ABSTRACT
Niclosamide (NIC) has demonstrated promising in vitro antiviral efficacy against SARS-CoV-2, the causative agent of the COVID-19 pandemic. Though NIC is already FDA-approved, administration of the currently available oral formulation results in systemic drug levels that are too low for the inhibition of SARS-CoV-2. We hypothesized that the co-formulation of NIC with an endogenous protein, human lysozyme (hLYS), could enable the direct aerosol delivery of the drug to the respiratory tract as an alternative to oral delivery, thereby effectively treating COVID-19 by targeting the primary site of SARS-CoV-2 acquisition and spread. To test this hypothesis, we engineered and optimized composite particles containing NIC and hLYS suitable for delivery to the upper and lower airways via dry powder inhaler, nebulizer, and nasal spray. The novel formulation demonstrates potent in vitro and in vivo activity against two coronavirus strains, MERS-CoV and SARS-CoV-2, and may offer protection against methicillin-resistance staphylococcus aureus pneumonia and inflammatory lung damage occurring secondary to SARS-CoV-2 infections. The suitability of the formulation for all stages of the disease and low-cost development approach will ensure rapid clinical development and wide-spread utilization.
ABSTRACT
AIM: To report an audit of the evaluation of suspected, unconfirmed cases of COVID-19 including chest computed tomography (CT), as compared to World Health Organization recommendations. METHODS: A clinical audit was undertaken examining the evaluation of patients with suspected COVID-19 with negative SARS-CoV-2 reverse transcriptase polymerase chain reaction (RT-PCR) results, with comparison to WHO recommendations. A retrospective chart review was undertaken for 90 patients examining investigations, in particular CT, used to clarify the diagnosis. RESULTS: Ninety patients underwent additional investigation. Seventy-five per cent adherence to WHO recommendations was observed. Fifty-two men (57.78%) and 38 (42.22%) women were investigated, with a median age of 69 years (range 20-96 years). Seventy-nine chest CT examinations demonstrated positive, indeterminate, and negative rates for COVID-19 of 3.79%, 24.1%, and 72.15% respectively. Three patients had discordant swab results with initially negative and subsequently positive results for SARS-CoV-2, resulting in false-negative rates of 5.1% for those retested. Combining discordant RT-PCR swab results, positive radiology, and patients treated as COVID-19-positive due to indeterminate radiology and highly consistent symptoms, resulted in a false-negative rate for initial SARS-CoV-2 RT-PCR swabs of 16.67%. CONCLUSION: Seventy-five per cent compliance with relevant WHO guidance and a false-negative rate for initial swabs of 16.67% was demonstrated. Further evidence is needed to fully determine the utility of chest CT in the diagnosis of COVID-19 in the context of initial false-negative RT-PCR results.