Pericytes Within A Pulmonary Neurovascular Unit in Coronavirus Disease 2019 Elicited Pathological Changes.

A pericyte-centered theory suggesting that embolisms occurring within the microvasculature of a neurovascular unit that can result in either parenchymal hemorrhage or intravascular congestion is presented here. Dysfunctional microvascular pericytes are characterized by their location in the neurovascular unit, either on the arteriole or venule side. Pathophysiological and pathological changes caused by coronavirus disease 2019 (COVID-19) include pulmonary hypertension, edema, focal hemorrhage, microvascular congestion, and thrombosis. In this paper, the application of the pericytes-centered hypothesis to COVID-19 has been presented by proposing the concept of a pulmonary neurovascular unit (pNVU). The application of this concept implies that human lungs contain approximately 300 million pNVUs. This concept of existing local regulation of microvascular blood flow is supported by the observation of pathophysiology in pulmonary embolism and in acute high-altitude illness. The autonomic control seen in these three disease states matches blood flow with oxygen supply in each pNVU to maintain physiological blood oxygen saturation level. This paper illustrates how the malfunction of microvascular pericytes may cause focal hemorrhage, edema or microvascular congestion and thrombosis. A bypass existing in each pNVU would autonomically deviate blood flow from a COVID-19-affected pNVU to other healthy pNVUs. This action would prevent systemically applied medicines from reaching the therapeutic threshold in COVID-19-affected pNVUs. While testing this hypothesis with experimental evidence is urgently needed, supporting therapy aimed at improving microcirculation or rebuilding the physiological function of microvascular pericytes is recommended as a potentially effective treatment of COVID 19.

Brain microvascular occlusive disorder in COVID-19: a case report.

We describe the case of a COVID-19 patient with severely impaired consciousness after sedation hold, showing magnetic resonance imaging (MRI) findings of (i) acute bilateral supratentorial ischemic lesions involving the fronto-parietal white matter and the corpus callosum and (ii) multiple diffuse susceptibility weighted imaging (SWI) hypointense foci, infra and supratentorial, predominantly bithalamic, suggestive of microhemorrhage or alternatively microthrombi. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) RNA was detected in the cerebrospinal fluid. Our findings suggest the occurrence of vascular damage, predominantly involving microvessels. The underlying mechanisms, which include direct and indirect penetration of the virus to the central nervous system and systemic cardiorespiratory complications, are yet to be elucidated, and a direct correlation with SARS-CoV-2 infection remains uncertain.

Coagulopathy and Thrombosis as a Result of Severe COVID-19 Infection: A Microvascular Focus.

Coronavirus disease of 2019 (COVID-19) is the clinical manifestation of the respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While primarily recognized as a respiratory disease, it is clear that COVID-19 is systemic illness impacting multiple organ systems. One defining clinical feature of COVID-19 has been the high incidence of thrombotic events. The underlying processes and risk factors for the occurrence of thrombotic events in COVID-19 remain inadequately understood. While severe bacterial, viral, or fungal infections are well recognized to activate the coagulation system, COVID-19-associated coagulopathy is likely to have unique mechanistic features. Inflammatory-driven processes are likely primary drivers of coagulopathy in COVID-19, but the exact mechanisms linking inflammation to dysregulated hemostasis and thrombosis are yet to be delineated. Cumulative findings of microvascular thrombosis has raised question if the endothelium and microvasculature should be a point of investigative focus. von Willebrand factor (VWF) and its protease, a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS-13), play important role in the maintenance of microvascular hemostasis. In inflammatory conditions, imbalanced VWF-ADAMTS-13 characterized by elevated VWF levels and inhibited and/or reduced activity of ADAMTS-13 has been reported. Also, an imbalance between ADAMTS-13 activity and VWF antigen is associated with organ dysfunction and death in patients with systemic inflammation. A thorough understanding of VWF-ADAMTS-13 interactions during early and advanced phases of COVID-19 could help better define the pathophysiology, guide thromboprophylaxis and treatment, and improve clinical prognosis.