Pathophysiology of thromboembolism in patients with COVID-19

Introduction and aim. A small number of critically ill patients with coronavirus disease (COVID-19) develop thromboembolism (arterial or venous), both micro- and macrovascular complications such as deep vein thrombosis, pulmonary embolism, and pulmonary arterial thrombosis. The objective of the study is to describe the pathophysiology of venous thromboembolism in patients with COVID-19. Material and methods. In this article a narrative review regarding pathophysiology of thromboembolism in patients with COVID-19. Analysis of the literature. The development of coagulopathy is a consequence of the intense inflammatory response associated with hypercoagulability, platelet activation, and endothelial dysfunction. The pathophysiology that relates pulmonary thromboembolism (PTE) with COVID-19 is associated with a hypercoagulable state. PTE is suspected in hospitalized patients presenting dyspnea, decreased oxygen requirement, hemodynamic instability, and dissociation between hemodynamic and respiratory changes. In COVID-19-associated coagulopathy, initially, patients present with elevated levels of fibrinogen and D-dimer, with minimal changes in prothrombin time and platelet count. The main risk factor for the development of pulmonary embolism is the increase in D-dimer that is associated with the development of PTE. The administration of iodine-based contrast agent to patients with COVID-19 would affect P-creatinine and renal function, where Ultrasound is viewed as cost-effective and highly portable, can be performed at the bedside. Conclusion. Acute respiratory distress syndrome severity in patients with COVID-19 can explain PTE as a consequence of an exaggerated immune response. © 2022 Publishing Office of the University of Rzeszow. All Rights Reserved.

Doxycycline inhibits SARS-CoV-2 replication in vitro

Introduction and Aim: We examined the effect of pre-and/or post-infection doxycycline on human nasal epithelial cell viability and SARS-CoV-2 (clinical strain IHUMI-3) replication in vitro. Materials and Methods: Human nasal epithelial cells, an in vivo SARS-CoV-2 target, were derived from healthy donor nasal epithelial stem/progenitor cells via in vitro differentiation. The cells were exposed to doxycycline at 0, 0.1, 0.5, 1, 5, 10, 50, and 100 μM before and/or after IHUMI-3 inoculation to determine the optimal inhibitory concentration. Viral replication was evaluated using quantitative reverse-transcription PCR, and doxycycline 50% cytotoxic concentration (CC50) and half-maximal effective concentration (EC50) were calculated. The peak serum concentration (Cmax) resulting from typical oral (100 or 200 mg) or intravenous (100 mg) doxycycline doses was estimated, and the Cmax/EC50 ratio was calculated as an index of potential clinical utility. Results: Doxycycline exhibited low cytotoxicity (CC50 > 100 μM) in human nasal epithelial cells and inhibited SARS-CoV-2 replication (EC50: 5.2 ± 3.3 μM) in a dose-dependent manner when administered pre-and/or post-infection. Reasonable oral or intravenous doses will help achieve effective concentrations in vivo. Conclusion: Early administration of this well-characterized, safe, and accessible drug may limit person-to-person transmission and prevent progression to severe coronavirus disease.