The estimated disease burden of COVID-19 in Japan from 2020 to 2021

BackgroundTo date, it is not fully understood to what extent COVID-19 has burdened society in Japan. This study aimed to estimate the total disease burden due to COVID-19 in Japan during 2020-2021. MethodsWe stratify disease burden estimates by age group and present it as absolute Quality Adjusted Life Years (QALYs) lost and QALYs lost per 100,000 persons. The total estimated value of QALYs lost consists of (1) QALYs lost brought by deaths due to COVID-19, (2) QALYs lost brought by inpatient cases, (3) QALYs lost brought by outpatient cases, and (4) QALYs lost brought by long-COVID. FindingsQALYs lost due to COVID-19 was estimated as 286,781{middle dot}7 for two years, 114{middle dot}0 QALYs per 100,000 population per year. 71{middle dot}3% of them were explained by the burden derived from deaths. Probabilistic sensitivity analysis showed that the burden of outpatient cases was the most sensitive factor. InterpretationThe large part of disease burden due to COVID-19 in Japan from the beginning of 2020 to the end of 2021 was derived from Wave 3, 4, and 5 and the proportion of QALYs lost due to morbidity in the total burden increased gradually. The estimated disease burden was smaller than that in other high-income countries. It will be our future challenge to take other indirect factors into consideration. FundingsThis research was funded by JSPS KAKENHI [Grant number 20K10546]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Impact of dementia, living in a long-term care facility, and physical activity status on COVID-19 severity in older adults

BackgroundJapan is fast becoming an extremely aged society and older adults are known to be at risk of severe COVID-19. However, the impact of risk factors specific to this population for severe COVID-19 caused by the Omicron variant of concern (VOC) are not yet clear. MethodsWe performed an exploratory analysis using logistic regression to identify risk factors for severe COVID-19 illness among 4,868 older adults with a positive SARS-CoV-2 test result who were admitted to a healthcare facility between 1 January 2022 and 16 May 2022. We then conducted one-to-one propensity score (PS) matching for three factors--dementia, admission from a long-term care facility, and poor physical activity status--and used Fishers exact test to compare the proportion of severe COVID-19 cases in the matched data. We also estimated the average treatment effect on treated (ATT) in each PS matching analysis. ResultsOf the 4,868 cases analyzed, 1,380 were severe. Logistic regression analysis showed that age, male sex, cardiovascular disease, cerebrovascular disease, chronic lung disease, renal failure and/or dialysis, physician-diagnosed obesity, admission from a long-term care facility, and poor physical activity status were risk factors for severe disease. Vaccination and dementia were identified as factors associated with non-severe illness. The ATT for dementia, admission from a long-term care facility, and poor physical activity status was -0.04 (95% confidence interval -0.07, -0.01), 0.09 (0.06, 0.12), and 0.17 (0.14, 0.19), respectively. ConclusionsOur results suggest that poor physical activity status and living in a long-term care facility have a substantial impact on the risk of severe COVID-19 caused by the Omicron VOC, while dementia might be associated with non-severe illness.

Post COVID-19 condition of the Omicron variant of SARS-CoV-2

BackgroundNo epidemiological data on post coronavirus disease (COVID-19) condition due to Omicron variant has been reported yet. MethodsThis was as a single-center, cross-sectional study, that interviewed via telephone the patients who recovered from Omicron COVID-19 infection (Omicron group), and surveyed via self-reporting questionnaire those patients infected with other strains (control group). Data on patients characteristics, information regarding the acute-phase COVID-19, as well as presence and duration of COVID-19-related symptoms were obtained. Post COVID-19 condition in this study was defined as a symptom that lasted at least 2 months within 3 months since the onset of COVID-19. We investigated and compared the prevalence of post COVID-19 condition in both groups after performing propensity score matching. ResultsWe conducted interviews for 53 out of 128 patients with Omicron, and obtained 502 responses in the control group. After matching, 18 patients each in Omicron and control group had improved covariate balance of the older adult, female sex, obese patients, and vaccination status. There were no significant differences in the prevalence of each post-acute COVID-19 symptoms between the two groups. The numbers of patients with at least one post-acute COVID-19 symptom in the Omicron and the control group were 1 (5.6%) and 10 (55.6%) (p=0.003), respectively. ConclusionThe prevalence of post Omicron COVID-19 conditions was less than that of the other strains. Further research with more participants is needed to investigate the precise epidemiology of post COVID-19 condition of Omicron, and its impact on health-related quality of life and social productivity.

