Genome-wide Association Study of Long COVID
Infections can lead to persistent or long-term symptoms and diseases such as shingles after varicella
zoster, cancers after human papillomavirus, or rheumatic fever after streptococcal infections 1,2 . Similarly,
infection by SARS-CoV-2 can result in Long COVID, a condition characterized by symptoms of fatigue
and pulmonary and cognitive dysfunction 3–5 . The biological mechanisms that contribute to the
development of Long COVID remain to be clarified. We leveraged the COVID-19 Host Genetics
Initiative6,7 to perform a genome-wide association study for Long COVID including up to 6,450 Long
COVID cases and 1,093,995 population controls from 24 studies across 16 countries. We identified the
first genome-wide significant association for Long COVID at the FOXP4 locus. FOXP4 has been
previously associated with COVID-19 severity6 , lung function 8 , and cancers 9 , suggesting a broader role
for lung function in the pathophysiology of Long COVID. While we identify COVID-19 severity as a
causal risk factor for Long COVID, the impact of the genetic risk factor located in the FOXP4 locus could
not be solely explained by its association to severe COVID-19. Our findings further support the role of
pulmonary dysfunction and COVID-19 severity in the development of Long COVID.