Two Nose Cells Most Likely Entry Points for COVID-19

The high transmission rate of SARS-CoV-2 could be largely thanks to 2 specific types of cells in the inner lining of the nose, according to new research.

A group of collaborators from the Human Cell Atlas Lung Biological Network wanted to gain a better understanding of exactly how the virus spreads, in hopes that such insights might help public health officials better understand how to slow or stop the spread of coronavirus disease 2019 (COVID-19).

First author Waradon Sungnak, PhD, of the Wellcome Sanger Institute, in the United Kingdom, and colleagues decided to search the Human Cell Atlas consortium of databases of single cell RNA sequencing, in search of the receptor protein ACE2 and the TMPRSS2 protease, which can activate SARS-SoV-2 entry.

The databases contained more than 20 different tissue cells from non-infected people. The tissue cells came from a variety of organs, including lung, eye, kidney, nasal cavity, and liver cells. Sungnak and colleagues wanted to find individual cells that expressed both key entry proteins.

“We then revealed that mucus-producing goblet cells and ciliated cells in the nose have the highest levels of both these COVID-19 virus proteins, of all cells in the airways,” said Sungnak, in a statement. “This makes these cells the most likely initial infection route for the virus.”

The findings were published in the journal Nature Medicine.

Though the two types of nose cells are the most likely entry points, Sungnak said that’s not to say it is the only place where the proteins are found. The study also showed cells in the cornea of the eye and in the lining of the intestine contained these entry proteins. Those findings suggest the eye and tear ducts are also likely entry points, and it may also be possible for fecal-oral transmission of the virus, they said.

Still, Martijn Nawijn, PhD, of the University Medical Center Groningen, in the Netherlands, said the nose cells offer the best explanation of the pandemic’s rapid spread.

“While there are many factors that contribute to virus transmissibility, our findings are consistent with the rapid infection rates of the virus seen so far,” he said, in the press release. “The location of these cells on the surface of the inside of the nose make them highly accessible to the virus, and also may assist with transmission to other people.”

Jayaraj Rajagopal, MD, of Massachusetts General Hospital, said the research is an important piece of the puzzle for investigators studying the pandemic. Rajagopal said the cellular bases of disease often don’t receive the same level of attention as the molecular bases, despite the links between the two. He said both a molecular and a cellular understanding of COVID-19 are important.

“In the case of COVID-19, knowing the cells that act as portals of viral entry and possible viral reservoirs helps us think about why a virus can be transmitted easily between people and why only some people progress to a lethal pneumonia,” he said.

Rajagopal said this study is particularly notable because it uses cells from the actual tissue cells that are infected in patients with the disease. This should help further investigators better understand which cells and tissues they ought to study as they work toward treatments and prevention methods.