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  1. Article ; Online: Plasma Markers of Disrupted Gut Permeability in Severe COVID-19 Patients.

    Giron, Leila B / Dweep, Harsh / Yin, Xiangfan / Wang, Han / Damra, Mohammad / Goldman, Aaron R / Gorman, Nicole / Palmer, Clovis S / Tang, Hsin-Yao / Shaikh, Maliha W / Forsyth, Christopher B / Balk, Robert A / Zilberstein, Netanel F / Liu, Qin / Kossenkov, Andrew / Keshavarzian, Ali / Landay, Alan / Abdel-Mohsen, Mohamed

    Frontiers in immunology

    2021  Volume 12, Page(s) 686240

    Abstract: ... 19) is associated with markers of disrupted gut permeability. We applied a multi-omic systems biology ... We found that severe COVID-19 is associated with high levels of markers of tight junction permeability and ... approach to analyze plasma samples from COVID-19 patients with varying disease severity and SARS-CoV-2 ...

    Abstract A disruption of the crosstalk between the gut and the lung has been implicated as a driver of severity during respiratory-related diseases. Lung injury causes systemic inflammation, which disrupts gut barrier integrity, increasing the permeability to gut microbes and their products. This exacerbates inflammation, resulting in positive feedback. We aimed to test whether severe Coronavirus disease 2019 (COVID-19) is associated with markers of disrupted gut permeability. We applied a multi-omic systems biology approach to analyze plasma samples from COVID-19 patients with varying disease severity and SARS-CoV-2 negative controls. We investigated the potential links between plasma markers of gut barrier integrity, microbial translocation, systemic inflammation, metabolome, lipidome, and glycome, and COVID-19 severity. We found that severe COVID-19 is associated with high levels of markers of tight junction permeability and translocation of bacterial and fungal products into the blood. These markers of disrupted intestinal barrier integrity and microbial translocation correlate strongly with higher levels of markers of systemic inflammation and immune activation, lower levels of markers of intestinal function, disrupted plasma metabolome and glycome, and higher mortality rate. Our study highlights an underappreciated factor with significant clinical implications, disruption in gut functions, as a potential force that may contribute to COVID-19 severity.
    MeSH term(s) COVID-19/immunology ; Female ; Gastrointestinal Microbiome/immunology ; Glycomics ; Haptoglobins/metabolism ; Humans ; Inflammation/immunology ; Intestines/physiology ; Lipidomics ; Male ; Metabolomics ; Middle Aged ; Permeability ; Protein Precursors/metabolism ; SARS-CoV-2/physiology ; Tight Junctions/metabolism
    Chemical Substances Haptoglobins ; Protein Precursors ; zonulin
    Language English
    Publishing date 2021-06-09
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2021.686240
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Corrigendum: Plasma Markers of Disrupted Gut Permeability in Severe COVID-19 Patients.

    Giron, Leila B / Dweep, Harsh / Yin, Xiangfan / Wang, Han / Damra, Mohammad / Goldman, Aaron R / Gorman, Nicole / Palmer, Clovis S / Tang, Hsin-Yao / Shaikh, Maliha W / Forsyth, Christopher B / Balk, Robert A / Zilberstein, Netanel F / Liu, Qin / Kossenkov, Andrew / Keshavarzian, Ali / Landay, Alan / Abdel-Mohsen, Mohamed

    Frontiers in immunology

    2021  Volume 12, Page(s) 779064

    Abstract: This corrects the article DOI: 10.3389/fimmu.2021.686240.]. ...

    Abstract [This corrects the article DOI: 10.3389/fimmu.2021.686240.].
    Language English
    Publishing date 2021-10-04
    Publishing country Switzerland
    Document type Published Erratum
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2021.779064
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Plasma 1,3-β-d-glucan levels predict adverse clinical outcomes in critical illness.

    Kitsios, Georgios D / Kotok, Daniel / Yang, Haopu / Finkelman, Malcolm A / Zhang, Yonglong / Britton, Noel / Li, Xiaoyun / Levochkina, Marina S / Wagner, Amy K / Schaefer, Caitlin / Villandre, John J / Guo, Rui / Evankovich, John W / Bain, William / Shah, Faraaz / Zhang, Yingze / Methé, Barbara A / Benos, Panayiotis V / McVerry, Bryan J /
    Morris, Alison

    JCI insight

    2021  Volume 6, Issue 14

    Abstract: ... hospitalized patients with COVID-19.CONCLUSIONBDG measurements offered prognostic information in critically ill ... biomarkers in serially collected plasma samples.RESULTSCompared with healthy controls, patients with ARF had ... of Pittsburgh Clinical and Translational Science Institute, COVID-19 Pilot Award and NIH grants (K23 HL139987 ...

    Abstract BACKGROUNDThe fungal cell wall constituent 1,3-β-d-glucan (BDG) is a pathogen-associated molecular pattern that can stimulate innate immunity. We hypothesized that BDG from colonizing fungi in critically ill patients may translocate into the systemic circulation and be associated with host inflammation and outcomes.METHODSWe enrolled 453 mechanically ventilated patients with acute respiratory failure (ARF) without invasive fungal infection and measured BDG, innate immunity, and epithelial permeability biomarkers in serially collected plasma samples.RESULTSCompared with healthy controls, patients with ARF had significantly higher BDG levels (median [IQR], 26 pg/mL [15-49 pg/mL], P < 0.001), whereas patients with ARF with high BDG levels (≥40 pg/mL, 31%) had higher odds for assignment to the prognostically adverse hyperinflammatory subphenotype (OR [CI], 2.88 [1.83-4.54], P < 0.001). Baseline BDG levels were predictive of fewer ventilator-free days and worse 30-day survival (adjusted P < 0.05). Integrative analyses of fungal colonization and epithelial barrier disruption suggested that BDG may translocate from either the lung or gut compartment. We validated the associations between plasma BDG and host inflammatory responses in 97 hospitalized patients with COVID-19.CONCLUSIONBDG measurements offered prognostic information in critically ill patients without fungal infections. Further research in the mechanisms of translocation and innate immunity recognition and stimulation may offer new therapeutic opportunities in critical illness.FUNDINGUniversity of Pittsburgh Clinical and Translational Science Institute, COVID-19 Pilot Award and NIH grants (K23 HL139987, U01 HL098962, P01 HL114453, R01 HL097376, K24 HL123342, U01 HL137159, R01 LM012087, K08HK144820, F32 HL142172, K23 GM122069).
    MeSH term(s) Biomarkers/blood ; COVID-19/immunology ; COVID-19/therapy ; Candida/immunology ; Candida/isolation & purification ; Capillary Permeability/immunology ; Critical Illness/therapy ; Female ; Gastrointestinal Microbiome/immunology ; Humans ; Immunity, Innate/immunology ; Male ; Middle Aged ; Predictive Value of Tests ; Prognosis ; Respiration, Artificial/adverse effects ; Respiration, Artificial/methods ; Respiratory Insufficiency/etiology ; Respiratory Insufficiency/therapy ; Respiratory System/immunology ; Respiratory System/microbiology ; SARS-CoV-2 ; Severity of Illness Index ; Survival Analysis ; beta-Glucans/blood
    Chemical Substances Biomarkers ; beta-Glucans ; beta-1,3-glucan (9051-97-2)
    Language English
    Publishing date 2021-07-22
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ISSN 2379-3708
    ISSN (online) 2379-3708
    DOI 10.1172/jci.insight.141277
    Database MEDical Literature Analysis and Retrieval System OnLINE

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