Histopathological pulmonary lesions in rhesus (Macaca mulatta) and cynomolgus (Macaca fascicularis) macaques experimentally infected with wild-type severe acute respiratory syndrome coronavirus 2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a viral pneumonia characterized by acute interstitial pneumonia and diffuse alveolar damage in humans. Non-human primates (NHPs) are widely used as preclinical animal models for vaccine development against SARS-CoV-2. However, the pathological changes in NHPs have been described only in selected facets and inconsistent nomenclature is used, making it difficult to interpret and compare the outcomes between studies. Here, we present a standardized methodology for histopathological evaluation of experimental infection outcomes in rhesus (Macaca mulatta) and cynomolgus (Macaca fascicularis) macaques. Evaluation criteria for vascular and epithelial changes in the early (3 days post infection [dpi]) and late (21 dpi) phases of the infection were developed, and a four-grade classification encompassing all the histopathological lung lesions was established. The grades of histopathological lung lesions were higher at 3 dpi compared with 21 dpi in both species of macaques, and there were no statistically significant differences in the grades between the two species at 3 dpi and 21 dpi. This study contextualized the pathological SARS-CoV-2 presentation and standardized the terminology and grading scale for lesion severity to facilitate histopathological examination in the macaque model. By referring to the standardized histopathological criteria and grades proposed here, comparable results with high reproducibility can be obtained in future studies of pathogenicity.