COVID-19: German Autopsy Study Of 43 Deceased COVID-19 Patients Reveals Shocking Findings Of How SARS-CoV-2 Virus Directly Damages The Brains
: German researchers from the University Medical Center, Hamburg-Eppendorf and University of Freiburg in a new detailed autopsy study involving 43 deceased COVID-19 patients have discovered shocking findings as to how the SARS-CoV-2 coronavirus ‘literally attacks’ the human host brains.
In the early stages of the pandemic, numerous researchers made claims that the SARS-CoV-2 could not cross the brain barrier and that the brains were safe from the virus. Then as neurological symptoms started to become more apparent, some later came up with the hypothesis that it was the cytokine storms that were affecting the brains and the central nervous system.
It was only about late May that smaller studies showed proof that the SARS-CoV-2 coronavirus was able to infiltrate the Central Nervous System and also directly attack the human host’s brain.
However this autopsy study involving 43 deceased patients showed a degree of consistency as to how the SARS-CoV-2 coronavirus attacks the brains over a short period of time.
Most of the patients died in hospitals, nursing homes, or at home, and were aged between 51 years and 94 years (median 76 years [IQR 70–86]).
The study team detected fresh territorial ischaemic lesions in six (14%) patients. 37 (86%) patients had astrogliosis in all assessed regions. Activation of microglia and infiltration by cytotoxic T lymphocytes was most pronounced in the brainstem and cerebellum, and meningeal cytotoxic T lymphocyte infiltration was seen in 34 (79%) patients. SARS-CoV-2 could be detected in the brains of 21 (53%) of 40 examined patients, with SARS-CoV-2 viral proteins found in cranial nerves originating from the lower brainstem and in isolated cells of the brainstem.
Interestingly the presence of SARS-CoV-2 in the CNS was not associated with the severity of neuropathological changes which implies that while the brain is under attack by the SARS-CoV-2 coronavirus, individuals or doctors might not be able to know till in a late stage of damage.
The study findings were published in the journal: Lancet Neurology
The new clinical report not only focused on brain changes in deceased COVID-19 patients but also accompanying neurological complications.
The study team led by Dr 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.
The study team said that some of the CNS effects seen with COVID-19 include:
-Anosmia – loss of smell
-Aguesia – loss of taste
-Haemorrhagic encephalopathy – bleeding within the brain and severe brain damage
-Posterior reversible encephalopathy syndrome
-Encephalitis or inflammation of the brain
-Meningitis or inflammation of the meninges
-Miller Fisher syndrome
All these conditions or symptoms have been reported in several published studies over the past few months of the pandemic.
The study team explains 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.” Or “Indirect mechanisms mediated by the cytokine storm induced by systemic SARS-CoV-2 infection.”
However with the study findings showing the actual SARS-CoV-2 coronavirus found in brain tissues, the former now seems more likely.
The study is the first to analyze in detail the post mortem findings of the brains of COVID-19 patients who had succumbed to the disease.
The study 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).
Specimens and samples of brain and neural tissues were obtained on autopsy.
The study 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.
The overall findings of the study were:
-6 patients or 14 percent had ischemic lesions in the brain
-About 86 percent of patients (37), there was the presence of astrogliosis in the studied regions of the brain
-It was found that the brain stem and cerebellum regions of the brain showed infiltration with cytotoxic T lymphocytes and activated microglia
-79 percent of patients (34) had an infiltration of cytotoxic T lymphocytes in the meninges
-Significantly SARS-CoV-2 was detected in the brains of 53 percent or 21 patients among the 40 studied for the virus
-Interestingly SARS-CoV-2 viral proteins were found in the cranial nerves originating from the lower brainstem and in some cells of the brainstem.
-Also SARS-CoV-2 virus in the CNS was not found to be associated with the severity of neuropathological changes in the study subjects
According to the research team, 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.
The study team 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 just be attributed to COVID-19.
The team said, “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 study team 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.
The team also stressed that that SARS-CoV-2 was detected by qRT-PCR or immunostaining in the brains of 21 (53%) of all tested patients. Furthermore, immunohistochemical analysis revealed viral proteins in the cranial nerves (either glossopharyngeal or vagal) originating from the lower medulla oblongata and in single cells within the medulla oblongata. Although qRT-PCR might lack sensitivity, and immunostaining for viral proteins is prone to artifacts, the study findings are consistent with those of previous studies of SARS-CoV, in which viral proteins could be seen in single cells in the brains of some patients who died following infection with the virus. https://pubmed.ncbi.nlm.nih.gov/16043521/
Hence, effects of SARS-CoV-2 on the brainstem could be correlates of, or contribute to, unusually rapidly deteriorating respiratory function, as has been observed in some patients with COVID-19 given non-invasive ventilation. https://pubmed.ncbi.nlm.nih.gov/32104915/
The presence of SARS-CoV-2 RNA and proteins in the brains of patients with COVID-19 in this study is in line with the hypothesis that SARS-CoV-2 can infiltrate the CNS. https://pubmed.ncbi.nlm.nih.gov/32359765/
The study team also said that they saw a surprisingly uniform presentation of neuropathological findings (ie, activation of microglia, infiltration with CD8-positive T cells) in patients, irrespective of the clinical severity of COVID-19 in each case. Notably, the neuropathological presentation in patients who died in a domestic setting or in a nursing home did not differ from that in patients who died in hospital wards or ICUs.
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