Long COVID is no longer a theory. An estimated 65 million people worldwide, including millions in the U.S., have had the condition or have it now, according to a new review article published in Nature Reviews Microbiology. Researchers, meanwhile have identified more than 200 different symptoms, spanning multiple organ systems. Fatigue, brain fog, post-exertional malaise, new-onset conditions like heart issues, diabetes, blood clots, stroke all have been reported, and many more.
By the CDCs definition, long COVID occurs when people experience new, returning or ongoing health problems beyond four weeks after their acute COVID infection. More broadly, long COVID is a still-emerging condition whose toll continues to grow, and although much has been learned about it, far remains unknownincluding the best ways to treat and prevent it.
I wish we had these answers, said Dr. Eric Topol, a preeminent COVID expert and the senior author on the exhaustive paper, which incorporated more than 200 peer-reviewed studies. Right now, we are long on mechanisms and short on treatment. Thats the summary of everything.
Here, Topol, who is also executive vice president of Scripps Research in San Diego, lays out the limits of what we know about long COVID and the urgency with which the government and researchers must act.
This conversation has been edited and condensed for clarity.
Can you give a general working definition of long COVID and describe who this is affecting and how?
Long COVID is the persistence of significant symptoms well after the virus wouldve had its acute illness. The problem with it is that its quite a mosaic of different organ systems and symptoms that can be involved. It could lean in one direction, like the autonomic nervous system, or it could lean toward the cardiovascular or respiratory systems. It can take people who are entirely functional, athletic, healthy, and make it difficult for them to get out of bed or difficult to walk just a block.
Are kids affected similarly?
Fortunately, they arent as apt to get it. It can follow the same pattern, but it is not as common.
Are you more likely to get long COVID if you had a severe illness rather than a mild illness?
Thats a really good question. It does appear that if youve had worse COVID acutely, youre going to have more organ systems involvedbut it doesnt mean that if your initial infection was mild, youre off the hook. You could still have things like a stroke, a deep vein thrombosis (blood clot) or an arrhythmiathose sorts of things. Its just not as common to have those hits to several organ systems as it is for the people who had severe COVID and had to be hospitalized.
Does vaccination reduce the risk of long COVID?
Vaccination clearly reduces the severity and the frequency of long COVID. The only debate is to what extent. (Estimates have ranged from 15% to 50%.) It doesnt fully prevent it. Theres only one way to prevent long COVID, and that is not to ever get COVID.
Are those infected with the new variants like XBB.1.5 more or less likely to develop long COVID?
It does appear that theres a lower chance of getting long COVID, but we dont know if its because of the variants or because people have had more vaccines and more natural infection immunity and combinations of those.
What do the numbers look like globally and in the U.S.? How many are affected by long COVID at this point?
Its hard to know exactly. Some people have had long COVID and are recovering or even fully recovered, while others are already three years into this. But most estimates are that 3% of the populationwhich would get us to 10 million is the minimum number of people in the U.S. with long COVID. The question is, how much more than that? Is it 15 or 20 million? And then theres obviously a spectrum of severity.
A woman tweeted that shed run more than 130 marathons, cycled Category 1 climbs, and hiked Mount Kilimanjaro, but that since COVID, her husband has to carry me to the bathroom due to neurological issues. Do we have any idea of the long-term spectrum, and how much of long COVID is debilitating?
There are lots of people like the woman you just described, and its more apt to be women in that severe group. We know that women are more susceptible to autoimmune diseases, like lupus, Sjogrens syndrome, systemic sclerosis, etc., so that goes along with it. Men can have severe cases, but its more apt to be in women.
What are some of the other proposed mechanisms of long COVID?
Inflammation is a common thread across all. It can affect the autonomic nervous system, and thats how you can get the neuropathy of postural orthostatic tachycardia syndrome [an abnormal heart rate increase that occurs with standing]. It can also affect the lining of blood vessels, so you can get clotting issues, and it can also be engendered by the gut microbiome being significantly affected and perpetuate the inflammation.
