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How do you research the effects of long COVID-19 on Black and brown people when most volunteers for medical studies are white?
Earlier this year, University of Minnesota researchers started recruiting participants for a study on long COVID. MRI scans, they believe, could help shed light on the reported neurological symptoms of long COVID, such as headaches and brain fog—effects which remain mysterious.
The COVID-BRAIN Project researchers especially want to study those effects in individuals hit hardest by the virus: Black, Latino and Native people. But of the 26 people who have been enrolled as participants so far, all are white and 19 are female.
That demographic snapshot may be frustrating for researchers, but it isn’t surprising: Most of the participants in long COVID surveys are white women, principal investigator Dr. Gulin Oz said, and most COVID research has skewed disproportionately white. This phenomenon not only exemplifies the hurdles of recruiting a diverse group of participants. It also increases Oz’s worry that people who may not be as vocal about their symptoms aren’t getting help.
“We don’t want to learn about long COVID only in the white population. That’s not good science and that’s not good representation,” said Oz, a professor in the Center for Magnetic Resonance Research in the University of Minnesota’s Department of Radiology.
Even though significant research on long COVID is starting to emerge, experts still haven’t scratched the surface on how racial differences may impact patients’ experiences. Most population-led studies haven’t included representative samples of the groups most affected by COVID: Black, Hispanic and Native populations.
A Scottish study published in the journal Nature, in October of this year, became the most recent big-population study of long COVID, looking at a large cohort of almost 100,000 participants. But Scotland is 96 percent white, the authors of the study acknowledge, so the study’s findings can’t be extrapolated to populations with more diversity.
The COVID-BRAIN Project has set the bar high: Researchers aim to enroll 20–25 percent Latino participants and 15 percent Black participants to reflect the U.S. demographics of COVID-19 patients. While there aren’t specific targets for Native American and Asian populations, the investigators hope to recruit participants from both groups.
LaToya Lewis, a 35-year-old St. Paul woman who had long COVID and whose son was hospitalized with COVID, hopes that such research could lead to decreased suffering in the Black community.
“If our culture responds differently to different things, it’s important to have that knowledge and the best treatment for our specific cultures, because at the end of the day, every life matters,” she said.
Defining long COVID
What, precisely, is “’long COVID-19”? That’s a complicated question for patients and researchers alike. The Centers for Disease Control and Prevention defines it as a condition in which symptoms of COVID persist for more than four weeks.
Symptoms vary from person to person and range from general issues (fatigue, coughing, chest pain, belly pain) to neurological issues (headaches, brain fog). Long COVID can be easily confused with other conditions such as chronic fatigue syndrome.
There are no treatments specific to long COVID yet, although doctors can help patients manage symptoms. For Lewis, long COVID meant not being able to smell anything for close to a year. But many people remain unable to work or participate in daily life, months after falling ill.
Public health officials also worry about the effects of long COVID on a population level: If 13.3 percent of people who get COVID are still sick after a month, as the CDC estimates, that could take a huge toll on the work force and the health-care system. Researchers and clinicians hope that better understanding the condition could help in the development of new treatments.
Oz had previously used MRI technology to study neurological issues and diabetes. She realized early in the pandemic, however, that she should pivot her brain research to study COVID.
She and others in her field were alarmed when they heard of individuals experiencing brain fog and headaches weeks after a COVID-19 diagnosis. Just months into the pandemic, Oz co-wrote a grant requesting funding from the National Institutes of Health to study possible effects of COVID on the brain.
In May 2020, Oz and collaborators from the Mayo Clinic and Harvard University Medical School decided, “Let’s study it long term, focusing on the groups most severely affected,” she said.
According to the Centers for Disease Control and Prevention, Native people are 2.7 times likelier than white, non-Hispanic people to be hospitalized for COVID-19 and 2.1 times likelier to die from the disease; Black people, are 2.3 times likelier to be hospitalized and 1.7 times likelier to die from for COVID-19; and Hispanic people are twice as likely to be hospitalized for COVID-19 and 1.8 times likelier to die from the disease.
“We really don’t know if they’re also at higher risk of long COVID,” Oz said. “We don’t see why not, but there’s not enough data out there.”
The researchers submitted a proposal in November 2020; the NIH approved the project in March 2021; and the grant for the five-year project started in July 2021. The team is now recruiting and screening participants at five sites: the University of Minnesota, the Mayo Clinic in Rochester, Houston Methodist Research Institute, Massachusetts General Hospital, and Johns Hopkins University School of Medicine.
The goal is to recruit 250 participants, including 50 from Minnesota, to gain a deeper understanding of how long COVID affects the brain. Participants will spend half a day in the clinic recording a medical history and undergoing a physical exam, a blood draw, and an MRI scan. They will also participate in memory and reasoning tests via a Zoom call. Participants receive a $150 stipend for participating in the study.
Recruiting participants from underrepresented communities isn’t always easy, but it’s essential in understanding the impact of COVID and developing treatments, Oz and others said.
“In the COVID-19 pandemic, people of color were more burdened,” said Manka Nkimbeng, an assistant professor in the U of M’s School of Public Health who is not involved in the COVID-BRAIN project. “So it just makes sense if you’re looking at long COVID to have a look at the communities burdened the most.”
