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  • 1
    Online Resource
    Online Resource
    Characteristics of hospitalized patients with COVID-19 during the first to fifth waves of infection: a report from the Japan COVID-19 Task Force
    Springer Science and Business Media LLC ; 2022
    In:  BMC Infectious Diseases Vol. 22, No. 1 ( 2022-12-12)
    Details
    In: BMC Infectious Diseases, Springer Science and Business Media LLC, Vol. 22, No. 1 ( 2022-12-12)
    Abstract: We aimed to elucidate differences in the characteristics of patients with coronavirus disease 2019 (COVID-19) requiring hospitalization in Japan, by COVID-19 waves, from conventional strains to the Delta variant. Methods We used secondary data from a database and performed a retrospective cohort study that included 3261 patients aged ≥ 18 years enrolled from 78 hospitals that participated in the Japan COVID-19 Task Force between February 2020 and September 2021. Results Patients hospitalized during the second (mean age, 53.2 years [standard deviation {SD}, ± 18.9]) and fifth (mean age, 50.7 years [SD ± 13.9] ) COVID-19 waves had a lower mean age than those hospitalized during the other COVID-19 waves. Patients hospitalized during the first COVID-19 wave had a longer hospital stay (mean, 30.3 days [SD ± 21.5], p  〈  0.0001), and post-hospitalization complications, such as bacterial infections (21.3%, p  〈  0.0001), were also noticeable. In addition, there was an increase in the use of drugs such as remdesivir/baricitinib/tocilizumab/steroids during the latter COVID-19 waves. In the fifth COVID-19 wave, patients exhibited a greater number of presenting symptoms, and a higher percentage of patients required oxygen therapy at the time of admission. However, the percentage of patients requiring invasive mechanical ventilation was the highest in the first COVID-19 wave and the mortality rate was the highest in the third COVID-19 wave. Conclusions We identified differences in clinical characteristics of hospitalized patients with COVID-19 in each COVID-19 wave up to the fifth COVID-19 wave in Japan. The fifth COVID-19 wave was associated with greater disease severity on admission, the third COVID-19 wave had the highest mortality rate, and the first COVID-19 wave had the highest percentage of patients requiring mechanical ventilation.
    Type of Medium: Online Resource
    ISSN: 1471-2334
    URL: Article
    DOI: 10.1186/s12879-022-07927-w
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2041550-3
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  • 2
    Online Resource
    Online Resource
    Gastrointestinal symptoms in COVID-19 and disease severity: a Japanese registry-based retrospective cohort study
    Springer Science and Business Media LLC ; 2024
    In:  Journal of Gastroenterology
    Details
    In: Journal of Gastroenterology, Springer Science and Business Media LLC
    Type of Medium: Online Resource
    ISSN: 0944-1174 , 1435-5922
    URL: Article
    DOI: 10.1007/s00535-023-02071-x
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2024
    detail.hit.zdb_id: 1473159-9
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  • 3
    Online Resource
    Online Resource
    The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force
    Springer Science and Business Media LLC ; 2022
    In:  Nature Communications Vol. 13, No. 1 ( 2022-08-22)
    Details
    In: Nature Communications, Springer Science and Business Media LLC, Vol. 13, No. 1 ( 2022-08-22)
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 2041-1723
    URL: Article
    DOI: 10.1038/s41467-022-32276-2
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2553671-0
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  • 4
    Online Resource
    Online Resource
    DOCK2 is involved in the host genetics and biology of severe COVID-19
    Springer Science and Business Media LLC ; 2022
    In:  Nature Vol. 609, No. 7928 ( 2022-09-22), p. 754-760
    Details
    In: Nature, Springer Science and Business Media LLC, Vol. 609, No. 7928 ( 2022-09-22), p. 754-760
    Abstract: Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge 1–5 . 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.
    Type of Medium: Online Resource
    ISSN: 0028-0836 , 1476-4687
    URL: Article
    DOI: 10.1038/s41586-022-05163-5
    RVK:
    TA 1000
    RVK:
    UA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 120714-3
    detail.hit.zdb_id: 1413423-8
    SSG: 11
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  • 5
    Online Resource
    Online Resource
    Single-cell analyses and host genetics highlight the role of innate immune cells in COVID-19 severity
    Springer Science and Business Media LLC ; 2023
    In:  Nature Genetics Vol. 55, No. 5 ( 2023-05), p. 753-767
    Details
    In: Nature Genetics, Springer Science and Business Media LLC, Vol. 55, No. 5 ( 2023-05), p. 753-767
    Abstract: Mechanisms underpinning the dysfunctional immune response in severe acute respiratory syndrome coronavirus 2 infection are elusive. We analyzed single-cell transcriptomes and T and B cell receptors (BCR) of 〉 895,000 peripheral blood mononuclear cells from 73 coronavirus disease 2019 (COVID-19) patients and 75 healthy controls of Japanese ancestry with host genetic data. COVID-19 patients showed a low fraction of nonclassical monocytes (ncMono). We report downregulated cell transitions from classical monocytes to ncMono in COVID-19 with reduced CXCL10 expression in ncMono in severe disease. Cell–cell communication analysis inferred decreased cellular interactions involving ncMono in severe COVID-19. Clonal expansions of BCR were evident in the plasmablasts of patients. Putative disease genes identified by COVID-19 genome-wide association study showed cell type-specific expressions in monocytes and dendritic cells. A COVID-19-associated risk variant at the IFNAR2 locus (rs13050728) had context-specific and monocyte-specific expression quantitative trait loci effects. Our study highlights biological and host genetic involvement of innate immune cells in COVID-19 severity.
    Type of Medium: Online Resource
    ISSN: 1061-4036 , 1546-1718
    URL: Article
    DOI: 10.1038/s41588-023-01375-1
    RVK:
    XA 10000
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 1494946-5
    SSG: 12
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  • 6
    Online Resource
    Online Resource
    Mapping the human genetic architecture of COVID-19
    Springer Science and Business Media LLC ; 2021
    In:  Nature Vol. 600, No. 7889 ( 2021-12-16), p. 472-477
    Details
    In: Nature, Springer Science and Business Media LLC, Vol. 600, No. 7889 ( 2021-12-16), p. 472-477
    Abstract: The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-19 1,2 , host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases 3–7 . They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.
    Type of Medium: Online Resource
    ISSN: 0028-0836 , 1476-4687
    URL: Article
    DOI: 10.1038/s41586-021-03767-x
    RVK:
    TA 1000
    RVK:
    UA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 120714-3
    detail.hit.zdb_id: 1413423-8
    SSG: 11
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  • 7
    Online Resource
    Online Resource
    Detecting Waning Serological Response with Commercial Immunoassays: 18-Month Longitudinal Follow-up of Anti-SARS-CoV-2 Nucleocapsid Antibodies
    American Society for Microbiology ; 2022
    In:  Microbiology Spectrum Vol. 10, No. 4 ( 2022-08-31)
    Details
    In: Microbiology Spectrum, American Society for Microbiology, Vol. 10, No. 4 ( 2022-08-31)
    Abstract: Past severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is an important determinant of protection from reinfection and of postvaccine immune responses. Herein, we conducted a follow-up analysis of health care workers previously infected with coronavirus disease 2019 (COVID-19) with the aim of evaluating different immunoassays for their capability in detecting the waning anti-SARS-CoV-2 immune responses and accuracy in documenting past SARS-CoV-2 infections. We evaluated serum antinucleocapsid antibody levels in convalescent individuals following a 1.5-year interval from SARS-CoV-2 infection. Three different commercial immunoassays that qualitatively measure serum antibodies targeting the SARS-CoV-2 nucleocapsid protein, namely, the Abbott Architect SARS-CoV-2 IgG, the Euroimmun anti-SARS-CoV-2 NCP enzyme-linked immunosorbent assay (ELISA) IgG, and the Roche Elecsys anti-SARS-CoV-2, were tested for comparison of detectability. A total of 38 individuals consented to participating in this follow-up analysis. From assay to assay, seropositivity rate at 18 months from infection varied from lowest at 42% to highest at 92%. The Roche Elecsys immunoassay, dependent on the dual-antigen antibody detection method and tuned for the detection of high avidity antibodies, was most capable of accurately documenting past SARS-CoV-2 infections. Different immunoassays showed variable capability of determining previous infection status under waning antibody concentrations. Immunoassays with lower detection limits are to be selected, and adjusted thresholds are to be considered in order to maximize the tests’ performance. IMPORTANCE Past SARS-CoV-2 infection is an important determinant of protection from reinfection and of postvaccine immune responses. Our results show that different immunoassays, by design, harbor variable capability of tracking SARS-CoV-2 infection under waning antibody concentrations. With each recovered patient standing at a unique time point along the decline curve of antibodies, precise estimation of COVID-19 cumulative incidence remains a challenge. Since future surveillance studies will be targeting more than ever heterogenous cohorts, selecting the appropriate immunoassay is crucial in order to assure reliable decisions about an individual’s previous infection status.
    Type of Medium: Online Resource
    ISSN: 2165-0497
    URL: Article
    DOI: 10.1128/spectrum.00986-22
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2022
    detail.hit.zdb_id: 2807133-5
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  • 8
    Online Resource
    Online Resource
    Table_1.docx
    Frontiers Media SA ; 2023
    In:  Frontiers in Immunology Vol. 14 ( 2023-1-19)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 14 ( 2023-1-19)
    Abstract: More people with a history of prior infection are receiving SARS-CoV-2 vaccines. Understanding the level of protection granted by ‘hybrid immunity’, the combined response of infection- and vaccine-induced immunity, may impact vaccination strategies through tailored dosing. A total of 36 infected (‘prior infection’) and 33 SARS-CoV-2 ‘naïve’ individuals participated. Participants provided sera six months after completing a round of BNT162b2 vaccination, to be processed for anti-spike antibody measurements and the receptor binding domain-ACE2 binding inhibition assays. The relationships between antibody titer, groups and age were explored. Anti-spike antibody titers at 6 months post-vaccination were significantly higher, reaching 13- to 17-fold, in the ‘prior infection’ group. Semi-log regression models showed that participants with ‘prior infection’ demonstrated higher antibody titer compared with the ‘naïve’ even after adjusting for age. The enhancement in antibody titer attributable to positive infection history increased from 8.9- to 9.4- fold at age 30 to 19- to 32-fold at age 60. Sera from the ‘prior infection’ group showed higher inhibition capacity against all six analyzed strains, including the Omicron variant. Prior COVID-19 led to establishing enhanced humoral immunity at 6 months after vaccination. Antibody fold-difference attributed to positive COVID-19 history increased with age, possibly because older individuals are prone to symptomatic infection accompanied by potentiated immune responses. While still pending any modifications of dosing recommendations (i.e. reduced doses for individuals with prior infection), our observation adds to the series of real-world data demonstrating the enhanced and more durable immune response evoked by booster vaccinations following prior infection.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2023.1087473
    DOI: 10.3389/fimmu.2023.1087473.s001
    DOI: 10.3389/fimmu.2023.1087473.s002
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2606827-8
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  • 9
    Online Resource
    Online Resource
    Nationwide survey of refractory asthma with bronchiectasis by inflammatory subtypes
    Springer Science and Business Media LLC ; 2022
    In:  Respiratory Research Vol. 23, No. 1 ( 2022-12-20)
    Details
    In: Respiratory Research, Springer Science and Business Media LLC, Vol. 23, No. 1 ( 2022-12-20)
    Abstract: Bronchiectasis and bronchiolitis are differential diagnoses of asthma; moreover, they are factors associated with worse asthma control. Objective We determined clinical courses of bronchiectasis/bronchiolitis-complicated asthma by inflammatory subtypes as well as factors affecting them. Methods We conducted a survey of refractory asthma with non-cystic fibrosis bronchiectasis/bronchiolitis in Japan. Cases were classified into three groups, based on the latest fractional exhaled NO (FeNO) level (32 ppb for the threshold) and blood eosinophil counts (320/µL for the threshold): high (type 2-high) or low (type 2-low) FeNO and eosinophil and high FeNO or eosinophil (type 2-intermediate). Clinical courses in groups and factors affecting them were analysed. Results In total, 216 cases from 81 facilities were reported, and 142 were stratified: 34, 40 and 68 into the type 2-high, -intermediate and -low groups, respectively. The frequency of bronchopneumonia and exacerbations requiring antibiotics and gram-negative bacteria detection rates were highest in the type 2-low group. Eighty-seven cases had paired latest and oldest available data of FeNO and eosinophil counts; they were analysed for inflammatory transition patterns. Among former type 2-high and -intermediate groups, 32% had recently transitioned to the -low group, to which relatively low FeNO in the past and oral corticosteroid use contributed. Lastly, in cases treated with moderate to high doses of inhaled corticosteroids, the frequencies of exacerbations requiring antibiotics were found to be higher in cases with more severe airway lesions and lower FeNO. Conclusions Bronchiectasis/bronchiolitis-complicated refractory asthma is heterogeneous. In patients with sputum symptoms and low FeNO, airway colonisation of pathogenic bacteria and infectious episodes are common; thus, corticosteroids should be carefully used.
    Type of Medium: Online Resource
    ISSN: 1465-993X
    URL: Article
    DOI: 10.1186/s12931-022-02289-y
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2041675-1
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  • 10
    Online Resource
    Online Resource
    Serological Testing Reveals the Hidden COVID-19 Burden among Health Care Workers Experiencing a SARS-CoV-2 Nosocomial Outbreak
    American Society for Microbiology ; 2021
    In:  Microbiology Spectrum Vol. 9, No. 2 ( 2021-10-31)
    Details
    In: Microbiology Spectrum, American Society for Microbiology, Vol. 9, No. 2 ( 2021-10-31)
    Abstract: We describe the results of testing health care workers, from a tertiary care hospital in Japan that had experienced a coronavirus disease 2019 (COVID-19) outbreak during the first peak of the pandemic, for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibody seroconversion. Using two chemiluminescent immunoassays and a confirmatory surrogate virus neutralization test, serological testing revealed that a surprising 42% of overlooked COVID-19 diagnoses (27/64 cases) occurred when case detection relied solely on SARS-CoV-2 nucleic acid amplification testing (NAAT). Our results suggest that the NAAT-positive population is only the tip of the iceberg and the portion left undetected might potentially have led to silent transmissions and triggered the spread. A questionnaire-based risk assessment was further indicative of exposures to specific aerosol-generating procedures (i.e., noninvasive ventilation and airway suctioning) having mediated transmission and served as the origins of the outbreak. Our observations are supportive of a multitiered testing approach, including the use of serological diagnostics, in order to accomplish exhaustive case detection along the whole COVID-19 spectrum. IMPORTANCE We describe the results of testing frontline health care workers, from a hospital in Japan that had experienced a COVID-19 outbreak, for SARS-CoV-2-specific antibodies. Antibody testing revealed that a surprising 42% of overlooked COVID-19 diagnoses occurred when case detection relied solely on PCR-based viral detection. COVID-19 clusters have been continuously striking the health care system around the globe. Our findings illustrate that such clusters are lined with hidden infections eluding detection with diagnostic PCR and that the cluster burden in total is more immense than actually recognized. The mainstays of diagnosing infectious diseases, including COVID-19, generally consist of two approaches, one aiming to detect molecular fragments of the invading pathogen and the other to measure immune responses of the host. Considering antibody testing as one trustworthy option to test our way through the pandemic can aid in the exhaustive case detection of COVID-19 patients with variable presentations.
    Type of Medium: Online Resource
    ISSN: 2165-0497
    URL: Article
    DOI: 10.1128/Spectrum.01082-21
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2021
    detail.hit.zdb_id: 2807133-5
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