Critical Care Medical Centers May Play an Important Role in Reducing the Risk of COVID-19 Death in Japan

Marked differences in COVID-19 mortalities have been observed among 47 prefectures in Japan. Here, we explored associations between COVID-19 mortalities and medical and public health capacities in individual prefectures. The following data by prefecture were abstracted from open resources provided by the Ministry of Health, Labour and Welfare in Japan as of May 24, 2020: total number of COVID-19 deaths; polymerase chain reaction (PCR)-positive ratio (i.e., number of patients with PCR-positive results/number of patients aiming diagnosis of COVID-19 or individuals in close contacted with COVID-19 patients); number of call centers, outpatient centers, and hospital beds specifically for patients diagnosed with COVID-19; and others. The primary outcome was COVID-19 mortality per million population. Multiple and simple linear regression models were applied. Two variables were significantly associated with COVID-19 mortality: PCR-positive ratio (P < 0.001) and number of critical care medical centers per million population (P = 0.001). PCR-positive ratio was positively associated with COVID-19 mortality (aR-sqr = 0.522). Low PCR-positive ratio, especially ≤ 4%, was associated with low COVID-19 mortality. Critical care medical centers may also play an important role in reducing the risk of COVID-19 death.


Introduction
The coronavirus disease 2019 (COVID-19) pandemic resulted in 337,687 deaths around the world [1] and 830 deaths in Japan consisting of 47 prefectures, as of May 24, 2020 [2]. Marked differences in COVID-19 mortalities have been observed among 47 prefectures in Japan. For example, mortalities have exceeded 20 per million population in Ishikawa, Toyama, and Tokyo, compared to less than 1 per million population in 24 other prefectures. Moreover, huge disparities exist in medical and public heath capacities per capita across the 47 prefectures. We therefore explored associations between COVID-19 mortalities and medical and public health capacities (e.g., hospital beds per population) in individual prefectures as an ecological study.

Methods
The following data by prefecture were abstracted from open resources provided by the Ministry of Health, Labour and Welfare in Japan as of May 24, 2020 [2, 3]: total number of COVID-19 deaths; polymerase chain reaction (PCR)-positive ratio (i.e., number of patients with PCR-positive results/ number of patients aiming diagnosis of COVID-19 or individuals in close contacted with COVID-19 patients); number of call centers, outpatient centers, and hospital beds specifically for patients diagnosed with COVID-19; and others. Moreover, minutes of the ambulance call to arriving at hospital was obtained from the Ministry of Public Management, Home Affairs, Posts and Telecommunications [4]. Four potential confounders were used for adjustment: population density (/km 2 ), percentage of the population ≥ 65 years old, university education (%), and mean income. The primary outcome was COVID-19 mortality per million population. Multiple and simple linear regression models were applied to screen and

Discussion
Low PCR-positive ratio, especially ≤ 4%, was associated with low COVID-19 mortality. Low PCR-positivity may imply that patients have easy access to PCR testing in the community, even if patients do not have signs or symptoms of typical pneumonia or display only mild symptoms. A greater number of critical care medical centers per million population was likewise associated with low COVID-19 mortality, whereas numbers of hospital beds, ICU beds, and other medical capacities per million population used in this analysis were not, suggesting that critical care medical centers may play an important role in reducing the risk of COVID-19 death in the community. Indeed, several reports with favorable outcomes from critical care medical centers have been reported [5][6][7][8]. They have the ability of managing veno-venous extracorporeal membrane oxygenation (ECMO) for critical COVID-19 patients [7,8]. Thus, it is important to have not only the equipment but also the medical personnel capable of treating critical condition in COVID-19 patients, including ECMO management.
The primary limitation of this study was the ecological design. Consequently, this study only proposes the hypothesis that capacities in PCR testing and critical care medical centers may be suitable targets for enhancement.

Conclusions
Low PCR-positive ratio, especially ≤ 4%, was associated with low COVID-19 mortality. Critical care medical centers may also play an important role in reducing the risk of COVID-19 death.

Compliance with Ethical Standards
Conflict of Interest This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Furthermore, none of the authors have any commercial or financial involvement in connection with this study that represent or appear to represent any conflicts of interest.
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain