| Reference | 1. West J Emerg Med. 2020 May 20;21(4):737-741. doi: 10.5811/westjem.2020.5.47658.<br />
Remdesivir for the Treatment of COVID-19: A Systematic Review of the Literature.<br />
Musa A(1)(2), Pendi K(3), Hashemi A(4), Warbasse E(1), Kouyoumjian S(5), Yousif J(1), Blodget E(6), Stevens S(1), Aly B(1), Baron DA(7).<br />
Author information: (1)Wayne State University School of Medicine, Detroit, Michigan. (2)Musa Biomedical Consulting, Anaheim, California. (3)Southern California University of Health Sciences, School of Professional Studies, Whittier, California. (4)William Carey University, College of Osteopathic Medicine, Hattiesburg, Mississippi. (5)Wayne State University School of Medicine, Department of Emergency Medicine, Detroit, Michigan. (6)University of Southern California Keck School of Medicine, Division of Infectious Diseases, Department of Medicine, Los Angeles, California. (7)Western University of Health Sciences, Office of the Provost, Pomona, California.<br />
In March 2020, the World Health Organization declared the spread of SARS-CoV-2 a global pandemic. To date, coronavirus disease-2019 (COVID-19) has spread to over 200 countries, leading to over 1.6 million cases and over 99,000 deaths. Given that there is neither a vaccine nor proven treatment for COVID-19, there is currently an urgent need for effective pharmacotherapy. To address the need for an effective treatment of SARS-CoV-2 during the worldwide pandemic, this systematic review of intravenous (IV) remdesivir was performed. Remdesivir, an anti-viral prodrug originally developed to treat Ebola virus disease, has shown broad spectrum activity against the Coronavirus family. A recent case report reported improvement of clinical symptoms with remdesivir in a patient with COVID-19. After conducting a systematic search of 18 clinical trial registries and three large scientific databases, we identified 86 potentially eligible items. Following removal of duplicates (n = 21), eligible studies were reviewed independently by two authors. After the first round of screening, inter-rater agreement was 98.5% (κ = 0.925). After the second round of full-text screening, inter-rater agreement was 100%. A total of seven ongoing and recruiting clinical trials of remdesivir (100-200 milligrams, intravenous [IV]) were included. We identified the following primary outcomes: patients discharged (n = 2); time to clinical status improvement (n = 2); improved O2 saturation (n = 2); body temperature normalization (n = 2); and clinical status (n = 1). Secondary outcomes in all identified studies included documentation of adverse events. Phase 3 trials are expected to be completed between April 2020-2023. Therefore, despite supportive data from in vitro and in vivo studies, the clinical effectiveness of IV remdesivir for treatment of COVID-19 and potential side effects remain incompletely defined in the human population.<br />
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2. Ann Intern Med. 2020 Oct 5. doi: 10.7326/M20-5752. Online ahead of print.<br />
Remdesivir for Adults With COVID-19 : A Living Systematic Review for an American College of Physicians Practice Points.<br />
Wilt TJ(1), Kaka AS(2), MacDonald R(3), Greer N(3), Obley A(4), Duan-Porter W(5).<br />
Author information:<br />
(1)Minneapolis VA Evidence Synthesis Program, Center for Care Delivery and Outcomes Research, and University of Minnesota School of Medicine, Minneapolis, Minnesota (T.J.W.). (2)Minneapolis VA Section of Infectious Diseases and University of Minnesota School of Medicine, Minneapolis, Minnesota (A.S.K.). (3)Minneapolis VA Evidence Synthesis Program, Center for Care Delivery and Outcomes Research, Minneapolis, Minnesota (R.M., N.G.). (4)VA Portland Health Care System and Oregon Health & Science University School of Medicine, Portland, Oregon (A.O.). (5)Minneapolis VA Evidence Synthesis Program, Center for Care Delivery and Outcomes Research and University of Minnesota School of Medicine, Minneapolis, Minnesota (W.D.).<br />
BACKGROUND: Few treatments exist for coronavirus disease 2019 (COVID-19). PURPOSE: To evaluate the effectiveness and harms of remdesivir for COVID-19. DATA SOURCES: Several databases, tables of contents of journals, and U.S. Food and Drug Administration and company websites were searched from 1 January through 31 August 2020.<br />