Predictive Model of Risk Factors of High Flow Nasal Cannula Using Machine Learning in COVID-19

BackgroundWith the rapid increase in the number of COVID-19 patients in Japan, the number of patients receiving oxygen at home has also increased rapidly, and some of these patients have died. An efficient approach to identify high-risk patients with slowly progressing and rapidly worsening COVID-19, and to avoid missing the timing of therapeutic intervention will improve patient prognosis and prevent medical complications. MethodsPatients admitted to medical institutions in Japan from November 14, 2020 to April 11, 2021 and registered in the COVID-19 Registry Japan were included. Risk factors for patients with High Flow Nasal Cannula invasive respiratory management or higher were comprehensively explored using machine learning. Age-specific cohorts were created, and severity prediction was performed for the patient surge period and normal times, respectively. ResultsWe were able to obtain a model that was able to predict severe disease with a sensitivity of 57% when the specificity was set at 90% for those aged 40-59 years, and with a specificity of 50% and 43% when the sensitivity was set at 90% for those aged 60-79 years and 80 years and older, respectively. We were able to identify lactate dehydrogenase level (LDH) as an important factor in predicting the severity of illness in all age groups. DiscussionUsing machine learning, we were able to identify risk factors with high accuracy, and predict the severity of the disease. Using machine learning, we were able to identify risk factors with high accuracy, and predict the severity of the disease. We plan to develop a tool that will be useful in determining the indications for hospitalisation for patients undergoing home care and early hospitalisation.

Impact of long-COVID on health-related quality of life in Japanese COVID-19 patients

BackgroundThe empirical basis for a quantitative assessment of the disease burden imposed by long-COVID is currently scant. We aimed to assess the disease burden caused by long-COVID in Japan. MethodsWe conducted a cross sectional self-report questionnaire survey. The questionnaire was mailed to 530 eligible patients, who were recovered from acute COVID-19 in April 2021. Answers were classified into two groups; participants who have no symptom and those who have any ongoing symptoms that lasted longer than four weeks at the time of the survey. We compared health-related quality of life scores estimated by the EQ-5D-3L questionnaire between these two groups after adjusting basic characteristics of the participants by propensity score matching. Results349 participants reported no symptoms and 108 reported any symptoms at the time of the survey. The participants who reported any symptoms showed a lower value on a Visual Analogue Scale (median 70 [IQR 60-80]) and on the EQ-5D-3L (median 0.81 [IQR 0.77-1.0]) than those reporting no symptoms (median 85 [IQR 75-90] and 1.0 [IQR 1.0-1.0], respectively). After adjusting for background characteristics, these trends did not change substantially (Visual Analog Scale: median 70 [IQR 60-80] vs 80 [IQR 77-90], EQ-5D-3L: median 0.81 [IQR 0.76-1.0] vs 1.0 [IQR 1.0-1.0]). ConclusionsDue to their long duration, long-COVID symptoms represent a substantial disease burden expressed in impact on health-related quality of life. Trial registrationNot applicable.

Risk factors associated with development and persistence of long COVID

BackgroundLong COVID has been a social concern. Though patient characteristics associated with developing long COVID are partially known, those associated with persisting it have not been identified. MethodsWe conducted a cross-sectional questionnaire survey of patients after COVID-19 recovery who visited the National Center for Global Health and Medicine between February 2020 and March 2021. Demographic and clinical data, and the presence and duration of long COVID were obtained. We identified factors associated with development and persistence of long COVID using multivariate logistic and linear regression analysis, respectively. ResultsWe analyzed 457 of 526 responses (response rate, 86.9%). The median age was 47 years, and 378 patients (84.4%) had mild disease in acute phase. The number of patients with any symptoms after 6 and 12 months after onset or diagnosis were 120 (26.3%) and 40 (8.8%), respectively. Women were at risk for development of fatigue (OR 2.03, 95% CI 1.31-3.14), dysosmia (OR 1.91, 95% CI 1.24-2.93), dysgeusia (OR 1.56, 95% CI 1.02-2.39), and hair loss (OR 3.00, 95% CI 1.77-5.09), and were at risk for persistence of any symptoms (coefficient 38.0, 95% CI 13.3-62.8). Younger age and low body mass index were risk factors for developing dysosmia (OR 0.96, 95% CI 0.94-0.98, and OR 0.94, 95% CI 0.89-0.99, respectively) and dysgeusia (OR 0.98, 95% CI 0.96-1.00, and OR 0.93, 95% CI 0.88-0.98, respectively). ConclusionWe identified risk factors for the persistence as well as development of long COVID. Many patients suffer from long-term residual symptoms, even in mild cases. SummaryOur cross-sectional questionnaire survey of patients recovering from COVID-19 revealed that women, young age, and low body mass index were risk factors for the development of multiple symptoms, and that even mild cases of COVID-19 suffered from long-term residual symptoms.

