Exposure modality influences viral kinetics but not respiratory outcome of COVID-19 in multiple nonhuman primate species
- Alyssa C Fears 1,2, Brandon J Beddingfield 1, Nicole R Chirichella 1, Nadia Slisarenko 1, Stephanie Z Killeen 1, Rachel K Redmann 1, Kelly Goff 1, Skye Spencer 1, Breanna Picou 1, Nadia Golden 1, Cecily C Midkiff 1, Duane J Bush 3, Luis M Branco 3, Matthew L Boisen 3, Hongmei Gao 4, David C Montefiori 4, Robert V Blair 1, Lara A Doyle-Meyers 1,5, Kasi Russell-Lodrigue 1, Nicholas J Maness 1,6, Chad J Roy 1,6
- 1Tulane National Primate Research Center, Covington, Louisiana, United States of America.
- 2Biomedical Science Training Program, Tulane University School of Medicine, New Orleans, Louisiana, United States of America.
- 3Zalgen Labs, LLC, Germantown, Maryland, United States of America.
- 4Duke University Medical Center, Duke Human Vaccine Institute, Durham, North Carolina, United States of America.
- 5Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana, United States of America.
- 6Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, Louisiana, United States of America.
- 0Tulane National Primate Research Center, Covington, Louisiana, United States of America.
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View abstract on PubMed
Summary
This summary is machine-generated.This study shows that SARS-CoV-2 infection in nonhuman primates causes similar lung damage regardless of how the virus is administered. This finding validates nonhuman primates as a model for studying COVID-19 and evaluating anti-fibrotic therapies.
Area Of Science
- Virology
- Comparative Pathology
- Primate Models
Background
- The emergence of SARS-CoV-2 has led to a global pandemic.
- Existing animal models often fail to replicate severe COVID-19 disease.
- This limits research into disease pathogenesis and medical countermeasures.
Purpose Of The Study
- To investigate if the route of SARS-CoV-2 experimental infection influences COVID-19 disease characteristics in nonhuman primates.
- To evaluate two species of nonhuman primates for their suitability as models for severe COVID-19.
Main Methods
- Two species of nonhuman primates (rhesus macaques and African green monkeys) were infected with SARS-CoV-2.
- Infection was administered via direct mucosal instillation or small particle aerosol.
- Viral loads, clinical signs, and pulmonary pathologies were assessed.
Main Results
- Both rhesus macaques and African green monkeys exhibited comparable viral loads across all compartments, irrespective of exposure route.
- Mucosal infection led to immediate clinical onset (1 day post-infection), while aerosol exposure resulted in later onset (7 days post-infection).
- Conserved pathologies included pulmonary myeloid cell influx, pleuritis, and impaired lung regeneration.
Conclusions
- Pulmonary pathologies in nonhuman primates are conserved across species and infection routes, offering insights into ARDS and lung damage.
- Nonhuman primate models closely mimic clinical responses, making them valuable for evaluating anti-fibrotic therapies for COVID-19 related lung injury.
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