An international team of researchers has found a genetic link to long-term symptoms after COVID-19. The identified gene variant is located close to the FOXP4 gene, which is known to affect lung function. The study, published in Nature Genetics, was led by researchers at Karolinska Institutet in Sweden and the Institute for Molecular Medicine Finland.

Biological causes behind persistent symptoms after COVID-19 infection, known as long COVID or post-COVID, remain unclear. Common symptoms include fatigue, cognitive difficulties, and breathing problems, which can reduce quality of life.

In an international collaboration – the Long COVID Host Genetics Initiative – researchers have analysed genetic data from 6,450 long COVID patients and more than a million controls across 24 studies from 16 countries. They found a gene variant that increases the risk of long COVID by about 60 percent. The genetic association was confirmed in an independent analysis involving an additional 9,500 cases.

Impaired lung function plays a key role

The gene variant is located right next to the gene FOXP4, which is involved in lung development and lung disease.

“Our findings suggest that impaired lung function plays a key role in developing long COVID,” says Hugo Zeberg, senior lecturer at the Department of Physiology and Pharmacology, Karolinska Institutet, and one of the lead researchers of the study. “While this gene variant significantly increases risk, it’s important to recognise it as just one part of a much larger puzzle,” he continues.

“Genetic studies can provide insights into disease risk factors and are particularly powerful for diseases where the exact mechanisms remain unknown,” says Hanna Ollila, FIMM-EMBL group leader at the Institute for Molecular Medicine Finland, University of Helsinki, and researcher at the Department of Anesthesia and Center for Genomic Medicine at Massachusetts General Hospital, who co-led the study.

See the published paper for information about funding and potential conflicts of interest.