Long COVID Ultrasound Trial

Ultrasound is widely used in human medicine because it is safe, non-invasive, and painless. The same kind of ultrasound that is used for imaging (for example, to visualize babies in utero) may be able to treat inflammatory diseases including Long COVID. In Long COVID, there can be a state of hyperinflammation that persists in those with symptoms months to years after infection. This hyperinflammatory state includes elevated proinflammatory cytokines such as interferon β (IFN-β), IFN-λ1, IFN-γ, CXCL9, CXCL10, interleukin-6 (IL-6), IL-8, IL-1β , and Tumor Necrosis Factor (TNF-α) in those with Long COVID. Prolonged inflammation in those with Long COVID plays a key role in its pathogenesis and in driving the persistent symptoms. This study will employ investigational ultrasound devices produced by SecondWave Systems called the MINI ultrasound system. This is a pilot single-arm intervention study in which up to 15 study participants will receive noninvasive splenic ultrasound therapy over eight weeks (five daily stimulation sessions per week). Participants will be enrolled in the study for a total of 12 weeks starting at Week 0. They will undergo a 4-week Baseline Period during which no intervention is delivered to determine how study outcomes may change over time. Then, after baseline outcomes are measured at Week 4, the investigational ultrasound interventional period will begin. Outcomes will be compared from baseline at Week 4 through the end of the 8-week intervention period at Week 12. Investigational splenic-ultrasound therapy will be delivered with the SecondWave MINI ultrasound system. The objective of the study is to assess the safety and potential efficacy of spleen ultrasound stimulation as an intervention for Long COVID in a pilot study. For ultrasound stimulation, a small wearable ultrasound device is positioned on the upper left abdomen area over the ribs. Study personnel will use an ultrasound imaging device to locate the spleen and to position the wearable MINI device in a proper location around the ribs area. Daily stimulation consists of an approximately 18-minute period for application of ultrasound to the spleen. Collection of long-COVID outcome data, patient-reported assessments, and blood draws collected at the 6 study visits to assess biomarkers of inflammation will be performed in each participant throughout the study. Stool samples will be collected at 4 timepoints to assess changes in microbiome and metabolomics over the study period. Movement activity and sleep monitoring will be collected throughout the day and correlated with other study outcomes. The study's primary outcome measure is the endurance shuttle walk test (ESWT) and the secondary outcome measure is the Chalder fatigue scale (CFQ-11). We will also investigate exploratory outcomes that will include other activity outcomes (e.g., total movement per day, sleep patterns), vital signs (e.g. heart rate and blood pressure), biomarker assessments (e.g., CRP, ESR, cortisol), cytokine assessments, microbiome and metabolomic related assessments, and device usability and experience assessments.