Frances Rossi’s enduring encounter with COVID-19 began in mid-February 2020. What she thought was a common cold had an unusual twist.
At the time, Rossi directed three choirs for a Catholic church in Denver. So it was a problem when she found she’d strangely lost one-third of her voice.
“It knocked out the middle range,” she recalled. “I could sing high and low but not in the middle at all. It absolutely wiped it out.”
A nagging dry cough also bothered Rossi, as well as sinus pressure and draining. She noticed after the cold that she could no longer walk up two flights of stairs in the church without holding the railing and having help with her guitar and sheet music. Just before the cold, she’d completed the trip without assistance.
As the days wore on, Rossi suffered a slew of additional, fluctuating symptoms, including dizziness, lightheadedness, nausea, heart palpitations, chest tightness, changes in blood pressure, redness in her fingers and toes, and extreme fatigue. In these early days of the pandemic – the first case in the United States had been confirmed only in late January – Rossi had trouble getting a COVID-19 test. But she knew there was nothing common about her cold.
“All I knew was something was going on and not resolving,” she said.
As the symptoms persisted through the spring of 2020, Rossi did her own research and was convinced she had COVID-19. It wasn’t until June, however, that an antibody test at UCHealth confirmed that she’d been infected.
More than two years later, however, Rossi still battles post-COVID symptoms, particularly chronic fatigue. She is one of millions of people in the United States with long COVID, meaning first-time symptoms that persist for three or more months after the original infection. Rossi is also part of a massive nationwide initiative to study long COVID, uncover its roots and develop new treatments and therapies for the condition, which remains notoriously difficult to pin down.
Long COVID research study site
The University of Colorado Anschutz Medical Campus is a recruitment site for the $1.15 billion National Institutes of Health-funded study, dubbed RECOVER. The four-year long COVID research study is enrolling and following patients from three groups: those who had COVID-19 and experienced long COVID symptoms, those who recovered without long COVID symptoms and healthy controls.
Recruits will complete baseline questionnaires and blood draws, with researchers using the information gleaned to search for clues to what drives the dizzying array of symptoms that plague long COVID sufferers like Frances Rossi.
“The bloodwork will hopefully delve into the mechanisms, such as the body’s immune response, inflammation and changes to the microbiome, that might underlie those who go on to develop long-term symptoms,” said Dr. Kristine Erlandson, co-principal site investigator for the RECOVER study and an associate professor of Medicine – Infectious Diseases at the University of Colorado School of Medicine.
“The trial is also designed to serve as a platform to roll out future intervention studies,” Erlandson added. In turn, the promise of trials for new therapies may encourage patients to join the RECOVER study, she said.
Long COVID study seeks new recruits — fast
Quickening the enrollment pace is a priority. The total national recruitment goal for adults, children and pregnant women is 40,000. As of early August, the trial had recruited nearly 6,800 adults, less than half the goal of 17,000. In Colorado, researchers hope to recruit 360 patients from UCHealth and Denver Health, Erlandson said. As of late July, she reported, about 80 patients had been recruited from UCHealth, with another 60 or so coming from Denver Health. To boost that number, the trial team recently hired a half-dozen new study coordinators, she added.
“We’re looking forward to a massive recruitment push,” Erlandson said.
That push won’t focus on long COVID patients. Erlandson said that self-referrals, as well as those from long COVID providers like the UCHealth Post-COVID Clinic, quickly filled those slots and created a waiting list of around 500. Per instructions from NIH, the study is now pursuing patients diagnosed with COVID-19 within the past four weeks, as well as those who have never been infected. With variations in the SAR-CoV-2 virus allowing COVID-19 to stubbornly hang on in communities, finding uninfected people has presented a bigger recruitment challenge than expected, Erlandson said.
“One of the difficulties we’ve had has been finding people in the uninfected population,” she said. “That number has been decreasing.”
Erlandson encouraged people who have never had COVID-19 to contact the study, even if they have comorbidities like diabetes or cardiovascular problems. Their contributions could further reveal the subtleties of long COVID. For example, how, if at all, does first-time shortness of breath differ in a patient with long COVID from the same problem in an uninfected patient with heart disease?
Goal is to boost enrollment in underserved communities
The Colorado team is also working on an entrenched clinical trial recruitment problem: increasing enrollment among racial and ethnic minorities, Erlandson said. It’s a goal specifically stated in the RECOVER adult study protocol. It won’t be sufficient to rely on self-referrals to address the issue, she added.
“We’re shifting our strategies to our community engagement group,” Erlandson said. “We want to focus on recruiting some of the underrepresented populations in research that have been disproportionately affected by COVID.”
The Centers for Disease Control and Prevention note the risk of hospitalization from a COVID-19 infection for Black people and Hispanic people was more than double than for white people. The comparative risk was nearly triple for American Indians and Alaska Natives.
