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Long covid linked to signs of ongoing inflammatory responses in blood

People who develop long covid after being hospitalised with severe covid-19 have raised levels of many inflammatory immune molecules compared with those who recovered fully after such a hospitalisation, according to a study of nearly 700 people.

The findings show that long covid has a real biological basis, says team member Peter Openshaw at Imperial College London. “People are not imagining it,” he says. “It’s genuinely happening to them.”

The researchers think the ongoing immune responses could be causing the symptoms of long covid. There are already some approved treatments that are designed to reduce these responses in other conditions, so the findings could lead to trials of these same drugs for the treatment of long covid.

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However, it is unclear whether the findings apply to people who develop long covid after milder SARS-CoV-2 infections that don’t require hospitalisation.

It is also possible that, in some cases, the ongoing immune responses are due to persistent infection with SARS-CoV-2 or the activation of dormant viruses in the body, such as Epstein-Barr virus, says team member Felicity Liew, also at Imperial. If so, damping down immune responses could be counterproductive.

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“Long covid is a complex condition,” says Liew. “There isn’t a single cause.”

The study by Liew and her colleagues involved measuring the levels of 368 immune molecules in the blood of 659 people who were hospitalised with covid-19, mostly early on in the pandemic. The 426 people who were still reporting symptoms more than three months later were compared with the 233 who reported being fully recovered.

The study found that the patterns of immune activation reflected the main kinds of symptoms people with long covid reported. The five main symptom types were fatigue; cognitive impairment; anxiety and depression; cardiorespiratory symptoms; and gastrointestinal symptoms.

For instance, people with gastrointestinal symptoms had higher blood levels of SCG3, a signalling protein that is also elevated in the faeces of people with irritable bowel syndrome.

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The findings won’t help with diagnosing whether people have long covid or not, says team member Chris Brightling at the University of Leicester in the UK. But once the condition has been diagnosed, testing for these molecules could help reveal what kind of long covid people have, and thus what kind of interventions might help, he says.

A study last year estimated that 36 million people in Europe had or have long covid. “Many people are still suffering,” says Brightling.

“I think it’s pretty clear from the results that the differences in blood protein levels do exist – but questions remain as to how the differences arise, in what way they might or might not cause the symptoms and how this might lead to effective treatments,” said Kevin McConway at the Open University in the UK, in a statement released by the Science Media Centre. “It remains possible that the findings don’t apply to people who were never hospitalised for covid,” he said.

Journal reference:

Nature Immunology DOI: 10.1038/s41590-024-01778-0

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