The rapid global spread of the COVID-19 pandemic has posed a significant challenge to various countries in terms of the capacity of hospitals to admit and care for patients during the crisis. To estimate hospital capacity during the COVID-19 pandemic, clinicians working in tertiary hospitals around the world were surveyed regarding available COVID-19 hospital statistics. Data were obtained from 8 tertiary centers in 8 countries including the United States, United Kingdom, Switzerland, Turkey, Singapore, India, Pakistan, and Japan. The correlation between the number of patients with COVID-19 per 1 million population vs. the maximum number of inpatients with COVID-19 in a representative tertiary hospital in each country was determined, as was the correlation between COVID-19 deaths per 1 million population vs. the maximum number of patients with COVID-19 in the intensive care unit (ICU). What was noteworthy was that none of the 8 hospitals reduced emergency room (ER) activity even at the peak of the pandemic although treatment of patients without COVID-19 decreased by 0-70% depending on the extent of the epidemic. Although various measures are being actively implemented to slow the spread of the virus and reduce the strain on the health care system, the reality is that there are still a significant number of hospitals at risk of being overloaded in the event of a future surge in cases.
Coronavirus disease 2019 (COVID-19) remains a threat worldwide over a year after the outbreak. Recently, several studies have reported that elevated serum troponin, which reflects myocardial injury, has a significant impact on worsening cardiovascular disease and the death of patients with COVID-19. In addition, magnetic resonance imaging (MRI) and echocardiography revealed abnormal myocardial findings in patients with COVID-19 who have recovered, as exemplified by a slight elevation of high-sensitivity troponin T (hsTnT). This editorial will discuss the impacts of SARS-CoV-2 on the heart of Japanese patients during infection and recovery and future perspectives.
Coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) originating in Wuhan, China, has spread globally very rapidly. The number of COVID-19 patients increased in Japan from late March to early April 2020. Since COVID-19 treatment methods with antiviral drugs were not established in March 2020, clinical trials began at a rapid pace worldwide. We participated in a global investigator-initiated clinical trial of the antiviral drug remdesivir. It took approximately two months to prepare for and start patient enrollment, 26 days to enroll all patients in Japan, and 32 days from the end of enrollment to the release of the first report, a fairly quick response overall. In the course of this clinical trial, we found some of the critical issues related to conducting an infectious disease clinical trial in Japan need to be addressed and tackled to support a rapid response. These included such things as the necessity of a research network to promote clinical research, a framework for a rapid review system of clinical trial notification, and better cooperation with outsourced teams. Furthermore, for Japan to take the lead in global collaborative research and development in the field of infectious diseases, it is necessary to develop further human resources and organization on a national basis. It is indispensable for Japan to establish a clinical trial system at the national level to prepare for future emerging and re-emerging infectious diseases.
Angiotensin converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2), two receptors on the cell membrane of bronchial epithelial cells, are indispensable for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. ACE2 receptor is increased among aged, males, and smokers. As smoking upsurges ACE2 expression, chronic obstructive pulmonary disease (COPD) patients are prone to SARS-CoV-2 infection, and are at a higher risk for severe forms of COVID-19 (coronavirus disease 2019) once infected. The expression of ACE2 and TMPRSS2 in asthma patients is identical (or less common) to that of healthy participants. ACE2 especially, tends to be low in patients with strong atopic factors and in those with poor asthma control. Therefore, it could be speculated that asthma patients are not susceptible to COVID-19. Epidemiologically, asthma patients are less likely to suffer from COVID-19, and the number of hospitalized patients due to exacerbation of asthma in Japan is also clearly reduced during the COVID-19 pandemic; therefore, they are not aggravating factors for COVID-19. Related academic societies in Japan and abroad still lack clear evidence regarding asthma treatment during the COVID-19 pandemic, and recommend that regular treatment including biologics for severe patients be continued.
Among 68 countries in the world, severity of the COVID-19 epidemic was correlated with the prevalence of α-1 antitrypsin (AAT) deficiency. For the severe variant, PI*Z, the correlation coefficient (CC) was 0.8584 for the number of patients and 0.8713 for the number of deaths. For the milder variant, PI*S, it was 0.5818 and 0.6326, respectively. In Japan, the number of patients and deaths correlated with the population size with a CC of 0.6667 and 0.7074 respectively, and was proportional to the population size to the power of 1.65 and 1.54. The prevalence of AAT deficiency also correlated with the epidemiological pattern of COVID-19. In countries with high prevalence of AAT deficiency, after the initial rise, the daily number of patients and that of deaths ran parallel at a high level for more than 6 months without sign of abatement. In countries with a low prevalence of AAT deficiency, after the first wave of the epidemic, the number of the deaths decreased continuously while the number of patients remained the same or even increased resulting in a decreasing case-fatality rate. When the cumulative number of deaths was plotted on the y-axis against the cumulative number of patients on the x-axis, plots fell on a straight line in countries with a high prevalence of AAT deficiency; while in countries with low a prevalence of AAT deficiency, a break appeared, after which the plots fell on flatter slope indicating decreasing case-fatality rate. The observation suggests emergence of an attenuated variant in countries with a low prevalence of AAT deficiency.
