COVID-19 is a systemic vascular hemopathy: insight for mechanistic and clinical aspects

Abstract

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is presenting as a systemic disease associated with vascular inflammation and endothelial injury. Severe forms of SARS-CoV-2 infection induce acute respiratory distress syndrome (ARDS) and there is still an ongoing debate on whether COVID-19 ARDS and its perfusion defect differs from ARDS induced by other causes. Beside pro-inflammatory cytokines (such as interleukin-1 β [IL-1β] or IL-6), several main pathological phenomena have been seen because of endothelial cell (EC) dysfunction: hypercoagulation reflected by fibrin degradation products called D-dimers, micro- and macrothrombosis and pathological angiogenesis. Direct endothelial infection by SARS-CoV-2 is not likely to occur and ACE-2 expression by EC is a matter of debate. Indeed, endothelial damage reported in severely ill patients with COVID-19 could be more likely secondary to infection of neighboring cells and/or a consequence of inflammation. Endotheliopathy could give rise to hypercoagulation by alteration in the levels of different factors such as von Willebrand factor. Other than thrombotic events, pathological angiogenesis is among the recent findings. Overexpression of different proangiogenic factors such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (FGF-2) or placental growth factors (PlGF) have been found in plasma or lung biopsies of COVID-19 patients. Finally, SARS-CoV-2 infection induces an emergency myelopoiesis associated to deregulated immunity and mobilization of endothelial progenitor cells, leading to features of acquired hematological malignancies or cardiovascular disease, which are discussed in this review. Altogether, this review will try to elucidate the pathophysiology of thrombotic complications, pathological angiogenesis and EC dysfunction, allowing better insight in new targets and antithrombotic protocols to better address vascular system dysfunction. Since treating SARS-CoV-2 infection and its potential long-term effects involves targeting the vascular compartment and/or mobilization of immature immune cells, we propose to define COVID-19 and its complications as a systemic vascular acquired hemopathy.

Targeting the Pentose Phosphate Pathway for SARS-CoV-2 Therapy

“…Given the potential role of TKT in SARS-CoV-2 replication identified here, elevated TKT levels may be one of the factors that predispose diabetes patients to experience severe COVID-19. Moreover, over-activation of the PPP has been suggested to drive hyperglycemia-associated vascular damage [ 22 ], and vascular damage is an integral part of COVID-19 pathology [ 23 ]. Thus, hyperglycemia-related PPP activity may further predispose diabetic patients to experience severe COVID-19.…”

Targeting the “sweet spot” in septic shock – A perspective on the endothelial glycocalyx regulating proteins Heparanase-1 and -2

“…In contrast, a substantial acquired Hpa-2 deficiency has been demonstrated in both murine sepsis models (LPS and CLP) as well as septic patients [22] , [65] . Recently, our group was able to show that Hpa-2 is also decreased in critically ill patients with COVID-19, a disease that can be complicated by overwhelming systemic inflammation and endotheliopathy [103] , [104] , [105] .…”

High Level of the Fibrin Degradation Products at Admission Predicts Parenchymal Hematoma and Unfavorable Outcome of Ischemic Stroke After Intravenous Thrombolysis

“…The FDP was widely studied as an indicator of disease severity and for differential diagnosis. The FDP was associated with the severity of coronavirus disease 2019 (COVID-19) and trauma ( 15 , 16 ). In patients with COVID-19, those with the higher FDP had higher risks of stroke ( 17 ).…”