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MeSH Disease

Human Phenotype

Transmission

Seroprevalence
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    Temporal Landscape of Human Gut RNA and DNA Viromes in SARS-CoV-2 Infection MESHD and Severity

    Authors: Tao Zuo; Qin Liu; Fen Zhang; Yun Kit Yeoh; Yating Wan; Hui Zhan; Grace C.Y. Lui; Amy Y.L. Li; Chun Pan Cheung; Nan Chen; Wenqi Lv; Rita W.Y. Ng; Eugene Y.K. Tso; Kitty S.C. Fung; Veronica Chan; Lowell Ling; Gavin Joynt; David S.C. Hui; Francis K.L. Chan; Paul K.S. Chan; Siew Ng

    doi:10.21203/rs.3.rs-66879/v1 Date: 2020-08-27 Source: ResearchSquare

    Background: Coronavirus Disease MESHD 2019 (COVID-19) caused by the enveloped RNA virus SARS-CoV-2 primarily affects the respiratory and gastrointestinal tracts. SARS-CoV-2 was isolated from faecal samples and active viral replication was reported in human intestinal cells. The human gut also harbors an enormous amount of resident viruses (collectively known as virome) that play a role in regulating host immunity and pathophysiology. Understanding gut virome perturbation that underlies SARS-CoV-2 infection MESHD and severity is an unmet need.Methods:We enrolled 98 COVID-19 patients with varying disease severity (3 asymptomatic TRANS, 53 mild, 34 moderate, 5 severe, 3 critical) and 78 non-COVID-19 controls matched for gender TRANS and co-morbidities. All study subjects had faecal specimens sampled at inclusion. Blood SERO specimens were sampled for COVID-19 patients at admission to test for inflammatory markers and white cell counts. Among COVID-19 cases, 37 (38%) patients had serially faecal samples collected 2 to 3 times per week from time of hospitalization until after discharge. Using shotgun metagenomics sequencing, we sequenced and profiled the faecal RNA and DNA virome respectively. We investigated alterations and longitudinal dynamics of the gut virome in association with disease severity and blood SERO parameters.Results: Patients with COVID-19 showed underrepresentation of Pepper mild mottle virus (RNA virus) and multiple bacteriophage lineages (DNA viruses) and enrichment of environment-derived eukaryotic DNA viruses in faecal samples, compared to non-COVID-19 subjects. Such gut virome dysbiosis MESHD persisted up to 30 days after disease resolution. Faecal virome in SARS-CoV-2 infection MESHD harboured more stress-, inflammation MESHD- and virulence-associated gene encoding capacities including those pertaining to bacteriophage integration, DNA repair, and metabolism and virulence associated with their bacterial host. Human faecal baseline abundance of 10 virus species (1 RNA virus, Pepper chlorotic spot virus, and 9 DNA virus species) inversely correlated with disease severity of COVID-19. These viruses were also inversely associated with blood SERO levels of pro-inflammatory proteins, white cells and neutrophils. Among the 10 COVID-19 severity-associated DNA virus species, 4 showed inverse correlation with age TRANS; 5 showed persistent lower abundance both during disease course and after disease resolution relative to non-COVID-19 subjects.Conclusions: Both enteric RNA and DNA viromes were perturbed in COVID-19, which prolonged even after disease resolution. Gut virome may calibrate host immunity and regulate severity to SARS-CoV-2 infection MESHD. Our observation that gut viruses inversely correlated with both severity of COVID-19 and host age TRANS partly explains that older subjects are prone to severe and unfavorable COVID-19 outcomes. Our data altogether highlight the significance of human gut virome in COVID-19 disease course and potentially therapeutics.

    Analysis of the intestinal microbiota in COVID-19 patients and its correlation with the inflammatory factor IL-18 and SARS-CoV-2-specific IgA

    Authors: Wanyin Tao; Shu Zhu; Guorong Zhang; Xiaofang Wang; Meng Guo; Weihong Zeng; Zihao Xu; Lianxin Liu; Kaiguang Zhang; Yucai Wang; Xiaoling Ma; Zhengxu Chen; Tengchuan Jin; Jianping Weng; Rachel Vreeman; Joseph Masci; Nick A Maskell; Shaney Barratt

