Postviral Dynamics and Dysfunction of the Autonomic Nervous System via Adherence-Independent Longitudinal Cardiopulmonary Monitoring

Viral illnesses frequently cause post-viral neuroinflammatory syndromes that remain poorly understood at a mechanistic level, are debilitating for patients and are challenging to monitor and treat for physicians. This problem has recently exploded in the context of COVID-19, which frequently precipitates a post-viral syndrome known as long-COVID. Post-viral syndromes often manifest as autonomic nervous system dysfunction due to the direct or indirect neuroinflammatory effects of the virus. Postural orthostatic tachycardia syndrome (POTS) is a post-viral dysautonomia experienced by patients as debilitating dizziness, fatigue, lightheadedness, palpitations and inability to perform daily activities or work. Despite this, post-viral POTS remains poorly understood, preventing prognostication and therapeutic intervention. Typically, it is managed with an initial objective diagnostic assessment of heart rhythm and autonomic function. However, for the remaining weeks, months and years, patients with POTS are followed by patient-reported symptoms as they trial a series of empiric medical and lifestyle interventions, often with limited relief. Today, we lack effective treatments for many patients with this condition. We are also unable to match the interventions with the patients who are most likely to benefit. Longitudinal diagnostics are needed to improve our understanding and management of post-viral POTS. The goal of this proposal is to leverage adherence-independent noncontact home bed mattress sensors to perform fully automated longitudinal monitoring of autonomic nervous system function from patterns of cardiopulmonary dynamics during sleep. We will use the data to define POTS endotypes with putative unique trajectories and responses to therapy. To collect this data, we will place a noncontact mechanical mattress sensor beneath the home bed mattresses of individuals with post-viral POTS and quantify cardiopulmonary coupling to infer autonomic nervous system function across time. The resulting 50,000-100,000 hours of cardiopulmonary physiology that we will passively collect will begin to define clusters of patients with distinct post-viral POTS trajectories and responses to therapy. If successful, our study will yield an unprecedented dataset that will inspire design of larger observational and intervention studies while providing a new tool for passively longitudinally monitoring post-viral neuroinflammatory dysautonomias like long-COVID. Less