Potential Biases of the Transmission Risks of COVID-19 estimated by Contact Tracing Surveys in Japan

Introduction: Contact tracing surveys are being conducted to identify and isolate close contacts of an identified patient to reduce the spread of coronavirus disease (COVID-19). However, the estimates of risk indexes based on information obtained from the surveys and normally used in practice can have biases comparing with true magnitude of risks of infection and spread.Method: We evaluated whether the estimates of the risk indexes obtained from information of the active epidemiological surveillance, contact tracing surveys in Japan, are suitable for quantitative assessment of the risk factors of COVID-19, using pseudo data via a simulation study. We discussed two types of risks considered in the issue of infectious disease, the probability of infection and that of spreading, and the estimates of these risks.Results and Discussion: A naive method to estimate the risks of infection and spreading of COVID-19 is to calculate the ratio of infected patients to close contacts and the ratio of patients who infected others to all the confirmed patients, respectively. However, these estimates could possibly have significant biases and result in being ineffective for both the exploration and the quantitative assessment of the risk factors in the following ordinary cases: a person contacts closely with many confirmed patients, or a confirmed patient contact closely with many people. Then, some steps are needed to reduce such possible biases for the estimation the risks of both the infection and spreading of COVID-19

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Table_1_Do changes in working hours increase stress in Japanese white-collar workers?.DOCX

IntroductionHigh stress at work is associated with negative health outcomes for workers, making stress prevention a critical challenge. Overtime work is an influential stress factor. This study, therefore, aimed to longitudinally evaluate how stress increased depending on changes in working hours among Japanese white-collar workers.MethodsWe targeted 3,874 participants who were full-time workers and were recognized as having low stress in a web-based cohort in 2018 (T1) and 2019 (T2). We performed univariate and multivariate logistic regression with the following variables: years of experience, years of education, medical background, income, and roommates.ResultsWe observed a greater increase in stress among female who worked 41–50 h per week at T1 and more than 50 hours per week at T2, and those who worked more than 50 h per week at T1 and 35–40/41–50 h per week at T2, compared to those who worked 41–50 h per week both at T1 and T2, with odds ratios (ORs) and 95% confidence intervals (95% CI) of OR = 2.09, 95% CI (1.18, 3,70); OR =1.86, 95% CI (1.14, 3.03), respectively. However, no association between change in working hours and stress was found among male.DiscussionThese results show that reducing stress requires decreasing working hours as well as identifying factors that lead to high stress.</p

Effect of overweight/obesity and metabolic syndrome on frailty in middle‐aged and older Japanese adults

Abstract Background The potential for developing frailty exists in middle‐aged and older adults. While obesity and metabolic syndrome (MetS) increase the risk of frailty in older adults, this relationship remains unclear in middle‐aged adults, who are prone to developing lifestyle‐related diseases. Objective To examine the effect of overweight/obesity and MetS on frailty development in middle‐aged and older Japanese adults using real‐world data. Methods This nationwide cohort study used exhaustive health insurance claims data of 3,958,708 Japanese people from 2015 to 2019 provided by the Japan Health Insurance Association. Participants aged ≥35 and < 70 years who received health checkups in 2015 were included. Multivariate logistic regression was used to assess the effect of body mass index (BMI) and MetS or MetS components (i.e., diabetes, hypertension, and dyslipidemia) in 2015 on frailty risk assessed using the hospital frailty risk score in 2019. Additionally, a subgroup analysis was performed to examine the interaction effects of MetS components and 4‐year weight change (%) on frailty risk among participants who were overweight and obese (BMI ≥25 kg/m2). Results In 2019, 7204 (0.2%) and 253,671 (6.4%) participants were at high and intermediate frailty risks, respectively. Obesity and MetS were independently associated with intermediate/high frailty risk (odds ratio (OR) 1.36, p < 0.05; OR 1.23, p < 0.05, respectively) and high frailty risk (OR 1.80, p < 0.05; OR 1.37, p < 0.05, respectively) in all participants. Although all MetS components were frailty risk factors, these effects diminished with age in both sexes. Subgroup analysis of patients with diabetes revealed that 5%–10% weight loss was associated with reduced frailty risk in both sexes. Conclusions Obesity, MetS, and MetS components were independent frailty risk factors in middle‐aged and older Japanese adults. Weight loss of up to 10% over 4 years prevented frailty in patients with diabetes who were overweight and obese

Prevalences of disease labels in patients with the top 10% cost and low to medium cost.

Prevalences of disease labels in patients with the top 10% cost and low to medium cost.</p

Demographic characteristics of the patients with the top 10% cost and low to medium cost.

Demographic characteristics of the patients with the top 10% cost and low to medium cost.</p

Forty-six chronic disease labels classified by the ICD10 codes.

Forty-six chronic disease labels classified by the ICD10 codes.</p