Unusually high numbers of macrophages (in brown) were detected in cross-sections of lungs from COVID-19 patients using immunohistochemical techniques. Blue counterstain detects nuclei of all cells in the cross-section. (CREDIT UC San Diego Health Sciences)
Key Highlights:
- PI3K gamma, identified in cancer research, also plays a crucial role in the immune response to COVID-19 by facilitating the entry of inflammatory cells into lung tissue.
- Eganelisib, a repurposed cancer drug, effectively inhibits PI3K gamma and prevents excessive immune response in severe COVID-19 cases.
- Targeting host immune responses rather than the virus itself shows promise in reducing inflammation and tissue damage associated with COVID-19.
- Further clinical trials are needed to validate the efficacy and safety of PI3K gamma inhibitors like Eganelisib for treating severe COVID-19 and other infectious diseases.
Researchers at the University of California San Diego have found that a molecule previously identified in cancer research plays a critical role in the immune response to COVID-19. The molecule, PI3K gamma, facilitates the entry of inflammatory myeloid cells into lung tissue infected with SARS-CoV-2, the virus causing COVID-19. This infiltration often leads to severe organ damage.
Published in Science Translational Medicine, the study demonstrates that inhibiting PI3K gamma with a repurposed cancer drug, Eganelisib, can prevent these myeloid cells from entering infected tissue. This novel approach aims to mitigate the excessive immune response seen in severe COVID-19 cases, potentially preventing irreversible tissue damage.
According to senior author Judith Varner, Ph.D., the traditional focus of COVID-19 treatments has been on targeting the virus itself. However, their approach targets the host immune response, specifically aiming to reduce inflammation and tissue fibrosis in the lungs.
In both human lung tissue samples and infected mice, the researchers observed a significant increase in myeloid cells during COVID-19 infection. Treatment with Eganelisib effectively blocked the entry of these cells into the tissue, thereby limiting their damaging effects.
The study highlights the dual role of myeloid cells in fighting infections and causing tissue damage when overly activated. "If the infection is too strong, these cells can overproduce damaging substances that harm the body," explained Varner.
While Eganelisib was fast-tracked for development in 2020, it has yet to receive FDA approval. Varner hopes that this research will encourage further exploration of PI3K gamma inhibitors for treating infectious diseases like COVID-19 and methicillin-resistant Staphylococcus aureus (MRSA).
Funding for the study was provided by various grants from the National Institutes of Health (NIH) and support from other institutions, underscoring the collaborative effort involved in this groundbreaking research.
Credit: Science Translational Medicine