In addition to respiratory symptoms, mounting evidence from SARS-CoV2-infected individuals show increasing numbers of patients develop CNS symptoms as well as neurological and neuroradiological alterations. This is not surprising as decades of research with murine coronaviruses (MuCoV), that are members of the Betacoronavirus genus and related to SARS-CoV, MERS-CoV and SARS-CoV2, have demonstrated the ability of these viruses to infect and persist within the CNS resulting in various histopathological features including neuroinflammation, encephalomyelitis, and demyelination. Indeed, the Betacoronaviruses are known to be potentially neuroinvasive. Supporting this are case reports including neuropathy and seizures in MERS-CoV2 patients and experimental infection of transgenic mice expressing the MERS CoV receptor DPP4 show evidence of MERS-CoV within the brain associated with increased expression of pro-inflammatory cytokines and chemokines. Patients that died from SARS-CoV infection were shown to have virus within the CNS in cortical neurons and these findings were further supported by evidence of neuronal degeneration and brain edema in SARS-CoV-infected patients. Development of a transgenic mouse expressing the SARS-CoV receptor, angiotensin converting enzyme 2 (ACE2), under control of the keratin promoter k18 (k18 hACE2 mice) by Perlman and colleagues showed both lung pathology as well as infection of the CNS with neurons being the primary target of infection. ACE2 is a receptor for SARS-CoV2 and experimental infection of k18 hAC2 mice with SARS-CoV2 results in COVID-19- associated symptoms including lung inflammation/pathology as well as CNS infection.
Currently, our main area of SARS-CoV2 research focuses on how SARS-CoV-2 infection affects disease progression in pre-clinical animal models of Alzheimer’s disease (AD).