Dynamic Molecular Changes in Brain, Lung, and Heart of Hamsters Infected With SARS-CoV-2: Insights From a Severe and Recovery Phase Model.

Abstract

The Global pandemic of coronavirus disease 2019 was initiated by the emergence of severe acute respiratory syndrome coronavirus 2. In addition to conventional pulmonary lesions, a range of neurological injury symptoms have been identified in clinical practice, but the aetiology of neurological disorders linked to SARS-CoV-2 infection remains poorly understood. Syrian hamsters, which are highly susceptible to SARS-CoV-2 infection, exhibit a disease phenotype similar to that observed in human COVID-19 patients. In this study, a hamster model of COVID-19 infection was used to analyze molecular changes in different tissues at various time points post infection with distinct strains using proteomic and phosphoproteomic approaches. Multi-omics analysis showed that SARS-COV-2 infection triggers sustained downregulation of the abundance and phosphorylation levels of neuronal and synapse-associated proteins in the brain, suggesting that neuronal damage persists even during the recovery period. Additionally, infections with SARS-CoV-2 may contribute to the onset of long-term symptoms of COVID-19 by impacting energy metabolism, neurotransmitter release, and synaptic transmission pathways. This study provides a comprehensive molecular profile of hamsters infected with different SARS-CoV-2 strains in different tissues, offering foundational insights into the pathogenic mechanisms of COVID-19.