Scientists explain why SARS-CoV-2 targets multiple organs

By Angela Betsaida B. Laguipo, BSNAug 31 2020

The coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has a growing list of signs and symptoms as the pandemic evolves.

Early on in the pandemic, the most common symptoms noted were coughing, fever, and difficulty breathing. However, as the virus spread across the globe, more symptoms were reported, including loss of smell and taste, fatigue, aches and pains, sore throat, diarrhea, headache, red eyes, and rashes.

The more severe symptoms include loss of speech and movement, chest pain or pressure, and shortness of breath. The infection was initially thought to be a respiratory disease, but as more people got infected, more reports of multiple organ involvement surfaced.

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

Now, a team of researchers at LSU Health New Orleans’ Neuroscience Center of Excellence and School of Medicine has explained the gateway receptor for SARS-CoV-2 and how it leads to the emergence of many complications as it targets many parts of the body.

The researchers explained that the reason why there is a broad range of symptoms and organs involved with SARS-CoV-2 infections is that there are many cell types in the body that has the angiotensin-converting enzyme 2 (ACE2) receptor, which the virus uses to enter the cells and trigger infection.

What is the ACE2 receptor?

The ACE2 is a protein found on the surface of many cell types, such as those in the lungs, heart, blood vessels, kidneys, liver, and the gastrointestinal tract. ACE2 also an enzyme that produces small proteins that regulate functions in the cell. It acts as a cellular doorway or receptor for the virus SARS-CoV-2.

The SARS-CoV-2 uses a spike-like protein on its surface to attach with the ACE2, forming a lock-key mechanism. When the virus binds to the cell, it enters and invades the cell.

The study

A recent study found ACE2 almost everywhere throughout the body, even in the eye, suggesting the visual system may provide an additional entry point for SARS-CoV-2 into the body.

The study, published in the journal Cellular and Molecular Neurobiology, suggests that a multipronged SARS-CoV-2 attack and widespread COVID-19 is all down to the abundance of the ACE2 receptor in the human body.

To arrive at the study findings, particularly the mechanism and pathways of the coronavirus infection and susceptibility to specific cell and tissue types, the team studied 85 human tissues for the presence of ACE2 receptors. The tissues tested were from organ systems, including the respiratory, digestive, reproductive, and renal. They also examined tissue samples from the eyes and 21 different regions of the brain.

From there, the team has found that aside from the commonly known areas where ACE2 receptors were found, they also found high ACE2 expression in the amygdala, brainstem, and the cerebral cortex.

The team said that this might explain why one of the most prominent symptoms of COVID-19 is the difficulty of breathing since the highest levels of ACE2 expression were detected in the pons and medulla oblongata, which are the body’s respiratory centers.

“The highest ACE2 expression level was found in the pons and medulla oblongata in the human brainstem, containing the medullary respiratory centers of the brain, and may in part explain the susceptibility of many CoV-19 patients to severe respiratory distress,” the team wrote in the paper.

The impact of SARS-CoV-2 on the respiratory centers may explain why many patients are vulnerable to severe respiratory distress, even in healthy patients without comorbidities.

The team also found ACE2 receptor activity in the eye, which means that the virus may enter the eye via respiratory droplets or aerosols. The eye may be an entry point for infection. Hence, the use of eyeglasses, face shields, and eye goggles may be as important as face masks in containing the spread of SARS-CoV-2.

“Several important research gaps remain. A real danger of SARS-CoV-2 infection is not only its highly transmissible and contagious nature and lethality, but also its simultaneous and multipronged attack on many human cell and tissue types involving vital and critical respiratory, immunological, vascular, renal-excretory, and neural systems as well as an unprecedented coordinated disruption of the complex neurophysiology, neurochemistry, neurobiology and neurology of the cells of the brain and central nervous system (CNS) that normally regulate these multiple physiological systems,” Dr. Walter J. Lukiw, Professor of Neuroscience, Neurology, and Ophthalmology at LSU Health New Orleans’ Neuroscience Center of Excellence and School of Medicine, said.