DISCUSSION
Nitazoxanide is a broad-spectrum antiparasitic and antiviral drug,
originally approved for the treatment of parasite-mediated infectious
diarrhea and enteritis, that has been tested for COVID-19 due to the
anti-inflammatory effects [19] and in vitro anti-viral
activity and promising clinical benefits against influenza and other
viruses [20-22]. Moreover, there is in vitro evidence that
nitazoxanide may induce a significant down-regulation of IL-6/JAK2/STAT3
[23] and may increase the eIF2α and PKR phosphorylation, critical
mediators involved in IFN-induced antiviral response [24].
Individual studies [15] have suggested that nitazoxanide reduces
SARS-CoV-2 viral load in Vero E6 cells by 75% at a minimal dose of 0.1
μM with no cytotoxic effects. High SARS-CoV-2 viral load was found to be
associated with lymphopenia, increased markers of inflammation, and poor
clinical outcomes in hospitalized patients with COVID-19 [25,26].
Therefore, the use of nitazoxanide might accelerate viral clearance,
improve clinical symptoms, and decrease the risk of hospitalization and
death for patients with SARS-CoV-2 infection.
Despite promising theoretical and experimental findings, this systematic
review showed no evidence of clinical benefits on the use of
nitazoxanide to treat patients with mild or moderate COVID-19. To date,
there is still no optimal approach toward COVID-19 management.
Symptomatic cases require supportive care with medical evaluation, risk
factor stratification for unfavorable clinical outcomes, and clinical
monitoring of symptoms. In outpatients, symptomatic treatment includes
analgesics and antipyretics. In the hospital setting, patients may need
supplemental oxygen and adequate management of pulmonary ventilation.
The use of dexamethasone has been indicated for patients with COVID-19
who are receiving respiratory support [27]. Recently, open-label
RCTs showed that prophylactic or therapeutic anticoagulation did not
result in clinical improvement for hospitalized patients with COVID-19,
except in the context of diagnosing a thromboembolic event [28,29].
Our study has some major limitations and include trials with a high-risk
of reporting and operational bias. Despite most studies were
double-blinded, changes in urine color caused by nitazoxanide could
potentially induce a high-risk of performance or detection bias. In one
trial [17], the patients received a vitamin B complex supplement to
mask any potential chromaturia attributed to nitazoxanide. Finally, the
results of this study cannot be generalized to severe or critical
COVID-19.
In this systematic review and meta-analysis, we found no current
evidence from blinded, placebo-controlled, RCT on the efficacy of
nitazoxanide in treating patients with COVID-19. The quality of evidence
for most outcomes analyzed in this study is limited. This living
systematic review should be updated as soon as the results of ongoing
RCT are published.