Long COVID: a drive to understand the pathophysiology and lived experience to improve patient outcomes
Abstract
Post-viral illnesses have been well-documented over the last century, with the Spanish flu pandemic of 1918‒1920 recognized as one of the first major public-health events. The largest pandemic of the current millennia so far, caused by severe acute respiratory syndrome coronavirus 2 (SARs-CoV-2), has resulted in over 7 million deaths worldwide.
The biggest burden of disease from this virus is caused by longstanding symptoms that patients experience, known as long COVID, which currently affect over 65 million individuals globally. Coronavirus disease 2019 (COVID-19) remains a threat to global health and the extent of the impact upon population health, social, and economic areas is still not completely understood. The COVID-19 pandemic has also widened health inequalities globally. Our research has aimed to provide insight into the pathophysiological understanding of long COVID and its impact on individuals across society. Data are being used to develop interventions that are effective, accessible and can improve patient outcomes.
Introduction
Our international and interdisciplinary research team has developed a profile of research activity that is capable of increasing the mechanistic understanding of long COVID. We have established a wide network of lived experience experts that is representative of the clinical picture of long COVID. Broadening the ethnic and demographic representation within long COVID research is important to ensure that the resulting interventions address the needs of patients holistically. Our philosophy is to develop research with patients and not for patients; this ensures that we are ingrained in the lived experience and are centred on addressing the key areas that affect patients’ daily life.
Creating space and roles for patients within the research has been pivotal to our success. Our lived experience experts design, lead, and deliver impactful research which has been published via traditional academic journals and public-engagement events to give hope to people living with the condition. The outcomes continue to make a real-world impact with patients.
Who should benefit?
Our focus is on people with longstanding health challenges following SARs-CoV-2 infection. Long COVID represents a persistent, episodic, and disabling symptom profile that broadly affects quality of life and functional status. In the early stages of the COVID-19 pandemic, it was foreseen that patients were at risk of developing persistent and episodic symptoms that widely impact quality of life and functional status. Our early clinical observations demonstrated a complex symptom profile underpinned by a multi-system pathology that is specific to each patient. The conundrum is to determine how we can address the persistent issues with the added challenge of long COVID being a remitting and unpredictable condition. The unmet health need in long COVID is that tens of millions of people are left with chronic symptoms and challenges that do not currently have proven interventions (pharmacological and non-pharmacological) that can address or resolve them and restore pre-COVID-19 quality of life. Indeed, it is known that those who have been most adversely affected have been left with irreversible damage and long-term disability.
Through our research, which is driven by lived experience, we have been creating a space to understand the challenges that patients experience and using this to inform the development of detailed pathophysiological investigations that can increase the mechanistic understanding. By creating a space to listen and respond to the firsthand accounts of patients, we feel we have a better foundation for the design of clinically relevant research that will lead to the development of interdisciplinary and condition-specific interventions that are safe, effective, and accessible for long COVID patients.
Patients have always been at the forefront of our clinical research, and we maintain a position that our research is achieved with patients and not for patients. This philosophy has allowed us to develop and hold strong relationships with patients—whom we consider to be the experts on their conditions. Our established patient and lived experience group is a hive of research activity that has resulted in the group delivering patient-led research projects and serving on several national (UK) and international committees.
The strength of this group has increased throughout the evolution of the COVID-19 pandemic and has yielded impactful research activity that seeks to address patient needs globally.
Engagement
Our philosophy to engrain research activity with lived experience is a fundamental part of our group’s identity, and we research with patients and not for them. Patient engagement and involvement are a fundamental part of our day-to-day research activity and are embedded within all aspects of the research process, including the creation of ideas, development of suitable methodologies, and data collection and dissemination (via traditional and non-traditional processes). We have an international patient research committee from around the world and some co-opted members who attend when they are able or needed. The entire group meets once a month to bring the members up to date with ongoing projects, and to discuss and plan upcoming research. Outside of the monthly meeting, group members support research projects and long COVID organizations from within and outside of the team; this input is more frequent and includes attendance and representation on trial master or steering groups and data-management groups. In these roles, patients have a prominent role alongside academics and clinicians and are part of all decision-making processes. One example of crucial involvement from our patient representatives was in the development of an adapted cardio-pulmonary exercise test protocol to determine impaired gas transfer in long COVID patients. Our patient representatives were cautious about the impacts of exercise on those who are at risk of post-exertional symptom exacerbation (PESE). By working closely with the patients and their lived experiences, we were able to devise strict inclusion criteria that excluded those who were at the greatest risk of harm from the trial. We also, based on their involvement, implemented a digital post-exercise symptom monitoring process where we could remotely observe and respond to any symptom exacerbation. The resulting study comprised 192 exercise trials across six sites globally, and one event of PESE was reported. We fully believe that the lived experience experts played a crucial role in developing a novel and safe exercise trial that has yielded important pathophysiological insight. Data analysis for this project is coming to an end at the moment and we plan to feedback to the group the key findings in April 2024. Our lived experience experts will be recognized in all academic publications and we have recently secured funding to take a lived experience expert to an international conference to be part of the dissemination.
Research
Our lived experience experts have been pivotal in shaping our research design and implementation approaches. More broadly their expertise has also revolutionized our approach to patient safety. In and around our research laboratory at Derby, UK, we have implemented key changes to the design and layout of the research space to ensure that it is suitable and accessible to all patients who come in to participate. This includes having dedicated parking less than 50 m from the lab, accessible changing and showering facilities that have been relocated to be closer to the research lab, a quiet resting space that can be used before and after each session, and a dedicated space where friends, families, and relatives can wait and access refreshments whilst patients are participating in research. Recognizing that long COVID symptoms can be exacerbated with subsequent COVID-19 infections we still operate strict masking, testing, and reporting processes for COVID-19. Every room in the building has been fitted with a high-efficiency particulate air (HEPA) filter and CO2 monitor as a preventative/protective method for anyone that comes into the research space. All of these provisions have been informed directly by our lived experience experts. While it might not be considered as an impact on the research, we believe that this demonstrates that we value our patients. We think that this is in part why we have experienced high levels of recruitment to all projects and have had markedly below sector levels of dropout—which has impacted the quality of the data collected. These approaches are also being replicated in other research sites that we collaborate with internationally. We remain committed to enhancing the evidence base with our patients and to developing restorative treatments and rehabilitation programmes.
