A Mouse-adapted SARS-CoV-2 Model for Investigating Post-acute Sequelae of COVID infection

Abstract

The coronavirus disease of 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), remains a major health issue after nearly 7 millions of death toll in the last four years. As the world is recovering with improving vaccines and antiviral treatments, the alarming rate of long-COVID, or Post-acute Sequelae of COVID-19 (PASC), calls for further investigations. Among a list of symptoms associated with multi-organ dysfunctions, the neurological complications are particularly intriguing, yet the underlying mechanisms remain elusive. With the recently developed mouse adapted SARS-CoV-2 stain, we are now able to model the mild COVID infection in C57BL/6 mice and study the chronic immune responses and subsequent damages in different organs long after the viruses are clearly naturally in the body. More specifically, we found adult C57BL/6J mice developed neurological impairments, including behavior changes related to sensorimotor coordination, depression- and anxiety-like behaviors, and inflammation in multiple organs including lung, liver and brain, which persisted over at least 4 weeks in mice even with mild infection. Therefore, this model can be used to further explopred the mechanisms of PASC, as well as potential intervention or therapeutic approaches.