Corpus overview


Overview

MeSH Disease

Human Phenotype

Transmission

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Seroprevalence

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    Proposal of selective wedge instillation of pulmonary surfactant for COVID-19 pneumonia HP pneumonia MESHD based on computational fluid dynamics simulation

    Authors: Hiroko Kitaoka; Hisato Kobayashi; Takayuki Takimoto; Takashi Kijima

    doi:10.21203/rs.3.rs-75938/v1 Date: 2020-09-11 Source: ResearchSquare

    Background: The most important target cell of SARS-CoV-2 is Type II pneumocyte which produces and secretes pulmonary MESHD surfactant (PS) that prevents alveolar MESHD collapse. PS instillation therapy is dramatically effective for infant respiratory distress HP respiratory distress MESHD syndrome but has been clinically ineffective for ARDS. Nowadays, ARDS is regarded as non-cardiogenic pulmonary edema HP pulmonary edema MESHD with vascular hyper-permeability regardless of direct relation to PS dysfunction. However, there is a possibility that the ineffectiveness of PS instillation for ARDS is due to insufficient delivery MESHD. Then, we performed PS instillation simulation with realistic human airway models by the use of computational fluid dynamics, and investigated how instilled PS would move in the liquid layer covering the airway wall and reach to alveolar regions MESHD.Methods: Two types of 3D human airway model were prepared: One was from the trachea to lobular bronchi and the other was from a sub-segmental bronchus to respiratory bronchioles. Thickness of the liquid layer covering the airway was assigned as 14 % of the inner radius of the airway segment. Initially existing liquid layer was assumed to be replaced by instilled PS. Flow rate of instilled PS was assigned a constant value, which was determined by the total amount and instillation time in clinical use. The PS concentration of the liquid layer during instillation was computed by solving advective-diffusion equation.Results: The driving pressure from the trachea to respiratory bronchioles was calculated at 317 cmH2O, which is about 20 times of a standard value in conventional PS instillation method where the driving pressure is given by difference between inspiratory and end-expiratory pressures of a ventilator. It means that almost all PS would not reach alveolar MESHD regions but move to and fro within the airway according to the change of ventilator pressure. On the other hand, the driving pressure from sub-segmental bronchus was calculated at 273 cm H2O, that is clinically possible by wedge instillation under bronchoscopic observation. Conclusions: The simulation study has revealed that selective wedge instillation under bronchoscopic observation should be tried for COVID-19 pneumonia HP pneumonia MESHD even before ARDS. It will be also useful for preventing secondary lung fibrosis MESHD

    Single-cell analysis reveals the function of lung progenitor cells in COVID-19 patients

    Authors: Wei Zuo; Zixian Zhao; Yu Zhao; Yueqing Zhou; Xiaofan Wang; Ting Zhang

    doi:10.1101/2020.07.13.200188 Date: 2020-07-13 Source: bioRxiv

    The high mortality of severe 2019 novel coronavirus disease MESHD (COVID-19) cases is mainly caused by acute respiratory distress HP respiratory distress MESHD syndrome ( ARDS MESHD), which is characterized by increased permeability of the alveolar MESHD epithelial barriers, pulmonary edema HP pulmonary edema MESHD and consequently inflammatory tissue damage. Some but not all patients showed full functional recovery after the devastating lung damage, and so far there is little knowledge about the lung repair process1. Here by analyzing the bronchoalveolar lavage fluid (BALF) of COVID-19 patients through single cell RNA-sequencing (scRNA-Seq), we found that in severe (or critical) cases, there is remarkable expansion of TM4SF1+ and KRT5+ lung progenitor cells. The two distinct populations of progenitor cells could play crucial roles in alveolar MESHD cell regeneration and epithelial barrier re-establishment, respectively. In order to understand the function of KRT5+ progenitors in vivo, we transplanted a single KRT5+ cell-derived cell population into damaged mouse lung. Time-course single-cell transcriptomic analysis showed that the transplanted KRT5+ progenitors could long-term engrafted into host lung and differentiate into HOPX+ OCLN+ alveolar MESHD barrier cell which restored the epithelial barrier and efficiently prevented inflammatory cell infiltration. Similar barrier cells were also identified in some COVID-19 patients with massive leukocyte infiltration. Altogether this work uncovered the mechanism that how various lung progenitor cells work in concert to prevent and replenish alveoli loss MESHD post severe SARS-CoV-2 infection MESHD.

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MeSH Disease
Human Phenotype
Transmission
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