The Long Term Residual Effects of COVID-Associated Coagulopathy

Abstract

During the acute phase of COVID-19, many patients experience a complex coagulopathy characterized by a procoagulant pattern. The present study investigates the persistence of hemostatic changes in post-COVID patients at a long-term follow up, and the link with the persistence of physical and neuropsychological symptoms. We completed a prospective cohort study on 102 post-COVID patients. Standard coagulation and viscoelastic tests were performed, along with an assessment of persistent symptoms and recording of acute phase details. A procoagulant state was adjudicated in the presence of fibrinogen > 400 mg/dL, or D-dimer > 500 ng/mL, or platelet count > 450,000 cells/µL, or a maxim clot lysis at viscoelastic test < 2%. A procoagulant state was identified in 75% of the patients at 3 months follow up, 50% at 6 months, and 30% at 12–18 months. Factors associated with the persistence of a procoagulant state were age, severity of the acute phase, and persistence of symptoms. Patients with major physical symptoms carry a procoagulant state relative risk of 2.8 (95% confidence interval 1.17–6.7, p = 0.019). The association between persistent symptoms and a procoagulant state raises the hypothesis that an ongoing process of thrombi formation and/or persistent microthrombosis may be responsible for the main physical symptoms in long-COVID patients.

Epidemiology and Predisposing Factors of Post-COVID Venous Thrombosis: A Concise Review

“…Ranucci and colleagues followed up to 18 months after an acute SARS-CoV-2 infection a total of 102 patients who recovered from COVID-19, and measured a number of hemostasis parameters to characterize the presence of a potential procoagulant state (i.e., plasma fibrinogen > 4 g/L, D-dimer > 500 ng/mL, or platelet count > 450 × 109/L, a maximum clot resolution on the viscoelastic test < 2%). 18 Overall, the rate of patients with a procoagulant state was found to be 75% at 3 months follow-up, decreased to 50% at 6 months but remained as high as 30% between 12 and 18 months follow-up. The main predictors of a persistent penitent procoagulant state were age (>60 years), severity of the acute infection, and persistence of symptoms over time.…”

Digital holo-tomographic 3D maps of COVID-19 microclots in blood to assess disease severity

“…Importantly, the size of the measured microclots in COVID-19 plasma samples using DHTM could be of potential clinical interest in regards to their ability to occlude microvasculature and thus impede oxygen transport ( 5 ). Microclots formed in the vascular system are likely to explain the heterogeneous symptomatology and multi-organ dysfunction observed in COVID-19 and long COVID patients ( 14, 44 ).…”

“…The World Health Organization defines long COVID as a condition in which individuals with a probable or confirmed infection with SARS-CoV-2 still experience COVID-19-related symptoms usually three months post-infection and lasting for at least two months, with no alternative diagnosis ( 13 ). Endotheliopathy, coagulopathy, and thrombosis are also now established complications of COVID-19 and can persist in individuals diagnosed with long COVID, contributing to the pathogenesis and clinical manifestations of these conditions ( 1, 14-16 ).…”

3D Holo-tomographic Mapping of COVID-19 Microclots in Blood to Assess Disease Severity

“…Coronavirus disease 2019 (COVID-19) is a complex disorder caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and affects many bodily functions, including excessive immunological response, autoimmunity, and endothelial dysfunction, that have been implicated in the risk of thrombotic events and coagulopathies. − While the acute phase of COVID-19 primarily manifests as a respiratory illness, with a wide range of symptoms including fever, headache, cough, fatigue, muscle pain, and shortness of breath, more severe clinical symptoms, such as systemic inflammatory response syndrome (SIRS), acute respiratory disease syndrome (ARDS), and neurological and cardiovascular complications, have been associated with processes underlying coagulopathies and endotheliopathies. ,, Currently, it is estimated that approximately 30% of individuals with COVID-19 continue to suffer from a variety of different symptoms involving specific or multiple organ systems, with neurological, neuropsychiatric, and cardiorespiratory clinical presentations, , a condition known as postacute sequelae of COVID (PASC) or long COVID. ,, Fatigue, cough, dyspnea, chest pain, headache, dizziness, cognitive impairment known as “brain fog”, and long-term smell and taste dysfunction are the most commonly reported symptoms in individuals suffering from long COVID. ,, The World Health Organization defines long COVID as a condition in which individuals with a probable or confirmed infection with SARS-CoV-2 still experience COVID-19-related symptoms usually three months postinfection and lasting for at least two months, with no alternative diagnosis . Endotheliopathy, coagulopathy, and thrombosis are also now established complications of COVID-19 and can persist in individuals diagnosed with long COVID, contributing to the pathogenesis and clinical manifestations of these conditions. ,− …”