Conducting cognitive assessments in Spanish
The researchers knew standard practices such as recruiting via websites probably wouldn’t reach the communities that the COVID-BRAIN project wants to include, Oz said. And they knew making a racially balanced cohort would present multiple challenges.
Consider just the work of adding a language besides English to a research project. Every document needs to be translated. The people involved in evaluating participants at each step must be able to administer exams in two languages. And the paperwork they use needs to be both translated and validated in the second language. The validation process can take years, so the researchers selected cognitive assessments that had already been validated in both English and Spanish.
In order to attract individuals who speak Spanish, the team hired study coordinator Alfredo Lorente, who is originally from Puerto Rico and speaks English and Spanish. The Harvard site also has a bilingual coordinator.
“Even if the participant doesn’t really need the information in Spanish, it’s a signal that we’re really trying to connect with that population,” Lorente said.
Much of his written translation work will be saved and reused in future research to be conducted in Spanish, he said.
The researchers also chose sites in a wide geographic area and in cities with more diversity; within cities, they’re planning outreach in specific communities.
In the Twin Cities, Lorente plans to set up tables at grocery stores such as Aldi’s and Cub in areas with a high percentage of Black and Latino populations. He also hopes to visit Catholic churches with high numbers of Latino parishioners and barber shops that serve Black clients, he said.
He describes feeling especially motivated by the project and its potential. “We know so little about this disease,” he said. “Science for so long has been so white and so male. The situation that has excluded so many people. So the work we are doing is so valuable. This will help medicine; it will help all the people who haven’t been helped in the past.”
Researchers confront a history of scientific malpractice
Oz acknowledges that many people of color are hesitant to participate in studies because of the history of harmful research practices in the U.S.
“But we need their help, and we need studies to represent them too,” she said. “People should not be shy about asking questions. It’s OK to see if they’re comfortable with the research—they don’t have to commit. They can say, this is not for me. We need everyone’s help to really get to the bottom of this.”
Some challenges go much deeper: It’s not easy to build trusting relationships with communities that experienced trauma from medical research. “For the longest time we researchers, myself included, underestimated how long it would take,” said Nkimbeng. There are practical concerns, too. Recruiting will take longer for studies that involve a bigger time commitment from participants.
The model she uses, for her own research on dementia, can take years. It involves getting to know communities without mentioning research and eventually assessing whether the community is ready to collaborate.
“It’s not research as usual,” she said. “It’s not going to a community with a survey and a token. It’s being in community, being there and being visible and having them trust you. The way we used to do it did not work.”
A method to unravel the mysteries of long COVID
Some medical studies have already used conventional imaging and blood testing of long COVID patients who experience symptoms such as brain fog and headaches. The riddle, Oz said: They often show normal results.
“So there’s a stigma, and a lot of people get sent back home being told, oh, everything is normal, it’s all in your head,” she said. “But these are real problems that a lot of people are experiencing. So what we’re trying to do is use more advanced techniques to understand the underlying causes and the biology of these symptoms so treatments can be devised.”
The COVID-BRAIN researchers use MRI technology to non-invasively study the brain. They measure brain connections, chemistry and other markers of brain health, such as blood flow. The researchers expect to see differences in participants experiencing long COVID, Oz said.
Smaller studies have used MRI technology to study hospitalized COVID patients. A large population study in the United Kingdom used MRI to examine effects of COVID in the brain, but those studies didn’t specifically study people with long COVID symptoms.
In the U of M study, researchers will scan participants who have had confirmed cases of COVID and who still have ongoing neurological symptoms such as headaches, brain fog, memory problems, and dizziness two or more months after infection. The research team will also re-scan these participants in two years. The same person, Dr. Kejal Kantarci at the Mayo Clinic, in Rochester, will read all participants’ MRI scans to ensure consistency.
It’s possible that biological reasons could explain potential differences between races, Dr. Kantarci said, or that health disparities could play a role. For instance, people of color typically have a higher percentage of pre-existing conditions. Past research has suggested that people of color, especially Black people, more often experience mixed pathologies, she said. For example, Black people with Alzheimer’s disease are more likely than white people to have related dementias. Imaging can help provide a better picture of those pathologies, she said.
It’s much too early to guess more precisely what they will find, Dr. Kantarci said, but any differences “have to be addressed and I think our study is ideal to do that.”
Researchers hope to start analyzing data in 2023, and may have results from the first round of participant visits in 2024.
If you want to participate in the long COVID brain study:
If you are at least 18 years old, you may be eligible to participate in the COVID-BRAIN Project. Criteria include:
- A confirmed case of COVID-19, or no exposures to COVID-19
- If you had COVID-19, long-lasting symptoms such as headaches, brain fog, and memory issues
- Ability to undergo MRI scanning
- Speak English or Spanish
If you are selected for the study and you agree to participate, you would visit the clinical site and join a video call that would include the following:
- Medical history collection
- Physical examination
- MRI scan
- Blood draw
- Memory and reasoning testing
- Phone calls to check on symptoms
- Possible second clinic visit after two years
Visit this website for more information.