Researchers have discovered that SARS-CoV-2, the virus that causes COVID-19, may be changing crucial white blood cells called neutrophils so that instead of working to destroy pathogens, they instead disrupt the activity of other immune cells that are battling the virus. This National Institutes of Health (NIH)-funded work may help explain how severe COVID can arise. The findings have been reported in Science Translational Medicine.
In this work, the investigators analyzed blood samples from 39 acute COVID-19 patients, and a small group of unaffected individuals. The samples were taken in 2020, before participants had been vaccinated. The SARS-CoV-2 virus appears to reprogram neutrophils so that they transform into a type of cell called polymorphonuclear myeloid derived suppressor cells (PMN-MDSCs).
Previous work has shown that PMN-MDSCs can tamp down the activity of other immune cells that fight viruses called T lymphocytes (T cells). This reprogramming may be one way more serious forms of COVID can happen, explained senior study author Andrea Cox, M.D., Ph.D., a professor at the Johns Hopkins University School of Medicine.
COVID is still killing at least 300 Americans every week. The risk of severe COVID complications varies widely depending on age and comordities, among other factors. These complications can include ICU stays, mechanical ventilation, and death.
Severe COVID-19 is known to be linked to unusually high levels of neutrophils. “Our goal was to find out whether these neutrophils had been reprogrammed by SARS-CoV-2, and if so, did they contribute to the shift from mild infection to a more serious form of COVID-19," explained first study author Leon Hsieh, Ph.D.
PMN-MDSCs that are linked to nonviral diseases such as cancer typically carry two surface proteins: lectin-type oxidized low-density lipoprotein receptor-1 (LOX-1) and programmed cell death ligand 1 (PD-L1). Hsieh noted that these proteins are detrimental to the immune system.
PD-L1 can bind to T cells and inhibit them in a variety of ways, including their ability to tell other immune cells that a pathogenic threat is present.
The role of LOX-1 on neutrophils is unclear. But the researchers found that people with severe COVID were more likely to carry neutrophils with LOX-1 and PD-L1 compared to those with mild COVID. When neutrophils were grown with SARS-CoV-2, they became (or differentiatied into) T cell-inhibiting PMN-MSDCs, added Hsieh.
But this did not happen when the neutrophils were grown with the H1N1 influenza virus. PMN-MDSCs have also not been associated with severe influenza infections.
“So, it appears that not all viruses can cause the differentiation,” said Hsieh.
The researchers also suggested that it may be possible tp treat people with severe COVID by using antibodies targeting PD-L1, particularly when antiviral drugs are not an option.
Sources: Johns Hopkins University School of Medicine, Science Translational Medicine