What do we know about reinfection? If someone didnt have long COVID initially, are they at risk?
Thats a really important area. You can still get long COVID on a second or third infection, unfortunately. Just because youve had some immune response from an infection doesnt prevent it. Its probably less common, just because part of the long COVID story is (patients) not having an ideal immune response, whether its insufficient or a hyper-response. But it isnt like the second infection is higher risk (for long COVID) than the first. This is very often misconstrued.
Can you talk about what was initially referred to as brain fog, but what were now recognizing can be true cognitive dysfunction?
Well, there are a lot of parallels to chemo brain. Its not that the virus infects brain cells directly, but it leads to inflammation in key areas of the brain that would be affected, like memory and executive function. This is very troubling because this is a common symptomit is way up on the list of what people report. We dont have a treatment to take care of this, and many people may have this.
Some people talk about the cognitive dysfunction being like Alzheimersor is it another form of dementia? Or is it that we just dont know?
Id say we just dont know. But thats the worry. What if this is progressive? What if it simulates what we see with neurodegenerative conditions? Im an eternal optimist, so Im hoping that the body is remarkable and will fight it and turn it around.
There have been some reports of COVID being associated with erectile dysfunction, lower sperm counts, low testosterone. Is male fertility a concernor female fertility, for that matter?
We know there are definite effects there. That hasnt been studied adequately either, but it certainly deserves study. It could be tied to less fertility in men, but we dont know. Because so many young men have been hit with COVID and long COVID, this is a concern, but there hasnt been nearly enough attention to that sequelae as there have been to the heart, the lungs and the brain.
Could the antiviral medication Paxlovid help those afflicted?
There has been some data whereby some people who had long COVID who took Paxlovid markedly improved their symptoms. These are more anecdotal right now, but it gives some credibility that in some people, the persistence of the virusthe reservoir of the virus and its remnantscould be helped with a drug that inactivates the virus. The question is is it going to help a small percent of people, like 1% or 2% , or will it help more?
Have there been large scale trials to test its effectiveness?
No, there havent been. And there should be. Theres no excuse for this We need to double down, quadruple down on doing the right trials, test all the candidate things that weve listed in the article. Paxlovid is obvious, and naltrexoneits obvious that we should be doing these studies, so theres just no excuse. With the amount of money that the NIH has devoted towards this, we should have these trials done by now, definitive trials. People are desperate, they need treatments. The predators are preying on them to come and have this treatment or that one, but theres nothing yet that has been proven to help.
Why isnt the U.S. government coordinating a stronger response, or why arent pharmaceutical companies jumping into this market and running large scale trials?
Its an incredibly important and fertile area, defining effective treatments, but the entries into it are very scant. Some of the potential treatments are very impractical, like hyperbaric oxygen chambers or apheresis. These are very expensive, hard to get to treatments. We need something that is practical, highly effective and widely accessible.
Would you consider long COVID a national health emergency in and of itself?
Theres a huge number of people who are disabled or compromised in their status because of it, (but) its been a slow moving train rather than an emergency. It has not been adequately respectedRight now, the response should be, lets do everything we can to prevent infections. Most importantly, what about these millions of people who are hurt, who are still sufferinghow can we help them get their lives back?
Do you think that there is an end date for long COVID?
Well only know 10 years from now, right? In 1918 with the influenza pandemic, Parkinsons showed up about 15 years later. It wasnt seen in the early years. We dont know if were going to see things that have not been manifested yet, because the longest duration is less than three years right now.
Knowing that we all want to get on with living our lives, remain fertile and not drop dead suddenly, how careful do we need to be?
We cant capitulate to the virus and be letting all our guards down. Getting boosters, taking precautions when youre in public indoor gatherings, improving our ventilationwe have things that can help prevent infections. Right now, people have moved on, but for those who havent had COVID or for those who get a reinfection, it isnt benign necessarily. You hope it is, but perhaps the biggest thing we havent discussed is the bit of the gamble. We just dont know whos really at risk. People want to dismiss this. But this is an inconvenient truth, long COVID.
