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NIHR funded study offers hope for targeted treatment of long COVID

Published: 11 April 2024

An NIHR and UK Research and Innovation (UKRI) funded study has revealed that long COVID leads to ongoing inflammation which can be detected in blood. 

This suggests that existing drugs which help treat conditions that affect the body’s immune system could be helpful in treating long COVID, and should be investigated in future clinical trials.

What is long COVID?

Long COVID is a recurrence of symptoms after COVID-19 infection. Most people recover from COVID within 12 weeks, but sometimes symptoms last longer. The main symptoms of long COVID are:

  • extreme tiredness
  • shortness of breath
  • problems with memory and concentration also known as ‘brain fog’

Long COVID affects millions of people across the world. 

These latest findings come from the largest UK study to date of more than 650 people who had been hospitalised with severe COVID-19. The study revealed that patients with prolonged symptoms showed evidence of immune system activation.

The study, which has been published in Nature Immunology, is from two collaborative UK-wide consortia, PHOSP-COVID and ISARIC-4C. These involve scientists and clinicians from universities across the UK, including Imperial College London and the Universities of Leicester, Edinburgh and Liverpool, among others.

The study was established by the NIHR Respiratory TRC (translational research collaboration) and delivered through the NIHR Clinical Research Network and supported by several parts of NIHR-funded infrastructure:

  • Imperial Biomedical Research Centre (BRC)
  • Leicester BRC
  • Oxford BRC
  • Manchester BRC
  • NIHR Academy
  • Liverpool Experimental Cancer Medicine Centre
  • NIHR Health Protection Research Unit (HPRU) in Respiratory Infections at Imperial College London
  • HPRU in Emerging and Zoonotic Infections at University of Liverpool

Dr Kate Holmes, Assistant Director of Collaborations, Infrastructure, at the NIHR, provided support in coordinating the charities group. She said: “Being able to bring charities, industry and NIHR infrastructure together through the NIHR Translational Research Collaborations is the key strength of the UK’s clinical research infrastructure. The PHOSP-COVID study was set up and led by the Respiratory TRC, involving other NIHR TRCs, including the Mental Health TRC, the Dementia TRC and the NIHR-BHF Cardiovascular Partnership.

"This collaboration enabled a rapid, cross-disciplinary response to the challenges of long COVID, which opens more doors into understanding and potentially treating this illness. This study showcases the strength of the NIHR clinical research infrastructure and we are hopeful and encouraged by the prospect of being able to provide treatments for this devastating condition in future.”

How the study worked

The research compared 426 people who were experiencing symptoms consistent with long COVID with 233 people who were also hospitalised for COVID-19 but had fully recovered. The researchers took samples of blood plasma and measured a total of 368 proteins known to be involved in inflammation and immune system modulation.

They found that, relative to patients who had fully recovered, those with long COVID showed a pattern of immune system activation indicating inflammation of myeloid cells and activation of a family of immune system proteins called the complement system.

Dr Felicity Liew, from Imperial’s National Heart & Lung Institute, said: “Our findings indicate that complement activation and myeloid inflammation could be a common feature of long COVID after hospitalisation, regardless of symptom type. 

“It is unusual to find evidence of ongoing complement activation several months after acute infection has resolved, suggesting that long COVID symptoms are a result of active inflammation. However, we can’t be sure that this is applicable to all types of long COVID, especially if symptoms occur after non-hospitalised infection.”

Hope for the future

Comprehensive information on the range of symptoms the patients were experiencing was collected, allowing researchers to map out the most common ones. The researchers suggest that this, as well as the traces being left in the blood by long COVID could be useful in designing clinical trials, especially for treatments that target immune responses and inflammation.

Professor Peter Openshaw from Imperial’s National Heart & Lung Institute and an ISARIC-4C lead investigator, said: “This study, which includes detailed clinical data on symptoms and a raft of inflammatory blood plasma markers, is an important step forward and provides crucial insights into what causes long COVID.

“This work provides strong evidence that long COVID is caused by post-viral inflammation but shows layers of complexity. We hope that our work opens the way to the development of specific tests and treatments for the various types of long COVID and believe that a ‘one size fits all’ approach to treatment may not work.”

Click to read the study, ‘Large scale phenotyping of long COVID inflammation reveals mechanistic subtypes of disease after COVID-19 hospitalisation’ 

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