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

セイジン カンゴガク ジッシュウ オヨビ ロウネン カンゴガク ジッシュウ ニオイテ カンゴガクセイ ガ ケンガク マタハ ジッシ シタ カンゴ キホン ギジュツ ノ ジッタイ ガクセイ ニヨル ジコヒョウカ チョウサ ノ ブンセキヨリ

看護系大学一校の成人看護学実習および老年看護学実習における看護学生の看護基本技術についてその見学または実施状況を明らかにし, 今後の講義・演習の内容や, 実習カリキュラムと実習施設, 実習指導の在り方等を検討するための基礎資料とすることを目的に, 文献等から選定した看護基本技術118項目の「見学」または「指導者の助言・監督下で実施」について調査した. 同大学で領域別看護学実習を履修した4年生のうち協力の得られた79名(回答率98.8%)のデータを分析した結果, 成人看護学実習・老年看護学実習の全般において, 環境整備, 清潔ケア, バイタルサイン測定, 病態・症状観察等の看護基本技術を見学または実施した学生が過半数を超えた. 一方, 呼吸, 排泄, 与薬, 救急, 症状・生体機能管理, 感染予防面の看護基本技術の見学または実施は, 全体の4分の1程度にとどまった. 学生が, 多様な治療を受ける患者の看護を学ぶことを通し, 臨地実習の場で見学や実施したことを振り返り, そして現象を関連付けて理解できる実習を編成することの重要性が示唆された.The purpose of this survey is to identify the current status of fundamental nursing skills performed by nursing students in adult and gerontological nursing practicums incorporated as part of a four-year baccalaureate nursing program. There were 118 survey items about fundamental nursing skills selected from the related literature. For each fundamental nursing skill the respondents were asked to answer, "have observed demonstration of this skill", "have performed this skill under the supervision of clinical nurse instructors" or "have not had any chance for observation or performance". Seventy-nine senior students (response rate: 98.8%) agreed to fill in and submit the survey sheet. The survey showed that more than half of the respondents had observed demonstration of, or had performed under supervision, such fundamental skills as management of the environment of care (cleanliness and safety of hospital beds and rooms), personal and hygiene care, vital sign measurement, assessment and monitoring of signs and symptoms in either adult or gerontological nursing practicum, or in both. In addition, about less than one-fourths of the respondents reported that they had observed demonstration of, or had performed under supervision, skills like respiratory care, elimination care, medication, monitoring and maintenance of vital functions and infection control. These results indicate the importance of arranging nursing practicums in such a way that students can learn a variety of nursing interventions and clinical skills in diverse care settings. Furthermore, nursing students need to be encouraged to learn through observation, performance under supervision and reflection so that they can understand the meaning of a variety of interconnected phenomena