Researchers have found a link between variants of the Apolipoprotein E (APOE) gene and higher mortality rates among those infected with COVID-19.

In this new study, lead author Benjamin Ostendorf of Rockefeller University and his team exposed 300 mice, all of which were engineered to carry the human APOE gene with varying alleles, to a version of SARS-CoV-2 modified for mice. Results showed that mice carrying the APOE3 gene variant had the lowest mortality rate. Those with APOE2 or APOE4, which is also known for its association with higher risk of Alzheimer’s, had higher mortality rates along with increased virus replication in the lungs, more inflammation, and more tissue damage. The researchers observed that APOE3 had stronger immune responses to the virus, keeping it from entering more cells than the other two variants. “Taken together, these results suggest that the APOE genotype impacts COVID outcomes in two ways,” Ostendorf says, “by modulating the immune response and by preventing SARS-CoV-2 from infecting cells.”

Searching for genetic predictors of COVID response severity is not a new idea. In January of this year, the Journal of Cellular and Molecular Medicine published a study in which researchers identified “complement-related genetic variants associated with the clinical outcomes of ICU hospitalization and death” of COVID-19 patients, then developed a neural network to predict outcomes. Their work was a success; the researchers found that “TBHD and C3a levels were significantly increased in severe COVID-19 patients” and their neural network accurately predicted the outcomes of COVID-19 patients. Other such studies were summarized and analyzed in eBioMedicine journal.

Used in conjunction with previous studies on genetic predictors for COVID mortality, clinicians may be able to leverage the knowledge from this new study in prioritizing vaccinations, boosters, and antiviral therapies among the populations.