Defining the neuroinvasive potential of SARS-CoV-2 in brain autopsies of COVID-19 patients and controls

Project Lead: Emily Happy Miller, Division of Infectious Diseases, Department of Medicine,

                    Columbia University Irving Medical Center-New York Presbyterian Hospital

Awarded: 2020, Seed funding-Covid-19 and encephalitis

Throughout my training I have been interested in how viruses affect their hosts. After receiving my PhD training in virology, I came to Columbia University Irving Medical Center to complete my Internal Medicine and Infectious Disease residency and fellowship training. New York City became the epicenter of the COVID-19 pandemic in the United States in Spring 2020. During this time, I helped care for patients with many different COVID-19 manifestations, including encephalopathy. I became involved with a number of research projects, including studies to better understand neurological manifestations of COVID-19. Currently, it is unclear whether the neurological manifestations are a consequence of direct infection of the CNS by the virus or due to secondary sequelae from the virus-induced systemic inflammatory response. We have one of the largest local populations of COVID-19 patients and one of the largest collections of brain autopsies of COVID-19 patients. Analysis of the brain tissue for the virus is essential to understand whether SARS-CoV-2 affects the brain directly or indirectly. We will utilize this large collection of brain autopsy samples to determine the presence of SARS-CoV-2 in the brain by quantitative reverse transcription-PCR and viral RNA staining.  Our study will elucidate possible routes of CNS infection by the virus and identify brain regions and cell types most vulnerable to either direct infection or the effects of systemic cytokines. This seed funding from the Encephalitis Society will provide valuable support for this work in understanding the role of the virus in the brain of people who died from COVID-19. We hope that this work will help shed light on how the virus may be contributing to neurological findings in patients who are alive and dealing with COVID-19 disease. This information will be critical for thoughtful design of diagnostic tools to treat neurological complications from COVID-19 and understanding the long-term effects of the virus on the CNS