The NIH-funded effort to address “the disparate impact of COVID-19 on racial and ethnic populations” began with the Community Engagement Alliance (CEAL), said Dr. Donald Nease, a Family Medicine physician at UCHealth AF Williams Family Medicine Clinic – Central Park and professor of Family Medicine with the CU School of Medicine. Nease is co-principal investigator for CO-CEAL, the Colorado chapter of the national alliance. It’s a partnership between the University of Colorado Anschutz Medical Campus and a host of community and state organizations.
A statewide effort to engage communities in long COVID research
CO-CEAL launched in April 2021, focusing on improving education and countering disinformation about COVID-19 and vaccinations in American Indian/Alaska Native and Black and Hispanic urban and rural communities. These spanned the Denver metro area, Pueblo, Fort Morgan, Weld County and the San Luis Valley. The group received funding for a second year in March, Nease said.
In the first phase, CO-CEAL worked closely with community members on two rounds of projects that included funding a video targeted at Black people that explained COVID-19 vaccines and why they were important; informational posters displayed on buses and at stops; links for more information about COVID-19; and information distributed at community meetings, Nease said. A second round focused on childhood vaccination, with Hispanic communities in the Denver area and the San Luis Valley independently deciding to use coloring books to help kids and their parents learn more about COVID-19 and how vaccines help to protect people from the disease.
Nease said CO-CEAL is now working with the RECOVER team to boost study enrollment among those hard-hit communities. That’s been a challenge throughout the COVID-19 pandemic, he said
“One of the things we saw very early on in some of the vaccine trials is that we weren’t reaching into the communities that were being pretty significantly impacted by COVID-19,” he said. “We saw that as something that needed to be addressed.”
Nease said CO-CEAL’s Community Clinical Trials Advisory Board has been meeting to discuss effective ways to get word of the RECOVER study out to Denver residents. The possibilities include using Denver Health’s network of primary care clinics that already serve as recruitment sites. Research liaisons with the Colorado Clinical and Translational Sciences Institute (CCTSI) who have contacts in communities with large racial and ethnic populations could also play a valuable role, Nease said.
In the near future, CO-CEAL plans community meetings for people to ask questions about the RECOVER study, Nease said. It’s the responsibility of recruiters, he added, to explain in plain language the benefits of the trial, not just to the scientific community, but to ordinary people.
“We find that the number-one thing is about trust and how we bring trusted messages to the community,” Nease said. “By listening to clergy and others closely connected to the communities, we can get our message out. We also want to be totally transparent about where we lack information about long COVID. The whole purpose is to build more understanding.”
Nease said he’ll attend meetings on the long COVID research study with co-PI Dr. Ricardo Gonzalez Fisher, a physician and researcher who works closely with Mexican immigrants and other underserved communities and is bilingual. He added that Gordon Duvall, a Clinical Trials Advisory Board member, will help to disseminate RECOVER study recruitment information at Aurora’s Salud Family Health Center, where he serves as medical and education director.
As one already enrolled in the RECOVER study, Frances Rossi hopes that her participation helps to shed light on long COVID and her frustrating issues with it. The pandemic ended her position as choir and music director, leaving her to play guitar and sing Sundays only at another church. Still, she gains sustenance from her music and from six grandchildren, two of whom lived in Denver until recently. Rossi also belongs to a long COVID support group on Facebook. The online exchanges were especially helpful during the early, confusing days of her illness.
“The group was a total revelation because I started hearing from people who had the same symptoms I had,” Rossi recalled. “I found I was not an isolated case and that it wasn’t just my body doing weird things.”
Some of the early symptoms linger, including concentration problems, occasional shortness of breath, chest tightness, and especially fatigue.
“I’ll think I’m over this. I have some energy, get excited and start doing things,” Rossi said. “Then I’ll overdo it and get back in the same pattern of exhaustion.” She said she’s learned to conserve her energy for important things that will require exertion, like singing on Sunday or spending time with her grandchildren.
She finds her mind as well as her body needs more rest. “There are times I know I’ve reached my capacity and my mind starts to shut down,” she said. Small but important changes bother her. For example, Rossi has noticed that while she crotchets, she sometimes now has difficulty keeping track of the number of stitches.
“I have to say aloud the number I am on,” she said.
Rossi said she decided to join the RECOVER study both for herself and for others.
“I feel like I want to be able to share my experience and I’m hoping that can help somebody understand the disease better. I’d like to contribute to that,” she said.
She also has a more personal purpose. “I want people to know that long COVID is real, and I would like them to know that long COVID is a reason not to get COVID in the first place,” Rossi said. “Even someone who thinks they are very healthy can get these long-lasting aftereffects from the disease. You may get through COVID just fine, but that may not be the end of it for you.”
To learn more about enrolling in the study, click here.