INTRODUCTION
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel single-stranded RNA virus associated with an acute pulmonary disease known as COVID-19. The binding between SARS-CoV-2 spike (S) protein and human receptor cells may lead to a dysregulated immune response with increased release of pro-inflammatory cytokines implicated in multi-organ damage and risk of death. Given the lack of effective and safe anti-viral agents against SARS-CoV-2, drug repurposing has played a critical role in the identification of rapidly available therapeutic solutions in treating patients with COVID-19 [1].
To date, only remdesivir and tocilizumab were approved by the US Food and Drug Administration (FDA) and other healthy agencies for the treatment of certain hospitalized patients with COVID-19. Other promising drugs including anti-malarial agents have also been tested in controlled clinical settings, but no benefits were found in preventing or treating patients with SARS-CoV-2 infection [2].After a comprehensive review by Sanders and colleagues [3] in April 2020 and a letter to the editor published by our research group in July 2020 in the American Journal of Physiology-Lung Cellular and Molecular Physiology [4] calling attention for the potential anti-viral effects of nitazoxanide and the need of high-quality trial evidence of nitazoxanide in the treatment of SARS-CoV-2 infection, 28 interventional studies were registered on ClinicalTrials.gov of which 8 were completed or published by June 2021.
The best evidence synthesis to assess treatment effects can be obtained through the identification, critical appraisal, and summary of results from blinded, placebo-controlled, randomized clinical trials (RCT) considered the gold standard in clinical research. The aim of this rapid and living systematic review and meta-analysis was to synthesize the available evidence on the efficacy and safety of nitazoxanide as a treatment option in patients with COVID-19.