Published online Jul 6, 2021. doi: 10.12998/wjcc.v9.i19.5135
Peer-review started: November 8, 2020
First decision: December 21, 2020
Revised: January 1, 2021
Accepted: May 20, 2021
Article in press: May 20, 2021
Published online: July 6, 2021
Processing time: 220 Days and 4.2 Hours
Ribavirin is a broad-spectrum nucleoside antiviral drug with multimodal mechanisms of action, which supports its longevity and quality as a clinical resource. It has been widely administered for measles and coronavirus infections. Despite the large amount of data concerning the use of ribavirin alone or in combination for measles, severe acute respiratory syndrome, Middle East respiratory syndrome, and coronavirus disease 2019 (COVID-19) outbreaks, the conclusions of these studies have been contradictory. Underlying reasons for these discrepancies include possible study design inaccuracies and failures and misinterpretations of data, and these potential confounds should be addressed.
To determine the confounding factors of ribavirin treatment studies and propose a therapeutic scheme for COVID-19.
PubMed database was searched over a period of five decades utilizing the terms “ribavirin” alone or combined with other compounds in measles, severe acute respiratory syndrome, Middle East respiratory syndrome, and COVID-19 infections. The literature search was performed and described according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Articles were considered eligible when they reported on ribavirin dose regimens and/or specified outcomes concerning its efficacy and/or possible adverse-effects. In vitro and animal studies were also retrieved. A chapter on ribavirin’s pharmacology was included as well.
In addition to the difficulties and pressures of an emerging pandemic, there is the burden of designing and conducting well-organized, double-blind, randomized controlled trials. Many studies have succumbed to specific pitfalls, one of which was identified in naturally ribavirin-resistant Vero cell lines in in vitro studies. Other pitfalls include study design inconsistent with the well-established clinical course of disease; inappropriate pharmacology of applied treatments; and the misinterpretation of study results with misconceived generalizations. A comprehensive treatment for COVID-19 is proposed, documented by thorough, long-term investigation of ribavirin regimens in coronavirus infections.
A comprehensive treatment strictly tailored to distinct disease stages was proposed based upon studies on ribavirin and coronavirus infections.
Core Tip: Documented by accumulated data from coronaviruses studies and considering six identified pitfalls to which most of the studies fall victim, the early antiviral treatment is crucial for reducing viral load, transmission, and preventing disease severity. In coronavirus disease 2019, initiation of interferon-β plus ribavirin plus lopinavir/ritonavir is beneficial when targeting selected patients early during Stage I, and is a regimen that can be administered while the patient is at home in quarantine. If disease progresses to Stages IIb-III, corticosteroids (mainly pulsed methylprednisolone) are effective, but if they fail or extrapulmonary systemic hyperinflammation syndrome develops, tocilizumab (or anakinra) should be co-administered.