Likely Entry Point for SARS-CoV-2 Identified in the Nose

In a study published today in Nature Medicine, scientists identified two cell types in the nose that are likely initial infection points for the COVID-19 coronavirus, SARS-CoV-2. These cells—nasal goblet and ciliated cells—have high levels of the entry proteins that the COVID-19 virus uses to get into cells. The results could help explain the high transmission rate of COVID-19.

For their study, the researchers analyzed multiple Human Cell Atlas (HCA) consortium datasets of single-cell RNA sequencing from more than 20 different tissues of non-infected people. These included cells from the lung, nasal cavity, eye, gut, heart, kidney, and liver. The researchers looked for which individual cells expressed both of two key entry proteins that are used by SARS-CoV-2 to infect our cells.

“We found that the receptor protein—ACE2—and the TMPRSS2 protease that can activate SARS-CoV-2 entry are expressed in cells in different organs, including the cells on the inner lining of the nose,” says first author Waradon Sungnak of the Wellcome Sanger Institute. “We then revealed that mucus-producing goblet cells and ciliated cells in the nose had the highest levels of both these COVID-19 virus proteins, of all cells in the airways. This makes these cells the most likely initial infection route for the virus.”

The two key entry proteins, ACE2 and TMPRSS2, were also found in cells in the cornea of the eye and in the lining of the intestine, suggesting potential routes of infection through the eye and tear ducts or through fecal–oral transmission.

The work was carried out as part of the global Human Cell Atlas consortium which aims to create reference maps of all human cells to understand health and disease. “As we’re building the Human Cell Atlas, it is already being used to understand COVID-19 and identify which of our cells are critical for initial infection and transmission,” says senior author Sarah Teichmann of the Wellcome Sanger Institute. “This information can be used to better understand how coronavirus spreads. Knowing which exact cell types are important for virus transmission also provides a basis for developing potential treatments to reduce the spread of the virus.”