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

Author

Listed:
  • Jian Zheng

    (University of Iowa)

  • Lok-Yin Roy Wong

    (University of Iowa)

  • Kun Li

    (University of Iowa)

  • Abhishek Kumar Verma

    (University of Iowa)

  • Miguel E. Ortiz

    (University of Iowa)

  • Christine Wohlford-Lenane

    (University of Iowa)

  • Mariah R. Leidinger

    (University of Iowa)

  • C. Michael Knudson

    (University of Iowa)

  • David K. Meyerholz

    (University of Iowa)

  • Paul B. McCray

    (University of Iowa
    University of Iowa)

  • Stanley Perlman

    (University of Iowa
    University of Iowa)

Abstract

The ongoing coronavirus disease 2019 (COVID-19) pandemic is associated with substantial morbidity and mortality. Although much has been learned in the first few 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 anosmia show no or only minor respiratory symptoms1. Studies in animals infected experimentally with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of COVID-19, provide opportunities to study aspects of the disease that are not easily investigated in human patients. Although the severity of COVID-19 ranges from asymptomatic to lethal2, most experimental infections provide insights into mild disease3. Here, using K18-hACE2 transgenic mice that were 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 time points after infection. Notably, although pre-treatment with convalescent plasma prevented most signs of clinical disease, it did not prevent anosmia. Thus, K18-hACE2 mice provide a useful model for studying the pathological basis of both mild and lethal COVID-19 and for assessing therapeutic interventions.

Suggested Citation

  • Jian Zheng & Lok-Yin Roy Wong & Kun Li & Abhishek Kumar Verma & Miguel E. Ortiz & Christine Wohlford-Lenane & Mariah R. Leidinger & C. Michael Knudson & David K. Meyerholz & Paul B. McCray & Stanley P, 2021. "COVID-19 treatments and pathogenesis including anosmia in K18-hACE2 mice," Nature, Nature, vol. 589(7843), pages 603-607, January.
  • Handle: RePEc:nat:nature:v:589:y:2021:i:7843:d:10.1038_s41586-020-2943-z
    DOI: 10.1038/s41586-020-2943-z
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    Cited by:

    1. Shelly J. Robertson & Olivia Bedard & Kristin L. McNally & Carl Shaia & Chad S. Clancy & Matthew Lewis & Rebecca M. Broeckel & Abhilash I. Chiramel & Jeffrey G. Shannon & Gail L. Sturdevant & Rebecca , 2023. "Genetically diverse mouse models of SARS-CoV-2 infection reproduce clinical variation in type I interferon and cytokine responses in COVID-19," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    2. Ankita Leekha & Arash Saeedi & K M Samiur Rahman Sefat & Monish Kumar & Melisa Martinez-Paniagua & Adrian Damian & Rohan Kulkarni & Kate Reichel & Ali Rezvan & Shalaleh Masoumi & Xinli Liu & Laurence , 2024. "Multi-antigen intranasal vaccine protects against challenge with sarbecoviruses and prevents transmission in hamsters," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    3. Ankita Leekha & Arash Saeedi & Monish Kumar & K. M. Samiur Rahman Sefat & Melisa Martinez-Paniagua & Hui Meng & Mohsen Fathi & Rohan Kulkarni & Kate Reichel & Sujit Biswas & Daphne Tsitoura & Xinli Li, 2024. "An intranasal nanoparticle STING agonist protects against respiratory viruses in animal models," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    4. Ronghui Liang & Zi-Wei Ye & Zhenzhi Qin & Yubin Xie & Xiaomeng Yang & Haoran Sun & Qiaohui Du & Peng Luo & Kaiming Tang & Bodan Hu & Jianli Cao & Xavier Hoi-Leong Wong & Guang-Sheng Ling & Hin Chu & J, 2024. "PMI-controlled mannose metabolism and glycosylation determines tissue tolerance and virus fitness," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    5. Lucie Bernard-Raichon & Mericien Venzon & Jon Klein & Jordan E. Axelrad & Chenzhen Zhang & Alexis P. Sullivan & Grant A. Hussey & Arnau Casanovas-Massana & Maria G. Noval & Ana M. Valero-Jimenez & Jua, 2022. "Gut microbiome dysbiosis in antibiotic-treated COVID-19 patients is associated with microbial translocation and bacteremia," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    6. Lei Peng & Yingxia Hu & Madeleine C. Mankowski & Ping Ren & Rita E. Chen & Jin Wei & Min Zhao & Tongqing Li & Therese Tripler & Lupeng Ye & Ryan D. Chow & Zhenhao Fang & Chunxiang Wu & Matthew B. Dong, 2022. "Monospecific and bispecific monoclonal SARS-CoV-2 neutralizing antibodies that maintain potency against B.1.617," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    7. Eakachai Prompetchara & Chutitorn Ketloy & Mohamad-Gabriel Alameh & Kittipan Tharakhet & Papatsara Kaewpang & Nongnaphat Yostrerat & Patrawadee Pitakpolrat & Supranee Buranapraditkun & Suwimon Manopwi, 2023. "Immunogenicity and protective efficacy of SARS-CoV-2 mRNA vaccine encoding secreted non-stabilized spike in female mice," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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