Increased von Willebrand and Factor VIII plasma levels in gynecologic patients with Post-Acute-COVID-Sequela (PASC)/Long COVID

Abstract

Up to 30 % of COVID-infected patients may develop post-acute sequelae of COVID-19 (PASC), also known as Long COVID (LC), a syndrome characterized by a variety of debilitating symptoms lasting for more than 3 months after the acute infection. While the pathophysiological mechanisms behind PASC/LC are not completely understood, growing evidence suggests that an important component of this syndrome may be related to persistent microvascular inflammation causing clumping/clotting of red blood cells and platelets and thrombotic complications. We retrospectively evaluated the plasma levels of von Willebrand factor (VWF), Factor VIII and D-dimer in 10 gynecologic patients (60 % with an endometrial or ovarian cancer diagnosis) affected by PASC/LC vs 5 control patients (60 % harboring endometrial or ovarian tumors). We found elevated VWF and Factor VIII levels in all 10 PASC/LC patients (means of 254 % and 229 %, respectively) vs none of the 5 randomly selected cancer control patients (means of 108 % and 95 %, respectively), p = 0.0046 and p < 0.0001, respectively. In contrast, no significant difference was noted in the levels of D-dimer in PASC/LC. Importantly, abnormally elevated VWF and Factor VIII levels were found to persist for at least 2 years in patients with Long COVID symptoms. VWF and Factor VIII but not D-dimer levels are significantly elevated in the plasma of PASC/LC cancer patients. Abnormally and persistently elevated VWF and Factor VIII levels may represent the results of persistent microvascular damage (i.e., spike-induced endotheliosis) and may be biomarkers of persistent inflammation in gynecologic patients with PASC/LC.

Keywords

• Long COVID
• PASC
• Von Willebrand factor
• Factor VIII
• Microclotting