A team including the Department of Twin Research and Genetic Epidemiology at King's College London, UK, and the NIHR Centre for Biomedical Research recently made a new observation: genetic factors play a role in half of the individual differences observed in the main symptoms of Covid-19.
The team published the above study "Self-reported symptoms of Covid-19 including symptoms most predictive of SARS-CoV- 2 infections, are heritable" online on the preprinted website medRxiv, which has not yet been peer-reviewed.
The research team developed a symptom-tracking app (C-19 Covid Symptom Tracker app, https://doi.org/10.1101/2020.04.02.20051334) to collect real-time data during the SARS-CoV-2 pandemic.
Already 2 million people have downloaded the app, which asks users daily if they have some common symptoms, including cough, fever, chest pain, delirium, and loss of smell.
The paper mentions that infectious diseases may exhibit a hereditary predisposition to infection and development, as well as the severity of the immune response, which can be influenced by host genetic factors.
Similar findings have been made in previous studies on H1NI infection. Therefore, the team hypothesized that the host genotype may influence susceptibility to infections such as SARS-CoV-2.
The research team included adult twins from the long-launched TwinsUK project who reported their current symptoms in this study.
Between March 25 and April 3, 2020, 2633 adult same-sex twins provided data.
The study is a classic twin study of Covid-19 symptoms based on a symptom-based machine learning algorithm and predicts the likelihood of individuals being infected.
The sample consisted of 728 complete pairs, of which 537 were identical twins (MZ) and 191 were dizygotic twins (DZ), representing 86.9% of females.
The genetic correlates of Covid-19 symptoms were: delirium = 49% (95% confidence interval, 24%-75%), fever = 41% (95% confidence interval, 12%-70%), lethargy = 32% (95% confidence interval, 1%-64%), loss of smell = 47% (95% confidence interval, 27%-67%), shortness of breath = 43% (95% confidence interval, 8%-77%), and diarrhea = 34% (95% confidence interval, 14%-55%).
But hoarseness of voice, cough, loss of appetite, chest pain, abdominal pain are determined by environmental factors.
The team also has real-time information about its current co-residence obtained via text message. To control for the effects of infection within the family, they repeated a similar study with twins who lived apart.
The results were similar, with the genetic correlation of Covid-19 symptoms being, fever = 41% (7%-74%), loss of smell = 48% (25%-72%), shortness of breath = 47% (12%-82%), but an increase in diarrhea (41%), delirium (37%) and a decrease in fatigue (24%).
Genetic correlations were also observed in the "Predicted Covid-19" area: 50% (29%-70%) in the overall sample and 54% (30%-77%) in the sample of near-siblings living separately.
"Predicted Covid-19" status was determined by a linear combination of self-reported age, sex, loss of sense of smell, severe or significant persistent cough, fatigue, and loss of appetite.
The study noted during the discussion session that symptoms associated with immune activation, such as fever, delirium, and lethargy, have a genetic probability of more than 35 percent.
A previous study showed that loss of smell was an important predictor of Covid-19, and this study showed a 48% genetic probability.
They argue that SARS-CoV-2 infection is not simply a random event, but is influenced to some extent by host genetics and may reflect interindividual differences in host immune response.
The research team analyzed that viral infections typically lead to T-cell activation, with IL-1, IL-6, and TNF-ฮฑ inflammatory mediators triggering flu-like symptoms such as fever.
This genetic-based difference in response will provide important clues to treatment and help identify a population at high risk of death, which tends to experience cytokine storms 1-2 weeks after symptoms appear.
Notably, the team also mentioned that subsequent nucleic acid testing by APP users (n=5238) proved that their model was already the best predictor of a positive SARS-CoV-2 response.
The team concluded that the purpose of this study was to assess the heritability of Covid-19 symptoms and to identify phenotypes suitable for genome-wide association studies.
And public health measures to identify people at increased genetic risk for serious infections would be useful to mitigate the economic impact of the blockade and social alienation policies.
Link to the paper: https://www.medrxiv.org/content/10.1101/2020.04.22.20072124v2
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