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.

The Relationship between Paresthesia and the Presence of Cardiac Dysautonomia in Patients with Post-COVID-19 Syndrome: A Preliminary Observational Study

“…The physiopathological mechanisms responsible for the deterioration of the ANS are still speculated and could include direct viral damage, toxic effects from cytokines, and immune responses produced by viral components [5,10]. Regardless of the mechanism, the possible participation of the ANS in the SARS-CoV-2 infection is backed by the frequent emergence of neurological symptoms (anosmia and dysgeusia) [5], as well as the sporadic emergence of conditions typically related to the dysfunction of the ANS (orthostatic hypotension and orthostatic tachycardia) in post-COVID-19 syndrome [5,6,10,11].…”

Microvascular Capillary and Precapillary Cardiovascular Disturbances Strongly Interact to Severely Affect Tissue Perfusion and Mitochondrial Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Evolving from the Post COVID-19 Syndrome

“…Various cardiovascular disturbances and abnormalities have been known for quite a long time in ME/CFS before COVID-19, including hypovolemia, low stroke volume, and high vasoconstrictor tone [1,[10][11][12][13]. Similar cardiovascular disturbances have been found in PCS or PCS-ME/CFS [1,3,[10][11][12][14][15][16]. To delineate them from the newly discovered findings of pathological blood components that must disturb capillary flow, we use the term precapillary cardiovascular disturbances.…”

“…Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a frequent, debilitating disease and is associated with a number of syndromes or conditions, including postural orthostatic tachycardia syndrome (POTS) [1,2], orthostatic intolerance (OI) [3], and small fiber neuropathy (SFN) [1]. ME/CFS shows a broad overlap of symptomatology with the Post-COVID-19 Syndrome (PCS).…”

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Comorbidities: Linked by Vascular Pathomechanisms and Vasoactive Mediators?

“…ME/CFS is associated with various syndromes, diseases or conditions, including mast cell activation (MCA) [ 4 , 5 ], endometriosis (EM) [ 6 , 7 , 8 , 9 , 10 ], postural orthostatic tachycardia syndrome (POTS) [ 11 , 12 ], orthostatic intolerance (OI) [ 13 ], and small fiber neuropathy (SFN) [ 12 , 14 ]. Even when diagnosed independently of each other, ME/CFS, endometriosis and MCA share many symptoms, such as fatigue, brain fog, cognitive impairment, pain and edema, just to name a few.…”