STUDY SELECTION: English-language, randomized trials of remdesivir treatments for adults with suspected or confirmed COVID-19. New evidence will be incorporated using living review methods.<br />
DATA EXTRACTION: Single-reviewer abstraction and risk-of-bias assessment verified by a second reviewer; GRADE (Grading of Recommendations Assessment, Development and Evaluation) methods used for certainty-of-evidence assessments. DATA SYNTHESIS: Four randomized trials were included. In adults with severe COVID-19, remdesivir compared with placebo probably improves recovery by a large amount (absolute risk difference [ARD] range, 7% to 10%) and may result in a small reduction in mortality (ARD range, -4% to 1%) and a shorter time to recovery or clinical improvement. Remdesivir may have little to no effect on hospital length of stay. Remdesivir probably reduces serious adverse events by a moderate amount (ARD range, -6% to -8%). Compared with a 10-day remdesivir course, a 5-day course may reduce mortality, increase recovery or clinical improvement by small to moderate amounts, reduce time to recovery, and reduce serious adverse events among hospitalized patients not requiring mechanical ventilation. Recovery due to remdesivir may not vary by age, sex, symptom duration, or disease severity.<br />
LIMITATIONS: Low-certainty evidence with few published trials, including 1 preliminary report and 2 open-label trials. Trials excluded pregnant women and adults with severe kidney or liver disease.<br />
CONCLUSION: In hospitalized adults with COVID-19, remdesivir probably improves recovery and reduces serious adverse events and may reduce mortality and time to clinical improvement. For adults not receiving mechanical ventilation or extracorporeal membrane oxygenation, a 5-day course of remdesivir may provide similar benefits to and fewer harms than a 10-day course.<br />
PRIMARY FUNDING SOURCE: U.S. Department of Veterans Affairs, Veterans Health Administration Office of Research and Development, Health Services Research and Development Service, and Evidence Synthesis Program.<br />
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3. Clin Epidemiol Glob Health. 2020 Aug 7. doi: 10.1016/j.cegh.2020.07.011. Online ahead of print.<br />
Remdesivir and its antiviral activity against COVID-19: A systematic review.<br />
Frediansyah A(1)(2), Nainu F(3), Dhama K(4), Mudatsir M(5)(6)(7), Harapan H(5)(6)(7).<br />
Author information:<br />
(1)Research Division for Natural Product Technology (BPTBA), Indonesian Institute of Sciences (LIPI), Wonosari, 55861, Indonesia. (2)Department of Pharmaceutical Biology, Pharmaceutical Institute, University of Tübingen, Tübingen, 72076, Germany. (3)Faculty of Pharmacy, Hasanuddin University, Tamalanrea, Makassar, 90245, Indonesia. (4)Division of Pathology, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, 243122, Uttar Pradesh, India. (5)Medical Research Unit, School of Medicine, Universitas Syiah Kuala, Banda Aceh, 23111, Indonesia. (6)Tropical Disease Centre, School of Medicine, Universitas Syiah Kuala, Banda Aceh, 23111, Indonesia. (7)Department of Microbiology, School of Medicine, Universitas Syiah Kuala, Banda Aceh, 23111, Indonesia.<br />
BACKGROUND: The aim of this study was to summarize the antiviral activities of remdesivir against SARS-CoV-2, the causative agent of COVID-19. METHODS: Available publications were systematically explored on some databases and gray literature was examined. Publications were discussed narratively. RESULTS: Remdesivir inhibits SARS-CoV-2 replication, reduces viral load, and exerts protective effects in SARS-CoV-2 infected animals. Remdesivir also reduces the pathological process, alleviates mild symptoms, and improves pulmonary lesions in SARS-CoV-2-infecetd animals. Remdesivir has been used as a compassionate drug for treating COVID-19 patients.<br />
CONCLUSION: Although remdesivir has shown potent antiviral activities, more efficacy assessments are urgently warranted in clinical trials.<br />
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