Erythrocyte, Platelet, Serum Ferritin, and P-Selectin Pathophysiology Implicated in Severe Hypercoagulation and Vascular Complications in COVID-19

• Published in: International journal of molecular sciences 2020-11, Vol.21 (21), p.8234
• Main Authors: Venter, Chantelle, Bezuidenhout, Johannes Andries, Laubscher, Gert Jacobus, Lourens, Petrus Johannes, Steenkamp, Janami, Kell, Douglas B, Pretorius, Etheresia
• Format: Article
• Language: English
• Subjects: Betacoronavirus - isolation & purification; Blood Coagulation - physiology; Blood Platelets - pathology; Blood Platelets - virology; Cardiovascular Diseases - blood; Cardiovascular Diseases - pathology; Cardiovascular Diseases - virology; Coronavirus Infections - blood; Coronavirus Infections - pathology; Coronavirus Infections - virology; COVID-19; erythrocytes; Erythrocytes - pathology; Erythrocytes - virology; Female; Ferritins - blood; Humans; Male; Middle Aged; oxygen saturation; P-selectin; P-Selectin - blood; Pandemics; platelets; Pneumonia, Viral - blood; Pneumonia, Viral - pathology; Pneumonia, Viral - virology; SARS-CoV-2; serum ferritin; Thrombosis - pathology; Thrombosis - virology
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21218234

Progressive respiratory failure is seen as a major cause of death in severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2)-induced infection. Relatively little is known about the associated morphologic and molecular changes in the circulation of these patients. In particular, platelet and erythrocyte pathology might result in severe vascular issues, and the manifestations may include thrombotic complications. These thrombotic pathologies may be both extrapulmonary and intrapulmonary and may be central to respiratory failure. Previously, we reported the presence of amyloid microclots in the circulation of patients with coronavirus disease 2019 (COVID-19). Here, we investigate the presence of related circulating biomarkers, including C-reactive protein (CRP), serum ferritin, and P-selectin. These biomarkers are well-known to interact with, and cause pathology to, platelets and erythrocytes. We also study the structure of platelets and erythrocytes using fluorescence microscopy (using the markers PAC-1 and CD62PE) and scanning electron microscopy. Thromboelastography and viscometry were also used to study coagulation parameters and plasma viscosity. We conclude that structural pathologies found in platelets and erythrocytes, together with spontaneously formed amyloid microclots, may be central to vascular changes observed during COVID-19 progression, including thrombotic microangiopathy, diffuse intravascular coagulation, and large-vessel thrombosis, as well as ground-glass opacities in the lungs. Consequently, this clinical snapshot of COVID-19 strongly suggests that it is also a true vascular disease and considering it as such should form an essential part of a clinical treatment regime.