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“There is no excuse for this”

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Long COVID is no longer a theory. An estimated 65 million people worldwide, including millions in the U.S., had the disease or have it now, according to a new review article published in Nature Reviews Microbiology. Meanwhile, researchers have identified more than 200 different symptoms, spanning multiple organ systems. Fatigue, brain fog, post-exertion sickness, recent onset conditions such as heart problems, diabetes, blood clots, stroke – all have been reported, and more.

By the CDC’s definition, long-term COVID occurs when people experience new, recurrent, or ongoing health problems beyond four weeks after an acute COVID infection. More broadly, the long-running COVID is a still-emerging condition whose numbers continue to grow, and while much has been learned about it, much remains unknown – including the best ways to treat and prevent it.

“I wish we had those answers,” said Dr. Eric Topol, a prominent COVID expert and senior author of the exhaustive paper, which incorporated more than 200 peer-reviewed studies. “Right now, we have too many mechanisms and too little treatment. That’s the sum of it all.”

Here, Topol, who is also an executive vice president at Scripps Research in San Diego, sets the limits of what we know about the long COVID and the urgency with which 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 it is affecting and how?

Long COVID is the persistence of significant symptoms well after the virus has had its acute illness. The problem is that it’s a mosaic of different organ systems and symptoms that can be involved. It can lean in one direction, like the autonomic nervous system, or it can lean in the cardiovascular or respiratory systems. It can take people who are fully functional, athletic, healthy, and make it difficult for them to get out of bed or walk just a block.

Are children affected in the same way?

Fortunately, they are not so apt to get it. It can follow the same pattern, but it’s not as common.

Are you more likely to have prolonged COVID if you have severe illness rather than mild illness?

That’s a very good question. It seems that if you’ve had COVID worse acutely, you’ll have more organ systems involved – but that doesn’t mean that if your initial infection was mild, you’re out of the woods. You can still have things like a stroke, a deep vein thrombosis (blood clot) or an arrhythmia – that sort of thing. It’s not as common to have these accesses to various organ systems as it is for people who have had severe COVID and had to be hospitalized.

Does vaccination reduce the risk of long COVID?

Vaccination clearly reduces the severity and frequency of prolonged COVID. The only debate is to what extent. (Estimates have ranged from 15% to 50%.) It doesn’t stop it entirely. There is only one way to prevent long COVID, and that is to never get COVID.

Are those infected with new variants like XBB.1.5 more or less likely to develop long-term COVID?

There seems to be a lower chance of getting long-term COVID, but we don’t know if that’s because of the variants or because people have received more vaccines and more natural immunity to the infection and combinations of them.

What do the numbers look like globally and in the US? How many are affected by the long COVID right now?

It’s hard to know exactly. Some people have had COVID for a long time and are recovering or even fully recovered, while others are three years into it. But most estimates are that 3% of the population — which would bring us to 10 million — is the minimum number of people in the US with long-term COVID. The question is, how much more than that? Is it 15 or 20 million? And then there’s obviously a gravity spectrum.

a woman tweeted that she has run more than 130 marathons, cycled Category 1 climbs and climbed Mount Kilimanjaro, but 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 long is COVID debilitating?

There are many people like the woman you just described, and there are more likely to be women in this severe group. We know that women are more susceptible to autoimmune diseases such as lupus, Sjögren’s syndrome, systemic sclerosis, etc. Men can get severe cases, but it is more likely to be in women.

What are some of the other proposed mechanisms for the long COVID?

Inflammation is a common trait in everyone. It can affect the autonomic nervous system, which is how you can get postural orthostatic tachycardia syndrome neuropathy [an abnormal heart rate increase that occurs with standing]. It can also affect the lining of your blood vessels, so you could have clotting issues, and it could also be generated by the gut microbiome being significantly affected and perpetuating inflammation.

What do we know about reinfection? If someone has not had long COVID initially, are they at risk?

