Longitudinal and quantitative fecal shedding dynamics of SARS-CoV-2, pepper mild mottle virus, and crAssphage

Peter J. Arts; J. Daniel Kelly; Claire M. Midgley; Khamal Anglin; Scott Lu; Glen R. Abedi; Raul Andino; Kevin M. Bakker; Bryon Banman; Alexandria B. Boehm; Melissa Briggs-Hagen; Andrew F. Brouwer; Michelle C. Davidson; Marisa C. Eisenberg; Miguel Garcia-Knight; Sterling Knight; Michael J. Peluso; Jesus Pineda-Ramirez; Ruth Diaz Sanchez; Sharon Saydah; Michel Tassetto; Jeffrey N. Martin; Krista R. Wigginton

doi:10.1128/msphere.00132-23

mSphere (Aug 2023)

Longitudinal and quantitative fecal shedding dynamics of SARS-CoV-2, pepper mild mottle virus, and crAssphage

Peter J. Arts,
J. Daniel Kelly,
Claire M. Midgley,
Khamal Anglin,
Scott Lu,
Glen R. Abedi,
Raul Andino,
Kevin M. Bakker,
Bryon Banman,
Alexandria B. Boehm,
Melissa Briggs-Hagen,
Andrew F. Brouwer,
Michelle C. Davidson,
Marisa C. Eisenberg,
Miguel Garcia-Knight,
Sterling Knight,
Michael J. Peluso,
Jesus Pineda-Ramirez,
Ruth Diaz Sanchez,
Sharon Saydah,
Michel Tassetto,
Jeffrey N. Martin,
Krista R. Wigginton

Affiliations

Peter J. Arts: Department of Civil and Environmental Engineering, University of Michigan , Ann Arbor, Michigan, USA
J. Daniel Kelly: Department of Epidemiology and Biostatistics, University of California , San Francisco, California, USA
Claire M. Midgley: National Center for Immunizations and Respiratory Diseases, Centers for Disease Control and Prevention , Atlanta, Georgia, USA
Khamal Anglin: Department of Epidemiology and Biostatistics, University of California , San Francisco, California, USA
Scott Lu: Department of Epidemiology and Biostatistics, University of California , San Francisco, California, USA
Glen R. Abedi: National Center for Immunizations and Respiratory Diseases, Centers for Disease Control and Prevention , Atlanta, Georgia, USA
Raul Andino: Department of Microbiology and Immunology, UCSF , San Francisco, California, USA
Kevin M. Bakker: Department of Epidemiology, University of Michigan , Ann Arbor, Michigan, USA
Bryon Banman: Department of Civil and Environmental Engineering, University of Michigan , Ann Arbor, Michigan, USA
Alexandria B. Boehm: Department of Civil & Environmental Engineering, Stanford University , Stanford, California, USA
Melissa Briggs-Hagen: National Center for Immunizations and Respiratory Diseases, Centers for Disease Control and Prevention , Atlanta, Georgia, USA
Andrew F. Brouwer: Department of Epidemiology, University of Michigan , Ann Arbor, Michigan, USA
Michelle C. Davidson: School of Medicine, University of California , San Francisco, California, USA
Marisa C. Eisenberg: Department of Epidemiology, University of Michigan , Ann Arbor, Michigan, USA
Miguel Garcia-Knight: Department of Microbiology and Immunology, UCSF , San Francisco, California, USA
Sterling Knight: Department of Civil and Environmental Engineering, University of Michigan , Ann Arbor, Michigan, USA
Michael J. Peluso: Division of HIV, Infectious Disease, and Global Medicine, UCSF , San Francisco, California, USA
Jesus Pineda-Ramirez: Department of Epidemiology and Biostatistics, University of California , San Francisco, California, USA
Ruth Diaz Sanchez: Department of Epidemiology and Biostatistics, University of California , San Francisco, California, USA
Sharon Saydah: National Center for Immunizations and Respiratory Diseases, Centers for Disease Control and Prevention , Atlanta, Georgia, USA
Michel Tassetto: Department of Microbiology and Immunology, UCSF , San Francisco, California, USA
Jeffrey N. Martin: Department of Epidemiology and Biostatistics, University of California , San Francisco, California, USA
Krista R. Wigginton: Department of Civil and Environmental Engineering, University of Michigan , Ann Arbor, Michigan, USA

DOI: https://doi.org/10.1128/msphere.00132-23
Journal volume & issue: Vol. 8, no. 4

Abstract

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ABSTRACT Wastewater-based epidemiology (WBE) emerged during the coronavirus disease 2019 (COVID-19) pandemic as a scalable and broadly applicable method for community-level monitoring of infectious disease burden. The lack of high-resolution fecal shedding data for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) limits our ability to link WBE measurements to disease burden. In this study, we present longitudinal, quantitative fecal shedding data for SARS-CoV-2 RNA, as well as for the commonly used fecal indicators pepper mild mottle virus (PMMoV) RNA and crAss-like phage (crAssphage) DNA. The shedding trajectories from 48 SARS-CoV-2-infected individuals suggest a highly individualized, dynamic course of SARS-CoV-2 RNA fecal shedding. Of the individuals that provided at least three stool samples spanning more than 14 days, 77% had one or more samples that tested positive for SARS-CoV-2 RNA. We detected PMMoV RNA in at least one sample from all individuals and in 96% (352/367) of samples overall. CrAssphage DNA was detected in at least one sample from 80% (38/48) of individuals and was detected in 48% (179/371) of all samples. The geometric mean concentrations of PMMoV and crAssphage in stool across all individuals were 8.7 × 104 and 1.4 × 104 gene copies/milligram-dry weight, respectively, and crAssphage shedding was more consistent for individuals than PMMoV shedding. These results provide us with a missing link needed to connect laboratory WBE results with mechanistic models, and this will aid in more accurate estimates of COVID-19 burden in sewersheds. Additionally, the PMMoV and crAssphage data are critical for evaluating their utility as fecal strength normalizing measures and for source-tracking applications. IMPORTANCE This research represents a critical step in the advancement of wastewater monitoring for public health. To date, mechanistic materials balance modeling of wastewater-based epidemiology has relied on SARS-CoV-2 fecal shedding estimates from small-scale clinical reports or meta-analyses of research using a wide range of analytical methodologies. Additionally, previous SARS-CoV-2 fecal shedding data have not contained sufficient methodological information for building accurate materials balance models. Like SARS-CoV-2, fecal shedding of PMMoV and crAssphage has been understudied to date. The data presented here provide externally valid and longitudinal fecal shedding data for SARS-CoV-2, PMMoV, and crAssphage which can be directly applied to WBE models and ultimately increase the utility of WBE.

Published in mSphere

ISSN: 2379-5042 (Online)
Publisher: American Society for Microbiology
Country of publisher: United States
LCC subjects: Science: Microbiology
Website: https://journals.asm.org/journal/msphere

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