Scientists explain how SARS-CoV-2 attacks the brain

The coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is mainly a respiratory illness. However, as the global pandemic evolves, many other manifestations appear, including neurological symptoms.

Previous reports show that COVID-19 does not only attack the lungs but other vital organs, too. These include the heart, kidneys, and the brain.

Now, a team of scientists at Yale University revealed the changes that happen in the brain caused by SARS-CoV-2, the virus that has caused over 27.86 million people and claimed over 903,000 lives.

Transmission electron micrograph of SARS-CoV-2 virus particles, isolated from a patient. Image captured and color-enhanced at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland. Credit: NIAID
Transmission electron micrograph of SARS-CoV-2 virus particles, isolated from a patient. Image captured and color-enhanced at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland. Credit: NIAID

Brain effects

Though COVID-19 is primarily a respiratory disease, SARS-CoV-2 affects multiple organ systems, including the circulatory system, the urinary system, and the central nervous system. Amid the pandemic, there is still no clear basis that the virus can infect the brain.

The researchers wanted to see what the virus does to the brain and how these changes manifest as symptoms. The study appears on the preprint server bioRxiv* prior to peer-review.

The study

To arrive at their findings, the scientists first used human brain organoids and found clear evidence of infection in the tissues, along with metabolic changes in the infected neurons. However, there is no evidence for the type I interferon responses, which have long been heralded as key contributors to effective antiviral responses.

Further, the team also examined the neuronal infection, which can be prevented either by blocking ACE2 with antibodies by administering cerebrospinal fluid from a patient with COVID-19.

In the second experiment, the researchers used laboratory mice, which have overexpressing human angiotensin-converting enzyme 2 (ACE2). The team has found that in vivo, the SARS-CoV-2 neuroinvasion and not respiratory infection, is tied to mortality or death.

The team explained that the brain is a site for the high replicative potential for SARS-CoV-2, which can cause neuronal death in human brain organoids. The team also used electron microscopy and identified viral particles coming from the endoplasmic reticulum, showing the ability of the virus to use the neuron cell machinery to replicate and spread.

The experiments also showed that single-cell RNA sequencing of the infected organoids exhibited metabolic neurons without interferon, which may indicate that the virus may trigger neuroinvasive consequences. The infected cells can also cause changes to their surroundings, which may impact the survival of nearby cells.

“Viral infection may induce locally hypoxic regions which aid in lowering the threshold for tissue damage in the context of an already oxygen-deprived state,” the team added.

In the third experiment, the team studied brain autopsies of patients who died from COVID-19. The team has detected SARS-CoV-2 in the cortical neurons, and they noted pathologic features tied to infection, with few minimal cells infiltrates.

“These results provide evidence for the neuroinvasive capacity of SARS-CoV2, and an unexpected consequence of direct infection of neurons by SARS-CoV-2,” the team wrote in the paper.

“We examined the potential for SARS-CoV-2 to infect neural tissues of both mice and human origin and demonstrate the potential consequences of its neuroinvasion. Our results suggest that neurologic symptoms associated with COVID-19 may be related to consequences of the direct viral invasion of the CNS,” they added.

Contradicting results

However, interestingly the results of this Yale study differ from another recent study by researchers at the Barts Health NHS Trust and the University of Cambridge. In that study, the researchers did not detect viral RNA of SARS-CoV-2 in the brain tissue of parents who succumbed to COVID-19.

The study’s findings suggest that the brain may not be affected by the direct effect of the virus or its spread. The virus’s effect on the brain may be due to a para-infectious phenomenon, linked to systemic hyperinflammatory and hypercoagulable syndromes.

“The prevention and treatment of these two conditions would be diametrically different, and only the correlation of post-mortem examination with antemortem clinical features and imaging will provide a robust understanding of the pathophysiological heterogeneity in what may superficially seem like a homogenous clinical phenotype,” the researchers wrote in the paper.

*Important Notice

bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal references:
Angela Betsaida B. Laguipo

Written by

Angela Betsaida B. Laguipo

Angela is a nurse by profession and a writer by heart. She graduated with honors (Cum Laude) for her Bachelor of Nursing degree at the University of Baguio, Philippines. She is currently completing her Master's Degree where she specialized in Maternal and Child Nursing and worked as a clinical instructor and educator in the School of Nursing at the University of Baguio.


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