CLEVELAND, Ohio — About a third of adults who get COVID-19 report having what is known as long COVID. And months after initial infection, a staggering number of those who haven’t recovered – up to 80% – have some trouble going about their daily activities.
According to a Brookings report in August, a conservative estimate of 16 million people had COVID-19 at the time. The CDC says it could be up to 19 million adults.
But whether 16 million or 19 million, one thing is clear: that’s a lot. Here in Cleveland and across the country, scientists and doctors are trying to figure out what’s wrong and how to help them.
The symptoms falling under the long COVID umbrella include everything from a persistent loss of taste and smell to fatigue so debilitating that the affected person is unable to return to work or daily life. In between, there are reports of brain fog, headaches, chronic gastrointestinal issues, increased incidences of diabetes, blood clots, cardiac arrhythmia and exercise intolerance.
To the untrained eye, the list of symptoms is dizzying and seems specific to each individual patient.
However, behind the scenes and so far largely outside of the media hype, researchers and clinicians have been making stubborn strides to not only classify and define what long COVID is, but also to identify the underlying mechanism of the disorder and how they might treat it.
One of the largest centers of research is right here in our own backyard at the University Hospitals Case Medical Center and the MetroHealth System.
The economic impact of the sheer volume of American workers who could be permanently disabled is worrying. In fact, it was of such concern that in December 2020, Congress allocated more than $1 billion to the National Institutes of Health to fund research into the prevention and treatment of long-lived COVID.
University Hospitals and MetroHeath System were joint recipients of one of the 15 grants that the NIH subsequently awarded to research institutions across the country in early 2021, and currently rank themselves as the largest in terms of the number of research topics.
To date, they have enrolled over 800 patients and hope to add 300 to 400 more, said Dr. Grace McComsey, an infectious disease specialist who is leading the project at UH.
The goal, McComsey said, is to uncover so-called biomarkers of COVID disease — any type of measurable biological change — that could identify and ultimately weed out patients who have had acute COVID infection and months after they have stopped having COVID symptoms had continued to have COVID symptoms had tested positive.
McComsey said that over the past year, she and the other researchers across the country have been collecting blood, saliva, urine or stool samples and cataloging the progression of symptoms in patients with and without COVID.
Eerily similar to HIV
McComsey, who has spent the past two decades studying HIV, said the data they’ve found so far paints a picture that’s eerily familiar.
“Now I look at it and I’m like, my goodness, it’s like deja vu,” McComsey said.
If you’re new to the idea that the behavior of the SARS-CoV-2 virus might bear similarities to HIV, you’re not alone. But McComsey said that for the HIV researchers who made the transition to studying this new coronavirus, the similarities that emerged were unmistakable.
To be clear, McComsey is not suggesting that the viruses themselves are similar. Corona viruses are not retroviruses like HIV, nor are they sexually transmitted like HIV. But it’s the way they make the people they infect sick that has caught their attention. It hides in the body and continues to wreak havoc on the various organ systems by fueling inflammation and interfering with the immune response.
“HIV patients don’t die from the virus itself. They die from immune activation — from the high rates of inflammation that cause cancer, heart disease, liver disease, and kidney disease,” she said.
“The only reason we can’t cure HIV is because the virus hides where the HIV drugs can’t get in. So it keeps fueling this severe inflammation. That is why someone like me who has studied HIV for the past 20 years has found that COVID is very similar to HIV. It’s a virus that causes a lot of inflammation. We see many conditions that are known to be due to inflammation, and now we have some evidence that they persist in different organs.”
McComsey refers to various published research papers that suggest SARS-Cov-2 can linger in various organ tissues long after nasal swabs and blood tests are negative.
An early pre-press autopsy study by the NIH found the virus throughout the body — in a variety of tissues, including muscle, fat, gut and brain tissue, in patients who have died from COVID, and in some cases in patients who were asymptomatic, or had mild infections and died many months later. According to the authors, this proves that SARS-Cov-2 can persist in the body for many months after infection.
Another study further suggests that the SARS-Cov2 virus may have stolen another page from the HIV playbook, hijacking ancient and normally dormant human DNA sequences in order to reverse-engineer its viral RNA and insert itself into our cells’ genomes to insert
Although the paper initially met with a firestorm of criticism and fear-mongering over the possibility that their findings raise the possibility that RNA-based COVID sequences in vaccines could somehow integrate into our DNA (the authors immediately dismissed that idea), some Scientists don’t find their theory so implausible, McComsey among them.
