Australian Study Identifies 32 Genes Driving Long COVID, Offering New Hope for Targeted Treatments
ADELAIDE, Australia — A groundbreaking study from the University of South Australia has pinpointed 32 genetic variants that appear to causally increase the risk of developing long COVID, a condition marked by persistent symptoms such as fatigue, brain fog, and chest pain months or even years after initial SARS-CoV-2 infection. Published this week in PLOS Computational Biology and Critical Reviews in Clinical Laboratory Sciences, the research marks a significant advance beyond previous studies that only identified associations between genes and long COVID.
The team, led by bioinformatics doctoral candidate Sindy Licette Piñero, developed a novel analytical framework combining Mendelian Randomization and Control Theory with large-scale multi-omics data—including genomic, epigenomic, transcriptomic, and proteomic information—to establish causal relationships between specific genes and long COVID susceptibility. This integrated approach allowed the researchers to prioritize 32 candidate genes, 13 of which had not been previously linked to the condition.
Long COVID affects an estimated 65 million people worldwide, with symptoms ranging from pulmonary dysfunction and muscle pain to dysautonomia—a disorder impacting autonomic nervous system functions such as blood pressure and heart rate. The condition can develop even in patients who initially experienced mild COVID-19 symptoms, complicating diagnosis and treatment. Estimates of long COVID prevalence vary widely, from 10% to 70% of COVID-19 cases.
The study also identified three distinct symptom-based subtypes of long COVID, each with unique biological underpinnings. This discovery may explain the wide variability in symptoms and suggests that personalized treatment strategies could be more effective than one-size-fits-all approaches. “This work represents a significant step toward customized management and treatment strategies for long COVID, ultimately improving patient outcomes,” the authors wrote.
Experts unaffiliated with the study have praised its innovative methodology but caution that further research is needed to translate genetic findings into clinical therapies. Art Schuermans, a researcher at the Broad Institute affiliated with KU Leuven University, noted, “While their approach is interesting, interpretability is a bit hampered by the complexity and multitude of approaches.” He emphasized the necessity of experimental validation, including animal models and clinical trials, to confirm whether targeting these genes can prevent or cure long COVID.
Similarly, Professor Chiranjib Chakraborty of Adamas University in India highlighted the importance of the study’s findings in the context of ongoing research into genetic factors influencing long COVID symptoms such as brain fog. “Thirteen might be discoveries. These genes are involved in the body’s response to the virus. They also play roles in immune function and cell growth,” he said. He stressed that clinical trials are essential to test gene- or protein-based markers identified in the study.
The researchers have made their analytical platform publicly available, encouraging other groups to validate and extend their findings across diverse patient cohorts. This open-science approach could accelerate the development of targeted diagnostics and therapies for long COVID.
Previous genetic studies, such as one identifying the FOXP4 gene’s association with long COVID, have laid important groundwork but lacked the causal evidence provided by this latest research. The integration of multiple data types and advanced modeling techniques represents a promising new direction in unraveling the complex biology of long COVID.
As the global health community continues to grapple with the long-term consequences of the pandemic, these insights offer hope for more effective interventions. For more information on ongoing research into COVID-19 and its long-term effects, visit the Centers for Disease Control and Prevention and the National Institutes of Health websites.
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