For millions of people, COVID-19 does not end with a negative test. Weeks or months after traces of the virus disappear from the nose and throat, symptoms may persist or recur. New ones may appear and stick around for months. People who suffer from prolonged COVID do so reluctantly for the long term, and it remains unclear who is most at risk of contracting the condition.
The researchers do not yet have a official definition of long COVIDand its symptoms are very varied (Serial number: 7/29/22). Some people struggle with extreme fatigue that interferes with their daily lives. Others can’t concentrate or struggle with memory in a thick mental fog. Others have organ damage or a persistent cough and shortness of breath.
“There are a variety of different types of ways that people can have COVID for a long time. It’s not just one thing,” says Leora Horwitz, an internal medicine physician at New York University’s Langone Health. “That’s what makes it so hard to study.”
This spectrum of symptoms makes it especially difficult to determine who is at high risk for long-term health problems from the disease. Some post-COVID conditions can stem from virus-induced damage or the stress of being hospitalized with severe illness. In other cases, the body’s own immune response to the virus could cause the damage. Or the virus may be hiding somewhere in the body, possibly the intestinehelping symptoms persist (Serial Number: 11/24/20). Different causes can have different risk pools, says Hannah Davis, co-founder of the Patient-Led Research Collaborative, a research and advocacy group studying long-term COVID.
There are some general clues as to who is at risk. Studies suggest that women are more likely than men to have persistent symptoms. COVID-19 patients with more than five symptoms in the first week of infection either pre-existing health conditions such as asthma you may be more likely to develop prolonged COVID. Age also appears to be a risk factor, although results are mixed regarding whether the burden falls on the elderly or middle-aged. Populations disproportionately affected by COVID-19 in general, including Black and Hispanic people, may similarly face disparities during extended periods of COVID. And while vaccination appears to protect people from long-term development of COVID, says Horwitz, how much is not yet clear.
Age is a risk factor for severe COVID-19, and the US Centers for Disease Control and Prevention lists more than 30 health problems, including cancer and lung diseases, which also increase risk. “Many researchers assume that these [risk factors] it will be the same for a long time and there is no scientific basis for that,” says Davis. There are many more that researchers could miss when it comes to prolonged COVID.
Using health records and screenings, and knowledge of ailments with symptoms similar to prolonged COVID, experts are hunting for those risk factors.
When it comes to better monitoring who is at risk for prolonged COVID, which is also known by the alias Post-Acute Sequelae of SARS-CoV-2 infection, electronic health records may hold important clues.
Horwitz is part of the US National Institutes of Health RECOVER initiative, which aims to understand the long-term impacts of COVID-19. One arm of the study involves mining millions of electronic health records to find potential patterns.
Studying millions of these records should identify potential risk factors that are rare in the general population but perhaps more common for people with prolonged COVID, says Horwitz. “That’s hard even in a cohort study of thousands.”
But health records aren’t perfect: They rely on doctors to record that patients have trouble sleeping or concentrating, or that they’re exhausted. “The things that people complain about, we’re really bad at writing those diagnoses down in the log,” says Horwitz. “So we miss that.”
To account for the shortcomings of health records, Horowitz and his colleagues are also directly studying thousands of people. Participants answer a questionnaire every three months so the team can identify what kind of symptoms people have and whether they are getting better or worse.
Then samples of blood, urine, stool, and saliva can reveal what is going on in the body. Tests on those samples can find out if the coronavirus is still around and causing problems, or if the immune system has learned to attack the body itself. Participants with abnormal test results will undergo additional specific testing.
“Unlike electronic health records where it’s unpredictable, like whether someone might have had a CT scan or not, here we say, ‘Okay, you’re having trouble breathing. We’ll take a look at your lungs,’” says Horwitz.
The study includes a variety of participants: adults and children, pregnant people, people who currently have COVID-19, and people who have died after having the disease.
Some of the potential risk factors the team is looking for include autoimmune diseases and other viral infections. The list may grow as more people join the study. “We’re trying to balance fishing versus making sure we’re at least catching things that might be in the water,” says Horwitz.
Among the shortages, however, are people who have never contracted the virus, important “checks” to highlight what is different about people who have contracted COVID-19.
So far, more than 7,000 people have signed up, and the group plans to recruit around 10,000 more. It’s a lot of data, but the first results may start coming in soon.
“We’ll probably try to take a tentative look at that data this fall,” says Horwitz. “It’s complicated because we deliberately wanted to sign up 18,000 people to have enough power to really see the things that matter to us. I don’t want to cheat and watch too soon, but we also know there’s a lot of interest.”
Some prolonged symptoms of COVID (brain fog, fatigue, and difficulty sleeping) reflect another illness: myalgic encephalomyelitis/chronic fatigue syndrome, or ME/CFS. Other prolonged symptoms of COVID, such as rapid heartbeat and dizziness, fall into the category of nervous system disorders called dysautonomia. Similar symptoms could belie similar risk factors.
However, potential risk factors for those conditions are largely missing from long-term COVID research, says Davis, who has had long-term COVID since March 2020. Among the possibilities scientists are considering are things like the Epstein virus. -Barr, migraines and some autoimmune diseases.
The Epstein-Barr virus could be big, says Davis. Infections are lifelong because the virus can hide in the body and possibly resurface. That virus has been linked to ME/CFS for decades, though the connection is tenuous, says Davis.
There are already some early indications of a link between the Epstein-Barr virus and prolonged COVID. Multiple studies have found evidence in blood samples from some long-term COVID patients that the immune system recently struggled with the Epstein-Barr virus, which can cause infectious mononucleosis, a disease characterized by extreme fatigue. Other studies have found signs of the virus itself. And in 2021, Davis and his colleagues found that 40 of 580 people with prolonged COVID symptoms who responded to an online survey reported having a current or recent Epstein-Barr virus infection.
With ME/CFS, it is possible that another illness caused by a different virus triggers the Epstein-Barr virus, which then causes fatigue syndrome. Given the parallels between that condition and prolonged COVID, some scientists question whether the two are actually the same illness, with the coronavirus now known as a trigger.
Examining health conditions that increase the chances of prolonged COVID could provide answers for both diseases, says Nancy Klimas, an immunologist at Nova Southeastern University in Fort Lauderdale, Florida. That’s in part because researchers can more easily identify people who developed persistent symptoms after an attack. of COVID-19 compared to unknown infections that may precede ME/CFS.
Also, “there is a big difference in these two fields and it is money,” says Klimas. He now has funding from the CDC to match long-term COVID patients to people who have ME/CFS. The team hopes that physical examinations and specialized tests will reveal whether the two diseases are really the same and will be a step towards understanding the mechanisms behind persistent symptoms.
Still, with COVID as a whole encompassing such a wide range of symptoms, it will take time to figure out who is at risk for what.
If COVID-19 were just a disease that affects the lungs, heart, or brain, the research might be easier, says Horwitz. “But we have to try everything.”