Evaluation of the Risk of Clinical Deterioration among Inpatients with COVID-19.

This study aims to assess the risk of severe forms of COVID-19, based on clinical, laboratory, and imaging markers in patients initially admitted to the ward. This is a retrospective observational study, with data from electronic medical records of inpatients, with laboratory confirmation of COVID-19, between March and September 2020, in a hospital from Juiz de Fora-MG, Brazil. Participants (n = 74) were separated into two groups by clinical evolution: those who remained in the ward and those who progressed to the ICU. Mann-Whitney U test was taken for continuous variables and the chi-square test or Fisher's exact test for categorical variables. Comparing the proposed groups, lower values of lymphocytes (p = <0.001) and increases in serum creatinine (p = 0.009), LDH (p = 0.057), troponin (p = 0.018), IL-6 (p = 0.053), complement C4 (p = 0.040), and CRP (p = 0.053) showed significant differences or statistical tendency for clinical deterioration. The average age of the groups was 47.9 ± 16.5 and 66.5 ± 7.3 years (p = 0.001). Hypertension (p = 0.064), heart disease (p = 0.048), and COPD (p = 0.039) were more linked to ICU admission, as well as the presence of tachypnea on admission (p = 0.051). Ground-glass involvement >25% of the lung parenchyma or pleural effusion on chest CT showed association with evolution to ICU (p = 0.027), as well as bilateral opacifications (p = 0.030) when compared to unilateral ones. Laboratory, clinical, and imaging markers may have significant relation with worse outcomes and the need for intensive treatment, being helpful as predictive factors.

Early use of nitazoxanide in mild COVID-19 disease: randomised, placebo-controlled trial.

BACKGROUND: Nitazoxanide is widely available and exerts broad-spectrum antiviral activity in vitro. However, there is no evidence of its impact on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: In a multicentre, randomised, double-blind, placebo-controlled trial, adult patients presenting up to 3 days after onset of coronavirus disease 2019 (COVID-19) symptoms (dry cough, fever and/or fatigue) were enrolled. After confirmation of SARS-CoV-2 infection using reverse transcriptase PCR on a nasopharyngeal swab, patients were randomised 1:1 to receive either nitazoxanide (500 mg) or placebo, three times daily, for 5 days. The primary outcome was complete resolution of symptoms. Secondary outcomes were viral load, laboratory tests, serum biomarkers of inflammation and hospitalisation rate. Adverse events were also assessed. RESULTS: From June 8 to August 20, 2020, 1575 patients were screened. Of these, 392 (198 placebo, 194 nitazoxanide) were analysed. Median (interquartile range) time from symptom onset to first dose of study drug was 5 (4-5) days. At the 5-day study visit, symptom resolution did not differ between the nitazoxanide and placebo arms. Swabs collected were negative for SARS-CoV-2 in 29.9% of patients in the nitazoxanide arm versus 18.2% in the placebo arm (p=0.009). Viral load was reduced after nitazoxanide compared to placebo (p=0.006). The percentage viral load reduction from onset to end of therapy was higher with nitazoxanide (55%) than placebo (45%) (p=0.013). Other secondary outcomes were not significantly different. No serious adverse events were observed. CONCLUSIONS: In patients with mild COVID-19, symptom resolution did not differ between nitazoxanide and placebo groups after 5 days of therapy. However, early nitazoxanide therapy was safe and reduced viral load significantly.

Spontaneous cystogenesis of Toxoplasma gondii in feline epithelial cells in vitro.

Toxoplasma gondii Nicolle et Manceaux, 1908 is an obligate intracellular parasite with the ability to infect mammals and birds. The only definitive hosts for T. gondii are felids, as the parasites form immature oocysts that are shed in the faeces. Here we introduce cat cells as a model for the study of experimental toxoplasmosis. We selected epithelial cells derived from cat kidneys (CRFK) as a target to determine the intracellular fate ofbradyzoites of the T. gondii ME49 strain. In parallel, we compared this infection using epithelial cells from the rat intestine (IEC-6), considering the enteroepithelial development that occurs in the cat. Different ratios of parasites to host cells were assayed over the course of a 14-day-infection. The intracellular development of T. gondii was dependent on the source of the epithelial cells and also on the parasite/host cell ratio. Cystogenesis was well established in the CRFK cell line at a ratio of 1:10 after 10-14 days of infection. This cellular model system opens a new field of investigation into the molecular aspects of the interactions between T. gondii and feline epithelial cells. The CRFK cell line appears to be a potential cellular model for large scale cyst production in vitro, which would allow a reduction in the number of animals used and/or replacement of animals by in vitro cultures.