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Our research identified the first reproducible genetic associations in long COVID, revealing thousands of previously unknown genetic patterns across multiple biological mechanisms – helping explain why symptoms and experiences vary so widely between people.
These findings underpin the Post COVID DNA Wellness Report to provide you with a deeper, more connected view of your genetic profile - correlating with the different symptoms experienced by people known to have long COVID in these research studies.
Video
Our Research
Long COVID and ME/CFS have affected the lives of over 400 million people worldwide. The diseases are now estimated to contribute to over $1 trillion of healthcare costs and lost economic productivity[1,2] – equivalent to 1% of global GDP.
In spite of their huge personal and public health impacts, there are still no tools to accurately diagnose patients and no drugs that treat the underlying causes of the diseases. This has led to widespread misunderstanding, lack of awareness, and even denial of the diseases in the clinical and social care communities, which further harms patients.
Research funding and engagement from pharmaceutical companies is also low, in large part because the disease is complex, and there was previously no reproduced, peer reviewed evidence for any genes associated with the disease due to the large number of disease symptoms and affected organs.[3]
Long COVID is biologically complex and involves several genes and mechanisms across almost every organ in the body.[4] Our research has shown that it is not caused by a single gene, and instead that combinations of genes are associated with the disease, and that different symptoms are influenced by different sets of genes (mechanisms).[5],[6]
Most DNA or genetic reports examine a small number of variants, one at a time. Our Post COVID DNA Wellness Report takes a different approach.
PrecisionLife's genetic analysis platform looks for combinations of genetic variants that appear together more frequently in people known to have long COVID in our research studies. These combinations are called genetic patterns.
Studying combinations reveals important connections between genes and biological processes that are impossible to find by looking at individual variants alone. This is why PrecisionLife's research has identified thousands more genetic patterns than other studies, and these results have been reproduced in multiple confirmatory research studies in different populations.
Our approach is based on our belief that there are many different causes of a disease across patients. They may have the same diagnosis because their symptoms appear similar, but that doesn’t mean the causes of their diseases are the same.
This is shown by our first ME/CFS study. The results showed genetically distinct subgroups of ME/CFS patients with different symptoms consistent with the mechanism affected by their genetic differences.
Patient stratification of ME/CFS, showing that patient subgroups with specific genetic disease patterns (the colored clusters) have symptoms consistent with the known functions of the genes in those disease patterns.
This means that drugs that benefit a patient with one group of genetic patterns (e.g. the green group) may not work for a patient who instead has a different group of genetic patterns (e.g. the orange group). This is because the cause of their disease (their disease ‘mechanism’) is different.
In fact, because ME/CFS and long COVID patients are already unwell, they are likely at a higher risk of getting side effects from drugs that could never have helped them.
Identifying the specific mechanisms driving disease in a patient is therefore crucial to choosing their most effective personalized treatment regimen, and whether they should be enrolled in a particular clinical trial.
References
1. Al-Aly, Z., Davis, H., McCorkell, L. et al. Long COVID science, research and policy. Nature Medicine 30, 2148–2164 (2024)
2. Bateman Horn Center / Optum Estimating Prevalence, Demographics, and Costs of ME/CFS (2019) Front. Pediatr. 8;6:412
3. Long-Term Long Covid (2023) https://erictopol.substack.com/p/long-term-long-covid
4. Davis HE, McCorkell L, Vogel JM, Topol EJ. Long COVID: major findings, mechanisms and recommendations. Nat Rev Microbiol. 2023 Mar;21(3):133-146. doi: 10.1038/s41579-022-00846-2
5. Das S, Taylor K, Kozubek J, Sardell J, Gardner S. Genetic risk factors for ME/CFS identified using combinatorial analysis. J Transl Med. 2022 Dec 14;20(1):598. doi: 10.1186/s12967-022-03815-8
6. Sardell JM, Das S, Pearson M, et al. Identification of novel reproducible combinatorial genetic risk factors for myalgic encephalomyelitis in the DecodeME patient cohort and commonalities with long COVID. J Transl Med. 2026 Apr 21;24(1):733. doi: 10.1186/s12967-026-08167-1
Published studies
Foundational research
14 genes linked to ME/CFS
Our first published study identified 14 genes associated with ME/CFS and showed how our analysis can reveal biological mechanisms that standard genetic approaches may miss. This helped lay the groundwork for our long COVID research.
Long COVID genetics discovery
73 genes linked to long COVID biology
In our first major long COVID genetics study, we identified 73 genes associated with severe and fatigue-dominant long COVID, helping show that different patient groups can involve different underlying biological mechanisms.
