Establishment of a Rapid Detection System for ISG20-Dependent SARS-CoV-2 Subreplicon RNA Degradation Induced by Interferon-α.

Inhaled nebulized interferon (IFN)-α and IFN-ß have been shown to be effective in the management of coronavirus disease 2019 (COVID-19). We aimed to construct a virus-free rapid detection system for high-throughput screening of IFN-like compounds that induce viral RNA degradation and suppress the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We prepared a SARS-CoV-2 subreplicon RNA expression vector which contained the SARS-CoV-2 5'-UTR, the partial sequence of ORF1a, luciferase, nucleocapsid, ORF10, and 3'-UTR under the control of the cytomegalovirus promoter. The expression vector was transfected into Calu-3 cells and treated with IFN-α and the IFNAR2 agonist CDM-3008 (RO8191) for 3 days. SARS-CoV-2 subreplicon RNA degradation was subsequently evaluated based on luciferase levels. IFN-α and CDM-3008 suppressed SARS-CoV-2 subreplicon RNA in a dose-dependent manner, with IC50 values of 193 IU/mL and 2.54 µM, respectively. HeLa cells stably expressing SARS-CoV-2 subreplicon RNA were prepared and treated with the IFN-α and pan-JAK inhibitor Pyridone 6 or siRNA-targeting ISG20. IFN-α activity was canceled with Pyridone 6. The knockdown of ISG20 partially canceled IFN-α activity. Collectively, we constructed a virus-free rapid detection system to measure SARS-CoV-2 RNA suppression. Our data suggest that the SARS-CoV-2 subreplicon RNA was degraded by IFN-α-induced ISG20 exonuclease activity.

Disaster Vulnerability of Hospitals: A Nationwide Surveillance in Japan.

OBJECTIVE: Hospital preparedness against disasters is key to achieving disaster mitigation for health. To gain a holistic view of hospitals in Japan, one of the most disaster-prone countries, a nationwide surveillance of hospital preparedness was conducted. METHODS: A cross-sectional, paper-based interview was conducted that targeted all of the 8701 registered hospitals in Japan. Preparedness was assessed with regard to local hazards, compliance to building code, and preparation of resources such as electricity, water, communication tools, and transportation tools. RESULTS: Answers were obtained from 6122 hospitals (response rate: 70.3%), among which 20.5% were public (national or city-run) hospitals and others were private. Eight percent were the hospitals assigned as disaster-base hospitals and the others were non-disaster-base hospitals. Overall compliance to building code, power generators, water tanks, emergency communication tools, and helicopter platforms was 90%, 84%, 95%, 43%, and 22%, respectively. CONCLUSION: Major vulnerabilities in logistics in mega-cities and stockpiles required for chronic care emerged from the results of this nationwide surveillance of hospitals in Japan. To conduct further intensive surveillance to meet community health needs, appropriate sampling methods should be established on the basis of this preliminary study. Holistic vulnerability analysis of community hospitals will lead to more robust disaster mitigation at the local level.

The great East Japan earthquake disaster: distribution of hospital damage in Miyagi Prefecture.

INTRODUCTION: In catastrophic events, a key to reducing health risks is to maintain functioning of local health facilities. However, little research has been conducted on what types and levels of care are the most likely to be affected by catastrophic events. Problem The Great East Japan Earthquake Disaster (GEJED) was one of a few "mega disasters" that have occurred in an industrialized society. This research aimed to develop an analytical framework for the holistic understanding of hospital damage due to the disaster. METHODS: Hospital damage data in Miyagi Prefecture at the time of the GEJED were collected retrospectively. Due to the low response rate of questionnaire-based surveillance (7.7%), publications of the national and local governments, medical associations, other nonprofit organizations, and home web pages of hospitals were used, as well as literature and news sources. The data included information on building damage, electricity and water supply, and functional status after the earthquake. Geographical data for hospitals, coastline, local boundaries, and the in undated areas, as well as population size and seismic intensity were collected from public databases. Logistic regression was conducted to identify the risk factors for hospitals ceasing inpatient and outpatient services. The impact was displayed on maps to show the geographical distribution of damage. RESULTS: Data for 143 out of 147 hospitals in Miyagi Prefecture (97%) were obtained. Building damage was significantly associated with closure of both inpatient and outpatient wards. Hospitals offering tertiary care were more resistant to damage than those offering primary care, while those with a higher proportion of psychiatric care beds were more likely to cease functioning, even after controlling for hospital size, seismic intensity, and distance from the coastline. CONCLUSIONS: Implementation of building regulations is vital for all health care facilities, irrespective of function. Additionally, securing electricity and water supplies is vital for hospitals at risk for similar events in the future. Improved data sharing on hospital viability in a future event is essential for disaster preparedness.