Research Suggests COVID-19 Exploits Body’s Defense Mechanism

In an effort to identify which cells are susceptible to the coronavirus disease 2019 (COVID-19), researchers at Boston Children’s Hospital and the Massachusetts Institute of Technology have found that one of the main biological defenses against viral infections may be exploited by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), the virus which causes COVID-19.

Earlier research on the pandemic has found that SARS-CoV-2 uses the ACE2 receptor to enter human cells and is helped by the TMPRSS2 enzyme. With this in mind, researchers Jose Ordovas-Montanes, PhD, and Alex K. Shalek, PhD, hoped to discover which cells in respiratory and intestinal tissue express both ACE2 and TMPRSS2.

Utilizing single-cell RNA sequencing, they found that typically less than 10% of human respiratory and intestinal cells make both the ACE2 receptor and TMPRSS2 enzyme, including goblet cells in the nose that secrete mucus; type II pneumocyte cells in the lungs that help maintain the alveoli; and 1 kind of enterocyte that lines the small intestine.

“Many existing respiratory cell lines may not contain the full mix of cell types, and may miss the types that are relevant,” said Ordovas-Montanes in a statement. “Once you understand which cells are infected, you can start to ask, ‘How do these cells work?’ ‘Is there anything within these cells that is critical for the virus’s life cycle?’”

These findings could raise new questions about the use of ACE inhibitors in patients with COVID-19, which some studies have linked to more severe cases, according to the study authors.

“ACE and ACE2 work in the same pathway, but they actually have different biochemical properties,” Ordovas-Montanes said in the statement. “It’s complex biology, but it will be important to understand the impact of ACE inhibitors on people’s physiological response to the virus.”

Although these findings are significant, in a statement, the team said their second finding surprised them more. According to the study authors, the ACE2 gene encodes the receptor used by SARS-CoV-2 to enter human cells. The gene is stimulated by interferon, which is one of the main biological defenses against a virus. The team found that interferon actually turned the ACE2 gene on at higher levels, which could potentially give the virus new portals through which to enter.

“ACE2 is also critical in protecting people during various types of lung injury,” Ordovas-Montanes said. “When ACE2 comes up, that’s usually a productive response. But since the virus uses ACE2 as a target, we speculate that it might be exploiting that normal protective response.”

Interferons are being investigated as a possible treatment for COVID-19, but their effects are not yet clear. According to Ordovas-Montanes, interferon may contain the virus in some patients while promoting more infection in others.

REFERENCE

How SARS-CoV-2 gets into respiratory tissue—and how it may exploit one of our defenses [news release]. EurekAlert; April 21, 2020. https://www.eurekalert.org/pub_releases/2020-04/bch-hsg042120.php. Accessed April 27, 2020.