Abstract
The novel coronavirus SARS-CoV-2, the causative agent of COVID-19 disease, has killed over five million people worldwide as of December 2021 with infections rising again due to the emergence of highly transmissible variants. Animal models that faithfully recapitulate human disease are critical for assessing SARS-CoV-2 viral and immune dynamics, for understanding mechanisms of disease, and for testing vaccines and therapeutics. Pigtail macaques (PTM, Macaca nemestrina) demonstrate a rapid and severe disease course when infected with simian immunodeficiency virus (SIV), including the development of severe cardiovascular symptoms that are pertinent to COVID-19 manifestations in humans. We thus proposed this species may likewise exhibit severe COVID-19 disease upon infection with SARS-CoV-2. Here, we extensively studied a cohort of SARS-CoV-2-infected PTM euthanized either 6- or 21-days after respiratory viral challenge. We show that PTM demonstrate largely mild-to-moderate COVID-19 disease. Pulmonary infiltrates were dominated by T cells, including CD4+ T cells that upregulate CD8 and express cytotoxic molecules, as well as virus-targeting T cells that were predominantly CD4+. We also noted increases in inflammatory and coagulation markers in blood, pulmonary pathologic lesions, and the development of neutralizing antibodies. Together, our data demonstrate that SARS-CoV-2 infection of PTM recapitulates important features of COVID-19 and reveals new immune and viral dynamics and thus may serve as a useful animal model for studying pathogenesis and testing vaccines and therapeutics.
Highlights
In late 2019, a novel coronavirus was found circulating in humans in China
The development of new drugs will rely on having animal models that reproduce the most severe disease seen in humans
In this study we tested whether pigtail macaques (PTM) might exhibit such severe disease, based on previous work showing this species is prone to more rapid and severe disease when infected with other viruses
Summary
In late 2019, a novel coronavirus was found circulating in humans in China. This virus showed substantial genomic similarities with the severe acute respiratory syndrome coronavirus (SARS-CoV) that caused an outbreak and panic in 2003[1] in addition to a number of bat sarbecoviruses[2]; it was named SARS-CoV-2[3]. SARS-CoV-2 is the causative agent of COVID-19 disease and a worldwide pandemic that has killed more than five million persons to date including 790,000 deaths in the United States. Though most infected individuals exhibit no or mild symptoms, a subset experience severe complications, including highly elevated pro-inflammatory cytokines and coagulation biomarkers, acute respiratory distress syndrome (ARDS), and death[4,5,6,7,8,9]. A deep understanding of the immunopathologic mechanisms of disease in those with advanced disease and of viral clearance in asymptomatic infection and those with mild disease is critical for the development of generation therapies and vaccines
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