Harvard, MIT Researchers Discover Subsets of Cells Especially Susceptible to COVID-19

Harvard and MIT researchers have found subsets of cells in the human nasal passages, lungs, and intestines that are particularly susceptible to COVID-19 infection, according to a study accepted to the scientific journal Cell Wednesday.

The team made the discovery based on previous knowledge that the virus’s “spike” protein — the main protein that allows it to bind to and enter human cells — typically binds to two cellular proteins: ACE2 and TMPRSS2.

Alexander K. Shalek, a faculty member in the Harvard-MIT Health Sciences and Technology program and senior author of the study, said the team looked at which cells contained the RNA that encoded ACE2 and TMPRSS2. Researchers then used a dataset of the different kinds of RNA found in various cell types to identify specific subsets of cells that might be most prone to producing ACE2 and TMPRSS2 and thus most susceptible to COVID-19 infection.

“One of the big questions to ask is, ‘Which cells within a given tissue are actively transcribing the RNAs for these proteins and therefore are likely first targets for infection?’” Shalek said.

Jose M. Ordovas-Montanes, a Harvard Medical School pediatrics professor and another senior author of the study, said the RNA data the team used does not show all information about cellular proteins, however.

“Messenger RNA encodes the potential to make a protein, but it doesn’t necessarily mean that at that point in time, that mRNA will be made into a protein,” Ordovas-Montanes said.

The team also discovered that interferon, a protein usually generated by human cells to fight viral infections, actually plays a role in increasing the expression of the ACE2 protein that binds to COVID-19’s spike protein.

“Interferon drives ACE2 — maybe for a virus that doesn’t utilize ACE2 to come in, like influenza,” Ordovas-Montanes said. “That might end up being protective, and there’s data in the literature to suggest that. But if the virus that you’re combatting now is utilizing ACE2 to gain a foothold in the host, we don’t know if there is a particular situation, a right time and place within the body, where a typically protective response can become detrimental.”

Ordovas-Montanes added that, despite the strides made in the study, scientists would need results from a “well-controlled clinical trial” to draw definitive conclusions.

“Our paper might provide some explanation eventually as to what people are seeing, but it’s far away from that,” he said.

The team plans to use their individual cell-based knowledge to help other researchers conducting analyses on COVID-19.

Shalek said he was pleasantly surprised throughout the research by the time, effort, and information volunteered by fellow scientists for his team’s work.

“What’s amazing is everybody coming together to tackle this problem, and people’s willingness to contribute unpublished data selflessly, and their willingness to support work regardless of whether or not we’d ever met them before or whether or not they knew us,” Shalek said. “It’s really cool to see the community push to tackle a problem of this level and of this nature.”

—Staff writer Ethan Lee can be reached at ethan.lee@thecrimson.com.