German researchers published a report on a series of cases on post mortem findings of COVID-19 patients who succumbed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection along with neurological complications. Their study titled “Neuropathology of patients with COVID-19 in Germany: a post-mortem case series” is published in the latest issue of The Lancet Neurology.
Background
Researchers led by Jakob Matschke explain that several symptoms of COVID-19 involve the central nervous system (CNS). It is not clear if 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 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
- Ischaemic stroke
- Haemorrhagic encephalopathy – bleeding within the brain and severe brain damage
- Posterior reversible encephalopathy syndrome
- Epileptic seizures
- Encephalitis or inflammation of the brain
- Meningitis or inflammation of the meninges
- Polyneuritis cranialis
- Guillain-Barré syndrome
- Miller Fisher syndrome
These have been reported in several published studies over the past few 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 SARS-CoV-2 infection.”
This is the first study that studied the post mortem findings of the brains of COVID-19 patients who had succumbed to the disease. This study included 43 patients aged between 51 and 94 years who had died under intensive care unit treatment.
Study design
This was a post-mortem case series where the neuropathological features in the brains of patients of COVID-19 were studied. The patients had died between March 13 and April 24, 2020, in Hamburg, Germany, in hospitals, nursing homes, or their own homes. The patients had all tested positive for SARS-CoV-2 by quantitative RT-PCR (qRT-PCR).
The samples of brain and neural tissues were obtained on autopsy. The team performed histological staining and immunohistochemical staining of the activated astrocyte cells of the brain, activated microglial cells of the brain and cytotoxic T lymphocytes present within the olfactory bulb, basal ganglia, brainstem, and cerebellum region of the brain. From the brain samples, they also tested for 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 overall findings of the study were:
- In 6 patients (14 percent) there were ischemic lesions in the brain
- Among 86 percent of patients (37), there was the presence of astrogliosis in the studied regions of the brain
- The brain stem and cerebellum regions of the brain showed infiltration with cytotoxic T lymphocytes and activated microglia
- Among 79 percent of patients (34), there was an infiltration of cytotoxic T lymphocytes in 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 the cranial nerves originating from the lower brainstem and in some cells of the brainstem.
- 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 it was seen that the gene coding for ACE2 was highest in oligodendrocyte cells of the brain.
Conclusions and implications
The researchers explained that astrocytes were key regulators of inflammatory and other processes in the brain, and since they rise in other critical illnesses, the astrocytosis seen in this study cannot be attributed to COVID-19. They wrote, “Activation of microglia and infiltration of cytotoxic T lymphocytes were mostly confined to the brainstem and cerebellum, with little involvement of the frontal lobe, in line with clinical findings pointing to an involvement of the brainstem.”
The authors of the study concluded that the neuropathological changes in patients with COVID-19 were generally mild, but there were prominent inflammatory changes in the brainstems of those who succumbed to the infection. They wrote, “There was no evidence for CNS damage directly caused 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).
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