Genetics and COVID-19 symptoms

April 28, 2020

LONDON, UK - Data from thousands of identical and non-identical twins using the COVID Symptom Tracker app shows that genetic makeup plays a significant role in determining whether or not someone is likely to develop symptoms of coronavirus infection.

While older people and those with underlying health conditions are known to be more at risk from COVID-19, it’s still a mystery as to why some people are severely affected while others are only mildly ill or have no symptoms at all. 

To find out how much of this variation in symptoms was due to underlying genetic differences in the population, researchers at King’s College London and health science company ZOE analysed data from 2,633 identical and non-identical twins who have been logging their daily health using the COVID Symptom Tracker app.

The twins using the app were recruited from TwinsUK - the most clinically detailed study of twins in the world. The study team is currently carrying out further research on the impact of COVID-19 by analysing in-depth information about their immune systems, diet, lifestyle, health history and gut bacteria (microbiome) previously gathered from the participants.

The team previously used data from more than 2 million users of the app across the UK to define a set of symptoms that are highly predictive of having COVID-19 - including persistent cough, fatigue, loss of smell or taste and skipping meals - even in the absence of a formal test for the virus.

The researchers investigated whether these highly predictive symptoms of likely COVID-19 infection were more or less common in identical twins (who share 100 per cent of their genes) compared with non-identical twins, who are as related as regular siblings.

Overall, the proportion of twins likely to have COVID-19 was the same as the proportion of infected individuals in the wider population of app users. 

Their analysis showed that roughly half of the difference in symptoms between people can be explained by underlying variations in their genes, while the rest is due to other factors such as amount of viral exposure (viral load), underlying health conditions, environment and lifestyle.

Loss of smell (anosmia) and confusion (delirium) were found to have the strongest genetic contribution. Symptoms related to the activation of the immune system, including fever and fatigue, were also found to have a significant genetic component.

The analysis only reveals the extent to which the variation between individual responses to COVID-19 is ‘in the genes’, and will lead to further work which will reveal exactly which genes or genetic variations underlie these differences. 

One particular gene of interest is the ACE2 receptor - the molecular ‘gateway’ by which the coronavirus attaches and enters cells - and research is ongoing to investigate whether variations in this gene increase the risk of infection. Variations in other genes, particularly those involved in the immune response, are prime candidates as they will also affect the severity of the illness. 

The findings have been submitted to a scientific journal for peer-review and are available as a pre-print on medRxiv.

Professor Frances Williams, one of the lead researchers for the TwinsUK study, said, “We are hugely grateful to all the twins who have taken the time to log their health daily using the COVID-19 Symptom Tracker to help us unpick the genetic influence on this terrible disease. We are continuing to sift through the valuable data gathered from the twins over the years to understand more about the underlying biology and progression of COVID-19, and potentially identify those who might be most at risk based on their genetic makeup.”

Additional notes:

  • Self-reported symptoms of covid-19 including symptoms most predictive of SARS-CoV-2 infection, are heritable. FMK Williams et al. (2020) medRxiv doi:10.1101/2020.04.22.20072124
  • Most of the twins using the COVID Symptom Tracker are female (87%), and the researchers explored how sex might work influence symptoms, finding that females were generally more symptomatic. The majority of the twins in the study are from white European ancestries, so it isn’t possible to explore the influence of diverse genetic backgrounds in this group of participants.
  • For more information about the app or to request an interview with one of the research team, please contact press@joinzoe.com.
  • The app is available to download from the Apple App Store and Google Play Store.
  • Daily research updates and data can be found here.

About TwinsUK

TwinsUK is a study of 15,000 identical and non-identical twins led by Professor Tim Spector at King’s College London. TwinsUK aims to understand the genetic and environmental contributors to health and disease. Studying twins allows researchers to separate the impact of genes (nature) from the environment and lifestyle (nurture). TwinsUK has produced over 700 publications over the course of 27 years. Twinsuk.ac.uk 

TwinsUK is funded by the Wellcome Trust, Medical Research Council, European Union, Chronic Disease Research Foundation (CDRF), Zoe Global Ltd and the National Institute for Health Research (NIHR)-funded BioResource, Clinical Research Facility and Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust in partnership with King’s College London. 

About King’s College London

King's College London is one of the top 10 UK universities in the world (QS World University Rankings, 2018/19) and among the oldest in England. King’s has more than 31,000 students (including more than 12,800 postgraduates) from some 150 countries worldwide, and some 8,500 staff.

King's has an outstanding reputation for world-class teaching and cutting-edge research. In the 2014 Research Excellence Framework (REF), eighty-four per cent of research at King’s was deemed ‘world-leading’ or ‘internationally excellent’ (3* and 4*).

Since our foundation, King’s students and staff have dedicated themselves in the service of society. King’s will continue to focus on world-leading education, research and service, and will have an increasingly proactive role to play in a more interconnected, complex world. Visit our website to find out more about Vision 2029, King’s strategic vision for the next 12 years to 2029, which will be the 200th anniversary of the founding of the university.  

World-changing ideas. Life-changing impact.

About ZOE

ZOE is a healthcare science company using data-driven research to tackle the world’s health issues. By using machine learning combined with digital technologies like mobile phones, ZOE enables very large-scale scientific studies to tackle issues like COVID-19, inflammation and the impact of nutrition on health. Located in London and Boston, ZOE was founded by Professor Tim Spector of King’s College London, machine learning leader Jonathan Wolf and digital entrepreneur George Hadjigeourgiou. ZOE has carried out the largest nutritional studies of their kind in the world, and was named one of the Deloitte Fast 50 Rising Stars in 2019 for the company’s contribution to science enabled by technology and machine learning. 

For more information on ZOE’s mission and science visit www.joinzoe.com or follow @ZOE on Instagram.

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