The burden of isolation to the individual: a comparison between isolation for COVID-19 and for other influenza-like illnesses in Japan

At present, there is scarce evidence about how much burden the isolation of COVID-19 patients is. We aimed to assess the differences between COVID-19 and other influenza like illnesses in disease burden brought by isolation. We conducted an online questionnaire survey of 302 people who had COVID-19 or other influenza-like illnesses (ILIs) and compared the burden of isolation due to sickness with one-to-one propensity score matching. The primary outcomes are the duration and productivity losses of isolation, the secondary outcome is quality of life (QOL) valuation on the day of the survey. Acute symptoms of outpatient COVID-19 and other ILIs lasted 17 (interquartile range [IQR] 9-32) and 7 (IQR 4-10) days, respectively. The length of isolation due to COVID-19 was 18 (IQR 10-33) days and that due to other ILIs was 7 (IQR 4-11) days, respectively. The monetary productivity loss of isolation due to COVID-19 was 1424.3 (IQR 825.6-2545.5) USD and that due to other ILIs was 606.1 (IQR 297.0-1090.9) USD, respectively. QOL at the time of the survey was lower in the COVID-19 group than in the "other ILIs" group (0.89 and 0.96, p = 0.001). COVID-19 infection imposes a substantial disease burden, even in patients with non-severe disease. This burden is larger for COVID-19 than other ILIs, mainly because the required isolation period is longer.

Impact of regional heterogeneity on the severity of COVID-19

BackgroundWe aimed to assess the impact of regional heterogeneity on the severity of COVID-19 in Japan. MethodsWe included 27,865 cases registered between January 2020 and February 2021 in the COVID-19 Registry of Japan to examine the relationship between the National Early Warning Score (NEWS) of COVID-19 patients on the day of admission and the prefecture where the patients live. A hierarchical Bayesian model was used to examine the random effect of each prefecture in addition to the patients backgrounds. In addition, we compared the results of two models; one model included the number of beds secured for COVID-19 patients in each prefecture as one of the fixed effects, and the other model did not. ResultsThe results indicated that the prefecture had a substantial impact on the severity of COVID-19 on admission. Even when considering the effect of the number of beds separately, the heterogeneity caused by the random effect of each prefecture affected the severity of the case on admission. ConclusionsOur analysis revealed a possible association between regional heterogeneity and increased/decreased risk of severe COVID-19 infection on admission. This heterogeneity was derived not only from the number of beds secured in each prefecture but also from other factors.

COVID-19 Vaccine Prioritisation in Japan and South Korea

BackgroundDue to a limited initial supply of COVID-19 vaccines, the prioritisation of individuals for vaccination is of utmost importance for public health. Here, we provide the optimal allocation strategy for COVID-19 vaccines according to age in Japan and South Korea. MethodsCombining national case reports, age-specific contact matrices, and observed periods between each stages of infection (Susceptible-Exposed-Infectious-Quarantined), we constructed a compartmental model. We estimated the age-stratified probability of transmission given contact (qi) using Bayesian inference method and simulated different vaccination scenarios to reduce either case numbers or death toll. We also performed sensitivity analyses on the proportion of asymptomatic cases and vaccine efficacy. FindingsThe model inferred age-stratified probability of transmission given contact (qi) showed similar age-dependent increase in Japan and South Korea. Assuming the reported COVID-19 vaccine efficacy, our results indicate that Japan and South Korea need to prioritise individuals aged 20-35 years and individuals aged over 60 years, respectively, to minimise case numbers. To minimise the death toll, both countries need to prioritise individuals aged over 75 years. These trends were not changed by proportions of asymptomatic cases and varying vaccine efficacy on individuals under 20 years. InterpretationWe presented the optimal vaccination strategy for Japan and South Korea. Comparing the results of these countries demonstrates that not only the effective contact rates containing qi but also the age-demographics of current epidemic in Japan (dominance in 20s) and South Korea (dominant cases over 50s) affect vaccine allocation strategy.

