image: The team at GCAT that initiated the work which made this international study on Long COVID possible.
Credit: IGTP
- GCAT is the only Spanish project to contribute to this international study
New insights into the complexities of Long COVID have been brought to light, thanks to an international collaborative effort with the participation of researchers from GCATGenomes for life, a strategic project of the Germans Trias i Pujol Research Institute (IGTP). A study published yesterday in Nature Genetics used the vast data from the COVID-19 Host Genetics Initiative to perform the first study examining the entire genetic code specifically focused on Long COVID.
The term "Long COVID", officially recognised by the World Health Organisation, describes symptoms that persist for months after the acute phase of a COVID-19 infection has subsided. This condition has become a significant concern worldwide with symptoms ranging from pulmonary issues and fatigue to cognitive disturbances.
A study published in the journal Nature Genetics has identified the first genome-wide significant association for Long COVID, which has been found at the FOXP4 gene. The study, conducted under the COVID-19 Host Genetics Initiative, included up to 6,450 individuals diagnosed with Long COVID and over a million controls from 16 countries. The analysis was conducted using data from participants in the GCAT cohort, coordinated by IGTP, that have been monitoring the COVID-19 pandemic in the Catalan population since 2020 with the collaboration of the Barcelona Institute for Global Health (ISGlobal)-a centre supported by the "la Caixa" Foundation, the COVICAT cohort (Cohort COVID in Catalonia).
The results suggest that the link between the FOXP4 gene and Long COVID is deeply connected to both how our lungs work and how our immune system responds to infections. Additionally, the researchers have discovered a strong relationship between severe cases of COVID-19 and Long COVID, in line with previous research. This raises the question: do all genetic variants that make someone more susceptible to COVID-19 and more affected by it also increase the risk of Long COVID? Not necessarily. The study has found that, while most genetic variants primarily affect how we respond to the SARS-CoV-2 virus or the severity of COVID-19, those related to the FOXP4 gene seem to play a significant role in the onset of Long COVID. This highlights potential biological factors that are crucial in Long COVID, associated with lung function and our immune response.
Rafael De Cid, scientific director of the GCAT project at IGTP and author of the study, states: "The study's findings will help categorise risk factors for Long COVID, a complex condition shaped by both risk factors-such as disease severity, chronic conditions, and obesity-and protective factors like vaccination, sleep, and exercise. These opposing influences contribute to symptom persistence and subtype variability, including gender differences. Their consideration and follow-up in future studies will aid in distinguishing subtypes and advancing personalised prevention and treatment strategies."
Long COVID continues to be a multifaceted disease with a wide variety of symptoms. Further research is needed to fully understand the mechanisms behind it. Nonetheless, this study provides genetic evidence of the pivotal role that lung health and function might have in the progression of this post-COVID condition.
Journal
Nature Genetics
Method of Research
Meta-analysis
Subject of Research
People
Article Title
Genome-wide association study of long COVID
Article Publication Date
21-May-2025
COI Statement
S.B. has ownerships in Intomics A/S, Hoba Therapeutics Aps, Novo Nordisk A/S, Lundbeck A/S, ALK abello A/S, Eli Lilly and Co and is managing board memberships in Proscion A/S and Intomics A/S. A.B., K.M.S.B., S.W., N.L.W., F.T., E.S. and E.T.C. are employees of Helix. A.D. received an honorarium from Gilead Sciences. A.L.G. and C.J. have funded research collaborations with Orion for collaborative research projects outside the submitted work. T.H. and H.E.O.B. have options in Sano Genetics. P.J.S. is a shareholder of Sano Genetics. T.H.K. has received consulting fees from Albireo, Boehringer Ingelheim, MSD and Falk Pharma. K.U.L. is cofounder and member of the scientific board of LAMPseq Diagnostics GmbH. T.N. has received speaking fee from Boehringer Ingelheim for talks unrelated to this research. M.E.K.N. is a current employee of Novartis Pharma AG. J.B.R.’s institution has received investigator-initiated grant funding from Eli Lilly, GlaxoSmithKline and Biogen for projects unrelated to this research. He is the CEO of 5 Prime Sciences (www.5primesciences.com), which provides research services for biotech, pharma and venture capital companies for projects unrelated to this research. V.F. is an employee of 5 Prime Sciences. C.D.S. reports grants and personal fees from AstraZeneca, Janssen-Cilag and ViiV Healthcare, personal fees and nonfinancial support from BBraun Melsungen, grants, personal fees and nonfinancial support from Gilead Sciences, personal fees from BioNtech, Eli Lilly, Formycon, Pfizer, Roche, Apeiron, GSK, Molecular partners, SOBI, AbbVie, MSD and Synairgen and grants from Cepheid. L.V.W. reports research funding from GlaxoSmithKline, Genentech and Orion Pharma, and consultancy for Galapagos and GlaxoSmithKline, outside of the submitted work. J.W. is a consultant for Roboscreen GmbH, Biogen GmbH, Immungenetics AG, Noselab GmbH, Roche Diagnostics International, Roche Pharma AG, Janssen-Cilag GmbH, Eisai GmbH, Boehringer Ingelheim and Lilly Deutschland GmbH and has received honoraries from Eisai GmbH, Biogen GmbH, AGNP e. V., Veranex, Med Update GmbH, Guangzhou Gloryren Medical Technology (China), Pfizer Pharma GmbH, Fachverband Rheumatologische Fachassistenz e. V., AWO Psychiatrie Akademie gGmbH, Neuroakademie E. V., Beijing Yibai Science und Technology Ltd., Abbott Laboratories GmbH, Lilly Deutschland GmbH, Simon & Kucher and streamedup! GmbH. The other authors declare no competing interests.