COVID-19 treatments and pathogenesis including anosmia in K18-hACE2 mice.
COVID-19 treatments and pathogenesis including anosmia in K18-hACE2 mice.
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COVID-19 治疗和发病机制，包括 K18-hACE2 小鼠的嗅觉丧失。
DOI：
10.1038/s41586-020-2943-z
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发表时间：
2021-01
期刊：
影响因子：
64.8
通讯作者：
Perlman S
中科院分区：
文献类型：
--
作者：
Zheng J;Wong LR;Li K;Verma AK;Ortiz ME;Wohlford-Lenane C;Leidinger MR;Knudson CM;Meyerholz DK;McCray PB Jr;Perlman S
持续的COVID-19疫情与高发病率及死亡率有关。尽管在疫情爆发的最初几个月已了解到很多情况，但COVID-19发病机制的许多特征仍有待确定。例如，嗅觉丧失是一种常见的表现，许多有此发现的患者没有或只有轻微的呼吸体征。对实验性感染SARS-CoV-2（COVID-19的病因）的动物进行的研究，为研究该疾病在人类患者中不易研究的方面提供了机会。虽然COVID-19的严重程度从无症状到致命不等，但大多数实验性感染都提供了对轻度疾病的见解。在这里，使用我们最初为SARS研究开发的K18-hACE 2小鼠，我们表明SARS-CoV-2感染会导致肺部严重疾病，在一些小鼠中，大脑也会发生严重疾病。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，我们表明，从恢复的COVID-19患者中输注恢复期血浆（CP）可以预防致命疾病。小鼠在感染后早期出现嗅觉丧失。值得注意的是，虽然用CP预处理预防了显著的临床疾病，但不能预防嗅觉丧失。因此，K18-hACE 2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提供了有用的模型。
The ongoing COVID-19 pandemic is associated with substantial morbidity and mortality. While 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 signs. Studies in animals experimentally infected with SARS-CoV-2, the cause of COVID-19, provide opportunities to study aspects of the disease not easily investigated in human patients. While COVID-19 severity ranges from asymptomatic to lethal, most experimental infections provide insights into mild disease. Here, using K18-hACE2 mice that we originally developed for SARS studies, 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. Further, we show that infusion of convalescent plasma (CP) from a recovered COVID-19 patient protected against lethal disease. Mice developed anosmia at early times after infection. Notably, while pretreatment with CP prevented significant 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.
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影响因子：
64.8
作者：
Muñoz-Fontela C;Dowling WE;Funnell SGP;Gsell PS;Riveros-Balta AX;Albrecht RA;Andersen H;Baric RS;Carroll MW;Cavaleri M;Qin C;Crozier I;Dallmeier K;de Waal L;de Wit E;Delang L;Dohm E;Duprex WP;Falzarano D;Finch CL;Frieman MB;Graham BS;Gralinski LE;Guilfoyle K;Haagmans BL;Hamilton GA;Hartman AL;Herfst S;Kaptein SJF;Klimstra WB;Knezevic I;Krause PR;Kuhn JH;Le Grand R;Lewis MG;Liu WC;Maisonnasse P;McElroy AK;Munster V;Oreshkova N;Rasmussen AL;Rocha-Pereira J;Rockx B;Rodríguez E;Rogers TF;Salguero FJ;Schotsaert M;Stittelaar KJ;Thibaut HJ;Tseng CT;Vergara-Alert J;Beer M;Brasel T;Chan JFW;García-Sastre A;Neyts J;Perlman S;Reed DS;Richt JA;Roy CJ;Segalés J;Vasan SS;Henao-Restrepo AM;Barouch DH
通讯作者：
Barouch DH
影响因子：
158.5
作者：
Ackermann, Maximilian;Verleden, Stijn E.;Jonigk, Danny
通讯作者：
Jonigk, Danny
影响因子：
12.4
作者：
Chow, YH;Plumb, J;Hu, J
通讯作者：
Hu, J
影响因子：
5.4
作者：
McCray, Paul B., Jr.;Pewe, Lecia;Perlman, Stanley
通讯作者：
Perlman, Stanley
影响因子：
15.1
作者：
Bryche, Bertrand;St Albin, Audrey;Meunier, Nicolas
通讯作者：
Meunier, Nicolas