In Japan, the differences in characteristics, severity, and mortality of novel coronavirus disease (COVID-19) patients between the first and second surges of infections have not been fully understood. This study is a retrospective cohort study of COVID-19 patients confirmed between February 1 and August 31, 2020 in Osaka Prefecture, Japan. Publicly available information on patients was collected from the website of Osaka Prefecture. Patients were divided into two groups according to the date of the positive laboratory test result: the first surge (February 1 to May 22) and the second surge (May 23 to August 31). Patients' characteristics were compared between the two groups. A multivariable Cox proportional-hazards model was applied to compare severity and mortality between the two groups, where sex, age group at the onset date, city of residence, and days to test positive were adjusted. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated. A total of 8,541 patients included 1,780 and 6,761 patients in the first and second surges, respectively. Age at the onset date was younger in the second surge (p < 0.001), and median of days from the onset date to the positive test date shortened from 7 to 6 days (p < 0.001). The multivariable Cox proportional-hazards model revealed that both severity and mortality were lower in the second surge than in the first surge (severity: HR: 0.51 [0.39-0.67]; mortality: HR: 0.37 [0.25-0.56]). In conclusion, severity and mortality were lower in the second surge than in the first surge among COVID-19 patients in Osaka Prefecture, Japan.
We assessed the consistency of seropositive results of three rapid immunoassays (Kits A, B, and C) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) compared to highly accurate serological tests (Abbott and Roche) among healthcare workers in a hospital in Tokyo. The seroprevalence of SARS-CoV-2 immunoglobulin G was 0.41%, 2.36%, and 0.08% using Kits A, B, and C, respectively. Of the 51 samples that were seropositive on any rapid test, all were seronegative on both the Abbott and the Roche assays. Given that the seroprevalence of SARS-CoV-2 immunoglobulin G varied widely according to the choice of rapid test and the rapid test results were inconsistent with the results of highly accurate tests, the diagnostic accuracy of rapid serological tests for SARS-CoV-2 should be assessed before introducing these tests for point-of-care testing or surveillance.
The aim of this study is to investigate myocardial damage in recovering coronavirus disease 2019 (COVID-19) patients with high-sensitivity troponin levels (hsTnT) and echocardiography. In this single-center cohort study, 215 COVID-19 recovered patients were recruited from all over Japan between April and September 2020. Demographic characteristics, hsTnT levels, and echocardiography data were collected for 209 patients, after excluding those without serum samples or good-quality echocardiographic images. The mean (± standard deviation) age was 44 (± 12) years (range: 36-55 years), and 50.7% of the patients were males. The median time interval (interquartile range) from COVID-19 onset to post-recovery examination was 56 days (34-96 days). Seventy-four recovered patients (35.4%) had hsTnT less than detection sensitivity (< 3 pg/mL) and 135 recovered patients (64.6%) had hsTnT ≥ 3 pg/mL. Ejection fraction was more than 50% in all cases. Left ventricular global longitudinal strain (LVGLS) and right ventricular free-wall longitudinal strain (RVFWLS) were reduced in 62 (29.7%) and 8 patients (3.8%), respectively. They were significantly associated with elevated hsTnT levels. In cases with hsTnT above 5 pg/mL, the LVGLS was greatly reduced to 19.0 ± 2.2% (p < 0.001). Multivariate linear regression analysis showed that elevated hsTnT level was an independent predictor of reduced LVGLS (standardized β = -0.34; p < 0.001). In recovered COVID-19 patients, even a slight increase in hsTnT above detection sensitivity was associated with decreased LVGLS. hsTnT and echocardiography may be useful tools to detect myocardial injury in recovered COVID-19 patients.
In Japan, clinical and experimental studies addressing COVID-19 have been increasing in number since early February 2020, with many case reports being published. Concurrently, many notifications and guidelines have been issued from the government and academic societies. Taking optimal measures at the prefectural level as well as the national level is necessary to prevent the spread of COVID-19. Surveying and analyzing details of the incidences of infected persons in each prefecture is extremely important. This report describes the epidemiological characteristics of COVID-19 observed in Okayama Prefecture, followed by discussion of the direction of public health actions to be taken in the future. We reiterate the crucial importance of reinforcing and maintaining current public health measures, including rapid and detailed compilation of information related to infected persons and their surroundings, appropriate blocking of viral transmission, and early containment of infected persons, to minimize the spread of infection especially during the overlapping epidemic period of influenza in Okayama Prefecture.
