小柯机器人

K18-hACE2小鼠可用于COVID-19疗法和发病机制的研究
2020-11-10 22:03

美国爱荷华大学Stanley Perlman、Paul B. McCray Jr等研究人员合作发现,K18-hACE2小鼠可用于COVID-19疗法和发病机制的研究。该研究于2020年11月9日在线发表于国际一流学术期刊《自然》。

通过使用最初为SARS研究而开发的K18-hACE2小鼠,研究人员表明SARS-CoV-2感染会在肺部以及某些小鼠的脑部引起严重疾病。在患有严重肺炎的小鼠中检测到血栓形成和血管炎的证据。此外,研究人员显示,从康复患者中注入COVID-19的恢复性血浆可预防致命性疾病。小鼠在感染后的早期就出现了嗅觉丧失。值得注意的是,尽管用恢复性血浆进行的预治疗可以预防明显的临床疾病,但不能预防嗅觉丧失。因此,K18-hACE2小鼠为研究轻度和致死性COVID-19的病理基础以及评估治疗干预措施提供了有用的模型。
 
据了解,COVID-19大流行与大量发病率和死亡率有关。尽管在大流行的最初几个月了解到很多,但COVID-19发病机理的许多特征仍有待确定。例如,嗅觉丧失是一种常见表现,许多有此发现的患者没有或只有轻微的呼吸道症状。实验性感染SARS-CoV-2(COVID-19的病因)的动物研究为了解人类患者中不易发现的疾病提供了机会。尽管COVID-19的严重程度从无症状到致死,但大多数实验性感染仅可提供对轻度疾病的见解。
 
附:英文原文

Title: COVID-19 treatments and pathogenesis including anosmia in K18-hACE2 mice

Author: Jian Zheng, Lok-Yin Roy Wong, Kun Li, Abhishek Kumar Verma, Miguel Ortiz, Christine Wohlford-Lenane, Mariah R. Leidinger, C. Michael Knudson, David K. Meyerholz, Paul B. McCray, Stanley Perlman

Issue&Volume: 2020-11-09

Abstract: The ongoing COVID-19 pandemic is associated with substantial morbidity and mortality. Although much has been learned in the first months of the pandemic, many features of COVID-19 pathogenesis remain to be determined. For example, anosmia is a common presentation and many patients with this finding show no or only minor respiratory signs1. Studies in animals experimentally infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of COVID-19, provide opportunities to study aspects of the disease not easily investigated in human patients. Although COVID-19 severity ranges from asymptomatic to lethal2, most experimental infections provide insights into mild disease3. Here, using K18-hACE2 mice that we originally developed for SARS studies4, we show that infection with SARS-CoV-2 causes severe disease in the lung, and in some mice, the brain. Evidence of thrombosis and vasculitis was detected in mice with severe pneumonia. Furthermore, we show that infusion of convalescent plasma from a recovered patient with COVID-19 protected against lethal disease. Mice developed anosmia at early times after infection. Notably, although pre-treatment with convalescent plasma prevented notable clinical disease, it did not prevent anosmia. Thus, K18-hACE2 mice provide a useful model for studying the pathological underpinnings of both mild and lethal COVID-19 and for assessing therapeutic interventions.

DOI: 10.1038/s41586-020-2943-z

Source: https://www.nature.com/articles/s41586-020-2943-z

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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