ABSTRACT
Objectives: With over 90 million cases reported in the globe, the COVID-19 pandemic caused by SARS-CoV-2 has been a serious public health crisis. Development of novel and specific antiviral drugs against the SARS-CoV-2 has been an urgent demand. One such drug is Favipiravir, initially developed as an antiviral drug against influenza. Now Favipiravir has received approvals for emergency use against SARS-CoV-2 in many countries. A better understanding of Favipiravir’s biodistribution and pharmacokinetics in vivo will facilitate the clinical development of antiviral drugs against the SARS-CoV-2. Herein, we reported the evaluation of [18 F]Favipiravir with PET in cross-species studies to demonstrate the drug’s biodistribu-tion and pharmacokinetics and investigate the potentially increased risk of neurodegenerative diseases and/or neuroinflammation to COVID-19. Methods: The radiosynthesis of [18 F]Favipiravir was via labeling a commercially available precursor, methyl-5-chloroisoxazolo[4,5-b] pyrazine-3-carboxylate with K[18F]F/K222 and K2CO3 in DMSO at 130°C for 10 min, followed by hydrolysis with NaOH (aq.) at 110°C for 15 min.1 The whole body distribution on CD-1 mice was performed at four time points (5, 15, 30, 60 min). PET studies were carried out in CD-1 mice and AD mice (5XFAD) and naïve rhesus monkeys. We also performed the radiometabolite analysis of [18 F]Favipiravir in plasma and brain of CD-1 mice at 30 min post-injection. Results: [18 F]Favipiravir was obtained in 29% isolated radiochemi-cal yield (decay corrected). The radiochemical purity of the tracer was greater than 99%. No sign of radiolysis was observed for [18F] Favipiravir up to 120 min after formulation with 10% EtOH/saline. High radioactivity accumulation was observed in blood, lung, liver, kidney, and bone (around or more than 5% ID/g, injected dose per gram of wet tissue). The radioactivity level reached a plateau in small intestine, kidney and liver at 30,15 and 5 min, respectively, followed by slow washout, indicating that [18F]Favipiravir was possibly eliminated via the hepatobiliary and urinary pathway. For the radio-metabolic analysis of [18F]Favipiravir, average 41% and 89% of the radioactivity was parent fraction in the mice brain and plasma at 30 min post-injection (n=2), respectively. In PET imaging of CD-1 mice, the standard uptake value (SUV) of [18F]Favipiravir in brain reached its max value of 0.5 at 10 min and slowly reduced to 0.4 at 60 min. The results of PET imaging of AD mice with [18 F]Favipiravir were similar with that of CD-1 mice. In PET imaging of Rhesus monkeys, the brain uptake of [18 F]Favipiravir reached the max value of 0.5 SUV at 5 min and subsequently decreased to 50-60% of the maximum at 60 min. Conclusion: The evaluation of [18F]Favipiravir has demonstrated with bio-distribution and PET in mice and NHPs. Further evaluation of pharmacokinetics of [18F]Favipiravir in whole body monkey scans and LPS-induced neuroinflammation models is underway.
ABSTRACT
Background: Appropriate human resources interventions to address healthcare workers’ concerns are key to maintaining confidence and morale of staff to combat a pandemic in any healthcare system. The objectives of this study are to analyze concerns of healthcare workers in public hospitals during the initial 3 months, throughout which the Hong Kong Hospital Authority implemented multiple measures to address staff needs. Methods: A retrospective study analyzing the immediate and longitudinal concerns of healthcare workers during the coronavirus disease 2019 (COVID-19) pandemic. All enquiries by unsolicited phone calls and WhatsApp messages raised over a 12-week period from 29/1/2020 to 22/4/2020 were reviewed and categorized. Thematic analysis of the enquiries was conducted, together with timing and frequency of enquiry categories. Results: A total of 1,868 enquiries were raised over the 12-week period. These enquiries comprised 740 (40%) in “recognition and staff wellbeing”, 573 (31%) in “infection control”, 357 (19%) in “duty arrangement” and the remaining 196 (10%) “others”. Conclusions: Spikes spread over the 12 weeks of data capture demonstrated major concern areas for a healthcare system in maintaining the morale and confidence of staff. Financial incentives introduced during the pandemic may have drawbacks around equity, defining thresholds for payments and setting precedence. A Human Resources App and e-bulletins were effective in rapidly communicating information to staff and allaying their fears, especially during the initial phase of the crisis. Further study of financial incentives to help decision-makers understand the impact and consequences of such approaches should be undertaken. © Journal of Hospital Management and Health Policy. All rights reserved.
ABSTRACT
Background: COVID-19 is a public health emergency of international concern. Its incidence rates and mortality are very high;however, so far, an effective drug treatment remains unknown. Based on the role of convalescent plasma therapy in previously identified viral pneumonias, patients with severe COVID-19 have been given this therapy. This systematic review and meta-analysis aimed to summarize the clinical evidence regarding the efficacy and safety of convalescent plasma therapy in the treatment of severe COVID-19. Methods: PubMed, Embase, Ovid, China Knowledge Network, China Biomedical, VIP Chinese Sci-tech Journal, Wanfang Database, and the International Clinical Trials Registry Platform were searched up to 21 June 2020, to identify clinical studies and registered trials on the use of convalescent plasma in the treatment of critically ill patients with COVID-19. Stata 13.0 was used to perform Meta-analysis. All records were screened as per the protocol eligibility criteria. Results: Nineteen clinical reports regarding convalescent plasma in the treatment of severe COVID-19 were included. Through systematic analysis, convalescent plasma was found to yield some efficacy on severe COVID-19 and had almost no obvious adverse reactions. Conclusion: Convalescent plasma therapy seems to yield some efficacy among patients with severe COVID-19 and almost no obvious adverse reactions were found. However, at present, the clinical evidence is insufficient, and there is an urgent need for support from high-quality clinical trial data. © 2020, Iranian Journal of Public Health. All rights reserved.