St. Louis researchers shape understanding of long COVID

It was March 2020, and Dr. Ziyad Al-Aly felt as disoriented as everyone else. With the onset of the COVID-19 pandemic, he was forced to work from home rather than at his office at the Washington University School of Medicine, where he is the director of clinical epidemiology, or at the Veterans Affairs St. Louis Health care System, where he is chief of research and development. He remembers brainstorming on Zoom calls with his research partners, Dr. Yan Xie and Dr. Benjamin Bowe, about what to do next.

“We knew we needed to address the challenges posed by the pandemic during this time of crisis,” Al-Aly says. “We literally pivoted overnight.”

His team began to study COVID-19, specifically the effects of long COVID, which didn’t even have a name when they began. Prior to March 2020, Al-Aly and his team had been studying the impact of the long-term use of heartburn medication, work that he still considers valuable. But he likens it to washing dishes when the neighbor’s house is on fire. “Sometimes you need to leave the dish unwashed and help put out the fire next door,” he says.

Al-Aly’s team’s research has helped transform the understanding of long COVID. With access to large sets of patient data through his role at the VA, his team has published more than a half-dozen scientific journal articles on long COVID. The New York Times, the Wall Street Journal, the Washington Post, Forbes, the Guardian, and many other outlets have covered his work, and the White House recently named Al-Aly as co-chair of a group tasked with developing the National Research Action Plan on Long COVID.

The Centers for Disease Control and Prevention define long COVID as a wide range of ongoing health problems that people develop after first being infected with the virus that causes COVID-19. Chronic fatigue and neurological problems, such as brain fog and difficulty sleeping, are among the most common of the 200 or so identified symptoms.

Equally alarming to Al-Aly are systemic problems, such as heart disease, diabetes, and kidney disease, which are now cropping up in some long COVID cases. “These chronic conditions can scar people for a lifetime,” he says.

These are the stakes that have kept Al-Aly working at marathon pace for more than two years. He admits he hasn’t had an ideal work-life balance since the pandemic began—while much of the country has moved on, he and his team are still in crisis mode.

He finds inspiration for his ongoing effort in the long COVID patient community. An important turning point came with a New York Times op-ed written early in the pandemic by patient Fiona Lowenstein, which became a rallying cry for others suffering from debilitating symptoms. Patients began to self-organize and eventually published the first-ever catalog of long COVID symptoms. As Al-Aly began following long COVID patient advocacy groups, it energized him and helped inform his research.

“If these patients, some of whom are disabled and in bed most of the day, can summon the energy and moral courage to keep advocating for themselves, I can convince myself to keep working on Saturdays and Sundays to make progress on these questions,” he says.

Much of Al-Aly’s work has been presenting his findings to other physicians and health care workers. And while he says some providers have been slow to recognize an illness with diffuse symptoms that can present anywhere in the body, science policy researcher Melissa Smallwood, author of a recently published paper on the impact of long COVID, believes that Al-Aly’s research can be beneficial for patients who have skeptical health care providers.

“It is an important tool in helping combat the narrative that long COVID is rare or doesn’t exist,” Smallwood says. “Anything that provides more concrete evidence that this not only exists but is a widespread complication of COVID is going to help.”

Although Al-Aly’s team has made progress in understanding long COVID, he fears the long-term implications, even as the original COVID-19 pandemic appears to be receding. His most recent paper finds that while vaccines are significant in preventing hospitalization and death from acute COVID, they are only slightly protective (15 percent) for long COVID. (Prior to this research, many scientists believed it was closer to 60 percent.) Al-Aly thinks what we’ve seen so far is only the beginning and that the “pandemic after the pandemic” may continue to unfold for years.

Despite the gravity of this prediction, Al-Aly offers hope to those who have been diagnosed with long COVID or suspect they have it. He urges patients to seek help as soon as possible, as early identification of long COVID can allow for treatment of the impacted systems. He also wants patients to know that help is available.

“You are not alone,” he says.

Not Throwin’ Away Our Shot

How St. Louis researchers continue to play a role in COVID vaccine research

1. At Saint Louis University’s Center for Vaccine Development, work continues on a number of fronts. Researchers are enrolling volunteers in an investigational COVID-19 booster vaccine trial that will test the safety, tolerability, and immune responses stimulated by different doses of Gritstone’s investigational second-generation boosters. A Phase 2 clinical trial is in the works to test additional COVID-19 vaccine boosters, and Dr. Daniel Hoft’s laboratory is developing a T cell–targeting universal coronavirus vaccine.

2. Washington University is participating in a nationwide clinical trial to determine the effectiveness of an omicron-specific booster of the Moderna vaccine. “We are evaluating the investigational booster now so that we can learn about the safety profile and how the body’s immune system responds if an omicron-specific booster is needed in the future,” Dr. Rachel Presti, the Washington University site leader for the clinical trial, said in a February press release.

3. Wash. U. also participated in a pediatric COVID-19 vaccine clinical trial, with local children ages 6 months to 11 years receiving the two-shot Moderna vaccine or placebo at St. Louis Children’s Hospital. In a press release last October, Dr. Carol Kao, one of the physicians overseeing the trial, said, “Vaccinating kids will allow them to be protected like adults are now and to indirectly protect others in their homes and communities.”

4. A multicenter study involving Wash. U. found that transplant recipients who are at high risk of developing severe COVID-19 infections should consider receiving three doses of a COVID-19 mRNA vaccine (e.g., the Pfizer-BioNTech and Moderna vaccines), which provides greater protection than two doses. Likewise, research found that a third vaccine dose may be beneficial for people on TNF inhibitors, a class of immunosuppressants used to treat rheumatoid arthritis and other autoimmune conditions.