Cortical Grey matter volume depletion links to neurological sequelae in post COVID-19 "long haulers"

Document Type

Journal Article

Publication Date



BMC neurology








Brain fog; COVID-19; Cognitive impairment; Long haulers; Neurologic sequelae of COVID-19; PASC; SARS-CoV-2; Voxel-based morphometry


OBJECTIVE: COVID-19 (SARS-CoV-2) has been associated with neurological sequelae even in those patients with mild respiratory symptoms. Patients experiencing cognitive symptoms such as "brain fog" and other neurologic sequelae for 8 or more weeks define "long haulers". There is limited information regarding damage to grey matter (GM) structures occurring in COVID-19 "long haulers". Advanced imaging techniques can quantify brain volume depletions related to COVID-19 infection which is important as conventional Brain MRI often fails to identify disease correlates. 3-dimensional voxel-based morphometry (3D VBM) analyzes, segments and quantifies key brain volumes allowing comparisons between COVID-19 "long haulers" and normative data drawn from healthy controls, with values based on percentages of intracranial volume. METHODS: This is a retrospective single center study which analyzed 24 consecutive COVID-19 infected patients with long term neurologic symptoms. Each patient underwent Brain MRI with 3D VBM at median time of 85 days following laboratory confirmation. All patients had relatively mild respiratory symptoms not requiring oxygen supplementation, hospitalization, or assisted ventilation. 3D VBM was obtained for whole brain and forebrain parenchyma, cortical grey matter (CGM), hippocampus, and thalamus. RESULTS: The results demonstrate a statistically significant depletion of CGM volume in 24 COVID-19 infected patients. Reduced CGM volume likely influences their long term neurological sequelae and may impair post COVID-19 patient's quality of life and productivity. CONCLUSION: This study contributes to understanding effects of COVID-19 infection on patient's neurocognitive and neurological function, with potential for producing serious long term personal and economic consequences, and ongoing challenges to public health systems.