Long COVID And Disease Severity

Why people who have less severe initial infections are less likely to experience long-term symptoms of COVID-19

This is what came up when I searched for “Long COVID” on Unsplash. Photo by kevin turcios on Unsplash

Long COVID remains one of the biggest topics on people’s minds when it comes to the pandemic. While the immediate impact of COVID-19 has reduced for most individuals - you’re much less likely to die of the disease now than when it first emerged in 2020 - there is still a lot of worry about catching the coronavirus and going on to develop long-term symptoms.

Whenever you discuss Long COVID, there’s a common claim that pops up - that everyone is at risk from the condition. The argument is usually framed as a health warning, telling people that every infection they have increases their risk of developing Long COVID, and so they should avoid infection if at all possible. This is also often accompanied by the claim that most cases of Long COVID had mild initial infections, implying that mild initial infections more commonly cause Long COVID than more severe ones.

This is all quite scary, because it implies that even if the short-term risks from COVID-19 are down, the long-term risks are still just as bad as they were in 2020. It’s also highly misleading. Your risk of Long COVID has never been lower than it is now, per infection, and is likely falling over time.

The issues with this argument come in two main forms.

1 - Base Rate Fallacy

The first issue with this argument is simple - there are far more people who have ‘mild’ COVID-19 infections, particularly in 2022/23/24, than those who have more severe issues. Depending on which study you look at, and how you define a ‘mild’ infection somewhere in the region of 90% of infections are ‘mild’. That means that most Long COVID cases will come from less severe infections by default, because the vast majority of COVID-19 cases are from this group anyway. This is an example of what’s called the base rate fallacy, because it is a misleading presentation of results that relies on not presenting the rate of the disease in context.

Why is this misleading? A recent study using the REACT dataset from the UK showed that people with severe symptoms were 7 times more likely to experience persistent Long COVID than those who reported mild disease, but also had about double as many mild/moderate patients as severe ones. Thus, only 47% of Long COVID cases came from severe disease, even though it was by far the biggest risk factor for developing Long COVID in this population.

2 - The Definition of ‘Mild’

The other thing that’s highly deceptive about this entire argument is the definition of the term ‘mild’. Take the screenshot above. That links to this article in The Conversation, which in turns references this paper. If you look at the actual paper, disease severity was dichotomized by hospitalization - people who didn’t go to hospital were considered ‘mild’, and people who went to hospital were ‘not mild’. This is common among COVID-19 papers, because they usually divide disease into not hospitalized, hospitalized, in ICU, and on a ventilator, but it’s not a particularly reasonable definition of the term ‘mild’ in the usual understanding.

When I say ‘mild’, most people think of having a slight cough and a headache for a week or two, but in these research papers it spans everything from no symptoms at all to being bedbound for a fortnight with a fever, sore throat, and an awful cough.

If you instead look at people’s self-rating of their disease state (i.e. how sick people thought they were), you find that any decrease in the severity of initial infection results in a dramatic drop in the proportion of people who report long-term symptoms. To put it another way, people who feel less unwell when they first get COVID-19 are MUCH less likely to say that they have long-term symptoms if you ask them months later.

Pictured: Less likely to result in Long COVID than someone lying in bed coughing furiously for a month. Photo by Clay Banks on Unsplash

Take the REACT data I referenced above. This was based on self-report, and had people rate the severity of their initial infection as asymptomatic, mild, moderate, or severe. Of those who had a severe infection, 24% reported Long COVID, compared to just 6% of those with moderate symptoms, 3% of those with mild symptoms, and 0% of those who said that they were asymptomatic initially.

The point is that if you define ‘mild’ as ‘not hospitalized’, then it’s true that most Long COVID cases come from ‘mild’ disease. But if you define ‘mild’ as ‘people thought their initial infection was mild’ then VERY FEW people who experience Long COVID had a ‘mild’ infection. In fact, if you look at the REACT data, of the 9,000 people who reported long-term symptoms only 1,137 (13%) said that their initial infection was ‘mild’ and none said that it was ‘asymptomatic’.

Everyone Is At Risk

This brings us back to the central point - is everyone at risk of Long COVID? Well, yes. But the more interesting question is whether everyone is at the same risk of Long COVID, and to that the answer is a definitive no.

There are a multitude of factors associated with developing Long COVID. Smokers are more likely to experience long-term symptoms than non-smokers. Older people are much more likely to get Long COVID than younger, and children less likely still. Women tend to be slightly more likely to have symptoms months after infection than men, as do people with pre-existing comorbidities.

Interestingly, women are less likely to die from initial COVID-19 infection than men, which may partially explain the higher risk of long-term symptoms (i.e. some measure of survivorship bias). Photo by Microsoft 365 on Unsplash

But the single biggest predictor of whether someone will eventually meet the clinical definition of Long COVID is how sick they feel when they have COVID-19. This is a finding that’s been replicated many times - for example, this 2022 study from Sweden found that people who reported “No or mild symptoms” in their initial infection were about 30% more likely to rate their current health as “very good” when compared to people who had “palpable illness” initially.

We also know that this is probably causal - i.e. that if you reduce the severity of initial symptoms, it makes Long COVID less likely as well. For example, numerous studies have shown that vaccines - particularly recent doses - reduce the average symptom severity of COVID-19 and drastically cut the risk of long-term symptoms. Similarly, a medication called metformin has been shown to reduce the risk of hospitalization and death due to COVID-19, and also drops the risk of people going on to have Long COVID by around 40%, based on a large randomized trial.

So while it is technically true that everyone is at risk of Long COVID, it’s true in the same way that the statement “everyone is at risk of a heart attack” is true. Yes, anyone can have a heart attack, but some people are extremely unlikely to experience one while others have a very high risk.

As I’ve written before, the risk of Long COVID has already decreased substantially since 2020 and is likely to fall further in the future, and it’s in part because of this finding. As the severity of acute disease drops, we are seeing fewer and fewer people report that their symptoms keep going for long periods of time as well.

Long COVID remains a scary condition with no real treatment, and my heart goes out to the people who got sick in 2020 and are still suffering years later. But the good news is that, at a population level, the risk of the condition has dropped quite a bit since the start of the pandemic, and will probably keep falling as time goes on. While Long COVID remains a public health problem - a small percentage of a big number is still a big number, after all - it is not the population level risk that it once was.

And as for disease severity? It definitely impacts whether people go on to develop Long COVID. People who have worse initial symptoms are much more likely to have bad long-term ones as well. It’s true to say that anyone can get Long COVID, but it’s also true to say that people who have mild initial symptoms probably won’t.