Efficacy of antiviral therapies for COVID-19: a systematic review of randomized controlled trials

(2022) 22:107 Vegivinti et al. BMC Infectious Diseases https://doi.org/10.1186/s12879-022-07068-0 Open Access RESEARCH Efficacy of antiviral therapies for COVID‑19: a systematic review of randomized controlled trials Charan Thej Reddy Vegivinti1, Kirk W. Evanson2, Hannah Lyons3,4, Izzet Akosman3,10, Averi Barrett3, Nicole Hardy3, Bernadette Kane2, Praneeth Reddy Keesari5, Yashwitha Sai Pulakurthi5, Erin Sheffels2*, Prasanth Balasubramanian1, Richa Chibbar6, Spandana Chittajallu7, Kathryn Cowie3, J. Karon3, Lauren Siegel3, Ranita Tarchand3, Caleb Zinn3, Nitin Gupta8,9, Kevin M. Kallmes3, Kavitha Saravu8,9 and Jillienne Touchette2 Abstract Background: Coronavirus disease 2019 (COVID-19) continues to pose a significant threat to public health worldwide. The purpose of this study was to review current evidence obtained from randomized clinical trials on the efficacy of antivirals for COVID-19 treatment. Methods: A systematic literature search was performed using PubMed to identify randomized controlled trials published up to September 4, 2021 that examined the efficacy of antivirals for COVID-19 treatment. Studies that were not randomized controlled trials or that did not include treatment of COVID-19 with approved antivirals were excluded. Risk of bias was assessed using the Scottish Intercollegiate Guidelines Network (SIGN) method. Due to study heterogeneity, inferential statistics were not performed and data were expressed as descriptive statistics. Results: Of the 2,284 articles retrieved, 31 (12,440 patients) articles were included. Overall, antivirals were more effective when administered early in the disease course. No antiviral treatment demonstrated efficacy at reducing COVID19 mortality. Sofosbuvir/daclatasvir results suggested clinical improvement, although statistical power was low. Remdesivir exhibited efficacy in reducing time to recovery, but results were inconsistent across trials. Conclusions: Although select antivirals have exhibited efficacy to improve clinical outcomes in COVID-19 patients, none demonstrated efficacy in reducing mortality. Larger RCTs are needed to conclusively establish efficacy. Keywords: Systematic review, COVID-19, Antiviral, SARS-CoV-2, Therapeutic, Randomized controlled trial Background Coronavirus disease 2019 (COVID-19) continues to present a significant challenge to healthcare systems worldwide, with approximately 269 million confirmed cases of the disease that have led to 5.3 million deaths as of December 12, 2021 [1]. COVID-19 develops from a viral *Correspondence: 2 Superior Medical Experts, 1425 Minnehaha Ave E, P.O. Box 6000545, St Paul, MN 55106, USA Full list of author information is available at the end of the article infection, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which can elicit exaggerated immune and inflammatory responses if the infection progresses [2]. As such, there are a wide variety of therapeutic strategies that have been used to treat the disease at various stages, including antiviral, antiretroviral, antimalarial, anti-inflammatory, corticosteroid, immunomodulatory, and immunoglobulin therapies [3]. Research on drug therapies for COVID-19 has relied heavily on results obtained from observational studies, many of which contain biases resulting from © The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativeco mmons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Vegivinti et al. BMC Infectious Diseases (2022) 22:107 demographical differences, patient/disease heterogeneity, differences in institutional practices and standards, and differences in healthcare infrastructure and financial support. As a result of the substantial heterogeneity across studies, a consensus on COVID-19 therapies has remained elusive. Antiviral drugs, such as remdesivir, represent promising drug candidates to attenuate viral and disease progression. Although there have been comprehensive presentations of outcomes associated with antiviral treatments for COVID-19 obtained from randomized controlled design, the number of relevant randomized controlled trials were limited in these studies because they were either published early in the pandemic [4] or had search dates that ended during the middle of the pandemic [5] and many new trails have been published in the past year. Additionally, while a more recent review has been published, it did not include a description of how the study was carried out and was not PRISMA compliant [6]. Here, we conducted a systematic review of RCTs that examined antiviral efficacy for COVID-19 treatment. Methods Literature search A systematic literature search was conducted to identify RCTs that investigated antiviral treatments of COVID-19 using PubMed through Nested Knowledge, an AutoLit platform for living systematic reviews [7]. The search terms used are listed in Table 1, and search filters or limits were not used. All fields were searched and the search was not limited to title/abstract. Databases used included Embase, PubMed, PubMed Central, and Web of Science. This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and MetaAnalyses (PRISMA) guidelines [8]. A review protocol was created by the authors in order to establish the framework for this systematic review and can be viewed on the Nested Knowledge platform [9]. Concepts outlined in the protocol were then developed into a custom tagging hierarchy in order to tag each study, which reflected specific evidence underneath the categories we laid out. For example, under outcomes, there is a node for Clinical Improvement that reflects an outcome we intended to gather from each study. Tagging of full-text articles was completed in order to trace concepts and link qualitative synthesis. The review was not registered. Study selection and quality assessment Studies published between November 1, 2019 and September 4, 2021 were considered. Prior to screening, all studies published before November 1, 2019 or not published in Englis (...truncated)