Variants in SARS-CoV-2 associated with mild or severe outcome

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Abstract

Introduction

The coronavirus disease 2019 (COVID-19) pandemic is a global public health emergency causing a disparate burden of death and disability around the world. The viral genetic variants associated with outcome severity are still being discovered.

Methods

We downloaded 155 958 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes from GISAID. Of these genomes, 3637 samples included useable metadata on patient outcomes. Using this subset, we evaluated whether SARS-CoV-2 viral genomic variants improved prediction of reported severity beyond age and region. First, we established whether including genomic variants as model features meaningfully increased the predictive power of our model. Next, we evaluated specific variants in order to determine the magnitude of association with severity and the frequency of these variants among SARS-CoV-2 genomes.

Results

Logistic regression models that included viral genomic variants outperformed other models (area under the curve = 0.91 as compared with 0.68 for age and gender alone; P < 0.001). We found 84 variants with odds ratios greater than 2 for outcome severity (17 and 67 for higher and lower severity, respectively). The median frequency of associated variants was 0.15% (interquartile range 0.09–0.45%). Altogether 85% of genomes had at least one variant associated with patient outcome.

Conclusion

Numerous SARS-CoV-2 variants have 2-fold or greater association with odds of mild or severe outcome and collectively, these variants are common. In addition to comprehensive mitigation efforts, public health measures should be prioritized to control the more severe manifestations of COVID-19 and the transmission chains linked to these severe cases.

Lay summary: This study explores which, if any, SARS-CoV-2 viral genomic variants are associated with mild or severe COVID-19 patient outcomes. Our results suggest that there are common genomic variants in SARS-CoV-2 that are more often associated with negative patient outcomes, which may impact downstream public health measures.

Article activity feed

  1. Hebah Al Khatib

    Review 2: "Variants in SARS-CoV-2 Associated with Mild or Severe Outcome"

    This preprint reports viral variants can improve classification of COVID-19 outcomes as compared with models using only age and region, with some individual variants associated with disease severity. Reviewers suggest major revisions to improve and clarify data analysis.

  2. Min Xie

    Review 1: "Variants in SARS-CoV-2 Associated with Mild or Severe Outcome"

    This preprint reports viral variants can improve classification of COVID-19 outcomes as compared with models using only age and region, with some individual variants associated with disease severity. Reviewers suggest major revisions to improve and clarify data analysis.

  3. SciScore for 10.1101/2020.12.01.20242149: (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

    Software and Algorithms
    SentencesResources
    FASTA sequences were aligned to the reference sequence, Wuhan-Hu-1 (NCBI: NC_045512.2; GISAID: EPI_ISL_402125) using Minimap2 (version 2.17).(13) Resulting VCF (Variant Call Format) files were annotated using SnpEff (version 5.0) and filtered using SnpSift.(14, 15) The shell scripts used for variant alignment and variant calling, along with the Python scripts used to perform the steps described below, are available on GitHub at https://github.com/mskar/variants.
    Minimap2
    suggeste…