Nikhil Prasad Fact checked by:Thailand Medical News Team Jun 20, 2025 2 weeks, 4 days, 8 hours, 45 minutes ago
Medical News: Scientists Reveal a Hidden Driver of Severe COVID Complications
Italian researchers from the University of Parma have discovered a previously underappreciated mechanism that could help explain the widespread blood vessel damage seen in people with severe COVID-19. In their new study, they found that specific immune system messengers—called cytokines—released by macrophages activated by the SARS-CoV-2 spike protein are triggering a harmful imbalance in the way blood vessel cells use a key amino acid called arginine.
COVID-19 Spike Protein Triggers Dangerous Arginine Imbalance in Blood Vessels
This
Medical News report dives into how this immune-driven reaction leads to disruptions in nitric oxide production, a critical substance that keeps blood vessels healthy and flexible. The findings could offer new clues for treating complications such as clotting, heart damage, and long COVID symptoms.
COVID-19 Is More Than a Lung Disease—It Wreaks Havoc on Blood Vessels
While COVID-19 initially gained attention as a respiratory disease, scientists now know it affects multiple organs—and blood vessels are especially vulnerable. The virus can damage the lining of blood vessels (known as the endothelium) both directly and indirectly through immune system overreactions.
The research team, led by Giulia Recchia Luciani, Rossana Visigalli, Valeria Dall’Asta, Bianca Maria Rotoli, and Amelia Barilli from the University of Parma’s Department of Medicine and Surgery, investigated how SARS-CoV-2 triggers this endothelial dysfunction. They focused on how immune cells called macrophages respond when exposed to the virus's spike protein, particularly the S1 subunit, which is key for the virus entering human cells.
They collected fluid from these activated immune cells and exposed it to human blood vessel cells in the lab. What they found was alarming—an intense drop in a molecule called eNOS (endothelial nitric oxide synthase) and a simultaneous spike in an enzyme called arginase. These two molecules normally maintain a delicate balance that controls blood vessel health. Disrupting that balance can lead to stiffness in blood vessels, inflammation, clotting, and even heart damage.
Arginine Imbalance Could Be Fueling Blood Clots and Long COVID
Arginine is a vital amino acid that acts as the raw material for producing nitric oxide, a gas that relaxes blood vessels and keeps blood flowing smoothly. But when arginase levels rise too high—as seen in this study—it starts to “steal” arginine away from the eNOS pathway. This results in reduced nitric oxide levels, contributing to blood vessel inflammation and increased clotting risk.
The team found that this imbalance was largely driven by two inflammatory molecules released by the immune system: TNF-alpha and IL-1β. These cytokines caused blood vessel cells to stop producing eNOS while simultaneously ramping up arginase levels. This double hit makes the body more prone to
vascular problems and poor oxygen delivery.
What’s even more surprising is that while the nitric oxide production dropped, the amount of arginine inside the cells actually increased. This was due to the overactivation of a specific transport protein called CAT2, which shuttles arginine into the cell. However, without proper eNOS function, the arginine couldn’t be used effectively to produce nitric oxide.
Potential Treatment Pathways Involving Baricitinib and Infliximab
To counteract this damaging cycle, the researchers tested two drugs—baricitinib, a JAK/STAT pathway inhibitor already approved for COVID-19 treatment, and infliximab, an antibody that blocks TNF-alpha. They found that infliximab was able to restore eNOS levels, while baricitinib helped reduce arginase overactivity. When used together, these drugs showed even stronger effects, suggesting that combination therapies could help prevent or treat COVID-induced vascular damage.
These findings support the idea that targeting the immune system's overreaction could be a powerful way to stop COVID-19 from damaging blood vessels, especially in severe or long-haul cases.
Why This Matters for Long COVID and Future Pandemics
Endothelial dysfunction is now recognized as a major player in many COVID-19 complications, including heart inflammation, strokes, organ failure, and long COVID. By showing how the spike protein indirectly sets off a chain reaction leading to blood vessel damage, this study offers a clearer picture of why these complications occur even after the virus itself is no longer detectable.
The identification of TNF-alpha and IL-1β as key culprits opens the door to using existing anti-inflammatory drugs to reduce the severity of COVID-related vascular issues. More research will be needed to confirm these results in clinical settings, but the groundwork has been laid.
Conclusion
This groundbreaking study by researchers at the University of Parma sheds light on a critical mechanism through which COVID-19 disrupts blood vessel function. The immune system’s response to the virus, especially through cytokines like TNF-alpha and IL-1β, appears to hijack arginine metabolism in a way that deprives the body of nitric oxide—a molecule essential for vascular health. The resulting imbalance between eNOS and arginase contributes to the serious cardiovascular and clotting complications seen in many COVID-19 patients. Promisingly, the study also shows that this harmful effect can be partially reversed using drugs like baricitinib and infliximab. These findings not only provide new insights into the vascular side of COVID-19 but may also help guide future treatment strategies for long COVID and similar inflammatory conditions.
The study findings were published in the peer reviewed International Journal of Molecular Sciences.
https://www.mdpi.com/1422-0067/26/12/5916
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Read Also:
https://www.thailandmedical.news/news/romanian-study-shows-that-arginine-supplements-can-help-with-post-cov
https://www.thailandmedical.news/news/long-covid-italian-randomized-clinical-trial-shows-that-l-arginine-plus-vitamin-c-supplementation-helps-in-long-covid
https://www.thailandmedical.news/news/breaking-sars-cov-2-encodes-circular-rnas-that-can-impair-endothelial-cells-and-cause-cardiovascular-issues
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