Patients with long Covid-19 may have raised VWF(Ag):ADAMTS13 ratio signifying abnormal blood clotting and patients with impaired exercise capacity were four times more at risk, suggests a new study reported in the journal Blood Advances.¹

Researchers from the UK sought to examine patients with long Covid for risk of thrombosis and its correlation with severity of symptoms. For this 330 patients, average age 46 years, attending an outpatient post-COVID clinic between July 2020 and May 2021were selected for this study. More than half of the study population was female (60%). The levels of Von Willebrand factor (VWF) and ADAMTS13 were measured and their ratio was analyzed. Elevated VWF to ADAMTS13 ratio due to high levels of VWF was indicative of a prothrombotic state. Out of the 330 included, 276 (84%) completed exercise tests, which included timed activities such as 1-minute sit to stand test and/or 6-minute walk test. Oxygen levels were measured during exercise using oxygen monitors. Blood lactate levels were also estimated before and during exercise.

VWF is a key factor in blood clotting, while ADAMTS13 is a protease that cleaves VWF and prevents its accumulation in blood vessels.

The von Willebrand factor antigen:ADAMTS13 ratio was 1.5 or higher in 28% of the entire study group.

Hypoxemia during exercise (≥3%) or raised lactate levels (>1 from baseline) post-exercise demonstrated an impaired exercise capacity; 56 of the 276 patients (20%) who completed their exercise tests had impaired exercise capacity. Patients with raised levels of blood clotting markers had four times higher probability of impaired exercise capacity. Fifty-five percent of patients with impaired exercise capacity had a raised VWF(Ag):ADAMTS13 ratio ≥1.5 (OR 4). 

Twenty-six percent of patients had high Factor VIII levels (2.1 - 5.1 IU/mL) while 18% had raised VWF(Ag) levels (1.7 - 3.3 IU/mL) indicating a hypercoagulable state in patients with post Covid-19 syndrome. D-dimer was elevated in just 13% of the participants.

Acute Covid-19 induces a hyperinflammatory and hypercoagulable state in the body, which increases the risk of thromboembolic events. Raised VWF(Ag):ADAMTS13 ratio is a marker for the prothrombotic state and is associated with severity of disease. Long Covid is an increasingly recognized complication of acute Covid-19 with many hospitals now offering dedicated post-Covid care clinics. The World Health Organization has recently defined it as a condition which “occurs in individuals with a history of probable or confirmed SARS CoV-2 infection, usually 3 months from the onset of COVID-19 with symptoms and that last for at least 2 months and cannot be explained by an alternative diagnosis”. The common symptoms include fatigue, shortness of breath, and cognitive dysfunction. However, its pathogenesis is still ill-understood.

This study has shed some light on the pathogenesis of long Covid and offers continuing “endothelial dysfunction and hypercoagulability” as a possible explanation for why some patients continue to experience symptoms even after recovery from acute Covid-19. It further suggests that patients with long Covid should be screened for VWF (Ag):ADAMTS13 ratio and exercise testing and may benefit from antithrombotic therapy.

Reference

1. Prasannan N, et al. Impaired exercise capacity in post-COVID syndrome: the role of VWF-ADAMTS13 axis. Blood Adv. 2022 May 11;bloodadvances.2021006944. doi: 10.1182/bloodadvances.2021006944.