Researchers from the University of Sydney have identified a distinctive protein in lung tissue that can neutralize the SARS-CoV-2 virus, blocking its entry into cells. This finding offers a potential explanation for why some people resist infection while others develop severe illness. The study appears in the journal PLOS Biology.
For a coronavirus to invade a cell, the virus’s spike protein must attach to the ACE2 receptor. These receptors are abundant in the lungs, which helps explain why respiratory symptoms are often the main signs of infection.
The new study reports that several molecules of another receptor, LRRC15, are present in the lungs of individuals who succumbed to COVID-19. LRRC15 also binds to the coronavirus spike protein, but unlike ACE2, it does not facilitate infection. Instead, the virus adheres to LRRC15 and becomes unable to enter cells, acting as a decoy in the airway environment.
LRRC15 production appears to increase after the immune system encounters SARS-CoV-2 particles. Scientists propose that in those who died from COVID-19, LRRC15 levels may be high but insufficient for protection, or they may be induced too late to influence the disease outcome. Conversely, some survivors might experience higher LRRC15 expression, a hypothesis that would require direct assessment of lung tissue through biopsy to confirm. This balance between timing and amount could help explain variable disease courses among patients.
As a point of independent corroboration, researchers note that teams at Imperial College London have independently linked the absence of LRRC15 in the bloodstream with more severe disease. This cross-validation strengthens the idea that LRRC15 plays a meaningful role in modulating infection severity, even though more work is needed to quantify its protective capacity and determine how it could be leveraged clinically.
Beyond its role in acute infection, LRRC15 is also found in fibroblast cells that guide the development of pulmonary fibrosis, a condition marked by tissue scarring and impaired lung function. The dual involvement of LRRC15 in both infectious processes and tissue remodeling suggests it could be a valuable target for future therapies. If scientists can harness LRRC15 pathways, they may improve strategies not only to prevent infection but also to limit long-term lung damage after illness.
Experts emphasize that while the LRRC15 finding is promising, it remains one piece of a complex puzzle. The study highlights how the lung’s molecular landscape shapes responses to the virus, but it does not yet establish a simple predictor of outcomes for every patient. Ongoing work aims to map how LRRC15 interacts with other immune pathways, how its expression varies among individuals, and how therapies could raise beneficial decoy activity without triggering unintended effects. The researchers also stress the importance of translating these insights into practical tools, such as biomarkers for risk assessment or interventions that encourage protective LRRC15 activity before severe disease develops.
In summary, the discovery of LRRC15’s decoy-like behavior adds to a growing picture of lung-specific factors that influence COVID-19 severity. The convergence of evidence from multiple research groups underscores the potential to develop preventative and therapeutic approaches that complement vaccination and antiviral drugs. As science progresses, LRRC15 may become part of a broader strategy to protect lung tissue and reduce the burden of COVID-19 and related respiratory conditions, including fibrosis, in populations across Canada and the United States. The findings invite careful follow-up studies and clinical investigations to determine how best to translate this molecular insight into patient care and public health interventions.