This is a very important area. You can still get long COVID from a second or third infection, unfortunately. Just because you had some immune response from an infection doesn’t stop it. It’s probably less common, if only because part of the long history of COVID is (patients) not having an optimal immune response, whether it’s insufficient or a hyper-response. But it’s not like the second infection is any higher risk (for long-term COVID) than the first. This is often misunderstood.

Can you talk about what was initially called brain fog, but what we are now recognizing could be true cognitive dysfunction?

Well, there are many parallels with the “chemo brain”. It’s not that the virus infects brain cells directly, but it leads to inflammation in key areas of the brain that would be affected, such as memory and executive function. This is very concerning because it’s a common symptom – it tops the list of what people report. We don’t have a treatment to take care of it, and many people can have it.

Some people talk about cognitive dysfunction being like Alzheimer’s disease – or is it another form of dementia? Or is it that we just don’t know?

I would say that we just don’t know. But that’s the concern. What if it’s progressive? What if it simulates what we see with neurodegenerative conditions? I’m an eternal optimist, so I hope the body is remarkable and fights it and bounces back.

There have been some reports that COVID is associated with erectile dysfunction, lower sperm count and low testosterone. Is male fertility a concern – or female fertility, for that matter?

We know there are definite effects there. This too has not been studied properly, but it certainly deserves study. It may be linked to less fertility in men, but we don’t know. Because so many young people have been hit with COVID and long COVID, this is a concern, but not enough attention has been paid to these aftereffects as there has been to the heart, lungs, and brain.

Could the antiviral drug Paxlovid help patients?

There is some data that some people who have had COVID for a long time and have taken Paxlovid have markedly improved their symptoms. These are more anecdotal now, but it does give some credence that, in some people, the persistence of the virus – the virus reservoir and its remnants – could be helped with a drug that inactivates the virus. The question is, will this help a small percentage of people, like 1% or 2%, or will it help more?

Have there been large-scale trials to test its effectiveness?

No, there wasn’t. And there should be. There’s no excuse for that… We need to double, quadruple to do the right tests, test all the candidate things we listed in the article. Paxlovid is obvious and naltrexone – it’s obvious that we should be doing these studies, so there’s no excuse. With the amount of money the NIH has devoted to this, we should have had these tests done by now, definitive tests. People are desperate, they need treatment. Predators are hunting them to come and do this or that treatment, but nothing has yet been proven to help.

Why isn’t the US government coordinating a stronger response, or why aren’t pharmaceutical companies stepping into this market and conducting large-scale trials?

It is an extremely important and fertile area defining effective treatments, but entries in it are very scarce. Some of the potential treatments are very impractical, such as hyperbaric oxygen chambers or apheresis. These are very expensive, hard to come by treatments. We need something that is practical, highly effective and widely accessible.

Would you consider the long COVID a national health emergency in its own right?

There are a large number of people who are disabled or compromised in their status because of this, (but) it has been a slow train rather than an emergency. It hasn’t been properly respected… At this point, the answer should be, let’s do everything we can to prevent infection. More importantly, what about those millions of people who are hurt, who are still suffering – how can we help them get their lives back?

Do you think there is an end date for the long COVID?

We won’t know for another 10 years, right? In 1918, with the influenza pandemic, Parkinson’s appeared about 15 years later. It was not seen in the early years. We don’t know if we’ll see things that haven’t manifested yet, because the longest duration is less than three years now.

Knowing that we all want to continue living our lives, remain fertile and not suddenly die, how careful do we need to be?

We cannot capitulate to the virus and let our guard down. Getting boosters, taking precautions when in public gatherings indoors, improving our ventilation – we have things that can help prevent infections. Right now, people have moved on, but for someone who hasn’t had COVID or who has had a re-infection, it’s not necessarily benign. You’d hope so, but perhaps the biggest thing we haven’t discussed is the betting part. We just don’t know who is really at risk. People want to dismiss that. But this is an inconvenient truth, long COVID.

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