Association Between Life Expectancy at Age 60 Years Before the COVID-19 Pandemic and Excess Mortality During the Pandemic in Aging Countries.

This cross-sectional study investigates the association between life expectancy before COVID-19 and excess mortality during the pandemic in aging countries.

SARS-CoV-2 Infection upon Leaving the Tokyo 2020 Olympic and Paralympic Games.

Objective Just before the Tokyo 2020 Olympic and Paralympic Games in Japan, the number of people infected with coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), started to increase at an unprecedented rate. This study investigated the effectiveness of vaccines in large-scale sporting events under difficult circumstances, such as during adherence to a bubble system and confinement inside the Olympic/Paralympic Village. Methods In collaboration with medical clinics inside and outside the Village, a prospective cohort study was conducted among overseas participants using the results of polymerase chain reaction (PCR) tests for SARS-CoV-2 upon leaving Japan. Results A total of 12,072 foreign participants were enrolled, 13 (0.11%) of whom had a positive PCR test result. None of these cases were broadcasters or members of the press, were tested outside the Olympic Village, or had a history of COVID-19 infection. The effectiveness of full vaccination and vaccination at least once (≥14 days ago) was 74% (95% confidence interval [CI]: 6-93%) and 81% (95% CI: 30-95%), respectively. Three breakthrough infections with the Delta variant were observed in 6,485 fully vaccinated participants (0.05%). The positivity rate was 0.09% among adherents to the bubble system and 0.28% among non-adherents, but this difference was not significant. Conclusion These findings indicate that even huge sporting events such as the Olympic and Paralympic Games can proceed while pandemics are ongoing in the host country by combining countermeasures such as vaccination, frequent testing, social distancing, and adherence to a bubble system.

Tokyo and New York: A Study in the Contrasting Effects of Socioeconomic Status on Coronavirus Disease 2019 Outcomes.

OBJECTIVES: It is still not known why cases of coronavirus disease 2019 during the first wave in Tokyo have fallen without lockdown restrictions. People with low socioeconomic status are not dominant among coronavirus disease 2019 patients in Tokyo in contrast with New York, where the opposite demographics have been in play. Thus, we set out to examine the association between socioeconomic status and the rate of coronavirus disease 2019 infections using public data from Tokyo. DESIGN: We obtained data from each of the 23 wards of Tokyo, showing population size, density, age, sex, number of graduates, income, and hospital attendance numbers. Coronavirus disease 2019 infections were gathered for 2 separate days: April 9, 2020, when new daily coronavirus disease 2019 infections were at their peak during the first wave in Japan; and May 9, 2020, to observe any changes in incidence over the preceding month. SETTING: The primary outcome was set as the number of coronavirus disease 2019 infections per 100,000 population. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: By conducting simple linear regression modeling, the incidence of cases on April 9 was associated significantly with four variables: population age greater than 65 years (%), university rate, hospital, and income. Using these four variables, multivariate linear regression analyses demonstrated that only income remained significant (p = 0.006 at April 9 and p = 0.03 at May 9). This indicates that the highest case numbers were dominant in high-income areas, and affected fewer patients in districts in the low-income areas. CONCLUSIONS: The result of the current study is exactly opposite to the data from New York. This may be considered one of the main reasons why the rate of death and new patients of coronavirus disease 2019 has been so low in Tokyo. That is, appropriate hygienic status, free access to hospital by ambulance, and universal health insurance system may contribute to the outcome in such low-income areas.

Vitamin D supplementation to prevent acute respiratory infections: a systematic review and meta-analysis of aggregate data from randomised controlled trials.

