Dr. Ziyad Al-Aly, clinical epidemiologist at the Washington University School of Medicine, talks about the effects of long-COVID.
Interview conducted by Ivanhoe Broadcast News in 2023.
How has COVID evolved over the past two years?
AL-ALY: Sure, the earthly early days of the pandemic, we started receiving calls and emails from patients that they’re not really recovering after COVID-19. And studies have done, showed us that they had long COVID. And over the past several years due to a variety of factors including vaccination itself, the fact that a lot of people are treated, and also that the virus mutated and changed over time. The symptomatology either prevalence of long COVID may have declined over time. And a symptomatology may have become a little bit milder than the original SARS COVID in March of 2020?
When you get long COVID, can you get COVID again?
AL-ALY: Yes, absolutely. If you have long COVID, you’re definitely susceptible to getting re-infected with COVID-19, again so forth. And there are potentially people with long COVID are actually at a higher risk of experiencing more adverse outcomes after the second part of infection.
And the thing about long COVID is not only are you dealing with COVID symptoms for months, but these things can affect your entire life.
AL-ALY: Yeah, absolutely. So when we talk about long COVID, and I know it’s ingrained in the public consciousness at long COVID is brain fog and fatigue, but it’s really much- much more than that. So long COVID is the umbrella term that encompasses all the long term health effects of SARS-CoV-2 infection. In some patients, it can manifest as fatigue or brain fog, and those may or may not improve with time. But it also in some patients, it can manifest as heart attacks or heart failure, or the heart problems, brain problems, gastrointestinal issues, kidney problems, and new onset diabetes. And arguably those conditions are lifelong conditions. Once the patient has diabetes, is it manageable? It’s absolutely manageable, but is it curable? Not necessarily so. It may not be curable. So some of the conditions or the consequences of SARS-CoV-2 infection that we lumped under the broad umbrella term of long COVID are lifelong conditions that people will have to grapple with for a lifetime.
What are the slong-term effects of long-COVID?
ALY-ALY: Sure. So, we started working on trying to characterize what are the neurologic manifestations, or neurologic problems or the brain problems that happen in people with long COVID. And initially what was on our mind brain fog. That’s really what most of our people talk about. This is what most of the patients talk about forgetfulness, in attention and in all of these problems that happen with brain fog. Or we didn’t know is that actually a lot of patients are actually having strokes. And we found that people are having brain inflammation. People are having even symptoms such as movement disorders or symptoms that are almost reminiscent of Parkinson’s disease or early Alzheimer’s disease. So it’s really the neurologic manifestations that we’ve been able to characterize following SARS-CoV-2 infection that fall under the umbrella of long COVID are much wider in scope than just plain fact that most people talk about. Again, SARS-CoV-2 infection can lead to problems and inflammation of the brain can lead to early Alzheimer’s disease. Symptoms reminiscent or very similar to the stuff that we see in Parkinson’s disease, movement disorders, seizures, chronic headache. In total, we were able to characterize about increased risk of about 44 conditions and the brain that affect people long after the initial infection with SARS-CoV-2, that’s under long COVID phase.
Does it affect people with those types of issues, like all those that you just listed, more people who had the vaccine or didn’t have a vaccine?
AL-ALY: So what we’ve found is that the people who didn’t have the vaccine certainly had this. And vaccine reduces the risk, but does not eliminate the risk of these manifestations, meaning that the risk is lower, but it’s not zero. And people who had been vaccinated and boosted. So vaccines will reduce but do not eliminate in all of these conditions.
Do you have a percentage?
AL-ALY: Overall, it varies between 30 percent and 50 percent risk reduction. That is significant, but it’s not total aggregation is still 50 percent, is still there. Even when you go from 30-50 percent and it’s still at me that the risk is 50 percent higher than people didn’t have the infection.
Does Paxlovid play any part of this? Can it reduce it even more?
Al-aly: Sure. So we also did analysis to try to understand whether people who take it back slow of it, the antiviral that target SARS-CoV-2 infection in the initial phase, ameliorate or reduce the risk of long COVID. And now as the case, the risk reduction was about 26 percent, meaning people who took back slow with in that acute phase within five days of having an infection or having a positive test for SARS-CoV-2 infection went on to have a 26 percent less risk of developing these long-term manifestations or the components of long COVID.
If you have COVID, you get COVID again, right?
AL-ALY: Absolutely. This is absolutely correct. So we analyze it initially in people who had only one infection on that first infection. But we also analyze it and people who had the re-infection, we find the same thing that even upon re-infection, you know people who took back-slow-vid of it generally fared better than people who did not take back-slow-vid. Specifically when it comes to the risk of long-term consequences or long COVID.
Would you use Paxlovid again? And would you use it again on the rebound one as well or would you not?
AL-ALY: So we’re very very familiar with a lot of patients. Like I said, I took back-slow for five days, on day five when I stopped back slow but I started getting rebounds are getting fever again or cough again. In some instances, people check their viral load and viral load increased after stopping back-slow-vid or finishing the course of back-slow-vid. We call that as rebound. So the studies have shown that the rebound is not higher and people who took back slowly than people who were not treated. Guess what. It’s a virus that it actually waxes and wanes in the body. So it goes up and down, and especially in the first 15 days of infection. So rebound is- is not more common after tax-slow-vid than people who did not get treated at all. And number 2, rebound is generally inconsequential. Does it really- in some patients results and maybe fever and feeling tired and that is the case for some patients, but does not really lead them to be hospitalized or needing to be hospitalized for those symptoms or worse, even having worse clinical outcomes. So it’s not. It’s inconsequential when it comes to clinical outcomes.
Do you know why it affects the brain and these types of problems afterwards?
