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

This article has been Reviewed by the following groups

Read the full article See related articles

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.

Article activity feed

  1. SciScore for 10.1101/2020.04.22.20072124: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    No key resources detected.


    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).


    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    The limitations include first, there is likely to be healthy volunteer bias. That said, our study was well powered to find moderate heritability. Second, many symptoms are non-specific and are prevalent in spring in the Northern hemisphere when allergies and seasonal flu are active, and are not indicative of infection status. We did have sufficient sample size of people reporting symptoms and viral test results to indicate accurately which symptom pattern provides the greatest positive predictive value. Our results could have been biased by MZ twins cohabiting more than DZ twins, but real time data collection allowed us to exclude cohabiting pairs. Finally, our twin sample is predominantly female for historical recruitment reasons and is not representative of non-European ancestries 5. The genetic influence on covid-19 symptoms may reflect genotype status of candidate genes such as ACE2R which encodes the target for viral attachment10. Further genetic work is underway to determine whether twins’ genotype at ACE2R influences either predicted positivity or symptoms and a global genetic study is underway (https://www.covid19hg.org/). Public health measures to identify those at increased genetic risk of severe infection would be useful as a way of mitigating the economic effects of lockdown and social distancing policies.

    Results from TrialIdentifier: No clinical trial numbers were referenced.


    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.


    Results from JetFighter: We did not find any issues relating to colormaps.


    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • No funding statement was detected.
    • No protocol registration statement was detected.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.