Orthostatic Intolerance after COVID-19 Infection: Is Disturbed Microcirculation of the Vasa Vasorum of Capacitance Vessels the Primary Defect?

Abstract

Following COVID-19 infection, a substantial proportion of patients suffer from persistent symptoms known as Long COVID. Among the main symptoms are fatigue,  cognitive dysfunction, muscle weakness and orthostatic intolerance (OI). These  symptoms also occur in myalgic encephalomyelitis/chronic fatigue (ME/CFS). OI is  highly prevalent in ME/CFS and develops early during or after acute COVID-19  infection. The causes for OI are unknown and autonomic dysfunction is  hypothetically assumed to be the primary cause, presumably as a consequence of  neuroinflammation. Here, we propose an alternative, primary vascular mechanism as  the underlying cause of OI in Long COVID. We assume that the capacitance vessel  system, which plays a key role in physiologic orthostatic regulation, becomes  dysfunctional due to a disturbance of the microvessels and the vasa vasorum,  which supply large parts of the wall of those large vessels. We assume that the  known microcirculatory disturbance found after COVID-19 infection, resulting from  endothelial dysfunction, microthrombus formation and rheological disturbances of  blood cells (altered deformability), also affects the vasa vasorum to impair the  function of the capacitance vessels. In an attempt to compensate for the vascular  deficit, sympathetic activity overshoots to further worsen OI, resulting in a  vicious circle that maintains OI. The resulting orthostatic stress, in turn,  plays a key role in autonomic dysfunction and the pathophysiology of ME/CFS.