Neuropathological Features of COVID-19

Objective: To report neuropathological findings and quantify SARS-CoV-2 viral burden for 18 consecutive coronavirus disease 2019 (COVID-19) autopsies. Background: COVID-19 is a respiratory disease caused by SARS-CoV-2, a virus known to infect lung epithelial cells, yet data about SARS-CoV-2 neuropathology in human brain autopsies is limited. Design/Methods: Brain tissue specimens were sampled from 18 subjects (10 standard areas), fixed in formalin, and stained with hematoxylin and eosin for histopathological analysis. SARSCoV-2 immunohistochemistry and reverse transcription quantitative polymerase chain reaction (RT-qPCR) were performed on 10 brain sections from 2 subjects and 2 sections (medulla and frontal lobe with olfactory nerve) from the remaining 16 subjects. Results: Median age was 62 years (interquartile range, 53 to 75), and 14 patients (78%) were men. Presenting neurologic symptoms were myalgia (n=3), headache (n=2), and decreased taste (n=1);11 received mechanical ventilation. Acute hypoxic injury was detected in cerebrum, hippocampus, and cerebellum in all patients;rare foci of perivascular lymphocytes (n=2) or focal leptomeningeal inflammation (n=1) were also detected. RT-qPCR showed limited evidence of viral RNA. In 10 unique specimens from two subjects, results were equivocal (viral load <5.0 copies/mm3) in 4 and 5 sections, respectively. In the remaining 16 patients, 3 medulla sections and 3 frontal lobe and olfactory sections were positive (5.0 to 59.4 copies/mm3) while the rest were equivocal or negative. SARS-CoV-2 viral load did not correlate with the interval between the onset of symptoms and death or histopathological findings. Immunohistochemical staining for SARS-CoV-2 nucleocapsid protein was negative in neurons, glia, endothelium, and immune cells. Conclusions: Histopathology of brain specimens revealed hypoxia with limited evidence of direct viral damage, including no viral protein. Concordantly, although SARS-CoV-2 was detected by RT-qPCR in some sections, viral load was low and did not correlate with other pathological features.