New clinical report on brain changes in deceased patients with COVID-19

German researchers published a report on a case series of post-mortem findings of COVID-19 patients who succumbed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection along with neurological complications. His study entitled “Neuropathology of patients with COVID-19 in Germany: a series of post-mortem cases” is published in the latest issue of The Lancet Neurology.

Background

Researchers led by Jakob Matschke explain that several COVID-19 symptoms involve the central nervous system (CNS). It is not clear whether these neurological symptoms are caused by SARS-CoV-2 or not. This study was an attempt to investigate the brain tissues of patients who died from COVID-19 for markers of inflammation and to look for the presence of SARS-CoV-2 in the CNS.

According to the researchers, some of the CNS effects seen with COVID-19 include:

• Anosmia: loss of smell
• Aguesia – loss of taste
• Dizziness
• Headache
• Ischemic stroke
• Hemorrhagic encephalopathy – bleeding within the brain and severe brain damage
• Posterior reversible encephalopathy syndrome
• Epileptic attacks
• Encephalitis or inflammation of the brain.
• Meningitis or inflammation of the meninges.
• Cranial polyneuritis
• Guillain-Barré syndrome
• Miller Fisher syndrome

These have been reported in various studies published during the final months of the pandemic, they wrote.

Hypothesis

The researchers explain that it is not clear how the virus infects the brain, but there are two theories related to it. These are:

• “Direct invasion of SARS-CoV-2 into the CNS”.
• “Indirect mechanisms mediated by the cytokine storm induced by systemic infection by SARS-CoV-2”.

This is the first study to look at post-mortem findings from the brains of COVID-19 patients who had succumbed to the disease. This study included 43 patients between the ages of 51 and 94 who had died in intensive care unit treatment.

Study design

This was a post-mortem case series where neuropathological features were studied in the brains of COVID-19 patients. The patients had died between March 13 and April 24, 2020 in Hamburg, Germany, in hospitals, nursing homes or in their own homes. All patients had tested positive for SARS-CoV-2 by quantitative RT-PCR (qRT-PCR).

Brain and neural tissue samples were obtained by autopsy. The team performed histological staining and immunohistochemical staining of activated astrocyte cells of the brain, activated microglial cells of the brain, and cytotoxic T lymphocytes present in the olfactory bulb, basal ganglia, brain stem and cerebellum region of the brain. From the brain samples, they also analyzed SARS-CoV-2 by qRT-PCR and by immunohistochemistry.

Results and findings

The study included 43 patients who had died in hospitals, nursing homes, or at home. The median age of the patients was 76 years. The general findings of the study were:

• In 6 patients (14 percent) there were ischemic lesions in the brain.
• Among 86 percent of the patients (37), astrogliosis was present in the studied regions of the brain.
• The brainstem and cerebellum regions of the brain showed infiltration with cytotoxic T lymphocytes and activated microglia.
• Among 79 percent of the patients (34), there was infiltration of cytotoxic T lymphocytes into the meninges.
• SARS-CoV-2 was detected in the brains of 53 percent or 21 patients among the 40 studied for the virus.
• SARS-CoV-2 viral proteins were found in cranial nerves that originate in the lower brain stem and in some cells of the brain stem.
• The SARS-CoV-2 virus in the CNS was not found to be associated with the severity of neuropathological changes in the study subjects.
• The angiotensin converting enzyme 2 (ACE2) receptor is known to be the entry point for the SARS CoV-2 virus, and the gene encoding ACE2 it was highest in oligodendrocyte cells of the brain.

Conclusions and repercussions

The researchers explained that astrocytes were key regulators of inflammatory and other processes in the brain, and since they increase in other critical illnesses, the astrocytosis seen in this study cannot be attributed to COVID-19. They wrote, “Microglial activation and cytotoxic T lymphocyte infiltration were primarily limited to the brain stem and cerebellum, with little frontal lobe involvement, consistent with clinical findings pointing to brainstem involvement.”

The study authors concluded that neuropathological changes in the COVID-19 patients were generally mild, but there were prominent inflammatory changes in the brainstem of those who succumbed to the infection. They wrote: “There was no evidence of CNS damage caused directly by SARS-CoV-2.”

This study was funded by the German Research Foundation, Federal State of Hamburg, EU (eRARE), German Center for Infection Research (DZIF).

New clinical report on brain changes in deceased patients with COVID-19