N-acetylcysteine (NAC) supplementation improves dyspnea and may normalize von Willebrand plasma levels in gynecologic patients with Post-Acute-COVID-Sequela (PASC)/Long COVID.

Objectives: A subset of COVID-infected cancer patients may develop post-acute sequelae of COVID-19 (PASC), also known as Long COVID (LC). While LC is considered multifactorial in its pathogenesis, growing evidence suggests that persistent microvascular inflammation (ie, spike-induced endotheliosis) causing chronically elevated levels of clotting factors including von Willebrand factor (vWF), clumping/clotting of red blood cells and platelets, and thrombotic complications may be at the root of PASC/LC symptoms. N-Acetylcysteine (NAC), a precursor of glutathione, is an inexpensive FDA-approved drug/supplement endowed with mucolytic, antioxidant, anti-inflammatory and thrombolytic properties. Multiple reports have recently demonstrated the potential clinical activity of NAC in COVID-19 patients. We retrospectively evaluated responses to NAC supplementation in a total of 9 PASC/LC patients, 3 of which reporting regular use of NAC, followed in our Gynecologic Oncology clinic. Methods: Gynecologic patients using NAC supplement (3 patients) vs controls (6 patients) with persistent LC/PASC symptoms and with elevated plasmatic vWF levels were identified in our Gynecologic Oncology clinic database and evaluated for improvement/normalization in LC/PASC symptoms and vWF levels. Results: Subjective improvement in shortness of breath, brain fog and fatigue with normalization of vWF levels were noted in 3 out of 3 PASC/LC patients using oral NAC (600-1200 mg BID) vs none of the randomly selected cancer control patients with PASC/LC (Fisher's exact P = 0.0119). Conclusions: These preliminary results suggest that NAC may represent an inexpensive, safe and potentially effective supplement to improve many PASC/LC-related symptoms. Prospective randomized studies with NAC in PASC/LC patients are needed to confirm these findings.