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

特発性拡張型心筋症の潜在的新規バイオマーカーとしての血清miRNA-489

藤田医科大

A case of angioimmunoblastic T-cell lymphoma presenting with migration of lung shadows

A 62-year-old woman presented with chronic cough. Chest CT showed multiple nodules and consolidation. Bronchoscopy could not confirm a specific diagnosis. Because her symptoms and lung opacities improved spontaneously, she was followed without treatment. Seven months later, chest radiography showed worsening of consolidation and a tumorous shadow. After performing cervical lymph node and lung tissue biopsies, we diagnosed her as having angioimmunoblastic T-cell lymphoma (AITL). Cases of AITL showing migration of lung shadows have not been reported. AITL development is influenced by immunodeficiency and reactivation of EBV, and migration of lung opacities may be related to the patient's immune status

A case of vertebral arteriovenous fistula in a patient undergoing maintenance hemodialysis

Abstract Background Vertebral arteriovenous fistula (AVF) is an uncommon vascular disorder and defined as abnormal connections of the extracranial vertebral artery or its branches into the neighboring vein or deep venous plexus. This can be spontaneous or traumatic in origin. Spontaneous cases may be congenital or associated with dysplasia of vascular wall. Traumatic cases are due either to blunt or penetrating trauma, or iatrogenic trauma. Case presentation A vertebral AVF was detected by carotid duplex ultrasonography, and an endovascular treatment was successfully performed in a 72-year-old woman with 1 year history of hemodialysis. Conclusion An extensive observation by carotid duplex ultrasonography is needed to detect vertebral AVF in patients who have a history of dialysis catheter insertion to internal jugular vein