Development of a screening platform to discover natural products active against SARS-CoV-2 infection using lung organoid models.

BACKGROUND: Natural products can serve as one of the alternatives, exhibiting high potential for the treatment and prevention of COVID-19, caused by SARS-CoV-2. Herein, we report a screening platform to test the antiviral efficacy of a natural product library against SARS-CoV-2 and verify their activity using lung organoids. METHODS: Since SARS-CoV-2 is classified as a risk group 3 pathogen, the drug screening assay must be performed in a biosafety level 3 (BSL-3) laboratory. To circumvent this limitation, pseudotyped viruses (PVs) have been developed as replacements for the live SARS-CoV-2. We developed PVs containing spikes from Delta and Omicron variants of SARS-CoV-2 and improved the infection in an angiotensin-converting enzyme 2 (ACE2)-dependent manner. Human induced pluripotent stem cells (hiPSCs) derived lung organoids were generated to test the SARS-CoV-2 therapeutic efficacy of natural products. RESULTS: Flavonoids from our natural product library had strong antiviral activity against the Delta- or Omicron-spike-containing PVs without affecting cell viability. We aimed to develop strategies to discover the dual function of either inhibiting infection at the beginning of the infection cycle or reducing spike stability following SARS-CoV-2 infection. When lung cells are already infected with the virus, the active flavonoids induced the degradation of the spike protein and exerted anti-inflammatory effects. Further experiments confirmed that the active flavonoids had strong antiviral activity in lung organoid models. CONCLUSION: This screening platform will open new paths by providing a promising standard system for discovering novel drug leads against SARS-CoV-2 and help develop promising candidates for clinical investigation as potential therapeutics for COVID-19.

Mortality prediction of patients in intensive care units using machine learning algorithms based on electronic health records.

Improving predictive models for intensive care unit (ICU) inpatients requires a new strategy that periodically includes the latest clinical data and can be updated to reflect local characteristics. We extracted data from all adult patients admitted to the ICUs of two university hospitals with different characteristics from 2006 to 2020, and a total of 85,146 patients were included in this study. Machine learning algorithms were trained to predict in-hospital mortality. The predictive performance of conventional scoring models and machine learning algorithms was assessed by the area under the receiver operating characteristic curve (AUROC). The conventional scoring models had various predictive powers, with the SAPS III (AUROC 0.773 [0.766-0.779] for hospital S) and APACHE III (AUROC 0.803 [0.795-0.810] for hospital G) showing the highest AUROC among them. The best performing machine learning models achieved an AUROC of 0.977 (0.973-0.980) in hospital S and 0.955 (0.950-0.961) in hospital G. The use of ML models in conjunction with conventional scoring systems can provide more useful information for predicting the prognosis of critically ill patients. In this study, we suggest that the predictive model can be made more robust by training with the individual data of each hospital.

Development of Spike Receptor-Binding Domain Nanoparticles as a Vaccine Candidate against SARS-CoV-2 Infection in Ferrets.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a causative agent of the CoV disease 2019 (COVID-19) pandemic, enters host cells via the interaction of its receptor-binding domain (RBD) of the spike protein with host angiotensin-converting enzyme 2 (ACE2). Therefore, the RBD is a promising vaccine target to induce protective immunity against SARS-CoV-2 infection. In this study, we report the development of an RBD protein-based vaccine candidate against SARS-CoV-2 using self-assembling Helicobacter pylori-bullfrog ferritin nanoparticles as an antigen delivery system. RBD-ferritin protein purified from mammalian cells efficiently assembled into 24-mer nanoparticles. Sixteen- to 20-month-old ferrets were vaccinated with RBD-ferritin nanoparticles (RBD nanoparticles) by intramuscular or intranasal inoculation. All vaccinated ferrets with RBD nanoparticles produced potent neutralizing antibodies against SARS-CoV-2. Strikingly, vaccinated ferrets demonstrated efficient protection from SARS-CoV-2 challenge, showing no fever, body weight loss, or clinical symptoms. Furthermore, vaccinated ferrets showed rapid clearance of infectious virus in nasal washes and lungs as well as of viral RNA in respiratory organs. This study demonstrates that spike RBD-nanoparticles are an effective protein vaccine candidate against SARS-CoV-2.

A Review of Contemporary Teleaudiology: Literature Review, Technology, and Considerations for Practicing.

The scope of teleaudiology has been noted with telehealth due to Coronavirus disease (COVID-19) recently. As the notion has been around us for more than 20 years ever since 1999, it is necessary to perceive the knowledge accurately and prepare for the successful implementation of it. Therefore, the literature review including screening and diagnostic audiometry, cochlear implants and hearing aids, and aural rehabilitation, telecommunications technology regarding several fields of teleaudiology, and considerations for practicing were identified. Although overall internet-based audiological services showed benefits in terms of outcome and accessibility, uncertainties of cost-effectiveness, the optimal level of support, and a need for further studies of many aspects for teleaudiology has arisen. In the view of technology, the store-and-forward (asynchronous/hybrid) and a real-time (synchronous) methods were introduced with one applied and nine registered patents recorded from 2004 to 2020 for the invention of teleaudiology in the United States. Also, 10 checklists were suggested for planning teleaudiology practice from prior experience in hosting the teleaudiology program. Conclusively, it is hoped that this review sheds light on recognizing and improving the existing teleaudiology services and helps overcome the challenges faced in the era of pandemic and untact world to come.