New national study of long-term impacts of lung damage from COVID-19

A new national study will investigate the long-term effects of lung inflammation and scarring from COVID-19.

New national study of long-term impacts of lung damage from COVID-19

The study, launched with £2 million of funding from UK Research and Innovation (UKRI) and led by Imperial College London, aims to develop treatment strategies and prevent disability.

Many recovering COVID-19 patients suffer from long-term symptoms of lung damage, including breathlessness, coughing, fatigue and limited ability to exercise.

COVID-19 can lead to inflammation in the lungs due to the infection and the immune system’s reaction to it. The inflammation may improve over time, but in some people it persists.

In severe cases, the lungs may become scarred. The scarring causes stiffness in the lungs, which can make it difficult to breathe and get oxygen to the bloodstream, resulting in long-term breathlessness and difficulty managing daily tasks.

This inflammation and scarring of the lungs is called ‘interstitial lung disease’.

Post-COVID-19 lung damage 

Now, this study, called the UK Interstitial Lung Disease Long-COVID19 (UKILD-Long COVID) study, will investigate whether post-COVID-19 lung damage will improve or worsen over time, how long it will last, and the best strategies for developing treatments.

Early evidence indicates that lung damage occurs in approximately 20% of patients discharged from hospital, but the effects on people who experience long-Covid in the community are currently unclear.

Matthew Gordon, 44, from Bristol, who was hospitalised with COVID-19 in January 2020, said of his experience: “Nearly two months on, I’m slowly recovering. The coughing has stopped, which is the greatest relief, and it’s no longer a struggle to breathe. However, my muscle strength is still very weak and doing mild exercise such as jogging, or even walking while talking, can make me short of breath. My latest review with the respiratory consultant a couple of weeks ago found there was still some slight crackling on my lungs and my lung capacity was reduced but had improved since January.

“During my time in hospital I took part in trials, such as REMAP-CAP treatment trial, and now I’m keen to take part in research to learn more about the long-term effects of COVID on the lungs of people like me and how we’re recovering.”

This study, led by researchers at Imperial College London, will bring together researchers and clinicians from 15 research centres and will include patients already in COVID-19 studies, such as the Post-hospitalisation COVID-19 study.

New treatments

Professor Gisli Jenkins, at Imperial’s National Heart and Lung Institute, who is leading the study, said: “This is an ambitious study that will help us understand how common and severe the long-term pulmonary consequences of COVID-19 are, and will help us develop new treatment approaches for people suffering from long-term lung inflammation as a result of COVID-19.”

“Breathlessness is a big problem for many people with long-COVID, particularly on exertion. For people with more severe lung scarring, this can be a devastating disease. We don’t yet know how frequent and how long-term the consequences will be. Even if the long-term outcomes are no worse than for people with similar lung damage from flu, the sheer numbers of people who have had COVID-19 are so huge.”

Science Minister Amanda Solloway said: “It is thanks to the pioneering work of our brilliant scientists and researchers that we now know so much more about COVID-19 than we did just one year ago – including the lasting effects it can have on patients. 

“Bringing together some of the UK’s finest researchers, this new nationwide study will analyse the full impact of lung damage caused by the disease, helping to inform new treatments that could benefit patients across the world, as we build back better from the pandemic.”

Professor Fiona Watt, Executive Chair of the Medical Research Council, part of UKRI which funded the study, said: “This research is key to understanding how and why the virus causes some people to suffer long-term lung effects after COVID-19 infection. It will be an important tool in developing more effective treatments for patients.”

To understand the full spectrum of lung impacts, the study will include a range from patients, from those who have been hospitalised or placed on a ventilator to those in the community who had less severe COVID-19.

They hope to recruit approximately 250 people with symptoms suggestive of possible lung scarring, such as breathlessness or a persistent cough, to find out more about their long-term lung damage at three and 12 months after COVID-19 infection.

Cutting-edge xenon MRI scans will be performed in a subset of patients. These use a safe, inert gas which is inhaled, so the scan can measure the effectiveness of gas exchange inside the lungs.

Professor Jim Wild, at the University of Sheffield, who is leading the MRI part of study, said “With novel and very sensitive lung imaging using hyperpolarised xenon MRI we can pick up early signs of gas exchange limitation in the lungs and map this on to structural changes in the CT images and monitor with time whether the patients go on to develop interstitial lung disease”

Genetic changes

They will also obtain samples of cells from the lungs of 50 people to look at how the lung cells have changed in response to the injury. This will include single cell sequencing – genetic analyses of immune and lung cells, to detect changes in gene expression (which genes are switched on an off).

To understand why some patients get severe lung disease following COVID-19, and others don’t, they will link together the clinical findings with the studies of the patients’ genes and markers in the blood.

Professor Ling-Pei Ho, from the MRC Human Immunology Unit, University of Oxford, one of the leads in the study, said: “Studying immune cells in the lungs of patients with post COVID lung abnormalities adds greatly to the understanding of why patients have these persistent inflammation and scarring. This study will be one of very few to do this and will use the latest technology in analysing these cells giving us the information of the highest resolution and potential causes for these lung problems.”

The study will initially follow-up patients over 12 months, then follow longer-term outcomes through patient records.

The researchers aim to use their findings to develop treatment strategies to prevent the development of severe scarring and disability following COVID-19.

Dr Karen Piper Hanley, at the University of Manchester, who will study the cells in the lungs, said: “This MRC award pulls together our best researchers and clinicians around the UK to build our understanding of COVID-19 and long-term lung damage post infection, which for some individuals can be devastating. By bringing together this collective knowledge and expertise, this project has the potential to impact patient care globally and develop new treatments to improve lung damage post-COVID-19.”

The study is funded as part of UKRI’s COVID-19 Agile Call, which has so far invested more than £180M in over 450 projects and consortia to address the impacts of the COVID-19 pandemic.