Why 'Long COVID' is an unhelpful term

And why is the length so variable?
12 March 2024

Interview with 

Ben Krishna, University of Cambridge

LONG-COVID

Person suffering with long Covid

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Given the broad range of symptoms, from brain fog, to fatigue, muscle pains and signs of nerve damage, it’s likely that Long COVID is not one single condition but an umbrella term uniting a host of different syndromes, all with different mechanisms, outcomes and best treatments. I went to see Cambridge University virologist Ben Krishna, who branched out into working on Long COVID during the pandemic. He agrees that “Long COVID” can be an unhelpful term…

Ben - So the problem with the terminology of long covid is just that it's a very broad and umbrella term. You can imagine three different people. You've had one person who was very, very sick with COVID-19 in 2020. They went to the hospital, they were put on oxygen, they were given what we call mechanical ventilations. They essentially had a tube put into their lungs and then their lungs were inflated artificially for a certain amount of time. And then eventually they've recovered and they've been discharged from the hospital. And you're thinking six months later, are they feeling back to where they were before COVID-19? The answer is probably no. But is that really Long COVID or is that really just them slowly recovering from the initial infection? You then have person two, they lost their taste and smell that hasn't come back for whatever reason. I don't think we exactly know what causes that yet, but for whatever reason, they can't go to restaurants.

But at the same time, they can go into work and they can do everything they normally do. It's just a taste and smell that's gone. And the third case, and these are perhaps in my opinion, the strangest cases where somebody got sick with COVID-19, they had the similar symptoms that a lot of people are familiar with. So they were in bed and feeling fatigued and most people got better and they went back to their normal lives. And for these people, they just didn't get better. And in some cases, it's been a year, sometimes two years, and these people still feel like the first early days of a viral infection and they just never recovered.

Chris - What do we think the underlying mechanisms of cases like that latter one might be?

Ben - So it's still quite controversial what might be causing it. There is a growing body of evidence that the immune system switches on and then fails to switch off. What exactly is causing that is not entirely clear. It could be, for example, that people got infected with the virus, the virus has infected some parts of their body and is still there at a very low level and is just continually making small amounts of virus. And as a result of this, their immune system is still on and still fighting the virus. And that's what's making them feel sick. Because we know that a lot of what really makes you feel sick when you've got a virus is actually the immune system's response fighting the virus, not the virus itself. Alternatively, it could be something autoimmune. So it could be that the immune system started off fighting the virus and now it mistakenly started attacking a part of the body that it's not supposed to. And actually a lot of long covid does look a bit like autoimmunity. Particularly many patients say they have cycles of symptoms, so they get better and then they get worse and they get better again. Or finally it could be something that we're just not aware of right now. It could be that the immune system is switched on, it's not switching off and it's for some reason that we just don't know about yet.

Chris - How are you trying to get underneath that and find out which of those, or whether all of them are behind this?

Ben - Our research suggested that the immune system had switched on in people who had COVID-19. And in most people it switched off. But in this small group of patients with long covid, it just was still switched on and it was particularly switched on. It was making one particular protein. This protein is called interferon gamma, and it is known to make you feel quite sick. We tried looking for viruses in these patients. So what we did was we took blood samples on these patients and then we just looked for signs that the virus is still there. We didn't find anything in the patient's blood. We were particularly interested in their intestines. So there's some data out there showing that patients continue harbouring the virus in their intestines and it comes out in their poo. That is actually where we're moving at the moment, is trying to understand that side of things.

Chris - If that is the case that either the virus has tickled the immune system and it's stayed locked on in some way, or the virus is hiding somewhere and tickling the immune system from a covert hiding place, possibly the gut. In either scenario, the immune system's overactive, what can we do to turn it off?

Ben - So this is why the mechanism is so important because you might approach those in completely different ways. If you are harbouring a small amount of virus somewhere in your body, you might actually be able to treat long covid by giving people antivirals. Alternatively, if it's autoimmune, an antiviral is going to do absolutely nothing. And actually what you want to do is to give people some sort of immunosuppressants. I have heard that there are clinical studies looking at both of those, but I haven't seen any convincing results one way or the other yet. But that is obviously something that people are very excited by.

Chris - Do you think this phenomenon is unique to SARS-CoV-2, the coronavirus that causes covid? Would other coronaviruses do this? Or more broadly, might all viruses be capable of doing this? So if we had a bad dose of flu, this could happen. And is it just that we got so many people all at once catching SARS-CoV-2, that it disclosed this phenomenon and it's always been there. We just didn't see it.

Ben - You've put it in better words than I could have right there. So yes, it's probably the case that you had this new virus. It turns up no one has any immunity to it. Everybody gets sick all at once. And so you get this big wave of people with what we call post viral syndromes. They're just sick for long periods of time after the virus. There is evidence from SARS-CoV-1 commonly called SARS. That was an outbreak that happened in East Asia, particularly South Korea and Japan and China back in 2003. There were patients there who got sick at the time and they were reporting years later that they still didn't feel better. I have seen some evidence that flus can do this. They had a patient who got Spanish flu in 1919 and were still sick into the 1920s, and they just didn't know what to do with this person. So yeah, there's this view now that maybe all viruses cause this, and if you have a brand new virus that springs across from animals and then causes the pandemic, you are going to get a big wave of post viral illness. And of course that's very worrying because we expect there will eventually be another pandemic. And so trying to understand long covid now might help prepare us for the next one.

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