C1 Esterase Inhibitor Shown to Ease Long COVID Fatigue and Neurological Symptoms
Nikhil Prasad Fact checked by:Thailand Medical News Team Nov 13, 2025 2 hours, 10 minutes ago
Medical News: C1 Inhibitor Offers Hope for Post-COVID Brain Fog and Fatigue
A groundbreaking study by researchers from the IMMUNOe Research Center in Colorado and Stanford University in California has found that the C1 esterase inhibitor (C1-INH), a protein known to regulate immune responses, could significantly improve depression, fatigue, and pain in people suffering from post-COVID-19 neurological symptoms.
C1 Esterase Inhibitor Shown to Ease Long COVID Fatigue and Neurological Symptoms
Many individuals who recover from COVID-19 continue to experience lingering issues such as memory loss, fatigue, brain fog, and depression—collectively referred to as Long COVID. Scientists believe these issues may stem from immune system dysregulation that disrupts brain and nerve functions. According to this
Medical News report, the study explored how restoring the balance of C1-INH might help correct this immune malfunction and alleviate symptoms.
Understanding the Immune Connection
The research focused on a phenomenon known as “Alzheimer’s of the Immune System,” a term used by the lead investigator Dr. Isaac Melamed to describe long-term immune dysfunction following infections. This condition involves low levels of C1-INH and abnormal signaling in Toll-like receptors (TLRs)—key components of the body’s defense system. Such dysfunction can trigger persistent inflammation in the brain, leading to depression, fatigue, and pain.
C1-INH acts as a natural regulator that prevents excessive immune activation and inflammation. By replenishing it, researchers hoped to calm the overactive immune response associated with Long COVID.
How the Study Was Conducted
The clinical trial enrolled 36 adults suffering from post-viral fatigue for more than four weeks after recovering from COVID-19. Participants were randomly assigned to receive either C1-INH infusions or a placebo for eight weeks, followed by a crossover to the opposite treatment. Each patient served as their own control, enhancing the reliability of the results.
Throughout the 16-week study, researchers assessed depression levels (using the Beck Depression Inventory-II), fatigue (Fatigue Severity Scale), pain, and cognitive function. Blood samples were also analyzed to evaluate immune activity by measuring inflammatory markers such as TNF-alpha, IL-1β, and IL-6.
Promising Results for Long COVID Sufferers
Patients treated with C1-INH showed a 32 percent reduction in depression scores, along with measurable improvements in fatigue and pain. These benefits were reversed once patients switched to the placebo phase, reinforcing the drug’s therapeutic potential. Additionally, the study found that Long COVID patients had substantially lower immune signaling—up to a 75 percent reduction in certain inflammatory responses—compared to healthy controls.
The therapy was well-tolerated, with no serious adverse effects re
ported. Minor side effects such as mild headache or dizziness were transient and similar to those observed in the placebo group.
Why This Matters
The findings suggest that Long COVID may not simply be a lingering viral condition but an immune-driven neurological disorder. By targeting immune dysregulation—particularly through the complement system and TLR pathways—treatments like C1-INH could restore balance and improve quality of life for millions of people affected by persistent post-COVID symptoms.
The study team emphasized that larger Phase 2 trials are already planned to confirm these results and to explore whether C1-INH could also benefit patients suffering from other post-infectious conditions like chronic fatigue syndrome and Lyme disease.
The study findings were published in the peer reviewed journal: Frontiers in Neurology.
https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2025.1523814/full
Examples of C1 Esterase Inhibitors
The main C1 esterase inhibitor (C1-INH) medications available today include both plasma-derived and recombinant options, marketed under the brand names Berinert, Cinryze, Haegarda, and Ruconest. Their generic forms are variations of C1 esterase inhibitor sourced from human plasma or produced recombinantly, with C1 esterase inhibitor (human) corresponding to Berinert, Cinryze, and Haegarda, while conestat alfa (recombinant) is marketed as Ruconest. These drugs are primarily used to treat or prevent hereditary angioedema (HAE) attacks, with Berinert approved for acute abdominal, facial, or laryngeal attacks in both adults and children; Cinryze and Haegarda authorized for routine prophylaxis in adults and pediatric patients aged six and above; and Ruconest indicated for treating acute HAE episodes in adults and adolescents. None of these medications are to be used without proper medical supervision by licensed doctors with extensive knowledge of these drugs.
For the latest on Long COVID, keep on logging to Thailand
Medical News.
Read Also:
https://www.thailandmedical.news/articles/long-covid
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