Shanghai Jiao Tong University: Getting the Big Picture of COVID-19 Infection

Image credit: Image from page 70 of “Leonardo da Vinci, artist, thinker and man of science;” (1898)” by Internet Archive Book Images is part of the public domain

The paper that we’ll be demystifying can be found here, if you want to follow along.

When the symptoms of COVID-19 come to mind, it’s generally confined to the lungs. Apart from a fever that spans the whole body, it’s thought of as a dry cough, sore throat, and pneumonia.  

However, there have been many cases of organ failure due to COVID-19 occurring outside of the lungs. Additionally, we don’t have a full picture of the long-term effects of COVID-19. Luckily, a team of researchers from Shanghai Jiao Tong University have investigated these far-reaching effects using single-cell RNA-seq.

Wait a sec, what’s single-cell RNA-seq?

“Single-cell” just means that the procedure was done individually for each cell. Researchers would take one liver cell or stomach cell at a time for examination. By looking at individual cells from all over the body, researchers should get an idea of how the whole body is affected by COVID-19.

To understand RNA-seq, or RNA sequencing, we need to take a step back.

DNA, the molecule containing our individual genetic code, is in every cell of our body. While unique to every person, the DNA in someone’s brain cells and the DNA in someone’s heart cells are the same. A DNA test wouldn’t be able to a researcher where in the body it was taken.

The difference lies in gene expression. A cell reads a certain section of the DNA strand, a gene, using it as an instruction manual to make proteins, chemicals specific to each type of cell. A cell will only express certain genes to make certain proteins, and only within a specific amount. For example, brain cells and stomach cells both have the genes for making stomach acid, but these genes are only expressed in certain stomach cells.

The bread and butter of RNA-seq, also known as the “Central Dogma of Molecular Biology” (File:Central dogma of molecular biology.svg – Wikimedia Commons. Published 2020. Accessed March 26, 2020.)

RNA-seq measures levels of gene expression. When a gene is being expressed, the first step is called transcription. It involves a copy of the gene being made in RNA, a molecule similar to DNA, that also can contain the information needed to make a protein. RNA-seq isolates these molecules and determines both which gene they came from and the amount of each present.     

The researchers at Shanghai Jiao Tong University use it to assess the levels of ACE2 expressed by different cells of the body. ACE2, or angiotensin converting enzyme II, sits on the outer surface of cells and acts as the target for the SARS-CoV-2 virus. By determining which cells express the gene for ACE2, the team could find out with corresponding organs are at risk during COVID-19 infection.

As expected, the respiratory system was a strong target. RNA from the lungs, nasal passages, respiratory tracts, and bronchus. The bronchus is the passage that allows air into the lungs through smaller respiratory tracts, which branch off from the bronchus. Lung and respiratory tract cells with found ACE2-positive, putting them at risk. The nasal passages and bronchus, however, were in the clear.

Their research showed bad news for the heart. Over 7.5% of heart muscle cells expressed ACE2, putting it at high risk as well. It’s theorized that the risk would be even higher if the SARS-CoV-2 virus finds it’s way into the blood, in a way called viremia.

When the team looked into the digestive system, they checked the esophagus, stomach, ileum (lower small intestine), as well as the liver. The liver and stomach seem to be at low risk, but the esophagus and ileum were classified as high risk. The ileum especially was 30% positive for ACE, making it extremely vulnerable.   

Finally, the team examined the urinary system, focusing on the bladder and kidneys. They found the proximal tubule of the kidney to be vulnerable, a region important for maintaining the body’s pH, as well as secreting important organic acids. Urothelial cells were also at high risk, the cells the lining the inside of the bladder and protect it from infection.

A risk map showing which organs are at a high risk (in red) and which are at a low risk (grey) (Zou X, Chen K, Zou J, Han P, Hao J, Han Z. Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection. Front Med. 2020. doi:10.1007/s11684-020-0754-0)

Armed with this knowledge, the team made a risk map to illustrate the regions at risk from COVID-19 infection. The team’s discoveries might account for the non-respiratory issues seen in COVID-19 patients. More importantly, this research will be invaluable in designing treatments to deal with any long-term, non-respiratory effects of COVID-19.

In the meantime, stay safe out there.

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