Cerebral Microvascular Injury in Severe COVID-19

John Conklin, Matthew P Frosch, Shibani Mukerji, Otto Rapalino, Mary Maher, Pamela W Schaefer, Michael H Lev, Ramon G Gonzalez, Sudeshna Das, Samantha N Champion, Colin Magdamo, Pritha Sen, George Kyle Harrold, Haitham Alabsi, Erica Normandin, Bennett Shaw, Jacob Lemieux, Pardis Sabeti, John A Branda, Emery N Brown, M Brandon Westover, Susie Y Huang, Brian L Edlow
medRxiv: the preprint server for health sciences 2020 July 24

IMPORTANCE: Microvascular lesions are common in patients with severe COVID-19. Radiologic-pathologic correlation in one case suggests a combination of microvascular hemorrhagic and ischemic lesions that may reflect an underlying hypoxic mechanism of injury, which requires validation in larger studies.

OBJECTIVE: To determine the incidence, distribution, and clinical and histopathologic correlates of microvascular lesions in patients with severe COVID-19.

DESIGN: Observational, retrospective cohort study: March to May 2020.

SETTING: Single academic medical center.

PARTICIPANTS: Consecutive patients (16) admitted to the intensive care unit with severe COVID-19, undergoing brain MRI for evaluation of coma or focal neurologic deficits.

EXPOSURES: Not applicable.

MAIN OUTCOME AND MEASURES: Hypointense microvascular lesions identified by a prototype ultrafast high-resolution susceptibility-weighted imaging (SWI) MRI sequence, counted by two neuroradiologists and categorized by neuroanatomic location. Clinical and laboratory data (most recent measurements before brain MRI). Brain autopsy and cerebrospinal fluid PCR for SARS-CoV 2 in one patient who died from severe COVID-19.

RESULTS: Eleven of 16 patients (69%) had punctate and linear SWI lesions in the subcortical and deep white matter, and eight patients (50%) had >10 SWI lesions. In 4/16 patients (25%), lesions involved the corpus callosum. Brain autopsy in one patient revealed that SWI lesions corresponded to widespread microvascular injury, characterized by perivascular and parenchymal petechial hemorrhages and microscopic ischemic lesions.

CONCLUSIONS AND RELEVANCE: SWI lesions are common in patients with neurological manifestations of severe COVID-19 (coma and focal neurologic deficits). The distribution of lesions is similar to that seen in patients with hypoxic respiratory failure, sepsis, and disseminated intravascular coagulation. Collectively, these radiologic and histopathologic findings suggest that patients with severe COVID-19 are at risk for multifocal microvascular hemorrhagic and ischemic lesions in the subcortical and deep white matter.

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