New Tactic to Speed Long COVID Treatments to Patients

Kaila Trawitzki was diagnosed with long COVID in November 2020 and, since then, has never recovered. The Sacramento, California, software engineering consultant said her ongoing symptoms, as well as the cost and risk for travel, make most onsite clinical research trials off limits.

But last year, when scientists at Yale University, New Haven, Connecticut, started recruiting patients for a long COVID treatment trial that would be conducted remotely rather than on site, she signed up immediately. “Knowing I could do it from home was really appealing to me,” said Trawitzki.

As many as 17 million people in the United States currently have long COVID, yet experts say trials have been slow to enroll patients, in part because traveling to central trial locations can be costly and difficult for people suffering from fatigue, nausea, shortness of breath, gastrointestinal issues, and more. The remote trials that allow participants to take most, if not all experimental therapies at home, allow even the sickest patients with long COVID to participate.

Researchers at Yale, and elsewhere, say remote trials could lead to greater participation and speed the development of sorely needed new treatments for those with long COVID.

Decentralized clinical trials (DCTs), where the research occurs outside of an academic site, became more popular during COVID-19 when travel restrictions and physical distances made onsite research more difficult. Not to mention that the technologies and ability to share data are improving.

DCTs are more efficient, avoid the risk for acute COVID reinfection, promote patient diversity, and lay the groundwork for how these types of trials — for long COVID and other conditions — will be conducted in the future.

The Yale study enlisted 100 patients with long COVID from across the country to determine whether 15 days of the antiviral Paxlovid would improve their symptoms. The medication arrived to patients by mail, and they didn’t know whether their medication was Paxlovid or a placebo.

Patients took the study drug twice daily for 15 days and were told to record their symptoms every evening. A representative from the study also came to each patient’s home to gather and record blood work, and some patients had their blood work done at a facility close to home. After the study, surveys were sent out periodically to check on patient symptoms.

Patient Accessibility

Remote clinical trials like this one are critical for patients who are severely affected by long COVID, said Akiko Iwasaki, PhD, an immunologist and molecular biologist at Yale School of Medicine, New Haven, Connecticut, who worked on the remote Long COVID (PAX LC) Trial.

“Many of them are not healthy enough to visit a clinic, and this gives them the freedom to still enroll in a trial,” said Iwasaki. “It’s much less taxing on patients especially those who are house- or bed-bound, and there’s no need to arrange travel.”

A More Efficient Approach

This more streamlined trial also reduces inefficiencies that come from having more than one academic center involved in a clinical trial, said Harlan Krumholz, MD, a cardiologist at Yale School of Medicine and principal investigator of the PAX LC Trial. Yale is the only academic center running the study.

“The more coordination necessary between trial sites, the more inefficiency and friction, creating added expense and sometimes delays,” said Krumholz. “You have more control over how everything works when it’s all centrally deployed and de-centrally implemented through a single site.

Risk for Reinfection

Such an approach is also helpful because many patients with long COVID have a fear of reinfection, said Carolyn Bramante, MD, MPH, an assistant professor of medicine at the University of Minnesota Medical School, Minneapolis, whose research focuses on remotely delivered interventions.

“It’s stressful to patients involved in onsite trials because of the concern of reinfection with being in person at a facility with sick patients, which can be a higher-risk setting,” Bramante said.

Cindy Mahler, 49, a Houston area-based aerospace engineer, got long COVID after a serious bout with acute COVID in March 2020. Her symptoms worsened after reinfection in January 2022. She enrolled in the Yale trial in February, attracted to the fact that it wouldn’t require her to travel.

“I still live my life to protect my immune system,” said Mahler. “I don’t want to get sick with anything because I want to continue making progress and getting stronger.”

Mahler’s concerns are well founded, according to an August 2023 study published in the International Journal of Molecular Sciences. It showed that the risk for cardiac, pulmonary, or neurological complications in patients with long COVID increased with each COVID-19 reinfection.

Promoting Diversity

The Yale study has also been able to reach rural communities and participants who might not have had access to these kinds of trials before, said Iwasaki, the Yale biologist.

The hope is that some of the key barriers — like the cost of travel and time off from work, which make it difficult for these underrepresented groups to enroll — are removed when a trial is remote.

A lack of diversity in long COVID clinical trials has been a concern among researchers from the start because it’s hard to have robust knowledge of a treatment if it hasn’t been tested on a wide variety of people. A December 2022 article published in JAMA Internal Medicine found that female, Asian, Black, and Hispanic participants were underrepresented in COVID treatment trials.

Laying the Groundwork

Additionally, the hope is that, with a better understanding of how to run DCTs, laboratories can transition the model to all sorts of studies.

“We created a decentralized trial across the entire country under the scrutiny of regulatory compliance,” said Krumholz.

Compliance matters because if the data aren’t compliant with the US Food and Drug Administration, then they can’t be used by pharmaceutical companies seeking agency approval for new treatments. Krumholz said that this will open the door to doing many more experiments so that we can learn faster and be able to better treat patients with long COVID.

“It’s like Kitty Hawk — it flies, and now we need to get fleets of these planes in the air,” he said.

Both Trawitzki and Mahler felt that their symptoms improved after the trial, though they don’t yet know whether they were given Paxlovid or a placebo and won’t find out until next month. But one thing they know for sure is that the Yale study gave them hope — hope that they are or will get better, and hope for the system as a whole.

For the first time, they felt like they were being heard, and that people finally understood that, especially in this patient population, traveling across the country to do clinical trials is often unrealistic. 

“I felt really supported throughout the study,” said Trawitzki.