HLA-B*15:01-positive severe COVID-19 patients lack CD8 T cell pools with highly expanded public clonotypes.

Understanding host factors driving asymptomatic versus severe disease outcomes is of key importance if we are to control emerging and re-emerging viral infections. HLA-B*15:01 has been associated with asymptomatic SARS-CoV-2 infection in nonhospitalized individuals of European ancestry, with protective immunity attributed to preexisting cross-reactive CD8 T-cells directed against HLA-B*15:01-restricted Spike-derived S peptide (B15/SCD8 T-cells). However, fundamental questions remained on the abundance and clonotypic nature of CD8 T-cell responses in HLA-B*15:01-positive patients who succumbed to life-threatening COVID-19.

Identification and replication of sex-dimorphic protein quantitative trait loci across multiple ancestries and their associations with diseases.

Males and females exhibit differences in proteome profiles associated with disease risk. However, sex-dimorphic protein quantitative trait loci (SD-pQTL) and their effects on sex differences in health disorders have not been thoroughly investigated. We conducted a sex-stratified, genome-wide association study on 2,922 proteins using data from 30,272 individuals of Caucasian ancestry from the UK Biobank and compared the estimated effects on protein levels of these variants in the men and women to identify SD-pQTLs.

Breakthrough Infection After a Primary Series of COVID-19 Vaccination Induces Stronger Humoral Immunity and Equivalent Cellular Immunity to the Spike Protein Compared with Booster Shots.

The long-term immune implications of administering more than four doses of COVID-19 vaccine and the impact of breakthrough infections are not fully understood. We conducted a follow-up cohort study on Japanese healthcare workers who received more than three doses of the BNT162b2 vaccine. We assessed both the anti-SARS-CoV-2 antibody titer and cellular immunity in 429 participants and investigated the numbers, types, and brands of COVID-19 vaccines administered, as well as the episodes of COVID-19 infections after the third dose.

Deciphering state-dependent immune features from multi-layer omics data at single-cell resolution.

Current molecular quantitative trait locus catalogs are mostly at bulk resolution and centered on Europeans. Here, we constructed an immune cell atlas with single-cell transcriptomics of >1.5 million peripheral blood mononuclear cells, host genetics, plasma proteomics and gut metagenomics from 235 Japanese persons, including patients with coronavirus disease 2019 (COVID-19) and healthy individuals.

Induced lung epithelial-like cells derived by direct reprogramming rescue influenza virus-induced lung injury in mice.

We recently reported that a combination of four transcription factors (Nkx2-1, Foxa1, Foxa2, and Gata6) directly reprograms mouse embryonic fibroblasts (MEFs) into differentiated self-renewable alveolar epithelial-like cells in a serum-free 3D organoid system. Here, we aimed to generate induced pulmonary epithelial-like cells in serum-containing culture (iPULsSC) using the same four transcription factors in a serum-containing 3D culture system. We found that the global gene expression profile of iPULsSC was similar to that of alveolar epithelial type II (AT2) and alveolar type I (AT1) cells.

Cefiderocol susceptibility of Stenotrophomonas maltophilia species complex and carbapenem-resistant Pseudomonas aeruginosa isolates from blood cultures at a university hospital in Tokyo, Japan.

Objective: Cefiderocol, a siderophore cephalosporin, has shown promise against carbapenem-resistant strains such as Pseudomonas aeruginosa and Stenotrophomonas maltophilia species complex. Despite its recent approval in Japan, susceptibility data remain limited. Therefore, this study evaluated the cefiderocol susceptibility of carbapenem-resistant P.

Direct reprogramming of mouse fibroblasts into self-renewable alveolar epithelial-like cells.

Direct reprogramming is a breakthrough technology that can alter the fate of cells without the passage of stem cells. However, direct reprogramming of somatic cells into pulmonary alveolar epithelial cells has not yet been achieved. Here, we report the direct reprogramming of mouse tail tips and embryonic fibroblasts into induced pulmonary alveolar epithelial-like cells (iPULs) using four transcription factor-coding genes (Nkx2-1, Foxa1, Foxa2, and Gata6) and three-dimensional culture.

Unraveling the COVID-19 Severity Hubs and Interplays in Inflammatory-Related RNA-Protein Networks.

The rapid worldwide transmission of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to severe cases of hypoxia, acute respiratory distress syndrome, multi-organ failure, and ultimately death. Small-scale molecular interactions have been analyzed by focusing on several genes/single genes, providing important insights; however, genome-wide multi-omics comprehensive molecular interactions have not yet been well investigated with the exception of GWAS and eQTLm, both of which show genetic risks. From April of 2020 until now, we have created a Japan-wide system, initially named the Japan COVID-19 Task Force.

Impact of long COVID on the health-related quality of life of Japanese patients: A prospective nationwide cohort study.

Background: Various prolonged systemic symptoms, forming the long coronavirus disease (COVID), have been observed in patients who have recovered from the acute phase of COVID-19. Although previous studies have reported that COVID-19 impacts health-related quality of life (HRQoL), the associations of long COVID symptoms and clinical characteristics with HRQoL remain unclear. This study aimed to clarify these associations using nationwide Japanese epidemiological data.

JOB: Japan Omics Browser provides integrative visualization of multi-omics data.

We present the Japan Omics Browser (JOB), which enables integrative analysis of human omics at different layers. JOB offers visualization of per-variant regulatory effects in the human blood at mRNA and protein level distinctively, quantified from statistical fine-mapping of mRNA-expression quantitative loci (eQTL) and protein QTLs (pQTLs) in 1,405 Japanese, together with fine-mapping results of 94 complex traits in UK Biobank. In addition, JOB shows per-tissue regulatory effect prediction score (EMS), trained via multi-task learning.

