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      Plasma Markers of Disrupted Gut Permeability in Severe COVID-19 Patients

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          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.

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          Most cited references53

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          Clinical Characteristics of Coronavirus Disease 2019 in China

          Abstract Background Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. Methods We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. Results The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. Conclusions During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.)
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            Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study

            Summary Background In December, 2019, a pneumonia associated with the 2019 novel coronavirus (2019-nCoV) emerged in Wuhan, China. We aimed to further clarify the epidemiological and clinical characteristics of 2019-nCoV pneumonia. Methods In this retrospective, single-centre study, we included all confirmed cases of 2019-nCoV in Wuhan Jinyintan Hospital from Jan 1 to Jan 20, 2020. Cases were confirmed by real-time RT-PCR and were analysed for epidemiological, demographic, clinical, and radiological features and laboratory data. Outcomes were followed up until Jan 25, 2020. Findings Of the 99 patients with 2019-nCoV pneumonia, 49 (49%) had a history of exposure to the Huanan seafood market. The average age of the patients was 55·5 years (SD 13·1), including 67 men and 32 women. 2019-nCoV was detected in all patients by real-time RT-PCR. 50 (51%) patients had chronic diseases. Patients had clinical manifestations of fever (82 [83%] patients), cough (81 [82%] patients), shortness of breath (31 [31%] patients), muscle ache (11 [11%] patients), confusion (nine [9%] patients), headache (eight [8%] patients), sore throat (five [5%] patients), rhinorrhoea (four [4%] patients), chest pain (two [2%] patients), diarrhoea (two [2%] patients), and nausea and vomiting (one [1%] patient). According to imaging examination, 74 (75%) patients showed bilateral pneumonia, 14 (14%) patients showed multiple mottling and ground-glass opacity, and one (1%) patient had pneumothorax. 17 (17%) patients developed acute respiratory distress syndrome and, among them, 11 (11%) patients worsened in a short period of time and died of multiple organ failure. Interpretation The 2019-nCoV infection was of clustering onset, is more likely to affect older males with comorbidities, and can result in severe and even fatal respiratory diseases such as acute respiratory distress syndrome. In general, characteristics of patients who died were in line with the MuLBSTA score, an early warning model for predicting mortality in viral pneumonia. Further investigation is needed to explore the applicability of the MuLBSTA score in predicting the risk of mortality in 2019-nCoV infection. Funding National Key R&D Program of China.
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              Imbalanced Host Response to SARS-CoV-2 Drives Development of COVID-19

              Summary Viral pandemics, such as the one caused by SARS-CoV-2, pose an imminent threat to humanity. Because of its recent emergence, there is a paucity of information regarding viral behavior and host response following SARS-CoV-2 infection. Here we offer an in-depth analysis of the transcriptional response to SARS-CoV-2 compared with other respiratory viruses. Cell and animal models of SARS-CoV-2 infection, in addition to transcriptional and serum profiling of COVID-19 patients, consistently revealed a unique and inappropriate inflammatory response. This response is defined by low levels of type I and III interferons juxtaposed to elevated chemokines and high expression of IL-6. We propose that reduced innate antiviral defenses coupled with exuberant inflammatory cytokine production are the defining and driving features of COVID-19.
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                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                09 June 2021
                2021
                09 June 2021
                : 12
                : 686240
                Affiliations
                [1] 1 The Wistar Institute , Philadelphia, PA, United States
                [2] 2 The Burnet Institute , Melbourne, VIC, Australia
                [3] 3 Department of Infectious Diseases, Monash University , Melbourne, VIC, Australia
                [4] 4 Rush Center for Integrated Microbiome and Chronobiology Research, Rush University , Chicago, IL, United States
                [5] 5 Department of Internal Medicine, Rush University Medical Center , Chicago, IL, United States
                Author notes

                Edited by: Nicholas Funderburg, The Ohio State University, United States

                Reviewed by: Michael Jay Corley, University of Hawaii, United States; Tengchuan Jin, University of Science and Technology of China, China

                *Correspondence: Mohamed Abdel-Mohsen, mmohsen@ 123456wistar.org

                This article was submitted to Viral Immunology, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2021.686240
                8219958
                34177935
                555dc163-a8a8-4b48-b120-5b367edfcb9d
                Copyright © 2021 Giron, Dweep, Yin, Wang, Damra, Goldman, Gorman, Palmer, Tang, Shaikh, Forsyth, Balk, Zilberstein, Liu, Kossenkov, Keshavarzian, Landay and Abdel-Mohsen

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 26 March 2021
                : 10 May 2021
                Page count
                Figures: 8, Tables: 3, Equations: 0, References: 53, Pages: 16, Words: 8903
                Funding
                Funded by: National Institute of Diabetes and Digestive and Kidney Diseases 10.13039/100000062
                Funded by: National Institute on Alcohol Abuse and Alcoholism 10.13039/100000027
                Funded by: National Institute on Aging 10.13039/100000049
                Funded by: National Institute of Neurological Disorders and Stroke 10.13039/100000065
                Funded by: National Institute of Allergy and Infectious Diseases 10.13039/100000060
                Funded by: National Institute of Allergy and Infectious Diseases 10.13039/100000060
                Funded by: National Institute of Neurological Disorders and Stroke 10.13039/100000065
                Funded by: National Institute of Allergy and Infectious Diseases 10.13039/100000060
                Funded by: National Cancer Institute 10.13039/100000054
                Funded by: Center for Scientific Review 10.13039/100005440
                Categories
                Immunology
                Original Research

                Immunology
                sars-cov-2,covid-19,microbial translocation,inflammation,zonulin,metabolomics,glycomics,lipidomics
                Immunology
                sars-cov-2, covid-19, microbial translocation, inflammation, zonulin, metabolomics, glycomics, lipidomics

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