Neuropathological Changes in Autopsied Brain Tissue of Patients With COVID-19

Neuropathological changes in patients with coronavirus disease 2019 are relatively mild, with neuroinflammatory changes in the brain stem most often found.

Neuropathological changes in patients with coronavirus disease 2019 (COVID-19) are relatively mild, with neuroinflammatory changes in the brain stem most often found, according to study results  published in Lancet Neurology.

The central nervous system-related symptoms of COVID-19 are secondary to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The objective of the current study was to assess the brain tissues of patients who died from COVID-19 to identify inflammatory markers, glial responses, and determine the whether SARS-CoV-2 gains access to the central nervous system.

This post-mortem case series included the brains of 43 (median age, 76 years; 63% men) patients from Hamburg, Germany, who died in hospitals, nursing homes, or at home. Patients were autopsied between March 13 and April 24, 2020. Inclusion criteria consisted of confirmed SARS-CoV-2 infection, with SARS-CoV-2 viral RNA detected by quantitative reverse-transcriptase-polymerase chain reaction (qRT-PCR). Additionally, included patients had high-quality brain tissue samples. Study researchers evaluated prior medical conditions, medical course prior to death, and ante-mortem diagnostic findings.

Of the 43 patients, 40 (93%) had adequate samples for detection of SARS-CoV-2 by immunohistochemistry, and 27 (63%) patients had samples available for the detection of the virus by qRT-PCR. Ischemic lesions in the brain were documented in 6 (14%) patients, and astrogliosis in 37 (86%) patients in the studied regions of the brain.

Activation of microglia and infiltration by cytotoxic T lymphocytes were most pronounced in the brainstem and cerebellum. Meningeal cytotoxic T lymphocyte infiltration was seen in 34 (79%) patients. Study researchers observed a high degree of astrogliosis and microgliosis in the olfactory bulb, but only minor infiltration by cytotoxic T lymphocytes.

SARS-CoV-2 RNA or proteins were detected in brain tissues of 21 (53%) patients, and both were identified in 8 (20%) patients. SARS-CoV-2 viral proteins were found in cranial nerves originating from the lower brainstem and in isolated cells of the brainstem.

There was no association observed between the presence of SARS-CoV-2 virus in the central nervous system and the severity of neuropathological changes in the brain.

The study had several limitations, including its descriptive design, the absence of age- and sex-matched controls, relatively small number of available post-mortem specimens, and no available clinical data to establish clinicopathological correlations.

“[N]europathological alterations in the brains of patients who die from COVID-19 are relatively mild, although the virus is able to gain access to the brain. The neuropathological alterations are most likely to be immune-mediated, and there does not seem to be fulminant virus-induced encephalitis nor direct evidence for SARS-CoV-2-caused CNS damage,” concluded the study researchers.


Matschke J, Lütgehetmann M, Hagel C, et al. Neuropathology of patients with COVID-19 in Germany: a post-mortem case series. Lancet Neurol. Published online October 5, 2020. doi:10.1016/S1474-4422(20)30308-2