Self-Reported Symptoms of COVID-19, Including Symptoms Most Predictive of SARS-CoV-2 Infection, Are Heritable

Abstract Susceptibility to infection such as SARS-CoV-2 may be influenced by host genotype. TwinsUK volunteers (n = 3261) completing the C-19 COVID-19 symptom tracker app allowed classical twin studies of COVID-19 symptoms, including predicted COVID-19, a symptom-based algorithm to predict true infection, derived from app users tested for SARS-CoV-2. We found heritability of 49% (32−64%) for delirium; 34% (20−47%) for diarrhea; 31% (8−52%) for fatigue; 19% (0−38%) for anosmia; 46% (31−60%) for skipped meals and 31% (11−48%) for predicted COVID-19. Heritability estimates were not affected by cohabiting or by social deprivation. The results suggest the importance of host genetics in the risk of clinical manifestations of COVID-19 and provide grounds for planning genome-wide association studies to establish specific genes involved in viral infectivity and the host immune response.

[1]  N. Akilli,et al.  Prevalence of Asymptomatic SARS-CoV-2 Infection , 2021, Annals of Internal Medicine.

[2]  M. Aslan,et al.  Correlation of chest CT and RT-PCR testing in coronavirus disease 2019 (COVID-19) in Turkey , 2021, Annals of Clinical and Analytical Medicine.

[3]  The role of host genetics in susceptibility to severe viral infections in humans and insights into host genetics of severe COVID-19: A systematic review , 2020, Virus Research.

[4]  J. Erdmann,et al.  Genomewide Association Study of Severe Covid-19 with Respiratory Failure , 2020, The New England journal of medicine.

[5]  F. García-Godoy,et al.  Taste and smell as chemosensory dysfunctions in COVID-19 infection. , 2020, American journal of dentistry.

[6]  W. Figg,et al.  TMPRSS2: Potential Biomarker for COVID‐19 Outcomes , 2020, Journal of clinical pharmacology.

[7]  S. Ng,et al.  Alterations in Gut Microbiota of Patients With COVID-19 During Time of Hospitalization , 2020, Gastroenterology.

[8]  The COVID-19 Host Genetics Initiative The COVID-19 Host Genetics Initiative, a global initiative to elucidate the role of host genetic factors in susceptibility and severity of the SARS-CoV-2 virus pandemic , 2020, European Journal of Human Genetics.

[9]  L. Tu,et al.  Implications of gastrointestinal manifestations of COVID-19 , 2020, The Lancet Gastroenterology & Hepatology.

[10]  M. Jorge Cardoso,et al.  Real-time tracking of self-reported symptoms to predict potential COVID-19 , 2020, Nature Medicine.

[11]  A. Zhernakova,et al.  Lack of Association Between Genetic Variants at ACE2 and TMPRSS2 Genes Involved in SARS-CoV-2 Infection and Human Quantitative Phenotypes , 2020, Frontiers in Genetics.

[12]  A. Sedaghat,et al.  Sinonasal pathophysiology of SARS‐CoV‐2 and COVID‐19: A systematic review of the current evidence , 2020, Laryngoscope investigative otolaryngology.

[13]  Ravi Philip Rajkumar,et al.  COVID-19 and mental health: A review of the existing literature , 2020, Asian Journal of Psychiatry.

[14]  Tim D. Spector,et al.  Rapid implementation of mobile technology for real-time epidemiology of COVID-19 , 2020, Science.

[15]  N. Vaninov In the eye of the COVID-19 cytokine storm , 2020, Nature Reviews Immunology.

[16]  K. Schulman,et al.  Covid-19 and Health Care's Digital Revolution. , 2020, The New England journal of medicine.

[17]  M. D. De Buyzere,et al.  The host’s angiotensin-converting enzyme polymorphism may explain epidemiological findings in COVID-19 infections , 2020, Clinica Chimica Acta.

[18]  G. Herrler,et al.  SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor , 2020, Cell.

[19]  Q. Tao,et al.  Correlation of Chest CT and RT-PCR Testing in Coronavirus Disease 2019 (COVID-19) in China: A Report of 1014 Cases , 2020, Radiology.

[20]  M. Hotopf,et al.  The behavioral, cellular and immune mediators of HIV-1 acquisition: New insights from population genetics , 2020, Scientific Reports.

[21]  M. Lipsitch,et al.  Defining the Epidemiology of Covid-19 - Studies Needed. , 2020, The New England journal of medicine.

[22]  T. Spector,et al.  TwinsUK: The UK Adult Twin Registry Update , 2019, Twin Research and Human Genetics.

[23]  Timothy R. Brick,et al.  OpenMx 2.0: Extended Structural Equation and Statistical Modeling , 2015, Psychometrika.

[24]  Klaus K. Holst,et al.  The liability threshold model for censored twin data , 2014, Comput. Stat. Data Anal..

[25]  Jordan W Smoller,et al.  The Genetics of Stress-Related Disorders: PTSD, Depression, and Anxiety Disorders , 2016, Neuropsychopharmacology.

[26]  Y. Keynan,et al.  The Role of Polymorphisms in Host Immune Genes in Determining the Severity of Respiratory Illness Caused by Pandemic H1N1 Influenza , 2013, Public Health Genomics.

[27]  A. Hill,et al.  Human genetic susceptibility to infectious disease , 2012, Nature Reviews Genetics.

[28]  Hsuan-Cheng Huang,et al.  Hepatitis B viraemia: its heritability and association with common genetic variation in the interferon γ signalling pathway , 2010, Gut.

[29]  Matteo Fumagalli,et al.  Genome-Wide Identification of Susceptibility Alleles for Viral Infections through a Population Genetics Approach , 2010, PLoS genetics.

[30]  J. Witte,et al.  Likelihood‐based approach to estimating twin concordance for dichotomous traits , 1999, Genetic epidemiology.

[31]  D. Falconer Introduction to quantitative genetics. 1. ed. , 1984 .

[32]  H. Akaike A new look at the statistical model identification , 1974 .

[33]  Cedric A. B. Smith,et al.  Introduction to Quantitative Genetics , 1960 .