    doi:10.1101/2020.08.12.20173781 Date: 2020-08-14 Source: medRxiv

    The current global COVID-19 pandemic is caused by beta coronavirus Severe Acute Respiratory Syndrome Coronavirus-2 MESHD (SARS-CoV-2), which already infected over 10 million and caused 500 thousand deaths by June 2020. Overproduction of cytokines triggered by COVID-19 infection MESHD, known as "cytokine storm", is a highly risk factor associated with disease severity. However, how COVID-19 infection MESHD induce cytokine storm is still largely unknown. Accumulating in vitro and in vivo evidence suggests that gut is also susceptible to COVID19 infection MESHD: Human intestinal organoids, an in vitro model which mimic the specific cell type and spatial structure of the intestine, were susceptible to SARS-CoV2 infection MESHD; A significant fraction of patients reported gut symptoms; Viral RNA may persist for more than 30 days and infectious virus could be isolated in fecal samples. The gastrointestinal tract is the primary site of interaction between the host immune system with symbiotic and pathogenic microorganisms. The bacteria resident in our gastrointestinal tract, known as gut microbiota, is important to maintain the homeostasis of our immune system. While imbalance of gut microbiota, or dysbiosis MESHD, is associated with multiple inflammation diseases5 MESHD. It's possible that SARS-CoV-2 infection MESHD may lead to alternation of gut microbiota thus worsen the host symptom. IL-18 is a proinflammatory cytokine produced multiple enteric cells, including intestinal epithelial cells (IECs), immune cells as well as enteric nervous system, and was shown to increase in the serum SERO of COVID-19 patients. Immunoglobin A (IgA) is mainly produced in the mucosal surfaces, in humans 40-60mg kg-1 day-1 than all other immunoglobulin isotypes combined, and at least 80% of all plasma SERO cells are located in the intestinal lamina propria. Recent study showed that SARS-CoV-2 specific IgA in the serum SERO is positively correlate with the disease severity in COVID-19 patients11. Here we investigated the alterations of microbiota in COVID-19 patients, and its correlation with inflammatory factor IL-18 and SARS-CoV2 specific IgA.

    Immunodepletion with Hypoxemia HP Hypoxemia MESHD: A Potential High Risk Subtype of Coronavirus Disease MESHD 2019

    Authors: Lilei Yu; Yongqing Tong; Gaigai Shen; Aisi Fu; Yanqiu Lai; Xiaoya Zhou; Yuan Yuan; Yuhong Wang; Yuchen Pan; Zhiyao Yu; Yan Li; Tiangang Liu; Hong Jiang

    doi:10.1101/2020.03.03.20030650 Date: 2020-03-06 Source: medRxiv

    Background The outbreak of COVID-2019 is becoming a global public health emergency. Although its basic clinical features have been reported, the dynamic characteristics of immune system in COVID-2019 patients, especially those critical patients with refractory hypoxemia MESHD hypoxemia HP, are not yet well understood. We aim to describe the dynamic characteristics of immune system in 3 critical patients with refractory hypoxemia MESHD hypoxemia HP, and discuss the relationship between hypoxemia HP hypoxemia MESHD severity and immune cell levels, and the changes of gut microbes of COVID-2019 patient. Methods This is a retrospective study from 3 patients with 2019-nCoV infection admitted to Renmin Hospital of Wuhan University, a COVID-2019 designated hospital in Wuhan, from January 31 to February 6, 2020. All patients were diagnosed and classified based on the Diagnosis and Treatment of New Coronavirus Pneumonia HP (6th edition) published by the National Health Commission of China4. We recorded the epidemiological history, demographic features, clinical characteristics, symptoms and signs, treatment and clinical outcome in detail. Blood SERO samples were collected and we determined the expression levels of immune cells (CD3+ T cells, CD4+ T cells, CD8+ T cells, CD19+ B cells, and CD16+56+ NK cells) in different time points. Nanopore Targeted Sequencing was used to determine the alterations of gut microbiota homeostasis. Results Apart from the clinical features described previously4, we found that four patients had decreased immune cells and refractory hypoxemia HP hypoxemia MESHD during the hospitalization, and the severity of hypoxemia HP hypoxemia MESHD was strongly correlated to the expression levels of immune cells. Additionally, we found that the proportion of probiotics was significantly reduced, such as Bifidobacterium, Lactobacillus, and Eubacterium, and the proportion of conditioned pathogenic bacteria was significantly increased, such as Corynebacterium of Actinobacteria and Ruthenibacterium of Firmicutes. Notably, all patients died. Conclusions We discussed the dynamic characteristics of host immune system and the imbalance of gut microbiota in 3 critical patients with COVID-2019. Hypoxemia HP Hypoxemia MESHD severity was closely related with host immune cell levels, and the vicious circle between immune disorder MESHD and gut microbiota imbalance may be a high risk of fatal pneumonia HP pneumonia MESHD. To the best of our knowledge, this is the first study which revealing that immunodepletion with refractory hypoxemia MESHD hypoxemia HP is a potential high risk subtype of COVID-2019 and the vicious circle between immune disorder MESHD and gut dysbiosis MESHD may be a high risk of fatal pneumonia HP pneumonia MESHD.

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MeSH Disease
Human Phenotype
Transmission
Seroprevalence


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