First gene linked to long COVID discovered

A gene linked with developing the condition long COVID, has been identified by a preliminary study.

Long COVID is a condition which follows infection with SARS-CoV-2, the virus that causes COVID-19, presenting multiple symptoms, including fatigue, reduced lung capacity and cognitive impairment. Scientists from the Karolinska Institute in Stockholm, Sweden, conducted research that involved a genome-wide association study (GWAS), derived from the COVID-19 Host Genetics Initiative, which seeks to uncover the genetic factors connected to developing severe COVID-19 infection.

Publishing their findings as a preprint in medRxiv, which has not yet been peer-reviewed, the authors wrote: 'The biological mechanisms that contribute to the development of long COVID remain to be clarified. We leveraged the COVID-19 Host Genetics Initiative to perform a GWAS for long COVID including up to 6450 long COVID cases and 1,093,995 population controls from 24 studies across 16 countries.'

Four meta-analyses were conducted using this data, each one featuring separate case and control definitions of COVID-19 infection and long COVID diagnosis, respectively. The results showed that individuals possessing the sequence of DNA near the FOXP4 gene had a 1.6-fold increase in risk of developing long COVID.

The FOXP4 locus has previously been linked to immune and lung function and as a contributing factor to severe COVID-19 infection. However, the FOXP4 gene's strong link to long COVID could not be explained purely through its connection to developing severe COVID-19 infection, which was only partially identified as a factor in many of the studies examined.

'This variant has a much stronger impact on long COVID than its impact on severity,' Dr Hugo Zeberg, a lead author of the study and assistant professor at the Karolinska Institute, explained.

Several of the data sets analysed by the researchers had been used in previous studies to identify the link between the FOXP4 gene and severe COVID-19 infection. Thus, some researchers such as Dr Zhongshan Cheng, a bioinformatician at St Jude's Research Hospital, Tennessee, suggested that performing the same analysis on separate data sets is needed to reinforce the study's findings.

'When causes, maybe multifactorial, [are] clearly understood, it will help to treat patients who will be more susceptible to develop long COVID and potentially prevent long COVID.' said Dr Stéphanie Longet, assistant professor in immunology at Jean Monnet University, France, who was not involved in the study.

Overall, the goal of this study and similar research on both COVID-19 infection and corresponding long COVID is to aid in the treatment of those diagnosed and the prevention of further cases. Other statistical investigations of DNA from individuals diagnosed with long COVID will also help in reaching this goal.

'It's very important that this type of study is being done. It will gain momentum and greater power as the case number increases.' said Professor Chris Ponting, chair of medical bioinformatics at the University of Edinburgh, who was also not involved in the study.