BACKGROUND: A 2017 meta-analysis of data from 25 randomised controlled trials (RCTs) of vitamin D supplementation for the prevention of acute respiratory infections (ARIs) revealed a protective effect of this intervention. We aimed to examine the link between vitamin D supplementation and prevention of ARIs in an updated meta-analysis. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, and the ClinicalTrials.gov registry for studies listed from database inception to May 1, 2020. Double-blind RCTs of vitamin D3, vitamin D2, or 25-hydroxyvitamin D (25[OH]D) supplementation for any duration, with a placebo or low-dose vitamin D control, were eligible if they had been approved by a research ethics committee, and if ARI incidence was collected prospectively and prespecified as an efficacy outcome. Studies reporting results of long-term follow-up of primary RCTs were excluded. Aggregated study-level data, stratified by baseline 25(OH)D concentration and age, were obtained from study authors. Using the proportion of participants in each trial who had one or more ARIs, we did a random-effects meta-analysis to obtain pooled odds ratios (ORs) and 95% CIs to estimate the effect of vitamin D supplementation on the risk of having one or more ARIs (primary outcome) compared with placebo. Subgroup analyses were done to estimate whether the effects of vitamin D supplementation on the risk of ARI varied according to baseline 25(OH)D concentration (<25 nmol/L vs 25·0-49·9 nmol/L vs 50·0-74·9 nmol/L vs >75·0 nmol/L), vitamin D dose (daily equivalent of <400 international units [IU] vs 400-1000 IU vs 1001-2000 IU vs >2000 IU), dosing frequency (daily vs weekly vs once per month to once every 3 months), trial duration (≤12 months vs >12 months), age at enrolment (<1·00 years vs 1·00-15·99 years vs 16·00-64·99 years vs ≥65·00 years), and presence versus absence of airway disease (ie, asthma only, COPD only, or unrestricted). Risk of bias was assessed with the Cochrane Collaboration Risk of Bias Tool. The study was registered with PROSPERO, CRD42020190633. FINDINGS: We identified 1528 articles, of which 46 RCTs (75 541 participants) were eligible. Data for the primary outcome were obtained for 48 488 (98·1%) of 49 419 participants (aged 0-95 years) in 43 studies. A significantly lower proportion of participants in the vitamin D supplementation group had one or more ARIs (14 332 [61·3%] of 23 364 participants) than in the placebo group (14 217 [62·3%] of 22 802 participants), with an OR of 0·92 (95% CI 0·86-0·99; 37 studies; I2=35·6%, pheterogeneity=0·018). No significant effect of vitamin D supplementation on the risk of having one or more ARIs was observed for any of the subgroups defined by baseline 25(OH)D concentration. However, protective effects of supplementation were observed in trials in which vitamin D was given in a daily dosing regimen (OR 0·78 [95% CI 0·65-0·94]; 19 studies; I2=53·5%, pheterogeneity=0·003), at daily dose equivalents of 400-1000 IU (0·70 [0·55-0·89]; ten studies; I2=31·2%, pheterogeneity=0·16), for a duration of 12 months or less (0·82 [0·72-0·93]; 29 studies; I2=38·1%, pheterogeneity=0·021), and to participants aged 1·00-15·99 years at enrolment (0·71 [0·57-0·90]; 15 studies; I2=46·0%, pheterogeneity=0·027). No significant interaction between allocation to the vitamin D supplementation group versus the placebo group and dose, dose frequency, study duration, or age was observed. In addition, no significant difference in the proportion of participants who had at least one serious adverse event in the vitamin supplementation group compared with the placebo group was observed (0·97 [0·86-1·07]; 36 studies; I2=0·0%, pheterogeneity=0·99). Risk of bias within individual studies was assessed as being low for all but three trials. INTERPRETATION: Despite evidence of significant heterogeneity across trials, vitamin D supplementation was safe and overall reduced the risk of ARI compared with placebo, although the risk reduction was small. Protection was associated with administration of daily doses of 400-1000 IU for up to 12 months, and age at enrolment of 1·00-15·99 years. The relevance of these findings to COVID-19 is not known and requires further investigation. FUNDING: None.

Differential Kinetics of Cycle Threshold Values during Admission by Symptoms among Patients with Mild COVID-19: A Prospective Cohort Study.

In the coronavirus disease 2019 (COVID-19) pandemic, more than half of the cases of transmission may occur via asymptomatic individuals, which makes it difficult to contain. However, whether viral load in the throat during admission is different between asymptomatic and symptomatic patients is not well known. By conducting a prospective cohort study of patients with asymptomatic or mild COVID-19, cycle threshold (Ct) values of the polymerase chain reaction test for COVID-19 were examined every other day during admission. The Ct values during admission increased more steadily in symptomatic patients and febrile patients than in asymptomatic patients, with significance (p = 0.01 and p = 0.004, respectively), although the Ct values as a whole were not significantly different between the two groups. Moreover, the Ct values as a whole were higher in patients with dysosmia/dysgeusia than in those without it (p = 0.02), whereas they were lower in patients with a headache than those without (p = 0.01). Patients who were IgG-positive at discharge maintained higher Ct values, e.g., more than 35, during admission than those with IgG-negative (p = 0.03). Assuming that viral load and Ct values are negatively associated, the viral loads as a whole and their changes by time may be different by symptoms and immune reaction, i.e., IgG-positive at discharge.

Vitamin D supplementation to prevent acute respiratory infections: systematic review and meta-analysis of aggregate data from randomised controlled trials.

