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

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, Shirley C. Sutton, Nathan Youlton, Ruchi Joshi, David Amar, Yosuke Tanigawa, Douglas Russo, Justin Wong, Jessie T. Lauzon, Jacob Edelson, Daniel Mas Montserrat, Yongchan Kwon, Simone Rubinacci, Olivier Delaneau, Lorenzo Cappello, Jaehee Kim, Massa J. Shoura, Archana N. Raja, Nathaniel Watson, Nathan Hammond, Elizabeth Spiteri, Kalyan C. Mallempati, Gonzalo Montero-Martín, Jeffrey Christle, Jennifer Kim, Anna Kirillova, Kinya Seo, Yong Huang, Chunli Zhao, Sonia Moreno-Grau, Steven G. Hershman, Karen P. Dalton, Jimmy Zhen, Jack Kamm, Karan D. Bhatt, Alina Isakova, Maurizio Morri, Thanmayi Ranganath, Catherine A. Blish, Angela J. Rogers, Kari Nadeau, Samuel Yang, Andra Blomkalns, Ruth O’Hara, Norma F. Neff, Christopher DeBoever, Sándor Szalma, Matthew T. Wheeler, Christian M. Gates, Kyle Farh, Gary P. Schroth, Phil Febbo, Francis deSouza, Omar E. Cornejo, Marcelo Fernandez-Vina, Amy Kistler, Julia A. Palacios, Benjamin A. Pinsky, Carlos D. Bustamante, Manuel A. Rivas and Euan A. Ashley ()
Additional contact information
Victoria N. Parikh: Stanford University School of Medicine
Alexander G. Ioannidis: Stanford University
David Jimenez-Morales: Stanford University School of Medicine
John E. Gorzynski: Stanford University School of Medicine
Hannah N. Jong: 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
Shirley C. Sutton: Stanford University School of Medicine
Nathan Youlton: 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
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
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
Amy Kistler: Chan Zuckerburg Biohub
Julia A. Palacios: Stanford University
Benjamin A. Pinsky: Stanford University School of Medicine
Carlos D. Bustamante: Stanford University
Manuel A. Rivas: Stanford University
Euan A. Ashley: Stanford University School of Medicine

Nature Communications, 2022, vol. 13, issue 1, 1-10

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-32397-8

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