the following groups: gastrointestinal, cardiovascular, neurological, stroke, thrombosis, anosmia and dysgeusia, ocular manifestations, nephrology, cutaneous manifestations, D-dimer, lymphocyte, anticoagulation, antivirals, convalescent plasma, immunosuppressants, corticosteroids, hydroxychloroquine, renin-angiotensin-aldosterone system, technology, diabetes mellitus, obesity, pregnancy, children, mental health, smoking, cancer, and transplant.
CONCLUSION Among the included articles, it is clear that further research is needed regarding treatment options and vaccines. With more studies, data will be less heterogeneous, and statistical analysis can be better applied to provide more robust clinical evidence. This study was not designed to give recommendations regarding the management of COVID-19.
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Affiliation(s)
- Mahmoud Nassar
- Department of Internal Medicine, Icahn School of Medicine at Mount Sinai/NYC H&H Queens, New York, NY 11432, United States
| | - Nso Nso
- Department of Internal Medicine, Icahn School of Medicine at Mount Sinai/NYC H&H Queens, New York, NY 11432, United States
| | - Mostafa Alfishawy
- Department of Infectious Diseases, Infectious Diseases Consultants and Academic Researchers of Egypt (IDCARE), Cairo 11221, Outside of the US, Egypt
| | - Anastasia Novikov
- Department of Internal Medicine, Icahn School of Medicine at Mount Sinai/NYC H&H Queens, New York, NY 11432, United States
| | - Salim Yaghi
- Department of Internal Medicine, Icahn School of Medicine at Mount Sinai/NYC H&H Queens, New York, NY 11432, United States
| | - Luis Medina
- Department of Internal Medicine, Icahn School of Medicine at Mount Sinai/NYC H&H Queens, New York, NY 11432, United States
| | - Bahtiyar Toz
- Department of Internal Medicine, Icahn School of Medicine at Mount Sinai/NYC H&H Queens, New York, NY 11432, United States
| | - Sofia Lakhdar
- Department of Internal Medicine, Icahn School of Medicine at Mount Sinai/NYC H&H Queens, New York, NY 11432, United States
| | - Zarwa Idrees
- Department of Internal Medicine, Icahn School of Medicine at Mount Sinai/NYC H&H Queens, New York, NY 11432, United States
| | - Yungmin Kim
- Department of Internal Medicine, Icahn School of Medicine at Mount Sinai/NYC H&H Queens, New York, NY 11432, United States
| | - Dawa Ongyal Gurung
- Department of Internal Medicine, Icahn School of Medicine at Mount Sinai/NYC H&H Queens, New York, NY 11432, United States
| | - Raheel S Siddiqui
- Department of Internal Medicine, Icahn School of Medicine at Mount Sinai/NYC H&H Queens, New York, NY 11432, United States
| | - David Zheng
- Department of Internal Medicine, Icahn School of Medicine at Mount Sinai/NYC H&H Queens, New York, NY 11432, United States
| | - Mariam Agladze
- Department of Internal Medicine, Icahn School of Medicine at Mount Sinai/NYC H&H Queens, New York, NY 11432, United States
| | - Vikram Sumbly
- Department of Internal Medicine, Icahn School of Medicine at Mount Sinai/NYC H&H Queens, New York, NY 11432, United States
| | - Jasmine Sandhu
- Department of Internal Medicine, Icahn School of Medicine at Mount Sinai/NYC H&H Queens, New York, NY 11432, United States
| | - Francisco Cuevas Castillo
- Department of Internal Medicine, Icahn School of Medicine at Mount Sinai/NYC H&H Queens, New York, NY 11432, United States
| | - Nadya Chowdhury
- Department of Internal Medicine, Icahn School of Medicine at Mount Sinai/NYC H&H Queens, New York, NY 11432, United States
| | - Ravali Kondaveeti
- Department of Internal Medicine, Icahn School of Medicine at Mount Sinai/NYC H&H Queens, New York, NY 11432, United States
| | - Sakil Bhuiyan
- Department of Internal Medicine, Icahn School of Medicine at Mount Sinai/NYC H&H Queens, New York, NY 11432, United States
| | - Laura Guzman Perez
- Department of Internal Medicine, Icahn School of Medicine at Mount Sinai/NYC H&H Queens, New York, NY 11432, United States
| | - Riki Ranat
- Department of Internal Medicine, Icahn School of Medicine at Mount Sinai/NYC H&H Queens, New York, NY 11432, United States
| | - Carlos Gonzalez
- Department of Internal Medicine, Icahn School of Medicine at Mount Sinai/NYC H&H Queens, New York, NY 11432, United States
| | - Harangad Bhangoo
- Department of Internal Medicine, Icahn School of Medicine at Mount Sinai/NYC H&H Queens, New York, NY 11432, United States
| | - John Williams
- Department of Internal Medicine, Icahn School of Medicine at Mount Sinai/NYC H&H Queens, New York, NY 11432, United States
| | - Alaa Eldin Osman
- Department of Internal Medicine, Icahn School of Medicine at Mount Sinai/NYC H&H Queens, New York, NY 11432, United States
| | - Joyce Kong
- Department of Internal Medicine, Icahn School of Medicine at Mount Sinai/NYC H&H Queens, New York, NY 11432, United States
| | - Jonathan Ariyaratnam
- Department of Internal Medicine, Icahn School of Medicine at Mount Sinai/NYC H&H Queens, New York, NY 11432, United States
| | - Mahmoud Mohamed
- Department of Medicine, Division of Nephrology, University of Tennessee Health Science Center, Knoxville City, TN 38103, United States
| | - Ismail Omran
- Department of Internal Medicine, Icahn School of Medicine at Mount Sinai/NYC H&H Queens, New York, NY 11432, United States
| | - Mariely Lopez
- Department of Medical, St. George's University, West Indies 38901, Grenada
| | - Akwe Nyabera
- Department of Internal Medicine, Icahn School of Medicine at Mount Sinai/NYC H&H Queens, New York, NY 11432, United States
| | - Ian Landry
- Department of Internal Medicine, Icahn School of Medicine at Mount Sinai/NYC H&H Queens, New York, NY 11432, United States
| | - Saba Iqbal
- Department of Internal Medicine, Icahn School of Medicine at Mount Sinai/NYC H&H Queens, New York, NY 11432, United States
| | - Anoosh Zafar Gondal
- Department of Internal Medicine, Icahn School of Medicine at Mount Sinai/NYC H&H Queens, New York, NY 11432, United States
| | - Sameen Hassan
- Department of Internal Medicine, Icahn School of Medicine at Mount Sinai/NYC H&H Queens, New York, NY 11432, United States
| | - Ahmed Daoud
- Department of Internal Medicine, Faculty of Medicine, Cairo University, Cairo 11221, Egypt
| | - Bahaaeldin Baraka
- Department of Oncology, Broomfiled Hospital, Mid and South Essex NHS Foundation Trust, ESSEX, Chelmsford 12422, United Kingdom
| | - Theo Trandafirescu
- Department of Critical Care Unit, Icahn School of Medicine at Mount Sinai/NYC H&H Queens, New York, NY 11432, United States
| | - Vincent Rizzo
- Department of Internal Medicine, Icahn School of Medicine at Mount Sinai/NYC H&H Queens, New York, NY 11432, United States
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Affiliation(s)
- Anjum S Kaka
- Minneapolis VA Health Care System and University of Minnesota School of Medicine, Minneapolis, Minnesota
| | | | | | - Timothy J Wilt
- Minneapolis VA Health Care System and University of Minnesota School of Medicine, Minneapolis, Minnesota
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