How the Covid-19 Virus Reprograms Immune Cells to Weaken the Body’s Defenses
A new study has revealed that the Covid-19 virus may directly interfere with the body’s immune system by reprogramming key immune cells, potentially explaining why some individuals develop severe illness while others experience only mild symptoms.
Researchers from Johns Hopkins University, in a study published in Science Translational Medicine and funded by the U.S. National Institutes of Health, found that the SARS-CoV-2 virus can alter the function of neutrophils—white blood cells that normally serve as the body’s first line of defense against infection.
In patients with severe Covid-19, neutrophils appear to undergo a transformation into cells that suppress the immune system rather than support it. Specifically, these neutrophils morph into what are known as PMN-MDSCs (polymorphonuclear myeloid-derived suppressor cells), which are typically found in cancer and other chronic diseases but are rarely seen in viral infections.
These PMN-MDSCs lose their infection-fighting abilities and instead begin to inhibit T cells—another crucial component of the immune system responsible for destroying virus-infected cells. The study found that these reprogrammed neutrophils express proteins such as LOX-1 and PD-L1, which are known to suppress T cell activity.
“This may help explain why some people develop severe illness,” said Dr. Andrea Cox, senior author of the study. “In some Covid infections, the virus appears to reprogram neutrophils into a different type of cell that suppresses T cells.”
To investigate further, researchers collected blood samples from 39 unvaccinated Covid-19 patients who had not been treated with immunosuppressive drugs, and compared them to samples from nine healthy individuals. They observed that in severe cases, neutrophils had “degranulated,” releasing their contents and transforming into PMN-MDSCs.
The same transformation occurred when healthy neutrophils were exposed to SARS-CoV-2 in the lab. However, exposure to the H1N1 influenza virus did not trigger this change, indicating a unique property of the coronavirus.
There may also be a therapeutic angle. When PD-L1-blocking antibodies—drugs used in cancer treatment—were added to the altered neutrophils in lab experiments, T cells were less suppressed and resumed their immune functions. This suggests that such therapies could be repurposed to help patients with severe Covid-19.
“This opens the door for potential treatments,” Cox said. “Combining PD-L1 antibodies with antiviral drugs, or using them alone in severe cases, could help restore immune function.”
This discovery sheds light on how SARS-CoV-2 may hijack the immune system and could pave the way for improved treatments to boost immunity in those hit hardest by the virus.
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