Proteomic and Metabolomic Characterization of SARS-CoV-2-Infected Cynomolgus Macaque at Early Stage

Although tremendous effort has been exerted to elucidate the pathogenesis of severe COVID-19 cases, the detailed mechanism of moderate cases, which accounts for 90% of all patients, remains unclear yet, partly limited by lacking the biopsy tissues. Here, we established the COVID-19 infection model in cynomolgus macaques (CMs), monitored the clinical and pathological features, and analyzed underlying pathogenic mechanisms at early infection stage by performing proteomic and metabolomic profiling of lung tissues and sera samples from COVID-19 CMs models. Our data demonstrated that innate immune response, neutrophile and platelet activation were mainly dysregulated in COVID-19 CMs. The symptom of neutrophilia, lymphopenia and massive cytokines storm, main features of severe COVID-19 patients, were greatly weakened in most of the challenged CMs, which are more semblable as moderate patients. Thus, COVID-19 model in CMs is rational to understand the pathogenesis of moderate COVID-19 and may be a candidate model to assess the safety and efficacy of therapeutics and vaccines against SARS-CoV-2 infection.

Automated summary

This study established a COVID-19 infection model in cynomolgus macaques and analyzed the underlying pathogenic mechanisms of moderate cases using proteomic and metabolomic profiling. The results showed dysregulation of innate immune response, neutrophil and platelet activation in the COVID-19 macaque models. The symptoms of neutrophilia, lymphopenia, and cytokine storm, which are typically seen in severe cases, were significantly attenuated in most of the macaques, resembling moderate cases. The macaque model could be a valuable tool for understanding the pathogenesis of moderate COVID-19 and evaluating the safety and efficacy of therapeutics and vaccines.