BACKGROUND: A 2017 meta-analysis of data from 25 randomised controlled trials of vitamin D supplementation for the prevention of acute respiratory infections revealed a protective effect of the intervention. Since then, 20 new RCTs have been completed. METHODS: Systematic review and meta-analysis of data from randomised controlled trials (RCTs) of vitamin D for ARI prevention using a random effects model. Pre-specified sub-group analyses were done to determine whether effects of vitamin D on risk of ARI varied according to baseline 25-hydroxyvitamin D (25[OH]D) concentration or dosing regimen. We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science and the ClinicalTrials.gov registry from inception to 1st May 2020. Double-blind RCTs of supplementation with vitamin D or calcidiol, of any duration, were eligible if they were approved by a Research Ethics Committee and if ARI incidence was collected prospectively and pre-specified as an efficacy outcome. Aggregate data, stratified by baseline 25(OH)D concentration, were obtained from study authors. The study was registered with PROSPERO (no. CRD42020190633). FINDINGS: We identified 45 eligible RCTs (total 73,384 participants). Data were obtained for 46,331 (98.0%) of 47,262 participants in 42 studies, aged 0 to 95 years. For the primary comparison of vitamin D supplementation vs. placebo, the intervention reduced risk of ARI overall (Odds Ratio [OR] 0.91, 95% CI 0.84 to 0.99; P for heterogeneity 0.01). No statistically significant effect of vitamin D was seen for any of the sub-groups defined by baseline 25(OH)D concentration. However, protective effects were seen for trials in which vitamin D was given using a daily dosing regimen (OR 0.75, 95% CI 0.61 to 0.93); at daily dose equivalents of 400-1000 IU (OR 0.70, 95% CI 0.55 to 0.89); and for a duration of ≤12 months (OR 0.82, 95% CI 0.72 to 0.93). No significant interaction was seen between allocation to vitamin D vs. placebo and dose frequency, dose size, or study duration. Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (OR 0.97, 95% CI 0.86 to 1.09). Risk of bias within individual studies was assessed as being low for all but three trials. A funnel plot showed left-sided asymmetry (P=0.008, Egger's test). INTERPRETATION: Vitamin D supplementation was safe and reduced risk of ARI, despite evidence of significant heterogeneity across trials. Protection was associated with administration of daily doses of 400-1000 IU vitamin D for up to 12 months. The relevance of these findings to COVID-19 is not known and requires investigation. FUNDING: None.

Relationship Between the Number of Patients Visiting Emergency Department and Tokyo Health System's Capacity During Early Stages of the First Wave of COVID-19.

The first coronavirus 2019 (COVID-19) patients were reported in China on December 12, 2019, and the first COVID-19 patients were reported in Japan on January 16, 2020. Here, we investigated the number of patients in Emergency Departments (EDs) in three major hospitals in Tokyo, and also briefly discussed about the relationship between the number of patients in EDs and health system's capacity. We compared the number of patients in 2020 to the average number of patients from 2016 to 2019. Numbers were compared in three periods: before the first COVID-19 patient was reported in Japan (January 1 to January 16), after the government encouraged social distancing (February 26 to March 10), and the interval between them (January 17 to February 25). The average number of daily patients in 2020 (n = 122) decreased by 17% compared to the average number of patients from 2016 to 2019 (n = 144) (Mann-Whitney test, p < 0.001). This phenomenon might be due to a fear of contracting the virus at hospitals, companies having their employees work remotely and postponing events, people following the Japanese Ministry of Health, Labour and Welfare's instructional guidelines for going to the hospital, prevention awareness becoming widespread, and a decreased number of tourists. The number of patients visiting Emergency Departments in Tokyo was decreased and the number of COVID-19 infections has remained within the health system's capacity during the early phase of COVID-19 first wave.

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.

BCG Vaccination and Mortality of COVID-19 across 173 Countries: An Ecological Study.

Ecological studies have suggested fewer COVID-19 morbidities and mortalities in Bacillus Calmette-Guérin (BCG)-vaccinated countries than BCG-non-vaccinated countries. However, these studies obtained data during the early phase of the pandemic and did not adjust for potential confounders, including PCR-test numbers per population (PCR-tests). Currently-more than four months after declaration of the pandemic-the BCG-hypothesis needs reexamining. An ecological study was conducted by obtaining data of 61 factors in 173 countries, including BCG vaccine coverage (%), using morbidity and mortality as outcomes, obtained from open resources. 'Urban population (%)' and 'insufficient physical activity (%)' in each country was positively associated with morbidity, but not mortality, after adjustment for PCR-tests. On the other hand, recent BCG vaccine coverage (%) was negatively associated with mortality, but not morbidity, even with adjustment for percentage of the population ≥ 60 years of age, morbidity, PCR-tests and other factors. The results of this study generated a hypothesis that a national BCG vaccination program seems to be associated with reduced mortality of COVID-19, although this needs to be further examined and proved by randomized clinical trials.