?:abstract
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SARS-CoV-2 is a coronavirus that sparked the current COVID-19 pandemic. To stop the shattering effect of COVID-19, effective and safe vaccines, and antiviral therapies are urgently needed. To facilitate the preclinical evaluation of intervention approaches, relevant animal models need to be developed and validated. Rhesus macaques (Macaca mulatta) and cynomolgus macaques (Macaca fascicularis) are widely used in biomedical research and serve as models for SARS-CoV-2 infection. However, differences in study design make it difficult to compare and understand potential species-related differences. Here, we directly compared the course of SARS-CoV-2 infection in the two genetically closely-related macaque species. After inoculation with a low passage SARS-CoV-2 isolate, clinical, virological, and immunological characteristics were monitored. Both species showed slightly elevated body temperatures in the first days after exposure while a decrease in physical activity was only observed in the rhesus macaques and not in cynomolgus macaques. The virus was quantified in tracheal, nasal, and anal swabs, and in blood samples by qRT-PCR, and showed high similarity between the two species. Immunoglobulins were detected by various enzyme-linked immunosorbent assays (ELISAs) and showed seroconversion in all animals by day 10 post-infection. The cytokine responses were highly comparable between species and computed tomography (CT) imaging revealed pulmonary lesions in all animals. Consequently, we concluded that both rhesus and cynomolgus macaques represent valid models for evaluation of COVID-19 vaccine and antiviral candidates in a preclinical setting. Author summary SARS-CoV-2 infection can have a wide range of symptoms. It can cause asymptomatic or mild disease, but can also have a severe, potentially deadly outcome. Vaccines and antivirals will therefore be crucial in fighting the current COVID-19 pandemic. For testing these prophylactic and therapeutic treatments, and investigating the progression of infection and disease development, animal models play an essential role. In this study, we compare the course of SARS-CoV-2 infection in rhesus and cynomolgus macaques. Both species showed moderate disease symptoms as shown by pulmonary lesions by CT imaging. Shedding of infectious virus from the respiratory system was also documented. This study provides a detailed description of the pathogenesis of a low-passage SARS-CoV-2 isolate in two macaque models and suggests that both species represent an equally good model in research for both COVID-19 prophylactic and therapeutic treatments.
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