Assessing Brain Capillaries in Coronavirus Disease 2019

David W. Nauen, MD, PhD¹; Jody E. Hooper, MD¹; C. Matthew Stewart, MD, PhD²; et al

doi:10.1001/jamaneurol.2021.0225

Evidence suggests brain involvement in coronavirus disease 2019 (COVID-19). Manifestations in acutely ill individuals often include confusion and alteration of consciousness. After this phase, many patients experience continued neurologic symptoms such as dysexecutive syndrome¹ or “brain fog.”² However, in autopsies from patients with COVID-19 who had neurologic abnormalities (reviewed in the study by Mukerji and Solomon³), investigations have largely not identified the chronic inflammation or marked neural changes typically associated with viral infection, and viral genetic material has been minimal or absent. It has been difficult to reconcile the experience of patients and clinicians that COVID-19 is altering cognition with tissue studies that show no evidence of encephalitis involving higher brain centers. We hypothesized that histopathology might provide insight. We report here a finding that may contribute in some cases, identified by analysis of brain tissue from patients who died of COVID-19.

Methods

The institutional review boards of Johns Hopkins University and Mass General Brigham approved this study, and the next of kin of each patient consented for use of tissues for research. We evaluated brain tissue from autopsies of patients with nucleic acid–proven severe acute respiratory syndrome coronavirus 2 infection and confirmed pulmonary pathology. We assessed the brains from the first 5 such cases at Johns Hopkins University; for 2 of these, only fragments of brain were available. Cases from Mass General Brigham were randomly selected from autopsies of individuals with COVID-19 performed between April 14 and May 15, 2020, and free of infarcts. Detailed information on these 15 patients as well as the 2 control patients without COVID-19 is provided in the eTable in the Supplement. COVID-19–negative cases were chosen because of comparable patient age and the presence of hypoxic-ischemic changes in brain. At autopsy, the cranium was opened with hand tools or a saw with a vacuum shroud to prevent aerosolization. Brains were fixed in neutral buffered formalin, 10%, for 2 weeks, then grossly examined and sectioned for microscopic assessment.

Results

In 5 cases (Table) in cortical capillaries, we identified large cell nuclei morphologically consistent with megakaryocytes (Figure, A). To further characterize these cells, we performed immunohistochemistry for CD61 and CD42b, markers of platelets and megakaryocytes. CD61 labels these cells (Figure, B), as does CD42b (Figure, C), confirming their megakaryocyte identity. The cells were distinct from platelet clusters, which were found in postmortem intravascular precipitates (Figure, D). Evaluation of the cortex of 2 patients who tested negative for COVID-19 who had hypoxic brain changes demonstrated no megakaryocytes on CD61.

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