Treatment of severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and coronavirus disease 2019 (COVID-19): a systematic review of in vitro, in vivo, and clinical trials

Theranostics. 2021 Jan 1;11(3):1207-1231. doi: 10.7150/thno.48342. eCollection 2021.

Abstract

Rationale: Coronavirus disease 2019 (COVID-19) has spread worldwide and poses a threat to humanity. However, no specific therapy has been established for this disease yet. We conducted a systematic review to highlight therapeutic agents that might be effective in treating COVID-19. Methods: We searched Medline, Medrxiv.org, and reference lists of relevant publications to identify articles of in vitro, in vivo, and clinical studies on treatments for severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and COVID-19 published in English until the last update on October 11, 2020. Results: We included 36 studies on SARS, 30 studies on MERS, and 10 meta-analyses on SARS and MERS in this study. Through 12,200 title and 830 full-text screenings for COVID-19, eight in vitro studies, 46 randomized controlled trials (RCTs) on 6,886 patients, and 29 meta-analyses were obtained and investigated. There was no therapeutic agent that consistently resulted in positive outcomes across SARS, MERS, and COVID-19. Remdesivir showed a therapeutic effect for COVID-19 in two RCTs involving the largest number of total participants (n = 1,461). Other therapies that showed an effect in at least two RCTs for COVID-19 were sofosbuvir/daclatasvir (n = 114), colchicine (n = 140), IFN-β1b (n = 193), and convalescent plasma therapy (n = 126). Conclusions: This review provides information to help establish treatment and research directions for COVID-19 based on currently available evidence. Further RCTs are required.

Keywords: COVID-19; MERS; SARS; coronavirus; mortality; therapeutic agent.

Publication types

  • Systematic Review

MeSH terms

  • Adenosine Monophosphate / analogs & derivatives
  • Adenosine Monophosphate / therapeutic use
  • Alanine / analogs & derivatives
  • Alanine / therapeutic use
  • Animals
  • Antiviral Agents / therapeutic use*
  • COVID-19 / mortality
  • COVID-19 / therapy*
  • COVID-19 Serotherapy
  • Carbamates / therapeutic use
  • Coronavirus Infections / mortality
  • Coronavirus Infections / therapy*
  • Disease Models, Animal
  • Drug Combinations
  • Drug Evaluation, Preclinical
  • Drug Therapy, Combination / methods
  • Humans
  • Imidazoles / therapeutic use
  • Immunization, Passive / methods
  • Pyrrolidines / therapeutic use
  • Randomized Controlled Trials as Topic
  • Severe Acute Respiratory Syndrome / mortality
  • Severe Acute Respiratory Syndrome / therapy*
  • Sofosbuvir / therapeutic use
  • Treatment Outcome
  • Valine / analogs & derivatives
  • Valine / therapeutic use

Substances

  • Antiviral Agents
  • Carbamates
  • Drug Combinations
  • Imidazoles
  • Pyrrolidines
  • remdesivir
  • Adenosine Monophosphate
  • Valine
  • daclatasvir
  • Alanine
  • Sofosbuvir