“This is a great opportunity. I would say it’s very likely, even likely,” she said.
Untangling long COVID-19 – first insights
The NIH-funded study McComsey is leading is called RECOVER — an acronym that stands for Researching COVID to Enhance Recovery — and has uncovered some important information.
* First, it was found that people with long-term COVID-19 are mostly women, around 75% of McComsey’s nearly 900 subjects are women, and not by choice. “We’re not looking for them,” she said. “These are the people who call us.”
* Second, researchers have found that although one’s risk of developing long COVID increases with the severity of initial infection, people can and do develop long COVID even after asymptomatic or infections classified as mild.
* Third, vaccination dramatically decreases a person’s chance of developing a long COVID. A fully vaccinated person is five times less likely to continue to have symptoms or adverse effects three months after their initial infection than a person who has not been vaccinated. And that, McComsey said, argues strongly for continued vaccination. “I’m not afraid of getting acute COVID,” she said. “I’m worried about Long COVID.”
* And finally, researchers have found that patients with long COVID generally have symptoms that fall into three categories, or phenotypes: fatigue, neurocognitive symptoms such as brain fog or headaches, and cardiovascular symptoms such as shortness of breath, abnormal heart rhythms, exercise intolerance, and blood clots. Patients may have more than one type, and some also have symptoms such as constipation, diarrhea, or loss of taste and smell that don’t seem to fit neatly into any of the three groups.
One explanation for the different clusters of symptoms is the persistent presence of the virus in certain tissues, where it is believed to continue to trigger an inflammatory response.
For example, someone who has a headache or brain fog may have a virus residing in their brain tissue, while someone with cardiovascular symptoms may have viruses in the heart, lungs, or vascular system. And a chronically elevated immune response and widespread inflammation throughout the body may partially explain why so many – more than 50% of Long-COVID sufferers – experience the devastating fatigue.
According to McComsey, the ongoing research on biomarkers could still help tease these subtypes a part.
She said anyone who currently has COVID-19 or has been infected in the past 30 days will be invited to participate in the study. They want to track changes in these biomarkers along with symptoms from the time of infection to symptom resolution and beyond, and they still need several hundred subjects. She also said it doesn’t matter if you’ve had COVID before because one of the things they hope to learn is whether the likelihood of developing Long COVID increases with each subsequent exposure.
Come with a treat
Meanwhile, she said they plan to begin phase two of their research — testing treatments — in the next few months.
These treatments can take many forms, including anti-inflammatory drugs, but the first clinical trials will likely be antiviral drugs specifically targeting SARS-Cov-2. The idea is that if the symptoms of long-standing COVID-19 are the result of the virus hiding in various body tissues, the obvious course of action is to eradicate and destroy it.
Easier said than done, of course, especially when that brain rooting is required.
Although several types of viruses can easily infect the brain, antiviral drugs have a much harder time getting into the brain from the bloodstream thanks to what’s known as the blood-brain barrier. This problem has been the bane of clinical HIV research for decades.
Research advances, but no guarantees
McComsey stressed that while they have made it clear Progress, there is still quite a long way to go and there are no guarantees.
For example, it is possible for the SARS-CoV-2 virus to cause organ damage, activate other dormant viruses in the body, or permanently and irreversibly change the balance of the immune system, leading to chronic flare-ups of inflammation in the body even in the absence of viruses.
“Unfortunately, antivirals might just weaken it — or do nothing at all,” she said. For this reason, the study also looks at anti-inflammatory drugs.
She said she knows the wait can be very difficult for those suffering without answers or treatments.
Many patients feel abandoned when their doctors can’t do anything for them and wonder why it’s taking so long. Doctors want to get it right, McComsey said, and unfortunately that takes time.
In the meantime, she hopes that knowing that an effort is being made to seek treatment will at least make them feel heard.
“People who sign up for the study always say that one of the stressors is that their doctor thought they were exaggerating the symptoms,” McComsey said. “I think now most people know this is real,” she said. “It’s very real.”
To volunteer or learn more about it RECOVER studycall 440-762-6843 (440-76COVID) or email [email protected].
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