Autonomic Functions in Post-Acute SARS-CoV-2 (PASC)

National Institute Of Neurological Disorders And Stroke

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Linked publications & trials

Abstract

In this reporting period, NIH Clinical Protocol 000094N, An Observational Study of Neurologic Function after COVID-19 Infection, has been amended to focus more on PASC-related fatigue, brain fog, and cardiovascular dysautonomia. The study calls for comprehensive testing of the extended autonomic system (EAS). Evidence is sought for abnormal reflexive regulation of blood pressure, low blood volume (hypovolemia), excessive shifts in blood volume during prolonged upright posture (orthostasis), sensory or autonomic nerve abnormalities (neuropathy) that can be visualized and quantified by microscopic examinations of skin biopsy tissues, dysregulation of central and peripheral systems that use the catecholamines dopamine or norepinephrine as chemical messengers, abnormalities of neuroendocrine system functions (including adrenaline), indices of central stress system activation, and panels of autoimmune markers. Research tests of autonomic cardiovascular functions under the amended 000094N protocol include continuous blood pressure recording during and after a breathing maneuver called the Valsalva maneuver and tilt table testing with multiple physiological parameters monitored non-invasively and serial blood sampling for plasma catechols. Blood volume is measured by an FDA-approved 131I-albumin technique. Skin biopsies are obtained for small fiber neuropathy and quantification of sympathetic noradrenergic innervation. Research tests assessing the central autonomic network include brain magnetic resonance imaging and lumbar puncture for levels of catecholamines and related neurochemicals. Blood tests examining the neuroendocrine component of the EAS include plasma adrenaline, renin activity, angiotensin II and angiotensin 1-7, aldosterone, copeptin, and corticotropin (ACTH)/cortisol. Blood tests to evaluate the immune component of the EAS include lymphocyte populations, cytokines, anti-neuronal nicotinic receptor (via collaboration with Univ. of Texas), and anti-G-protein coupled receptor antibodies (via collaboration with the Univ. of Lund/Karolinska Institutet). Cerebrospinal fluid (CSF) tests related to immune/autoimmune functions include single cell RNA sequencing, oligoclonal bands, and cytokines. Depending on provision of resources to carry out the study, planned completion is in 2 years, with an additional year for data analysis and publications. Also depending on resources, small clinical trials are planned, with participants recruited through the 000094N protocol. For instance, patients with low blood volume (hypovolemia) may improve with intravenously administered fluids or a salt-retaining steroid; those with an excessive orthostatic shift in blood volume may improve with an inflatable abdominal binder; those with high circulating levels of antibodies targeting EAS components may improve with plasma exchanges or intravenous immunoglobulin; those with markers of cellular autoimmunity (high levels of particular chemicals called cytokines) may improve with drugs targeting those cytokines or with anti-inflammatory steroids such as methylprednisolone; and those with large adrenaline responses to standard laboratory stressors (e.g., tilt table testing) may improve with treatments targeting adrenaline release or effects.