World's first cell therapy trial for post COVID-19 fibrotic lung disease

A first in human cell therapy trial for the treatment of post COVID-19 lung scarring has recruited and treated its first patients.

The Monocytes as an Anti-fibrotic treatment after COVID-19 (MONACO) cell therapy study is the world’s first Phase 1 trial for the condition that has advanced to a stage where it has been given to patients.

Early estimates indicate that 2% of all patients who had COVID-19, including those who were not hospitalised, will have suffered a degree of fibrotic lung scarring as a result of the infection. This estimate is even higher in patients who were admitted to intensive care. These statistics indicate that globally over 3.5 million people may have a degree of post COVID-19 lung scarring to date.

The study is led by Mr Ashish Patel, consultant vascular surgeon at Guy’s and St Thomas’ and a clinical senior lecturer within the King’s BHF Centre for Excellence, School of Cardiovascular Medicine and Sciences.

It looks at the safety and efficacy of using a novel cell therapy treatment to reverse lung fibrosis using the body’s own cells (monocytes and macrophages) which are engineered in the laboratory to have anti-fibrotic properties. With their name derived from Greek – where ‘macro’ means large, and ‘phage’ means eating, – macrophages are a type of white blood cell with the power to devour cellular and excess scar tissue formed in injured lungs as they heal during acute COVID-19 infection.

Lung scarring causes a significant decline in lung function, a long term debilitating reduction in exercise capacity and reduced quality of life in these patients.

The development of the MONACO Cell Therapy Study and production of the treatment were supported by the world class infrastructure and facilities of the NIHR Guy’s and St Thomas’ Biomedical Research Centre (BRC). The novel cell therapy used in this study was manufactured within the cutting edge facilities, and with the expert support of highly trained staff within the NIHR BRC’s Advanced Therapies Manufacturing platform at Guy’s Hospital.

Five patients with fibrotic lung disease following recovery from COVID-19, were the first people in the world to receive the experimental cell therapy treatment within the NIHR Clinical Research Facility (CRF) at Guy’s Hospital.

Clinical research within the NHS has adapted to address the unmet diagnostic and treatment needs of patients with COVID-19 – with regulatory and ethical approval processes just as thorough as pre COVID-19 – but significantly accelerated. 

Prior to the pandemic, MONACO’s trial lead, Mr Patel was working alongside another vascular surgeon, Professor Bijan Modarai, with the aim of delivering these cells into the legs of patients with peripheral vascular disease to prevent amputation. Once the pandemic hit, and with an increasing number of patients who had recovered from COVID-19 infection presenting with post COVID-19 lung scarring, they saw the potential to re-purpose their therapy to potentially treat this lung scarring. With the generous permission of their funders – the Rosetrees Trust (who fund innovative research) – for the original study to be re-purposed, the MONACO Cell Therapy study was born.

Commenting on progress of the study so far Mr Ashish Patel said: “I am very proud of how quickly our team has been able to progress this study from concept when the first wave hit to dosing patients with the cell therapy product. Our research is focussed on developing novel advanced therapies and their translation from the laboratory to the bedside and it has been fantastic being part of a truly translational piece of clinical research. Successful delivery of this experimental cell therapy into patients marks an important milestone in establishing its safety, before it is considered for treating larger numbers of patients who are affected by post COVID-19 fibrotic lung disease.

“I would like to extend my gratitude to the five incredible patients who have come through their severe COVID-19 illness and been so willing to participate in this first in human study. We could not have done this without their support.”

One of the patients to receive MONACO’s experimental cell therapy is Mike Salmon, who contracted COVID-19 in late March 2020. He spent almost three months as a patient at Guy’s and St Thomas’ including five weeks on a ventilator. He was one of the first patients that research nurse, Lily Benton – who had previously worked as an intensive care nurse – cared for whilst re-deployed to the Intensive Care Unit (ICU). They met again when Mike was referred to participate in the MONACO trial.

Speaking of his memory of being ill in hospital and then meeting research nurse Lily, he said: “I don’t remember anything after I had been told I had COVID-19. It was a couple of days before I was put on a ventilator from what I’ve been told afterwards. I was clearly very seriously ill. After five weeks in ICU I spent another seven weeks in hospital and I am extremely grateful to everyone at Guy’s and St Thomas’ for their excellent care and support.

“There must have been scores of people who looked after me in ICU, but to meet Lily, who had been able to tell me about what happened to me during those first few weeks in ICU has been brilliant. Taking part in this study, while it may or may not help in improving my breathing, is my way of helping and thanking the teams at Guy’s and St Thomas’ who saved my life, so that they can develop new treatment for patients just like me.”

Looking back at how they first met Lily said: “I first cared for Mike shortly after being re-deployed to one of the ICUs, and he was extremely poorly. In the first few weeks of the pandemic many of us had a fear of the unknown – a lot of our patients were very ill, and we were dealing with a disease that particularly at first we didn’t know a lot about. It was pretty tough but our teams dealt with it so well.

“In those early weeks seeing Mike make progress was a seminal moment for me. Seeing him begin to get better after a few very tough weeks gave me the strength to carry on. Spotting Mike’s name on the screening log for the MONACO study was really special -seeing a patient that I looked after in ICU, out of ICU, and living their life has been amazing. And it’s a real privilege to look after Mike on the MONACO trial where we hope that the cell treatment will help reverse some of the lung scarring that he sustained as a result of COVID-19.”

Ashish Patel added: “The rapid delivery of this study so far has been made possible by the fantastic infrastructure of the NIHR Guy’s and St Thomas’ BRC, including the very talented team within the BRC’s Advanced Therapies Manufacturing unit, as well as the regulators who have been excellent at closely working with us throughout this journey. The tireless efforts of the MONACO team including Frederica Francia and Lily Benton, our vascular research nurses, has enabled us to set up the study and recruit patients in very quickly.

“As a vascular surgeon, respiratory disease is not my area of expertise and I am extremely grateful to colleagues and collaborators at Guy’s and St Thomas’, especially Dr Alex West, consultant respiratory physician and lead of the KHP Interstitial Lung Disease Service.”

The trial is now closed to recruitment. If you are interested in taking part in COVID-19 studies please visit the NIHR website to find out which trials are currently recruiting participants.