Value of ¹²³I-MIBG SPECT for the assessment of dysautonomia in patients with long COVID

Increasing numbers of COVID-19 patients, continue to experience symptoms months after recovering from mild cases of COVID-19. Amongst these symptoms, several are related to neurological manifestations, including fatigue, anosmia, hypogeusia, headaches and hypoxia. However, the involvement of the autonomic nervous system, expressed by a dysautonomia, which can aggregate all these neurological symptoms has not been prominently reported. Here, we hypothesize that dysautonomia, could occur in secondary COVID-19 infection, also referred to as “long COVID” infection. 39 participants were included from December 2020 to January 2021 for assessment by the Department of physical medicine to enhance their physical capabilities: 12 participants with COVID-19 diagnosis and fatigue, 15 participants with COVID-19 diagnosis without fatigue and 12 control participants without COVID-19 diagnosis and without fatigue. Heart rate variability (HRV) during a change in position is commonly measured to diagnose autonomic dysregulation. In this cohort, to reflect HRV, parasympathetic/sympathetic balance was estimated using the NOL index, a multiparameter artificial intelligence-driven index calculated from extracted physiological signals by the PMD-200 pain monitoring system. Repeated-measures mixed-models testing group effect were performed to analyze NOL index changes over time between groups. A significant NOL index dissociation over time between long COVID-19 participants with fatigue and control participants was observed ( p  = 0.046). A trend towards significant NOL index dissociation over time was observed between long COVID-19 participants without fatigue and control participants ( p  = 0.109). No difference over time was observed between the two groups of long COVID-19 participants ( p  = 0.904). Long COVID-19 participants with fatigue may exhibit a dysautonomia characterized by dysregulation of the HRV, that is reflected by the NOL index measurements, compared to control participants. Dysautonomia may explain the persistent symptoms observed in long COVID-19 patients, such as fatigue and hypoxia. Trial registration: The study was approved by the Foch IRB: IRB00012437 (Approval Number: 20-12-02) on December 16, 2020.

New Findings What is the central question of this study? We sought to investigate whether carotid stiffness, carotid intima–media thickness and the aortic augmentation index are altered in young adults 3–4 weeks after contraction of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) compared with young healthy adults. What is the main finding and its importance? We found that carotid stiffness, Young's modulus and the aortic augmentation index were greater in young adults who tested positive for SARS‐CoV‐2 compared with healthy young adults. These findings provide additional evidence for detrimental effects of SARS‐CoV‐2 on young adult vasculature, which might have implications for cardiovascular health. Abstract Contracting severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has been observed to cause decrements in vascular function of young adults. However, less is known about the impact of SARS‐CoV‐2 on arterial stiffness and structure, which might have additional implications for cardiovascular health. The purpose of this study was to assess the carotid artery stiffness and structure using ultrasound and the aortic augmentation index (AIx) using applanation tonometry in young adults after they tested positive for SARS‐CoV‐2. We hypothesized that carotid artery stiffness, carotid intima–media thickness (cIMT) and aortic AIx would be elevated in young adults with SARS‐CoV‐2 compared with healthy young adults. We evaluated 15 young adults (six male and nine female; 20 ± 1 years of age; body mass index, 24 ± 3 kg m −2 ) 3–4 weeks after a positive SARS‐CoV‐2 test result compared with young healthy adults (five male and 10 female; 23 ± 1 years of age; body mass index, 22 ± 2 kg m −2 ) who were evaluated before the coronavirus 2019 pandemic. Carotid stiffness, Young's modulus and cIMT were assessed using ultrasound, whereas aortic AIx and aortic AIx standardized to 75 beats min −1 (AIx@HR75) were assessed from carotid pulse wave analysis using SphygmoCor. Group differences were observed for carotid stiffness (control, 5 ± 1 m s −1 ; SARS‐CoV‐2, 6 ± 1 m s −1 ), Young's modulus (control, 396 ± 120 kPa; SARS‐CoV‐2, 576 ± 224 kPa), aortic AIx (control, 3 ± 13%; SARS‐CoV‐2, 13 ± 9%) and aortic AIx@HR75 (control, −3 ± 16%; SARS‐CoV‐2, 10 ± 7%; P  < 0.05). However, cIMT was similar between groups (control, 0.42 ± 0.06 mm; SARS‐CoV‐2, 0.44 ± 0.08 mm; P  > 0.05). This cross‐sectional analysis revealed higher carotid artery stiffness and aortic stiffness among young adults with SARS‐CoV‐2. These results provide further evidence of cardiovascular impairments among young adults recovering from SARS‐CoV‐2 infection, which should be considered for cardiovascular complications associated with SARS‐CoV‐2.

Objective: To report a case series of dysautonomia associated with COVID-19 infection. Methods: This is a retrospective review of patients evaluated in the autonomic clinic at our institution with suspected signs and symptoms of dysautonomia who underwent formal evaluation, including autonomic testing. Results: Six patients were identified with signs and symptoms suggestive of dysautonomia who underwent autonomic testing. All patients had symptoms typical of COVID-19 infection, though none were hospitalized for these or other symptoms. All patients reported symptoms of postural lightheadedness and near-syncope, fatigue, and activity intolerance. Five patients reported the onset of autonomic symptoms concomitant with other COVID-19 symptoms, with the other patient reporting symptom onset 6 weeks following initial COVID-19 symptoms. Autonomic testing demonstrated an excessive postural tachycardia in 4 patients, a hypertensive response with head-up tilt in 3 patients, orthostatic hypotension in 1 patient, and sudomotor impairment in 1 of the patients with excessive postural tachycardia. Conclusions: We present clinical features and results of autonomic testing in 6 patients with a history COVID-19 infection. While all patients reported typical features of orthostatic intolerance, fatigue, and activity intolerance, the results of autonomic testing were heterogenous, with orthostatic hypotension in 1 patient, excessive postural tachycardia typical of postural tachycardia syndrome in 4 patients, and postural hypertension in 3 patients.