Independent validation
Long COVID findings reproduced in the US
We tested our earlier long COVID findings in the All of Us research program and found strong reproducibility. Around 80% of the evaluated genetic signatures were reproduced, covering 92% of the genes identified in the original study - a first in long COVID research - confirming many of our original findings.
Shared biology
Long COVID and ME/CFS show important overlap
Comparing our long COVID findings with data from the DecodeME Study showed that 76 of 180 long COVID-linked genes tested were also associated with ME/CFS, highlighting important shared biology while reinforcing the complexity of both conditions.
Research milestones
We found 259 candidate core ME/CFS genes in DecodeME and showed that these reproduced in independent UK Biobank research populations. This definitively showed that ME/CFS is a very polygenic and heterogenous disease, which has major consequences for every future research study.
We also found that 76 of the 180 long COVID genes that we had identified were also present in ME/CFS. This shows there is significant shared pathophysiology between these diseases but they are distinct.
Major progress
Genes identified and reproduced
180 long COVID genes and 259 candidate core ME/CFS genes
Major disease mechanisms
8 major mechanisms significantly associated with the diseases (5 shared)
Drug repurposing candidates
56 drug repurposing candidates with strong genetic evidence in ME/CFS and 230 in long COVID, with 23 of these potentially having benefit to both diseases
The release of our Post COVID DNA Wellness Report is the first step in a large research agenda for PrecisionLife.
Targeted drug repurposing
We are collaborating with groups around the world to design and run targeted drug repurposing clinical trials to find effective therapies for ME/CFS and long COVID patients.
Matching patients to trials
We are also helping other drug repurposing trials to better select their patients using our patient stratification tools to maximize the chances of successful trials.
Predicting GLP-1 response
We have identified genetic biomarkers that predict the efficacy and side-effect profiles of GLP-1 receptor agonist drugs (like Wegovy, Mounjaro, Zepbound etc.) to identify long COVID and ME/CFS patients who may benefit from these drugs without finding their side effects overwhelming.
Testing personalized GLP-1s
We will be working with leading scientists to run clinical studies testing microdosed GLP-1 drugs in combination with other medications based on the patient’s ability to benefit from GLP-1 and not suffer side effects.
We have reason for hope
This brings all the previous work together to find new repurposing treatments for ME/CFS and long COVID as quickly and cost-effectively as possible. We’re recruiting patients who have specific mechanisms driving their disease, where we have already identified that there is a safe, well-tolerated generic drug that might help patients who have that disease mechanism.
If these trials are successful, we can demonstrate to pharmaceutical companies that ME/CFS and long COVID are not too complex to make effective drugs. These are huge unserved patient communities and having the clinical validation that we can find disease causing genes, that drugs targeting these genes can bring clinical benefit to patients, and that we can even predict which patients are likely to benefit from these drugs, will be a game changer for pharma companies’ appetite for investment in these diseases.
Successful validation would provide unprecedented confidence that we have the tools to accelerate and derisk novel disease biology, creating a very large and currently unserved opportunity to improve people's lives.
There’s still a huge amount of work to do, but thanks to our work with and support from patients, disease charities and clinical groups, we now have many more ways forward and new opportunities that could lead to treatments, diagnostics, and even preventive medicine for millions of people.
These long COVID and ME/CFS projects have been funded by PrecisionLife, with contributions from Innovate UK and the Complex Disorders Alliance.
We gratefully acknowledge the Action for ME patient and public involvement team and thank the DecodeME, Sano GOLD, and UK Biobank participants, and the wider network of patients for their contributions without whom this research would not have been possible. This work also uses data provided by patients and collected by the NHS as part of their care and support, for which we are also grateful.
The Post COVID DNA Wellness Report is a personalized genetic report that analyzes 1,670 genetic patterns across six key areas of biology affected by long COVID, based on PrecisionLife's world-leading research.
Discover what stands out in your DNA, explore the genes and biological mechanisms most relevant to you, and gain personalized biological context that can help you better understand your genetic profile and have more focused conversations about your health.
Order now to also receive the interactive Post COVID Wellness Guide summarizing all the published information about post COVID biology, lifestyle changes and supplements.
The report does not diagnose, detect, predict, prevent, monitor, treat, or manage long COVID or any other medical condition and is not intended for clinical use. It does not provide personalized medical, lifestyle, nutritional, supplement or treatment recommendations. If you have concerns about your health or symptoms, consult a qualified healthcare professional.
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