The quantitative reverse transcription polymerase chain reaction method using nasopharyngeal swabs (NPS RT-qPCR) is regarded as the reference standard for diagnosing coronavirus disease 2019 (COVID-19). However, when using NPS RT-qPCR at busy airport quarantine stations, there are constraints on testing capacity, time, travelers’ tolerance, and availability of personal protective equipment for quarantine officers. A feasible alternative is therefore needed to test incoming travelers, especially when passenger numbers increase with the resumption of business, tourism, and economic activities. To explore alternatives to NPS RT-qPCR, we collected nasopharyngeal, anterior nasal, and saliva samples chronologically over days 1-7 from asymptomatic COVID-19 air travelers who were under quarantine at a designated facility, and we then compared test results for 9 different methods, comprising RT-qPCR (including the reference method), loop-mediated isothermal amplification (LAMP), and qualitative and quantitative antigen testing. We evaluated sensitivity for 97 person-day samples independently to evaluate asymptomatic travelers regardless of their testing date and period of asymptomatic status upon entry. Sensitivity of the different tests varied from 46.6% to 81.0%, but this was improved from 72.7% to 100.0% when the viral load was > 104 copies/sample on NPS RT-qPCR. Thus, most high-risk asymptomatic travelers with higher viral load would be detected by the tests evaluated. Quantitative antigen testing using saliva samples showed 90.9% sensitivity and provided quicker results, and should be an acceptable alternative to NPS RT-qPCR at busy airport quarantine stations. We discuss the implications of our exploratory findings for establishing a comprehensive and feasible testing strategy for COVID-19 among air passengers.
Many large international cities, such as Shanghai, are facing the threat of more imported cases of COVID-19 because of the frequent flow of people and objects at home and abroad. In the face of the complex and changing disease status of the international community, dealing with this disease effectively is a great challenge to the city's existing public health emergency response capacity and also a major test of designated COVID-19 hospitals. Here, we share our experience as a designated COVID-19 hospital in Shanghai, China in terms of i) A Professional Multi-disciplinary Team, ii) Personalized Treatment Plans for Patients in Severe or Critically Ill Condition, iii) Well-organized Classification of Patients, iv) Establishment of Transitional Wards, v) Nosocomial Infection Prevention and Control, and vi) Identification and Reporting of the Asymptomatic in the hopes that these approaches can serve as a reference for healthcare providers and medical staff who are fighting the pandemic.
WHO Regional Office for the Western Pacific (WPRO) organized an online meeting connecting WHO Collaborating Centres (WHO CCs) in the region on 25 August 2020, to share experiences and promote networking on COVID-19 response. The meeting shared regional update on situation and responses, and COVID-19 related experiences of selected WHO CCs, followed by discussions on opportunities for enhancing collaboration between WPRO and WHO CCs. Priorities of WPRO’s support to countries included a health systems approach rather than single intervention. On behalf of WHO CCs in Japan, the National Center for Global Health and Medicine (NCGM) delivered a presentation on the results of a survey about COVID-19 related activities of these WHO CCs. These activities were categorized into collaboration with WHO, research and development, public health responses, and clinical services. Collaboration with WHO included sending consultants through the scheme of GOARN, strengthening of COVID-19 testing, and contribution to development of WPRO guidelines. Research and development involved establishment of a nationwide registry of COVID-19 clinical data. Following the meeting, NCGM further enhanced its activities as WHO CC. Since WHO CCs in the country have a wide range of expertise that could contribute to health system strengthening, it is worthwhile for the WHO CCs to consider amending existing work plans for supporting countries in the region to incorporate a health systems approach as part of COVID-19 response strategies.
COVID-19 causes very serious issues all over the world. In Japan, the number of new infections in Tokyo exceeded 2,000 for the first time on 7 January 2021, and the situation is becoming increasingly serious. Japan is in the midst of its third big outbreak. Japanese society will face several challenges regarding children's mental health during the COVID-19 pandemic. In order to develop healthy minds in children, it is important to view the changes in children's minds in a positive light and promote their healthy emotional development while correctly fearing COVID-19. This sense of social stagnation and uncertainty is likely to increase feelings of insecurity and isolation among children. It is also important to prevent the repetition of child abuse in the home due to parental unemployment, alcohol problems, and reduced contact with non-family members in stay home and the recession as a result of COVID-19. During the pandemic, adults should be sensitive to the unusual behavior of children. We propose six suggestions of care for children during the COVID-19 pandemic.
The coronavirus disease 2019 (COVID-19) pandemic has affected presentations of conditions unrelated to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection itself. We investigated the pandemic's effect on incidence and characteristics of pulmonary embolism (PE) cases without the infection. We retrospectively compared non-COVID PE patients during January 16-August 31, 2020 (COVID period) with PE patients during the same period in 2017-2019 (Pre-COVID period). The number of out-of-hospital onset cases was significantly higher during the pandemic than during each of the pre-COVID years. Also, the patients in the COVID period were older, more likely to be free of thrombotic predispositions, had higher mortality risks of PE, and were more likely to arrive at the hospital on emergency transport. Sedentary lifestyles during the pandemic seem to have had considerable effects on presentations of PE.