An interesting study came to my attention this week that has me thinking much more about the dynamics of the interaction between influenza A virus (IAV) and the SARS-CoV-2 virus in a way that hadn’t occurred to me before.

The investigators infected a cell culture with IAV and then used spike protein from SARS-CoV-2 attached to a marker to study uptake of the spike protein. They found that “cells became highly sensitive (up to 10,000-fold) to the pseudo-SARS-CoV-2 virus after infection with IAV at different doses.”

They proceeded to repeat the experiment, but instead using live SARS-CoV-2 virus and then measured some of the genetic sequences that were produced as a metric for viral replication. They found that “cells that are inherently susceptible to SARS-CoV-2, IAV preinfection further increased SARS-CoV-2 infectivity by > 5-fold.” This suggests the production of far more of the COVID virus if they are already infected with influenza A, meaning that they will be much sicker but also much more likely to spread COVID because of the higher viral load.

They continued their study in mice. “A significant increase in SARS-CoV-2 viral load was observed in lung homogenates from coinfected mice compared to homogenates from SARS-CoV-2 single-infected mice…The lung histological data further illustrate that IAV and SARS-CoV-2 coinfection induced more severe lung pathologic changes, with massive cell infiltration and obvious alveolar necrosis, compared to SARS-CoV-2 single infection or mock infection.”

They went on to test a few other respiratory viruses to see if the same COVID virus amplification would occur, and it didn’t. This suggests that there is something unique about IAV that enhances COVID infection. In addition, they studied ACE-2 receptor (the binding site for COVID) expression and found that cell cultures infected with IAV expressed THREE TIMES as many ACE-2 receptors. In coinfection of the two viruses, ACE-2 expression increased 5-28x based on the cell culture line used.

My interpretation of the increased ACE-2 expression is that it suggests that someone who is coinfected with both IAV and COVID is MORE susceptible to infections that use the ACE-2 receptor to infect cells.

At this point, you might be wondering why this grabbed my attention since it seems obvious that getting infected with two different viruses simultaneously is bad for someone.

H5N1 is a type of an influenza A virus.