Intermittent versus Daily Therapy for Noncavitary Complex Pulmonary Disease: An Open-Label Randomized Trial.

Patients with noncavitary nodular bronchiectatic (NB) complex pulmonary disease (MAC-PD) are treated intermittently three times per week, although no randomized controlled trials have been conducted comparing three times weekly with daily therapy. To assess the tolerability, safety, and efficacy of intermittent versus daily treatment in patients with previously untreated noncavitary NB MAC-PD. In an open-label study, patients were randomly assigned to the intermittent therapy group receiving clarithromycin 1,000 mg, rifampicin 600 mg, and ethambutol 25 mg/kg (maximum 1,000 mg) three days per week or the daily therapy group receiving clarithromycin 800 mg, rifampicin 450 mg, and ethambutol 15 mg/kg (maximum 750 mg) daily for 1 year.

Predicting coronavirus disease 2019 severity using explainable artificial intelligence techniques.

Predictive models for determining coronavirus disease 2019 (COVID-19) severity have been established; however, the complexity of the interactions among factors limits the use of conventional statistical methods. This study aimed to establish a simple and accurate predictive model for COVID-19 severity using an explainable machine learning approach. A total of 3,301 patients ≥ 18 years diagnosed with COVID-19 between February 2020 and October 2022 were included.

Germline variants and mosaic chromosomal alterations affect COVID-19 vaccine immunogenicity.

Vaccine immunogenicity is influenced by the vaccinee's genetic background. Here, we perform a genome-wide association study of vaccine-induced SARS-CoV-2-specific immunoglobulin G (IgG) antibody titers and T cell immune responses in 1,559 mRNA-1273 and 537 BNT162b2 vaccinees of Japanese ancestry. SARS-CoV-2-specific antibody titers are associated with the immunoglobulin heavy chain (IGH) and major histocompatibility complex (MHC) locus, and T cell responses are associated with MHC.

Contribution of germline and somatic mutations to risk of neuromyelitis optica spectrum disorder.

Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disease characterized by optic neuritis and transverse myelitis, with an unclear genetic background. A genome-wide meta-analysis of NMOSD in Japanese individuals (240 patients and 50,578 controls) identified significant associations with the major histocompatibility complex region and a common variant close to CCR6 (rs12193698; p = 1.8 × 10, odds ratio [OR] = 1.

Erector Spinae Muscle to Epicardial Visceral Fat Ratio on Chest CT Predicts the Severity of Coronavirus Disease 2019.

Background: Chest computed tomography (CT) is a valuable tool for diagnosing and predicting the severity of coronavirus disease 2019 (COVID-19) and assessing extrapulmonary organs. Reduced muscle mass and visceral fat accumulation are important features of a body composition phenotype in which obesity and muscle loss coexist, but their relationship with COVID-19 outcomes remains unclear. In this study, we aimed to investigate the association between the erector spinae muscle (ESM) to epicardial adipose tissue (EAT) ratio (ESM/EAT) on chest CT and disease severity in patients with COVID-19.

Coronary Artery Calcification on Chest Computed Tomography as a Predictor of Cardiovascular Adverse Events in Patients With COVID-19 - A Multicenter Retrospective Study in Japan.

Background: Coronary artery calcification (CAC) detected through chest computed tomography (CT) strongly predicts cardiovascular events in asymptomatic individuals undergoing primary prevention. Few studies with limited sample sizes have investigated the predictive value of CAC for cardiovascular complications in COVID-19. This study examined the impact of CAC on cardiovascular complications using a large-scale COVID-19 database.

Blood DNA virome associates with autoimmune diseases and COVID-19.

Aberrant immune responses to viral pathogens contribute to pathogenesis, but our understanding of pathological immune responses caused by viruses within the human virome, especially at a population scale, remains limited. We analyzed whole-genome sequencing datasets of 6,321 Japanese individuals, including patients with autoimmune diseases (psoriasis vulgaris, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), pulmonary alveolar proteinosis (PAP) or multiple sclerosis) and coronavirus disease 2019 (COVID-19), or healthy controls. We systematically quantified two constituents of the blood DNA virome, endogenous HHV-6 (eHHV-6) and anellovirus.

The relationship between long COVID, labor productivity, and socioeconomic losses in Japan: A cohort study.

Objectives: We examined shifts in labor productivity and their economic ramifications among adult patients with long COVID in Japan.

Methods: A total of 396 patients were categorized into three groups based on symptom progression: non-long COVID, long COVID recovered, and long COVID persistent. Patient-reported outcomes were assessed at three time intervals: 3, 6, and 12 months after COVID-19 diagnosis.

Sectm1a Depletion Promotes Neutrophil Recruitment during Pneumococcal Pneumonia.

Airway epithelial cells (AECs) play an essential role in the immune response during bacterial pneumonia. Secreted and transmembrane 1a (Sectm1a) is specifically expressed in AECs during early (SP) infection. However, its function remains largely unexplored.

Optimal incubation duration of liquid cultures for assessing culture negative conversion in patients with Mycobacterium avium complex and Mycobacterium abscessus pulmonary diseases.

Purpose: Mycobacterial liquid culturing typically requires six weeks or longer, primarily because of the slow growth rate of Mycobacterium tuberculosis. This study aimed to evaluate the potential of shortening the duration of mycobacterial liquid culturing in healthcare settings with high prevalence rates of non-tuberculous mycobacteria.

Methods: We retrospectively analyzed the relationship between mycobacterial species and time to positive testing of liquid cultures from sputum samples using the Mycobacteria Growth Indicator Tube system over a 3.