Polymorphisms in the ACE2 Locus Associate with Severity of COVID-19 Infection

  1. Luke Wooster
  2. Christopher J. Nicholson
  3. Haakon H. Sigurslid
  4. Christian L. Lino Cardenas
  5. Rajeev Malhotra

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Abstract

Data from clinical studies suggests a strong association between underlying cardiometabolic disease and worse outcomes in COVID-19. Given that the SARS-CoV-2 virus has a unique marked affinity to the human angiotensin-converting enzyme 2 (ACE2) receptor, one potential explanation behind this phenomenon may involve the higher expression of ACE2 receptor in these patients. Here, we analyzed association between polymorphisms in the ACE2 locus and COVID-19 severity in 62 patients found to be COVID-19 positive by polymerase chain reaction. Of these patients, 23 required hospitalization due to COVID-19 infection. Of 61 ACE2 single nucleotide polymorphisms (SNPs) genotyped in this patient cohort, 10 were significantly associated with tissue expression of ACE2. Logistic regression adjusted for age and for sex identified six of these ten SNPs to be significantly associated with hospitalization. These results provide preliminary evidence of a genetic link between the ACE2 genotype and COVID-19 disease severity and suggest that the ACE2 genotype may inform COVID-19 risk stratification and need for more intense therapy.

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    SciScore for 10.1101/2020.06.18.20135152: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: This study was approved by the Partners institutional review board (IRB protocol #2020P000982).
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableACE2 is located on the X chromosome but has been shown to escape X inactivation.10 Therefore, logistic regression analysis adjusted for age and sex (Plink v1.07) was performed using allelic count where males were 0 or 1 and females 0, 1, or 2.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    ACE2 is located on the X chromosome but has been shown to escape X inactivation.10 Therefore, logistic regression analysis adjusted for age and sex (Plink v1.07) was performed using allelic count where males were 0 or 1 and females 0, 1, or 2.
    Plink
    suggested: (PLINK, RRID:SCR_001757)

    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: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    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.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • 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.

  2. Version published to 10.1101/2020.06.18.20135152v1 on medRxiv