Where are we at with long COVID?

As Omicron races across the globe, it’s hard to draw our attention away from the short-term effects of COVID-19. But up to a third of infected people are currently experiencing illness that lasts many more months: post-acute COVID-19 syndrome (PACS), or long COVID.

So what do we know now? Is Omicron likely to change things? And does vaccination still help?

Have we figured out what long COVID is, exactly?

In October 2021, the WHO announced a formal case definition of long COVID: symptoms that persist for usually at least three months after becoming ill with COVID-19, that can’t be explained by another diagnosis.

“Common symptoms include fatigue, shortness of breath, cognitive dysfunction but also others and generally have an impact on everyday functioning,” reads the definition.

This is still a relatively vague definition – like many other chronic illnesses, long COVID can exhibit itself in different ways.

Researchers still haven’t nailed down a clear cause for these symptoms – it may be an immune response, or the virus persisting, a combination of these, or something else. But research is starting to close in on specific parts of the immune system reaction that are linked to long COVID.

The University of New South Wales’ Kirby Institute is running the long-term ADAPT study, which has been collecting data on long COVID patients for nearly two years. The project recently released a paper in Nature Immunology showing that long COVID patients who’d contracted the virus in March 2020 had a distinct immunological signature.

“It gives us a first look at an immunological profile – I don’t think it’s an exhaustive immunological profile,” says co-author Professor Anthony Kelleher, director of the Kirby Institute and collaborator on the ADAPT study.

Some of the things the researchers found – such as higher levels of certain proteins called interferons – could potentially explain some long COVID symptoms, like fatigue and brain fog.

“What we haven’t shown is that it’s actually causing those things,” says Kelleher. It’s also still a mystery why these proteins are present in higher amounts.

New data is filtering in all the time – like links between gut bacteria and long COVID, such as this study in Gut.

Another just-published paper in Nature Communications has spotted a number of immunological and health-based risk factors for contracting long COVID. This paper also shows the immune system is linked to long COVID in certain ways, but it leaves many questions unanswered.

“We are still at the beginning of understanding PACS (also known as ‘long-COVID’), which might have several underlying causes,” says Professor Onur Boyman, corresponding author on the paper and a researcher at the University of Zurich, Switzerland.

This paper also found that certain immune responses (along with asthma, and some other health conditions) predisposed some patients to long COVID.

“We hypothesised that a ‘misguided’ or suboptimal immune response could be one of the causes predisposing to PACS,” says Boyman.

Both researchers say that there are some similarities between their findings and other immune-related chronic illnesses such as chronic fatigue syndrome, but there is also plenty that is as yet unique to long COVID.

Will Omicron cause long COVID in the same way as other variants?

We don’t know yet. We’ll probably find out by May.

The reason for this prediction is the case definition of long COVID: symptoms exist more than three months after getting sick with COVID-19. If we can’t officially define patients as having long COVID, it’s very difficult to collect consistent clinical data on them.

As Omicron was first spotted in Australia in late November, it’s going to take until at least March for anyone who contracted it to be formally defined as having long COVID. After that, it will take some time for researchers to draw clearer conclusions.

So, between March and May 2022 is when we’ll start to see information filtering in about Omicron and long COVID.

Complicating this is that severe health effects from a COVID-19 case can still be short-term. People who go into intensive care may make a full recovery, while those with a mild initial illness may not.

“The surprising thing about the description of long COVID, from my point of view, is that it’s not just a matter of more severe disease,” says Kelleher.

“The people that have ended up in intensive care will have a much more prolonged convalescence, simply because they’ve been battered around by the virus and there’s a lot more repair. Whether that’s just recovering from all the insults and complications that go with a prolonged hospital stay and a prolonged illness, or whether it’s long COVID, they need to tease that apart.”

It’s possible that Omicron may present differently as a chronic illness to long COVID from previous variants.

There is increasing evidence that Omicron preferentially infects cells in the upper respiratory tract, rather than the lungs.

“It is potentially possible that the change in tropism, and the cells that get infected – particularly if it’s something like antigen persistence – then the generation of auto-immune phenomena might change,” says Kelleher.

Will vaccines help against long COVID?

Vaccines lower your risk of getting infected, and thus also lower your risk of getting long COVID. But breakthrough infections can still happen, particularly with Omicron.

It is, again, difficult to see what this looks like in an Australian context – because a majority of the population wasn’t fully vaccinated until October, and prior to Omicron there had been few breakthrough infections.

A new preprint (non-peer reviewed) study based on 3,000 Israeli participants has found that vaccinated people who caught COVID-19 were as likely to report long-term symptoms as those who hadn’t caught the virus at all. While this is welcome news, there have still been confirmed cases of long COVID in vaccinated people, too.

There’s a collection of evidence that suggests that – as with COVID infection in the first place – vaccination reduces but doesn’t eliminate the risk of long COVID.

“Based on the findings of our and other studies, a severe COVID-19 disease course is a risk factor for developing PACS,” says Boyman.

“Thus, strategies to better control SARS-CoV-2 infection and inflammation are important, including vaccination against SARS-CoV-2, SARS-CoV-2-directed therapeutic antibodies, and anti-viral and anti-inflammatory medication.”

So, though mild infections can still cause long COVID, vaccination reduces the risk of severe infection and thus long COVID.

Kelleher says that their discovery also hints at a lower risk of long COVID because of vaccination. In this case, it’s because vaccination primes the immune system to react faster.

“Because vaccination primes both the T and B cells – memory cells – to be ready, and instead of taking seven days to turn on, taking 24–72 hours to turn on, that might change the likelihood of you getting something like long COVID,” he says.

In both cases, it may be a while before we know for sure. Nevertheless, vaccination is still one of the best available ways to protect yourself.

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