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Researchers Trace the Spread of SARS-CoV-2 From Nose to Brain

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A study has found that the coronavirus SARS-CoV-2, the cause of the COVID-19 pandemic, may be able to access the brain by spreading through the border between our nasal system and neural tissue. The findings offer answers to the baffling array of neurological symptoms produced by COVID-19 and the rare but previously unexplained detection of SARS-CoV-2 genetic materials in regions of the brain.

The research, published in
Nature Neuroscience, was authored by researchers at Charité – Universitätsmedizin Berlin.

SARS-CoV-2: An unwelcome guest in the brain

A distinguishing feature of COVID-19 has been the range of symptoms reported by patients worldwide. The virus primarily affects the respiratory system, but the characteristic loss of smell and taste and fatigue reported by over a third of patients suggests that SARS-CoV-2 spreads into the nervous system and brain. Nevertheless, researchers have struggled to demonstrate this intrusion clearly, although some
studies have shown evidence of viral genetic material in the brain and the cerebrospinal fluid that circulates within it after death.

The present study, led jointly by Dr
Helena Radbruch and Prof Dr Frank L. Heppner, examined the bodies of 33 patients who had died with COVID-19. Firstly, the team used a technique called reverse-transcription quantitative polymerase chain reaction (RT-qPCR) to look for evidence of SARS-CoV-2 genetic material, RNA, in the brain, nose and a part of the throat called the nasopharynx.

Some of the highest levels of viral RNA were found in a region called the olfactory mucosa. In this region, specialized cells called olfactory epithelium cells are coated in a layer of mucus that allows odor to dissolve and be detected by nearby olfactory receptor neurons that relay smell information to the brain. It was this interface that the authors identified as being a likely entry point for SARS-CoV-2 to reach the brain. Viral infiltration here would explain some of the sensory symptoms reported by COVID-19 patients.

Further immunohistochemical testing was conducted on slices of tissue taken from the olfactory mucosa. Here, neural cells showed detectable levels of SARS-CoV-2 proteins and RNA. Elsewhere, SARS-CoV-2 viral RNA was found in three patients’ cerebellums, a center of motor control found at the back of the brain, and six patients had detectable virus in their medulla, a region of the brainstem that controls base, involuntary functions such as sneezing and vomiting. 

Pathology explained?

As a final analysis, the team explored the occurrence of brain blood clots, which have been reported in clinical data from some COVID-19 patients. In 6 of 33 patients analyzed, evidence of clotting and subsequent stroke-related brain damage was identified.

The authors noted that visualizing incredibly small number of viral particles in the brain is far from straightforward and that other viral particles may kill the cells they infect, preventing their detection. The presence of viral particles in areas of the brain with no connection to the olfactory system, such as the cerebellum, say the authors, suggest that there may be other ways that SARS-CoV-2 can access the brain that have not yet been identified.

Prof Gitte Moos Knudsen, chair of the Department of Neurology and Neurobiology Research Unit at Copenhagen University Hospital, who was not involved in the study, said, “The findings are not surprising. Central nervous system entry through the nasal epithelium is a recognized mode of viral uptake and would not be unique to SARS-CoV-2.”