Risk factors for severity on admission and the disease progression during hospitalization in a large cohort of COVID-19 patients in Japan

ObjectivesTo investigate the risk factors contributing to severity on admission. Additionally, risk factors on worst severity and fatality were studied. Moreover, factors were compared based on three points: early severity, worst severity, and fatality. DesignA observational cohort study utilizing data entered in a Japan nationwide COVID-19 inpatient registry, COVIREGI-JP. SettingAs of August 31, 2020, 7,546 cases from 780 facilities have been registered. Participating facilities cover a wide range of hospitals where COVID-19 patients are admitted in Japan. ParticipantsParticipants who had a positive test result on any applicable SARS-CoV-2 diagnostic tests, and were admitted to participating healthcare facilities. A total of 3,829 cases were identified from January 16 to May 31, 2020, of which 3,376 cases were included in this study. Primary and secondary outcoe measuresPrimary outcome was severe or non-severe on admission, determined by the requirement of mechanical ventilation or oxygen therapy, SpO2, or respiratory rate. Secondary outcome was the worst severity during hospitalization, judged by the requirement of oxygen and/or IMV/ECMO. ResultsRisk factors for severity on admission were older age, male, cardiovascular disease, chronic respiratory disease, diabetes, obesity, and hypertension. Cerebrovascular disease, liver disease, renal disease or dialysis, solid tumor, and hyperlipidemia did not influence severity on admission; however it influenced worst severity. Fatality rates for obesity, hypertension, and hyperlipidemia were relatively lower. ConclusionsThis study segregated the comorbidities driving severity and death. It is possible that risk factors for severity on admission, worst severity, and fatality are not consistent and may be propelled by different factors. Specifically, while hypertension, hyperlipidemia, and obesity had major effect on worst severity, their impact was mild on fatality in the Japanese population. Some studies contradict our results; therefore, detailed analyses, considering in-hospital treatments, are needed for validation. Trial registrationUMIN000039873. https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000045453 Strengths and limitations of this studyO_LIIn this article, we studied the disease progression of COVID-19, by comparing the risk factors on three points: early severity, worst severity, and fatality. C_LIO_LIOur results are useful from a public health perspective, as we provide risk factors for predicting the severity on admission and disease progression from patients background factors. C_LIO_LIThis study pointed out the possibility that risk factors of the severity on admission, worst severity, and fatality are not consistent and may be propelled by different factors. C_LIO_LIOur data were collected from hundreds of healthcare facilities; thus data accuracy may be questionable. C_LIO_LIAlso, treatment type, dosage, duration, and combination varied immensely across the facilities and we did not consider treatments prior to and during hospitalization in the analysis. C_LI

Efficacy of remdesivir in Japanese patients hospitalised with COVID-19: A large observational study using the COVID-19 Registry Japan

ObjectivesAlthough several randomised controlled trials have compared the efficacy of remdesivir with that of placebo, there is limited evidence regarding its effect in the early stage of nonsevere COVID-19 cases. MethodsWe evaluated the efficacy of remdesivir on the early stage of nonsevere COVID-19 using the COVID-19 Registry Japan, a nationwide registry of hospitalised COVID-19 patients in Japan. Two regimens (start remdesivir therapy within 4 days from admission vs. no remdesivir during hospitalisation) among patients without the need for supplementary oxygen therapy were compared by a three-step processing (cloning, censoring, and weighting) method. The primary outcome was supplementary oxygen requirement during hospitalisation. Secondary outcomes were 30-day fatality risk and risk of invasive mechanical ventilation or extracorporeal membrane oxygenation (IMV/ECMO). ResultsThe data of 12,657 cases met our inclusion criteria. The start remdesivir regimen showed a lower risk of supplementary oxygen requirement (hazard ratio: 0.861, p < 0.001). Both 30-day fatality risk and risk of IMV/ECMO introduction were not significantly different between the two regimens (hazard ratios: 1.05 and 0.886, p values: 0.070 and 0.440, respectively). ConclusionsRemdesivir might reduce the risk of oxygen requirement during hospitalisation in the early stage of COVID-19; however, it had no positive effect on the clinical outcome and reduction of IMV/ECMO requirement.

Effect of evacuation of Japanese residents from Wuhan, China, on preventing transmission of novel coronavirus infection: a modelling study

ObjectiveIn late January 2020, the Japanese government carried out three evacuations by aircraft from Wuhan, China, to avoid further cases of coronavirus disease 2019 (COVID-19) among Wuhans Japanese residents. Evacuation by aircraft may be an effective countermeasure against outbreaks of infectious diseases, but evidence of its effect is scarce. This study estimated how many COVID-19 cases were prevented among the Japanese residents of Wuhan by the evacuation countermeasure. ResultsEleven imported COVID-19 cases were reported on Feb 1 from among the total 566 evacuees who returned to Japan. In the case of no evacuations being made, the cumulative number of COVID-19 cases among Wuhans Japanese residents was estimated to reach 25 (95% CI [20, 29]) on Feb 8 and 34 (95% CI [28, 40]) on Feb 15. A 1-week delay in the evacuation might be led to 14 additional cases and a 2-week delay to 23 additional cases. Evacuation by aircraft can contribute substantially to reducing the number of infected cases in the initial stage of the outbreak.