UNITE Study (UMN-GE) for COVID-19

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 COVID-19. COVID-19 is a disease
caused by infection with the SARS-CoV-2 virus. Some COVID-19 patients develop a severe
respiratory disease called acute respiratory distress syndrome and this disease is caused, in
part, by a significant increase in inflammatory factors. Clinical therapies that reduce this
elevated inflammation in the body (e.g., inflammation molecules in your body called
cytokines) may be capable of diminishing symptoms in severe cases of COVID-19.

Multiple studies in animals with hyper-inflammation conditions (e.g., inflammatory arthritis
and sepsis/LPS injections) and recent human studies (e.g., for the treatment of joint
inflammation in Rheumatoid Arthritis) have shown that ultrasound applied to the spleen can
suppress blood/genetic markers of inflammation. Similar inflammatory markers, or cytokines,
are elevated in the lungs of COVID-19 patients and believed to cause severe symptoms. Splenic
ultrasound can potentially lower these inflammatory cytokines without hindering antibody
production, leading to clinical improvements in COVID-19 patients.

This study will employ ultrasound devices produced by General Electric (GE LOGIQ E10 device
with C1-6 ultrasound probe) that are currently used in hospitals and approved for diagnostic
imaging by the FDA. The ultrasound energies applied to the spleen in this study in COVID-19
patients will not exceed what is currently approved for diagnostic imaging with those GE
ultrasound devices.

There will be two groups in this study with 15 participants in each group. One group will
receive ultrasound application to the spleen, in addition to the standard clinical care. A
control group will receive standard clinical care without splenic ultrasound. Each ultrasound
application session will last about 15-20 minutes per day for 7 days, unless the participant
is discharged sooner. For ultrasound stimulation, a small gel-coated probe is positioned on
the upper left abdomen area over the ribs. The ultrasound session includes a period of 5-10
minutes when study personnel use the ultrasound device to locate the spleen and to position
the ultrasound probe in a proper location around the ribs area, and an approximately
10-minute period for application of ultrasound to the spleen. Collection of clinical outcome
data and daily blood draws will be performed in each participant throughout the study.
Additional data collected from each participant during their routine clinical care beyond
their study involvement will also be analyzed together with the study data to evaluate the
specific aims of the clinical trial.