BACKGROUND: Neurologic events have been reported in patients with coronavirus disease 2019 . However, a modelbased evaluation of the spatial distribution of these events is lacking. PURPOSE: Our aim was to quantitatively evaluate whether a network diffusion model can explain the spread of small neurologic events.

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Background Neuropathology caused by the coronavirus disease 2019 (COVID-19) has been reported across several studies. The characterisation of the spatial distribution of these pathology remains critical to assess long and short-term neurological sequelae of COVID-19. To this end, Mathematical models can be used to characterise the location and aetiologies underlying COVID-19-related neuropathology. Method We performed a systematic review of the literature to quantify the locations of small neurological events identified with magnetic resonance imaging (MRI) among COVID-19 patients. Neurological events were localised into the Desikan-Killiany grey and white matter atlases. A mathematical network diffusion model was then used to test whether the spatial distribution of neurological events could be explained via a linear spread through the structural connectome of the brain. Findings We identified 35 articles consisting of 123 patients that assessed the spatial distribution of small neurological events among COVID-19 patients. Of these, 91 patients had grey matter changes, 95 patients had white matter changes and 72 patients had confirmed cerebral microbleeds. White matter events were observed within 14 of 42 white matter bundles from the IIT atlas. The highest proportions (26%) of events were observed within the bilateral corticospinal tracts. The splenium and middle of the corpus callosum were affected in 14% and 9% of the cases respectively. Grey matter events were spatially distributed in the 41 brain regions within the Desikan-Killiany atlas. The highest proportions (~10%) of the events were observed in areas including the bilateral superior temporal, precentral, and lateral occipital cortices. Sub-cortical events were most frequently identified in the Pallidum. The application of a mathematical network diffusion model suggested that the spatial pattern of the small neurological events in COVID-19 can be modelled with a linear diffusion of spread from epicentres in the bilateral cerebellum and basal ganglia (Pearsons r=0.41, p<0.001, corrected). Interpretation To our knowledge, this is the first study to systematically characterise the spatial distribution of small neurological events in COVID-19 patients and test whether the spatial distribution of these events can be explained by a linear diffusion spread model. The location of neurological events is consistent with commonly identified neurological symptoms including alterations in conscious state among COVID-19 patients that require brain imaging. Given the prevalence and severity of these manifestations, clinicians should carefully monitor neurological symptoms within COVID-19 patients and their potential long-term sequelae.