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Deconvoluting complex correlates of COVID-19 severity with a multi-omic pandemic tracking strategy

Author

Listed:
  • Victoria N. Parikh

    (Stanford University School of Medicine)

  • Alexander G. Ioannidis

    (Stanford University
    Stanford University)

  • David Jimenez-Morales

    (Stanford University School of Medicine)

  • John E. Gorzynski

    (Stanford University School of Medicine
    Stanford University School of Medicine)

  • Hannah N. Jong

    (Stanford University School of Medicine
    Stanford University School of Medicine)

  • Xiran Liu

    (Stanford University)

  • Jonasel Roque

    (Stanford University School of Medicine)

  • Victoria P. Cepeda-Espinoza

    (Stanford University)

  • Kazutoyo Osoegawa

    (Stanford Blood Center, Stanford Health Care)

  • Chris Hughes

    (Stanford University School of Medicine
    Stanford University School of Medicine)

  • Shirley C. Sutton

    (Stanford University School of Medicine
    Stanford University School of Medicine)

  • Nathan Youlton

    (Stanford University School of Medicine
    Stanford University School of Medicine)

  • Ruchi Joshi

    (Stanford University School of Medicine)

  • David Amar

    (Stanford University School of Medicine)

  • Yosuke Tanigawa

    (Stanford University)

  • Douglas Russo

    (Stanford University)

  • Justin Wong

    (Stanford University)

  • Jessie T. Lauzon

    (Stanford University)

  • Jacob Edelson

    (Stanford University)

  • Daniel Mas Montserrat

    (Stanford University)

  • Yongchan Kwon

    (Stanford University)

  • Simone Rubinacci

    (University of Lausanne)

  • Olivier Delaneau

    (University of Lausanne)

  • Lorenzo Cappello

    (Stanford University)

  • Jaehee Kim

    (Cornell University)

  • Massa J. Shoura

    (Stanford University School of Medicine
    Stanford University School of Medicine)

  • Archana N. Raja

    (Stanford University School of Medicine)

  • Nathaniel Watson

    (Stanford University School of Medicine)

  • Nathan Hammond

    (Stanford University School of Medicine)

  • Elizabeth Spiteri

    (Stanford University School of Medicine)

  • Kalyan C. Mallempati

    (Stanford Blood Center, Stanford Health Care)

  • Gonzalo Montero-Martín

    (Stanford Blood Center, Stanford Health Care)

  • Jeffrey Christle

    (Stanford University School of Medicine)

  • Jennifer Kim

    (Stanford University School of Medicine)

  • Anna Kirillova

    (University of Pittsburgh and Carnegie Mellon University)

  • Kinya Seo

    (Stanford University School of Medicine)

  • Yong Huang

    (Stanford University School of Medicine)

  • Chunli Zhao

    (Stanford University School of Medicine)

  • Sonia Moreno-Grau

    (Stanford University)

  • Steven G. Hershman

    (Stanford University School of Medicine)

  • Karen P. Dalton

    (Stanford University School of Medicine)

  • Jimmy Zhen

    (Stanford University School of Medicine)

  • Jack Kamm

    (Chan Zuckerburg Biohub)

  • Karan D. Bhatt

    (Chan Zuckerburg Biohub)

  • Alina Isakova

    (Stanford University)

  • Maurizio Morri

    (Chan Zuckerburg Biohub)

  • Thanmayi Ranganath

    (Stanford University School of Medicine)

  • Catherine A. Blish

    (Stanford University School of Medicine)

  • Angela J. Rogers

    (Stanford University School of Medicine)

  • Kari Nadeau

    (Stanford University School of Medicine
    Stanford University School of Medicine)

  • Samuel Yang

    (Stanford University School of Medicine)

  • Andra Blomkalns

    (Stanford University School of Medicine)

  • Ruth O’Hara

    (Stanford University School of Medicine)

  • Norma F. Neff

    (Chan Zuckerburg Biohub)

  • Christopher DeBoever

    (Takeda Development Center, Americas, Inc)

  • Sándor Szalma

    (Takeda Development Center, Americas, Inc)

  • Matthew T. Wheeler

    (Stanford University School of Medicine)

  • Christian M. Gates

    (Illumina, Inc)

  • Kyle Farh

    (Illumina, Inc)

  • Gary P. Schroth

    (Illumina, Inc)

  • Phil Febbo

    (Illumina, Inc)

  • Francis deSouza

    (Illumina, Inc)

  • Omar E. Cornejo

    (Washington State University)

  • Marcelo Fernandez-Vina

    (Stanford Blood Center, Stanford Health Care
    Stanford University School of Medicine)

  • Amy Kistler

    (Chan Zuckerburg Biohub)

  • Julia A. Palacios

    (Stanford University
    Stanford University)

  • Benjamin A. Pinsky

    (Stanford University School of Medicine
    Stanford University School of Medicine)

  • Carlos D. Bustamante

    (Stanford University)

  • Manuel A. Rivas

    (Stanford University)

  • Euan A. Ashley

    (Stanford University School of Medicine
    Stanford University School of Medicine)

Abstract

The SARS-CoV-2 pandemic has differentially impacted populations across race and ethnicity. A multi-omic approach represents a powerful tool to examine risk across multi-ancestry genomes. We leverage a pandemic tracking strategy in which we sequence viral and host genomes and transcriptomes from nasopharyngeal swabs of 1049 individuals (736 SARS-CoV-2 positive and 313 SARS-CoV-2 negative) and integrate them with digital phenotypes from electronic health records from a diverse catchment area in Northern California. Genome-wide association disaggregated by admixture mapping reveals novel COVID-19-severity-associated regions containing previously reported markers of neurologic, pulmonary and viral disease susceptibility. Phylodynamic tracking of consensus viral genomes reveals no association with disease severity or inferred ancestry. Summary data from multiomic investigation reveals metagenomic and HLA associations with severe COVID-19. The wealth of data available from residual nasopharyngeal swabs in combination with clinical data abstracted automatically at scale highlights a powerful strategy for pandemic tracking, and reveals distinct epidemiologic, genetic, and biological associations for those at the highest risk.

Suggested Citation

  • Victoria N. Parikh & Alexander G. Ioannidis & David Jimenez-Morales & John E. Gorzynski & Hannah N. Jong & Xiran Liu & Jonasel Roque & Victoria P. Cepeda-Espinoza & Kazutoyo Osoegawa & Chris Hughes & , 2022. "Deconvoluting complex correlates of COVID-19 severity with a multi-omic pandemic tracking strategy," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32397-8
    DOI: 10.1038/s41467-022-32397-8
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    References listed on IDEAS

    as
    1. Hugo Zeberg & Svante Pääbo, 2020. "The major genetic risk factor for severe COVID-19 is inherited from Neanderthals," Nature, Nature, vol. 587(7835), pages 610-612, November.
    2. Erola Pairo-Castineira & Sara Clohisey & Lucija Klaric & Andrew D. Bretherick & Konrad Rawlik & Dorota Pasko & Susan Walker & Nick Parkinson & Max Head Fourman & Clark D. Russell & James Furniss & Ann, 2021. "Genetic mechanisms of critical illness in COVID-19," Nature, Nature, vol. 591(7848), pages 92-98, March.
    Full references (including those not matched with items on IDEAS)

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