Mor more than three years into the Covid pandemic, there are a host of important unanswered questions about long-term Covid that are severely limiting the ability of healthcare providers to treat patients with the disease, according to US doctors and scientists.
That information vacuum remains as much of the U.S. has moved away from the pandemic, while long-haul Covid carriers continue to face stigma and questions about whether their symptoms are real, providers say.
But while there is little new information about long Covid, doctors say they remain confident that researchers will find answers to fundamental questions about the disease, such as: apart from being infected with the virus itself, what actually causes long Covid?
“We don’t have our finger on the pulse of what’s wrong, what’s biologically causing it, and that’s a big problem,” said Dr. Mark Sala, co-director of the Northwestern Medicine Comprehensive Covid-19 Center. “It’s hard to target drugs or treatments without having a biological basis for why someone feels so fatigued from exercise.”
In addition to the uncertainty surrounding the underlying causes of long Covid, there are also challenges in research due to how Covid can cause so many different symptoms. The Centers for Disease Control and Prevention list includes fatigue, respiratory problems and difficulty thinking or concentrating, but also notes that “post-Covid conditions may not affect everyone in the same way.”
“Everyone has a different constellation of symptoms,” said Dr. Steven Deeks, an infectious disease specialist at the University of California, San Francisco. “Some people get better over time, some people grow taller and weaker, some people get worse,” and so it’s difficult for researchers to determine when a study should end and compare a drug with a placebo.
This ambiguity creates something of a Catch-22 for research advancement efforts. Pharmaceutical companies want to have biomarkers – meaning a defined characteristic used to measure a condition – before investing in research to find a drug to treat long-term Covid, and because there aren’t any, they won’t conduct the expensive trials that could to help identify biomarkers.
“In academia, we struggle to come up with a definition [of the condition] it’s going to work, and we hope to engage people who regulate clinical trials, and we hope to engage industry once we make some progress,” said Deeks, who is also considered an expert on HIV.
The medical field also lacks a clear understanding of long-term Covid, in part because the National Institutes of Health (NIH) initially focused on its symptoms rather than addressing the underlying problem, said Dr. Ezekiel Emanuel, a bioethicist at the University of Pennsylvania.
That “was exactly the wrong approach,” Emanuel said. “It’s a big, major problem, and what we were initially going to try was Band-Aids.”
Answering questions about the underlying problems with long Covid could take years, researchers said.
The virus has been around for three years, which compared to other diseases is a very short time to understand the condition and develop treatments, Sala said.
But for those with the disease, it doesn’t matter that three years isn’t that long in terms of research. Hannah Davis, co-founder of the Patient-Led Research Collaborative, a group of researchers who also have long-standing Covid, contracted the virus in March 2020 and remains disabled because she has neurocognitive problems and chronic fatigue, among other symptoms. She previously worked in the field of machine learning and artificial intelligence.
She argued that there was no significant urgency to conduct trials for drugs that could treat the condition. The co-chair of the NIH’s $1.2 billion long-case study Covid initiative acknowledged his frustration with the pace of research and said it “took too long” to start enrolling patients, according to Stat.
“These clinical trials really need to start immediately because we’re not going to see results from them for years, and people are hitting the three-year mark and they’re suffering,” Davis said.
Meanwhile, Sala continues to see about the same number of patients at the Northwestern Center as earlier in the pandemic, although these are now more often people who continue to suffer from symptoms such as brain fog or unusual fatigue after exercise than people who were on a ventilator for months in an intensive care unit.
Long-term Covid patients are often the most distressed by the condition’s cognitive effects, Sala said.
“In their social circles, they noticed that they had a hard time just finding words and remembering things. It’s very frustrating for them when other people see,” Sala said.
The physical symptoms of prolonged Covid also continue to disrupt people’s lives.
In Sala’s hometown of Chicago, Jonathan Toews, star and captain of the Blackhawks, recently announced his retirement from the NHL team because he continues to suffer from lingering Covid and Chronic Immune Response Syndrome.
“That’s the guy that I think surprises people the most,” Sala said. “Someone who was athletic, ran marathons, and then all of a sudden they can’t get back on their feet or do what they wanted to do, athletically, before. It’s the individual that really has that stigma attached to it.
This lack of biomarkers also not only hampers research, but can also have a detrimental effect on patients’ mental health, Sala said. The only way to tell if a person has long covid is to ask people how they are feeling.
With something like iron deficiency anemia, “it’s very visible in your labs and you can have a good explanation for your friends. Here, all your tests are normal and you start thinking, ‘Is it all in my head?'” Sala said.
While patients and providers are frustrated by the pace of research, people studying the virus say they are making progress. For example, in June researchers reported finding a fragment of the virus in the blood of people with persistent Covid up to a year after the initial infection. This finding could serve as a biomarker for the condition, Deeks said.
Once researchers discover how the virus can affect a person’s immune system, it could also provide answers to questions about other chronic and acute diseases, Emanuel said.
“I really think the breakthrough here is going to be profound for our understanding of human immunology,” Emanuel said. “I think we will understand very clearly what can go wrong in the immune system.”