Neurological manifestations of coronavirus infections, before and after COVID-19: a review of animal studies

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This virus, which was first identified in December 2019 in China, has resulted in a yet ongoing viral pandemic. Coronaviridae could potentially cause several disorders in a wide range of hosts such as birds and mammals. Although infections caused by this family of viruses are predominantly limited to the respiratory tract, Betacoronaviruses are potentially able to invade the central nervous system (CNS) as well as many other organs, thereby inducing neurological damage ranging from mild to lethal in both animals and humans. Over the past two decades, three novel CoVs, SARS-CoV-1, MERS-CoV, and SARS-CoV-2, emerging from animal reservoirs have exhibited neurotropic properties causing severe and even fatal neurological diseases. The pathobiology of these neuroinvasive viruses has yet to be fully known. Both clinical features of the previous CoV epidemics (SARS-CoV-1 and MERS-CoV) and lessons from animal models used in studying neurotropic CoVs, especially SARS and MERS, constitute beneficial tools in comprehending the exact mechanisms of virus implantation and in illustrating pathogenesis and virus dissemination pathways in the CNS. Here, we review the animal research which assessed CNS infections with previous more studied neurotropic CoVs to demonstrate how experimental studies with appliable animal models can provide scientists with a roadmap in the CNS impacts of SARS-CoV-2. Indeed, animal studies can finally help us discover the underlying mechanisms of damage to the nervous system in COVID-19 patients and find novel therapeutic agents in order to reduce mortality and morbidity associated with neurological complications of SARS-CoV-2 infection.