There is a critical need to identify the underlying biomedical mechanisms associated with Long Covid and ME/CFS. Many studies have shown that COVID-19 can have long-term health impacts, including but not limited to increased cardiovascular disease risk, neurological/cognitive impairments, and immune system disturbances.

While evidence demonstrates a link between Long Covid and immune dysfunction, characterized by disruptions or ‘exhaustion’ of specific immune cell populations, our understanding of the precise nature and extent of their functional abnormalities remains incomplete. Further research is necessary to elucidate the specific mechanisms involved, particularly focusing on the functional impairments of affected immune cells or processes.

To fully understand why our immune system malfunctions, especially in scenarios like post-infection associated illnesses, we must delve deeper into the intricate workings of our cells, specifically focusing on metabolic programming. This includes the critical role of mitochondria, often likened to powerhouses of the cell, which are responsible for energy production and play a crucial role in influencing how our immune system fights off pathogens and maintains overall health. Additionally, epigenetic changes, such as modifications in DNA methylation and histone modification, can affect how genes are expressed, influencing immune cell function and contributing to persistent immune dysfunction and metabolic changes.

When these essential “energy centres” and regulatory mechanisms are disrupted, a cascade of effects can occur, potentially contributing to a range of symptoms such as muscle weakness, fatigue, and cognitive impairment. Interestingly, these symptoms often overlap with those observed in infection-associated chronic conditions, suggesting a potential link between metabolic dysfunction and certain post-infection complications. This overlap highlights the importance of incorporating the study of immune cell metabolic function, or immunometabolic programming, into our understanding of immune dysfunction, particularly in the context of infection-associated chronic conditions.

Our Research Approaches 

To address these complex issues, our research will focus on several key areas:

1. Deep Immune Profiling: We will perform deep immune cell profiling in the blood of participants by simultaneously measuring over 40 markers on individual cells within one sample. This approach provides a comprehensive assessment of all main immune cell subsets, (including  effector or functional states), to enable assessment of their potential immunomodulatory, metabolic or effector function associated with immune dysfunction.

2. Immunometabolic Function Assessment: We aim to investigate metabolic pathway dependencies in immune cells using specialised assays that explore metabolic pathways at a single-cell level.

3. Immunometabolic programming: We will explore whether immune cells (within functional differences/impairments) display evidence of epigenetic changes and/or exhibit trained immunity signatures.

4. Immunometabolic profiling: Through collaboration (read more here), we aim to ultise a suite of powerful spectroscopic tools (eg high field NMR spectroscopy and mass spectrometry) for comprehensive molecular profiling and biomarker discovery for disease monitoring. 

5. Inflammatory markers/proteins: We aim to include assessment of any key potential biomarkers that evolve either through our research, or global research efforts.

Research project collaborations:

1. Evidence-based management of Long COVID: A 3-year project funded by the Health Research Council of New Zealand to provide an evidence platform for the delivery of health services to manage Long COVID. We are leading one of the aims of this project: Determining biomarkers of immune dysfunction in Long COVID. Our role: biomedical assay development (immune dysfunction) and assessment in a control-matched long covid cohort.

2. Investigating alterations in the expression of small RNA molecules (miRNA) in ME/CFS (and Long Covid-ME/CFS): A 3 year project funded by the Mason Foundation (Australia) to explore combining small RNA molecules (miRNA) profiling with immunometabolic analysis to uncover deeper insights into the molecular mechanisms driving ME/CFS and identify potential biomarkers. Our role: contribution of ME/CFS (and ME/CFS-Long Covid) patient cohort samples and immunometabolic assays.