PASC following mild COVID-19 infection caused a significant decline in orthostatic cerebral blood flow velocity (-20.0%) compared to healthy controls (-3.0%), alongside small fiber neuropathy.
Observational (n=34)
No
PASC following mild COVID-19 is associated with multisystem involvement including cerebrovascular dysregulation, small fiber neuropathy, and dysautonomia, similar to but distinct from POTS.
Absolute Event Rate: -20% vs -3%
p-value: p=0.001
OBJECTIVE: The purpose of this study was to describe cerebrovascular, neuropathic, and autonomic features of post-acute sequelae of coronavirus disease 2019 ((COVID-19) PASC). METHODS: This retrospective study evaluated consecutive patients with chronic fatigue, brain fog, and orthostatic intolerance consistent with PASC. Controls included patients with postural tachycardia syndrome (POTS) and healthy participants. Analyzed data included surveys and autonomic (Valsalva maneuver, deep breathing, sudomotor, and tilt tests), cerebrovascular (cerebral blood flow velocity CBFv monitoring in middle cerebral artery), respiratory (capnography monitoring), and neuropathic (skin biopsies for assessment of small fiber neuropathy) testing and inflammatory/autoimmune markers. RESULTS: Nine patients with PASC were evaluated 0.8 ± 0.3 years after a mild COVID-19 infection, and were treated as home observations. Autonomic, pain, brain fog, fatigue, and dyspnea surveys were abnormal in PASC and POTS (n = 10), compared with controls (n = 15). Tilt table test reproduced the majority of PASC symptoms. Orthostatic CBFv declined in PASC (-20.0 ± 13.4%) and POTS (-20.3 ± 15.1%), compared with controls (-3.0 ± 7.5%, p = 0.001) and was independent of end-tidal carbon dioxide in PASC, but caused by hyperventilation in POTS. Reduced orthostatic CBFv in PASC included both subjects without (n = 6) and with (n = 3) orthostatic tachycardia. Dysautonomia was frequent (100% in both PASC and POTS) but was milder in PASC (p = 0.002). PASC and POTS cohorts diverged in frequency of small fiber neuropathy (89% vs 60%) but not in inflammatory markers (67% vs 70%). Supine and orthostatic hypocapnia was observed in PASC. INTERPRETATION: PASC following mild COVID-19 infection is associated with multisystem involvement including: (1) cerebrovascular dysregulation with persistent cerebral arteriolar vasoconstriction; (2) small fiber neuropathy and related dysautonomia; (3) respiratory dysregulation; and (4) chronic inflammation. ANN NEUROL 2022;91:367-379.
Novák et al. (Sat,) conducted a observational in Post-Acute Sequelae of COVID-19 (PASC) (n=34). PASC (following mild COVID-19) vs. Healthy controls and POTS patients was evaluated on Mean cerebral blood flow velocity (CBFv) drop at 10 min of the tilt test (%) (p=0.001). PASC following mild COVID-19 infection caused a significant decline in orthostatic cerebral blood flow velocity (-20.0%) compared to healthy controls (-3.0%), alongside small fiber neuropathy.
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