How new research confirmed long COVID genetic associations, paving the way for precision diagnostics and treatments

At least 65 million people globally are estimated to have long COVID - debilitating and persistent symptoms present long after initial COVID-19 infections. However, despite causing huge personal and public health impacts, we still have no tools to accurately diagnose patients and no drugs that treat long COVID’s underlying causes. This is in large part because there has been no fully replicated evidence for any genes associated with the condition. However, groundbreaking new research is changing that.

In a previous analysis of genetic data from the UK Sano GOLD long COVID study, PrecisionLife researchers became the first to identify genes that were highly associated with long COVID – creating new possibilities for potential precision diagnostic and therapeutic approaches to address the massive unmet medical need by targeting these genes.

The findings have potential implications for improving diagnostic criteria, developing accurate diagnostic tools, and prioritizing new treatments for long COVID and related conditions.

To confirm these discoveries, PrecisionLife, as part of its partnership with Metrodora Institute and Metrodora Foundation, aimed to reproduce its previous findings in an independent and more diverse dataset from the US National Institutes of Health’s All of Us (AoU) Research Program. 

88% of the genes identified in the original study were confirmed as also being associated with long COVID in the AoU population. This is a very positive result given that no genes have been replicated in previous studies. 7 out of 9 genes previously found to be in common between long COVID and ME/CFS were also reproduced, strengthening the genetic explanation as to why the two conditions share certain similarities.

The development of effective new disease-modifying treatments in neurodegenerative and neuropsychiatric disorders has been hindered by their inherent genetic complexity, environmental influences and clinical variability. Precision medicine approaches to neurological diseases, such as the use of tofersen to treat patients with specific SOD-1 mutations in ALS, are in their infancy but are fundamental to making meaningful progress and creating effective new therapeutic options in diseases such as ALS, Alzheimer’s and schizophrenia, which still have huge unmet medical need. 

To find new ways of diagnosing and treating complex diseases we first must understand the mechanisms underpinning their key pathological changes, how these relate to different patient subgroups, and which drugs might be useful in reducing their effects – this is the basis of precision neuroscience.

Why does reproducing the associated genes matter?

Understanding which genes are associated with long COVID will help doctors better manage the condition by identifying people who may be at higher risk and guiding the development of new treatments. It will help researchers focus in on key genetic targets against which existing and new drugs can be tested.

Replicating results across separate, and especially diverse, populations strengthens confidence in findings. This means that the identified genes are much more likely to play a real role in long COVID, rather than appearing by chance. These insights enable the development of targeted therapies and accurate diagnostics, so that healthcare providers can personalize treatments based on a patient’s genetic profile, improving diagnosis, treatment options, and potentially even preventing severe cases of long COVID in those most at risk.

People with long COVID and ME/CFS have suffered from a lack of awareness and often denial of their condition in health and social care communities. This study confirms the significant role of genetics in long COVID and further emphasizes its underlying biological basis, enabling a more consistent definition of long COVID diagnosis that can guide a path to effective treatment.

These findings bring us closer to understanding long COVID across different groups of people, helping to speed up the development of accurate tests and new treatments for long COVID, ME/CFS, and similar chronic conditions.

Translation to the clinic: turning research into patient benefit

“These findings redefine our understanding of the genetic components of long COVID, laying the foundation for precision medicine approaches that could revolutionize care for the millions of patients living with the condition,” said Steve Gardner, CEO of PrecisionLife.

Notably, many of these genes were present across different racial and ethnic groups, including white, black/African American, and Hispanic/Latino, suggesting the genetic links apply broadly and are not limited to one population, meaning these findings may have broader clinical application and could promote better health equity.

“Many studies in our space are not replicable and this adds to mounting frustration amongst clinicians and patients around diagnosing and treating complex conditions, like long COVID. Metrodora Foundation and PrecisionLife are unlocking new hope for patients everywhere, and we’re committed to driving this important work forward," said Rohit Gupta, Principal Investigator for the MetX and MELO studies at Metrodora Institute. “We’re already uncovering crucial insights into this chronic condition and the wide array of debilitating symptoms.”

This research may also lead to new treatment options by utilizing medications that already exist. The initial study identified 13 drugs that could be repurposed to help treat the condition based on the underlying genetic mechanisms. 11 out of the 13 genes for which these drug repurposing candidates had been identified were reproduced in this new analysis. This lends weight to their prioritization for clinical efficacy trials that will evaluate their use as safe and effective new treatments.

"Patients with complex conditions, like long COVID, simply can’t wait. They are suffering daily,” said Amy Rochlin, Executive Director of the Metrodora Foundation. "We care deeply about getting patients the answers they deserve, and we’re committed to driving progress forward with urgency.”

About the MELO Study

The MELO (ME and long COVID) Study is an ongoing clinical study which aims to evaluate biomarkers in ME/CFS and long COVID with the goal of creating accurate tests, discovering new and repurposed drug candidates, and improving the understanding of the biological drivers of these conditions. The MELO Study, funded by a generous donation from the Metrodora Foundation, features a collaboration between the Metrodora Institute—with its decentralized platform for patient engagement, specimen collection, and genotyping—and PrecisionLife, which has contributed its unique disease insights, test designs, and repurposing candidates.

To get involved or find out more about the MELO Study visit www.metrodorainstitute.co/melo-study and join the Metrodora Connect research platform through the MyDataHelps app to find out about new studies and clinical trials. Click here to download the app for iOS. Click here to download the app for Android. Use the code BMDSMX when registering to enter Metrodora Connect.

Follow our progress

The full scientific paper published to share the long COVID reproduction study has been made available on medRxiv, the pre-print server for health sciences, here: https://doi.org/10.1101/2025.02.04.25320937.

To read more about our research in long COVID and ME/CFS, visit www.precisionlife.com/longcovid-me

For updates from each partner involved in this innovative work, visit their websites:
PrecisionLife - PrecisionLife.com
Metrodora Foundation - Metrodora.org
Metrodora Institute - MetrodoraInstitute.co