To report neuropathological findings and quantify SARS-CoV-2 viral burden for 18 consecutive coronavirus disease 2019 (COVID-19) autopsies.

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.

Brain tissue specimens were sampled from 18 subjects (10 standard areas), fixed in formalin, and stained with hematoxylin and eosin for histopathological analysis. SARS-CoV-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.

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.

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.