UVA Health Launches Two National Clinical Trials to Combat Long COVID

• UVA Health has joined two NIH-sponsored clinical trials targeting sleep disorders and autonomic dysfunction in long COVID patients, addressing conditions affecting potentially 50 million Americans.
• The RECOVER-SLEEP trial is testing medications including Solriamfetol and Modafinil for hypersomnia, while also examining light therapy and Melatonin for complex sleep disturbances in post-COVID patients.
• The RECOVER-AUTONOMIC study focuses on treating postural orthostatic tachycardia syndrome (POTS) with intravenous immunoglobulins or ivabradine, alongside non-drug interventions like compression belts and high-salt diets.

UVA Health researchers have launched participation in two major national clinical trials aimed at understanding and treating long COVID, a condition that may affect between 5% and 30% of people who have had COVID-19 infections—potentially impacting up to 50 million Americans.

The trials are part of the National Institutes of Health's Researching COVID to Enhance Recovery (RECOVER) Initiative, which seeks to address the persistent symptoms that continue to affect millions of Americans months after their initial COVID-19 infection.

"It's estimated that between 5% and 30% of people who had COVID-19 may experience symptoms of long COVID," said Dr. Alexandra Kadl, director of UVA Health's post-COVID clinic, which has been operating since July 2020. "Given that pretty much all Americans have had at least one episode of COVID, the estimates right now are that maybe 50 million Americans could be affected by it in different severities."

Understanding Long COVID

Long COVID is now defined as a chronic disease that persists at least three months after COVID infection. According to Dr. Kadl, it can manifest in approximately 200 different symptoms that are severe enough to alter patients' lifestyle and ability to work.

The most common symptoms observed at UVA Health's long COVID clinic include respiratory complaints like chronic cough and shortness of breath, sleep issues, gastrointestinal problems, and neurological symptoms.

Many patients face significant challenges beyond their physical symptoms. "We see patients coming in who are extremely frustrated because they look fairly normal. They look not sick, but they cannot function, they cannot take care of their families, they cannot take care of their jobs, and it is incredibly frustrating," Dr. Kadl explained.

RECOVER-SLEEP Trial

The first trial, RECOVER-SLEEP, focuses on two distinct patient populations with different sleep disturbances following COVID-19 infection:

1. Patients with hypersomnia, who sleep significantly more than before their COVID-19 infection to the point where it interferes with daily activities
2. Patients with complex sleep disturbances, who experience poor sleep quality or problems falling asleep

Participants with hypersomnia will receive either a placebo or one of two medications: Solriamfetol or Modafinil. Those with complex sleep disturbances will be randomized to receive either low-intensity or high-intensity light therapy, combined with either a placebo or Melatonin.

RECOVER-AUTONOMIC Trial

The second trial, RECOVER-AUTONOMIC, targets adults who developed symptoms of postural orthostatic tachycardia syndrome (POTS) after COVID-19 infection. POTS symptoms include dizziness, fatigue, and rapid heart rate, especially when changing positions from lying down to standing.

"This is a group of people who have a normal heart and lungs, but somehow, they don't work together," Dr. Kadl said. "Blood pools in your legs and is not able to move up to your heart and areas that need it because the regulation of the heart is disturbed."

The study has two treatment arms:

1. One group will receive either intravenous immunoglobulins (IVIG), which contain antibodies to help the body fight infection, or a placebo
2. The second group will receive either ivabradine, an oral medication that reduces heart rate, or a placebo

All participants will receive non-drug care that includes weekly phone calls from study coordinators, compression belts, and high-salt diets—interventions commonly recommended for POTS patients.

Patient Screening and Eligibility

To determine eligibility for the RECOVER-AUTONOMIC trial, researchers conduct several tests, including a tilt table test. During this procedure, patients lie flat on a table and are gradually tilted upward while their blood pressure and heart rate are monitored. Significant changes may indicate eligibility for the trial.

People who may qualify include "anybody who starts to feel lightheaded, dizzy when they walk or exercise, even when the exercise is minimal," according to Dr. Kadl.

The Challenge of Long COVID

Managing long COVID presents unique challenges for healthcare providers. Dr. Kadl noted that many patients' symptoms are dismissed as personal weaknesses rather than being recognized as serious medical conditions, though they are very real and debilitating.

The UVA Health long COVID clinic continues to enroll patients in both studies, offering hope to those suffering from persistent symptoms following COVID-19 infection. These trials represent important steps toward developing effective treatments for a condition that continues to affect millions of Americans long after the acute phase of infection has passed.