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Background: Nitazoxanide exerts antiviral activity in vitro and in vivo and anti-inflammatory effects, but its impact on patients hospitalized with COVID-19 pneumonia is uncertain. Methods: A multicentre, randomized, double-blind, placebo-controlled trial was conducted in 19 hospitals in Brazil. Hospitalized adult patients requiring supplemental oxygen, with COVID-19 symptoms and a chest computed tomography scan suggestive of viral pneumonia or positive RT-PCR test for COVID-19 were enrolled. Patients were randomized 1:1 to receive nitazoxanide (500 mg) or placebo, 3 times daily, for 5 days, and were followed for 14 days. The primary outcome was intensive care unit admission due to the need for invasive mechanical ventilation. Secondary outcomes included clinical improvement, hospital discharge, oxygen requirements, death, and adverse events within 14 days. Results: Of the 498 patients, 405 (202 in the nitazoxanide group and 203 in the placebo group) were included in the analyses. Admission to the intensive care unit did not differ between the groups (hazard ratio [95% confidence interval], 0.68 [0.38-1.20], p = 0.179); death rates also did not differ. Nitazoxanide improved the clinical outcome (2.75 [2.21-3.43], p < 0.0001), time to hospital discharge (1.37 [1.11-1.71], p = 0.005), and reduced oxygen requirements (0.77 [0.64-0.94], p = 0.011). C-reactive protein, D-dimer, and ferritin levels were lower in the nitazoxanide group than the placebo group on day 7. No serious adverse events were observed. Conclusions: Nitazoxanide, compared with placebo, did not prevent admission to the intensive care unit for patients hospitalized with COVID-19 pneumonia. Clinical Trial Registration: Brazilian Registry of Clinical Trials (REBEC) RBR88bs9x; ClinicalTrials.gov, NCT04561219.
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BACKGROUND: Zika virus (ZIKV) is a recently emerged arbovirus, which infection during pregnancy is associated with a series of congenital malformations, collectively denominated Congenital Zika Syndrome (CZS). Following infection, ZIKV RNA has a median duration period of 10 days in plasma and up to 6 months in semen in immunocompetent adult individuals. Moreover, ZIKV is able to replicate and persist in fetal brains and placentas, consequently, infection is associated with pregnancy loss, albeit the pathogenic mechanisms are still unknown. CASE PRESENTATION: Here we report a CZS case of an infant born during the ZIKV outbreak in northeast Brazil, the child presented recurrent episodes of seizures with prolonged presence of ZIKV RNA on the central nervous system (CNS) and blood. ZIKV RNA was identified and partially sequenced from a sample of cerebrospinal fluid (CSF) obtained from the infant with 6 months of life, and later from another sample after the infant completed 17 months of life. Commonly congenital infections were discarded based on STORCH (syphilis, toxoplasmosis, rubella, cytomegalovirus and herpes simplex virus) negative laboratory results. Presence of specific ZIKV antibodies on both mother and children confirmed the association of severe microcephaly and ZIKV infection, diagnosed after birth. CONCLUSIONS: Altogether, our data raise the possibility that CZS cases may result in prolonged viral presence, these findings could be useful for therapy and diagnostic recommendations.