AL-ALY: So the short answer, we don’t want to completely understand why SARS-CoV-2 with an R in the name. When we say SARS-CoV-2, it’s a respiratory virus and are in SARS stands for respiratory. We don’t really know why SARS-CoV-2 attacks the brain and other organs. Well, we know so far is that SARS COVID-2 has something called the spike protein on it. And luck would have it that the spike protein engages a lot of receptors on human cells, including the ACE2 receptor, which is nearly ubiquitously present on all cell types, including brain cells. You can start thinking about it or conceptualizing it at almost the lock and key mechanism that the virus has a spike protein on top of it, the surrounding it. And then that is the key that engages a lock on the surface of a cell. And that lock on the surface of human cells is supposed to keep the cell tight and protected from any invading virus. So it looks like that the spike protein may play a central role in explaining why SARS, again, a respiratory virus, attacks so many human cells, attacks so many or result in organ dysfunction in nearly every organ system.
Can having long-COVID spike your cholesterol?
AL-ALY: Yes, so we’ve done studies to characterize this. Now we’ve known from the very early phase of the pandemic that some people were coming back to clinical all metabolic problems. And we’ve seen anecdotal observations here and there that people are coming back with high cholesterol. But we didn’t really know if this is really truly due to SARS CoV-2, due to COVID-19. We did those analyses, analyzing about 150,000 people who had COVID-19 compared to more than 11 million controls. What we found is that people who got COVID-19 in the year that follows the infection had a significant spike in their cholesterol and the LDL level or triglyceride levels and also the reduction in HDL, the good cholesterol. They’re really more of the bad and less of the good. And the first year that follows SARS-cov-2 infection is very clearly that again, SARS CoV-2 this virus. So we all thought as a respiratory virus is not necessarily only a respiratory virus that it certainly can lead them metabolic dysfunction, including increased risk of high cholesterol.
Then, after that year, does the cholestoral come back to the norm or not?
AL-ALY: This is really brilliant question. We don’t know yet. We’re looking at that. We’re looking at two years and three years now, but we have data on two years and we’re looking at the pandemic has been going on for three years plus, so we’re collecting data for the third year of the pandemic would have anybody interested to know if these are permanent changes, that means, these patients have high cholesterol forever or for a long period of time or does have high cholesterol sort of go down after the first year of infection. We still don’t know that yet.
How does long-COVID affect gastrointestinal issues?
AL-ALY: So, this is again, why is motivated by a lot of observations-a lot of anecdotes from patients. Patient is telling us that I’ve never had any GI issues before. Now, I got SARS CoV-2 and all of a sudden I’m having problems with constipation I’ve never ever had or problems with abdominis can I am so abdominal pain or diarrhea I’ve never ever had or all of a sudden my liver function tests shot up. I went to them like primary care physician, never ever had any liver problem. Now my liver function has shot up. So we started listening to again, always to the patient community and what they’re telling us is what they’re experiencing. And we went back and looked in our data. Again, amassing a cohort of about 150,000 people with COVID-19 compared them to more than 11 million people without COVID-19. What we found in the first year after infection, people with COVID-19 had all gastrointestinal issues. Those are-could be in some patients, peptic ulcer disease, gerd, gastroesophageal reflux disease, acid related disorders, sent at the stomach or the guts start over secreating acids and people would feel heartburn or manifestations related to acid disorders. We saw evidence of some people having inflammation of the pancreas or the liver, and in some instances, motility disorders. Some patients having diarrhea or constipation. Some other people have abdominal pain or cramps. So it really varies from patient to patient. That’s really what is enormously complicated about COVID. It’s not all one thing. It’s really pretty much a lot of different things that can manifest differently in different patients. But it’s very clear that at least in the first year after COVID-19, a lot of people were experiencing- 150,000 people were experiencing GI problems or GI issues.
Are all these problems with people who have long-COVID or just people who have gotten COVID?
AL-ALY: So all of these are people who have COVID, but all these conditions because they persist that are actually exist for longer than the first 30 days after infection. These are classified under the umbrella term of long COVID.
Could this pandemic be a lifetime pandemic for these people?
AL-ALY: So that’s what we’re worried about. What we’re worried about is that this pandemic for the people who are affected by it in the sense that they got COVID-19 and subsequently had new onset diabetes, heart problems, gastrointestinal problems, heart issues or brain problems. Some of those conditions are chronic conditions that will last with these people for a lifetime. And that’s going to mean that long after this pandemic, receipts from public view, we all know and on May 11th, the government will declare the end of public health emergency. And for a lot of Americans, for a lot of us and for a lot of people around the world with the pandemic will receive from public view, what we’re worried about is that we’re going to be left with literally millions of people who have new onset condition that they would not have otherwise had, had they not had an infection with COVID-19 or SARS CoV-2. And these conditions will affect these people, will affect their ability to work, their ability to maintain relationships that are societal well-being of the people around them and also impact the economy and has a tremendous impact on the health system in the sense that the health system will have to actually accommodate, and treat and care for these patients. And that’s going to be an additional workloads, so to speak, on the health system. So long after this pandemic recedes from public view, we’re gonna be left with the legacy or the aftermath of this pandemic. And that’s, you can think of it as the one when the tsunami hits and the water recedes, the one that earthquake stops or the earth stop shaking. You’re going to be left with a damage. And we’re going to have to do a damage assessment and figuring out like how many people really will need long-term care. How are we going to do about their disability? What we’re going to do about inability to potentially come back to the labor force? How are we going to compensate for that? What health systems are going to do to be able to deal with this increased workload and to the carrying for all these patients? And really the impact, the overall impact on societal well-being.
END OF INTERVIEW
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