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Myeloid cell-driven nonregenerative pulmonary scarring is conserved in multiple nonhuman primate species regardless of SARS-CoV-2 infection modality

Alyssa C Fears, Brandon J Beddingfield, Nicole R Chirichella, Nadia Slisarenko, Stephanie Z Killeen, Rachel K Redmann, Kelly Goff, Skye Spencer, Breanna Picou, Nadia Golden, Duane J Bush, Luis M Branco, Matthew L Boisen, Hongmei Gao, David C Montefiori, Robert V Blair, Lara A Doyle-Meyers, Kasi Russel-Lodrigue, Nicholas J Maness, View ORCID ProfileChad J Roy
doi: https://doi.org/10.1101/2021.11.28.470250
Alyssa C Fears
1Tulane National Primate Research Center, Covington, Louisiana, USA
2Biomedical Science Training Program, Tulane University School of Medicine, New Orleans, Louisiana, USA
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Brandon J Beddingfield
1Tulane National Primate Research Center, Covington, Louisiana, USA
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Nicole R Chirichella
1Tulane National Primate Research Center, Covington, Louisiana, USA
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Nadia Slisarenko
1Tulane National Primate Research Center, Covington, Louisiana, USA
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Stephanie Z Killeen
1Tulane National Primate Research Center, Covington, Louisiana, USA
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Rachel K Redmann
1Tulane National Primate Research Center, Covington, Louisiana, USA
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Kelly Goff
1Tulane National Primate Research Center, Covington, Louisiana, USA
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Skye Spencer
1Tulane National Primate Research Center, Covington, Louisiana, USA
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Breanna Picou
1Tulane National Primate Research Center, Covington, Louisiana, USA
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Nadia Golden
1Tulane National Primate Research Center, Covington, Louisiana, USA
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Duane J Bush
3Zalgen Labs, LLC, Germantown, MD, USA
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Luis M Branco
3Zalgen Labs, LLC, Germantown, MD, USA
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Matthew L Boisen
3Zalgen Labs, LLC, Germantown, MD, USA
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Hongmei Gao
4Duke University Medical Center, Duke Human Vaccine Institute, Durham, North Carolina, USA
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David C Montefiori
4Duke University Medical Center, Duke Human Vaccine Institute, Durham, North Carolina, USA
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Robert V Blair
1Tulane National Primate Research Center, Covington, Louisiana, USA
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Lara A Doyle-Meyers
1Tulane National Primate Research Center, Covington, Louisiana, USA
5Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana, USA
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Kasi Russel-Lodrigue
1Tulane National Primate Research Center, Covington, Louisiana, USA
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Nicholas J Maness
1Tulane National Primate Research Center, Covington, Louisiana, USA
6Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, Louisiana, USA
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Chad J Roy
1Tulane National Primate Research Center, Covington, Louisiana, USA
6Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, Louisiana, USA
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  • ORCID record for Chad J Roy
  • For correspondence: croy@tulane.edu
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Abstract

The novel coronavirus SARS-CoV-2 has caused a worldwide pandemic resulting in widespread efforts in development of animal models that recapitulate human disease for evaluation of medical countermeasures, and to dissect COVID-19 immunopathogenesis. We tested whether route of experimental infection substantially changes COVID-19 disease characteristics in two species (Macaca mulatta; rhesus macaques; RM, Chlorocebus atheiops; African green monkeys; AGM) of nonhuman primates. Species-specific cohorts of RM and AGM Rhesus macaques (Macaca mulatta, RMs) and African green monkeys (Chlorocebus aethiops, AGMs) were experimentally infected with homologous SARS-CoV-2 by either direct mucosal instillation or small particle aerosol in route-discrete subcohorts. Both species demonstrated equivalent infection initially by either exposure route although the magnitude and duration of viral loading was greater in AGMs than that of the RM. Clinical onset was nearly immediate (+1dpi) in mucosally-exposed cohorts whereas aerosol-infected animals began to show signs +7dpi. Myeloid cell responses indicative of the development of pulmonary scarring and extended lack of regenerative capacity in the pulmonary compartment was a conserved pathologic response in both species by either exposure modality. This pathological commonality may be useful in future anti-fibrosis therapeutic evaluations and expands our understanding of how SARS-CoV-2 infection leads to ARDS and functional lung damage.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted November 30, 2021.
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Myeloid cell-driven nonregenerative pulmonary scarring is conserved in multiple nonhuman primate species regardless of SARS-CoV-2 infection modality
Alyssa C Fears, Brandon J Beddingfield, Nicole R Chirichella, Nadia Slisarenko, Stephanie Z Killeen, Rachel K Redmann, Kelly Goff, Skye Spencer, Breanna Picou, Nadia Golden, Duane J Bush, Luis M Branco, Matthew L Boisen, Hongmei Gao, David C Montefiori, Robert V Blair, Lara A Doyle-Meyers, Kasi Russel-Lodrigue, Nicholas J Maness, Chad J Roy
bioRxiv 2021.11.28.470250; doi: https://doi.org/10.1101/2021.11.28.470250
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Myeloid cell-driven nonregenerative pulmonary scarring is conserved in multiple nonhuman primate species regardless of SARS-CoV-2 infection modality
Alyssa C Fears, Brandon J Beddingfield, Nicole R Chirichella, Nadia Slisarenko, Stephanie Z Killeen, Rachel K Redmann, Kelly Goff, Skye Spencer, Breanna Picou, Nadia Golden, Duane J Bush, Luis M Branco, Matthew L Boisen, Hongmei Gao, David C Montefiori, Robert V Blair, Lara A Doyle-Meyers, Kasi Russel-Lodrigue, Nicholas J Maness, Chad J Roy
bioRxiv 2021.11.28.470250; doi: https://doi.org/10.1101/2021.11.28.470250

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