Article Impact Level: HIGH Data Quality: STRONG Summary of Nature Genetics, 1–16. https://doi.org/10.1038/s41588-025-02100-w Dr. Vilma Lammi et al.
Points
- This genome-wide association study found that a genetic variant near the FOXP4 gene increases the risk of developing long COVID by approximately 60 percent.
- The FOXP4 gene is essential for lung function, and its association with long COVID appears independent of its known link to severe acute COVID-19.
- Researchers analyzed data from over 6,400 long COVID cases and more than one million controls across 24 studies in 16 countries, confirming findings in a replication cohort.
- The results emphasize the role of pulmonary-related genetic factors in predisposing individuals to persistent symptoms like fatigue and respiratory issues following SARS-CoV-2 infection.
- This discovery provides a foundation for future research into targeted therapies and risk assessment tools for long COVID, particularly those aimed at improving lung health.
Summary
This study investigated the genetic underpinnings of long COVID, a condition characterized by persistent symptoms such as fatigue, cognitive dysfunction, and pulmonary issues following SARS-CoV-2 infection. The genome-wide association study (GWAS) involved 6,450 long COVID cases and 1,093,995 population controls from 24 studies across 16 countries. Researchers identified a genetic variant near the FOXP4 gene, previously associated with lung function and disease. The findings suggest that this variant increases the risk of developing long COVID by approximately 60%, confirmed in a replication cohort of 9,500 long COVID cases and 798,835 controls.
FOXP4, a transcription factor critical for lung physiology and pathology, was shown to play a significant role in the development of long COVID. The association with long COVID was independent of its previously identified relationship with severe COVID-19. The study underscores the importance of lung function in the pathophysiology of long COVID, highlighting how genetic factors influencing pulmonary function can predispose individuals to prolonged symptoms post-infection. The identified gene variant is located close to FOXP4, implicating its role in the persistence of COVID-related health issues, particularly in lung-related symptoms.
This research adds a genetic dimension to understanding long COVID, providing insights into its biological mechanisms. While the FOXP4 variant is a significant risk factor, it is recognized as just one element of the broader genetic and environmental landscape contributing to long COVID. The study’s findings may pave the way for future research into targeted treatments for long COVID, particularly those focusing on lung function restoration. They may help identify individuals at higher risk for long-term complications following COVID-19 infection.
Link to the article: https://www.nature.com/articles/s41588-025-02100-w
References Lammi, V., Nakanishi, T., Jones, S. E., Andrews, S. J., Karjalainen, J., Cortés, B., O’Brien, H. E., Ochoa-Guzman, A., Fulton-Howard, B. E., Broberg, M., Haapaniemi, H. H., Kanai, M., Pirinen, M., Schmidt, A., Mitchell, R. E., Mousas, A., Mangino, M., Huerta-Chagoya, A., Sinnott-Armstrong, N., … Ollila, H. M. (2025). Genome-wide association study of long COVID. Nature Genetics, 1–16. https://doi.org/10.1038/s41588-025-02100-w
