Orthostatic Intolerance in Long-Haul COVID after SARS-CoV-2: A Case-Control Comparison with Post-EBV and Insidious-Onset Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients

Abstract

Background: As complaints of long-haul COVID patients are similar to those of ME/CFS patients and as orthostatic intolerance (OI) plays an important role in the COVID infection symptomatology, we compared 14 long-haul COVID patients with 14 ME/CFS patients with a post-viral Ebstein-Barr (EBV) onset and 14 ME/CFS patients with an insidious onset of the disease. Methods: In all patients, OI analysis by history taking and OI assessed during a tilt test, as well as cerebral blood flow measurements by extracranial Doppler, and cardiac index measurements by suprasternal Doppler during the tilt test were obtained in all patients. Results: Except for disease duration no differences were found in clinical characteristics. The prevalence of POTS was higher in the long-haul patients (100%) than in post-EBV (43%) and in insidious-onset (50%) patients (p = 0.0002). No differences between the three groups were present in the prevalence of OI, heart rate and blood pressure changes, changes in cerebral blood flow or in cardiac index during the tilt test. Conclusion: OI symptomatology and objective abnormalities of OI (abnormal cerebral blood flow and cardiac index reduction during tilt testing) are comparable to those in ME/CFS patients. It indicates that long-haul COVID is essentially the same disease as ME/CFS.

Long COVID: major findings, mechanisms and recommendations

“…The mechanisms of and overlaps between long COVID and connective tissue involvement, mast cells and inflammatory conditions such as endometriosis are particularly understudied and should be focused on. Because of the high prevalence of ME/CFS, POTS and other postinfectious illnesses in patients with long COVID, long COVID research should include people who developed ME/CFS and other postinfectious illnesses from a trigger other than SARS-CoV-2 in comparator groups to improve understanding of the onset and pathophysiology of these illnesses 113 . Additionally, there is a known immune exhaustion process that occurs between the second and third year of illness in ME/CFS, with test results for cytokines being different between patients who have been sick for shorter durations (less than 2 years) than for those who have been sick for longer durations 43 .…”

“…Long COVID research has found mitochondrial dysfunction including loss of mitochondrial membrane potential 105 and possible dysfunctional mitochondrial metabolism 106 , altered fatty acid metabolism and dysfunctional mitochondriondependent lipid catabolism consistent with mitochondrial dysfunction in exercise intolerance 107 , redox imbalance 108 , and exercise intolerance and impaired oxygen extraction 100,109,110 . Studies have also found endothelial dysfunction 29 , cerebral blood flow abnormalities and metabolic changes 81,[111][112][113] (even in individuals with long COVID whose POTS symptoms abate 114 ), extensive neuroinflammation 42,80 , reactivated herpesviruses 18,21,27 , deformed red blood cells 64 Dysautonomia, particularly POTS, is commonly comorbid with ME/CFS 116 and also often has a viral onset 117 . POTS is associated with G protein-coupled adrenergic receptor and muscarinic acetylcholine receptor autoantibodies, platelet storage pool deficiency, small fibre neuropathy and other neuropathologies 118 .…”

Long-Haul COVID Patients: Prevalence of POTS Are Reduced but Cerebral Blood Flow Abnormalities Remain Abnormal with Longer Disease Duration

“…The mechanisms underlying the finding that POTS is less frequently observed later in the disease are not clear. Hypothetically, an excess sympathetic drive in the acute phase of COVID-19 may disappear, leading to fewer POTS signs and symptoms [ 26 ]. In addition, mechanisms causing chronotropic incompetence may emerge with a longer duration of illness, such as changes in the vagal and sympathetic balance, changes in baroreceptor sensitivity as well as differences in stretching forces, [ 27 , 28 , 29 ], or changes in myocardial receptor density [ 30 ].…”

A global need for more awareness of dysautonomia in postviral syndromes

“…Data sharing is not applicable to this article as no new data were created or analyzed in this study. Manoj Sivan 1,2 Vikki Mckeever 3,4 Michael Natt 5 Julia Newton…”

“…1 Postviral syndromes are linked to long-term sequelae including myalgic encephalitis/chronic fatigue syndrome (ME/CFS), fibromyalgia, chronic pain, and other persistent physical symptoms (PPS) which often includes fatigue as a predominant and disabling aspect. 2,3 A common underlying impairment in many of these patients is autonomic dysfunction (dysautonomia) which presents with an array of symptoms including fatigue, postexertional malaise (PEM), orthostatic intolerance (including postural orthostatic tachycardia syndrome [POTS]), palpitations, dizziness, exercise intolerance, pain, brain fog, gastrointestinal symptoms, and temperature dysregulation. 4 A recent study from a UK specialist long COVID service suggests a prevalence of 38% of patients reporting dysautonomia symptoms on the NASA Lean Test.…”