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Functional Immune Deficiency Syndrome via Intestinal Infection in COVID-19

Erica T. Prates, Michael R. Garvin, Mirko Pavicic, Piet Jones, Manesh Shah, Christiane Alvarez, David Kainer, Omar Demerdash, B Kirtley Amos, Armin Geiger, John Pestian, Kang Jin, Alexis Mitelpunkt, Eric Bardes, Bruce Aronow, View ORCID ProfileDaniel Jacobson
doi: https://doi.org/10.1101/2020.04.06.028712
Erica T. Prates
1Oak Ridge National Laboratory, Biosciences Division, 1 Bethel Valley Road, MS 6420, Oak Ridge, TN 37830, USA
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Michael R. Garvin
1Oak Ridge National Laboratory, Biosciences Division, 1 Bethel Valley Road, MS 6420, Oak Ridge, TN 37830, USA
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Mirko Pavicic
1Oak Ridge National Laboratory, Biosciences Division, 1 Bethel Valley Road, MS 6420, Oak Ridge, TN 37830, USA
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Piet Jones
1Oak Ridge National Laboratory, Biosciences Division, 1 Bethel Valley Road, MS 6420, Oak Ridge, TN 37830, USA
2University of Tennessee Knoxville, The Bredesen Center for Interdisciplinary Research and Graduate Education, 444 Greve Hall, 821 Volunteer Blvd. Knoxville, TN 37996-3394, USA
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Manesh Shah
1Oak Ridge National Laboratory, Biosciences Division, 1 Bethel Valley Road, MS 6420, Oak Ridge, TN 37830, USA
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Christiane Alvarez
1Oak Ridge National Laboratory, Biosciences Division, 1 Bethel Valley Road, MS 6420, Oak Ridge, TN 37830, USA
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David Kainer
1Oak Ridge National Laboratory, Biosciences Division, 1 Bethel Valley Road, MS 6420, Oak Ridge, TN 37830, USA
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Omar Demerdash
1Oak Ridge National Laboratory, Biosciences Division, 1 Bethel Valley Road, MS 6420, Oak Ridge, TN 37830, USA
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B Kirtley Amos
5University of Kentucky, Department of Horticulture, N-318 Ag Sciences Center, Lexington, KY 40546-0091, USA
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Armin Geiger
1Oak Ridge National Laboratory, Biosciences Division, 1 Bethel Valley Road, MS 6420, Oak Ridge, TN 37830, USA
2University of Tennessee Knoxville, The Bredesen Center for Interdisciplinary Research and Graduate Education, 444 Greve Hall, 821 Volunteer Blvd. Knoxville, TN 37996-3394, USA
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John Pestian
1Oak Ridge National Laboratory, Biosciences Division, 1 Bethel Valley Road, MS 6420, Oak Ridge, TN 37830, USA
3Biomedical Informatics, Cincinnati Children’s Hospital Research Foundation
4University of Cincinnati, S.10.200, 240 Albert Sabin Way, Cincinnati, OH 45229, USA
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Kang Jin
3Biomedical Informatics, Cincinnati Children’s Hospital Research Foundation
4University of Cincinnati, S.10.200, 240 Albert Sabin Way, Cincinnati, OH 45229, USA
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Alexis Mitelpunkt
3Biomedical Informatics, Cincinnati Children’s Hospital Research Foundation
4University of Cincinnati, S.10.200, 240 Albert Sabin Way, Cincinnati, OH 45229, USA
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Eric Bardes
3Biomedical Informatics, Cincinnati Children’s Hospital Research Foundation
4University of Cincinnati, S.10.200, 240 Albert Sabin Way, Cincinnati, OH 45229, USA
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Bruce Aronow
3Biomedical Informatics, Cincinnati Children’s Hospital Research Foundation
4University of Cincinnati, S.10.200, 240 Albert Sabin Way, Cincinnati, OH 45229, USA
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Daniel Jacobson
1Oak Ridge National Laboratory, Biosciences Division, 1 Bethel Valley Road, MS 6420, Oak Ridge, TN 37830, USA
2University of Tennessee Knoxville, The Bredesen Center for Interdisciplinary Research and Graduate Education, 444 Greve Hall, 821 Volunteer Blvd. Knoxville, TN 37996-3394, USA
6University of Tennessee Knoxville, Department of Psychology, Austin Peay Building, Knoxville TN 37996, USA
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  • ORCID record for Daniel Jacobson
  • For correspondence: jacobsonda@ornl.gov
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Abstract

Using a Systems Biology approach, we integrated genomic, transcriptomic, proteomic, and molecular structure information to provide a holistic understanding of the COVID-19 pandemic. The expression data analysis of the Renin Angiotensin System indicates mild nasal, oral or throat infections are likely and that the gastrointestinal tissues are a common primary target of SARS-CoV-2. Extreme symptoms in the lower respiratory system likely result from a secondary-infection possibly by a comorbidity-driven upregulation of ACE2 in the lung. The remarkable differences in expression of other RAS elements, the elimination of macrophages and the activation of cytokines in COVID-19 bronchoalveolar samples suggest that a functional immune deficiency is a critical outcome of COVID-19. We posit that using a non-respiratory system as a major pathway of infection is likely determining the unprecedented global spread of this coronavirus.

One Sentence Summary A Systems Approach Indicates Non-respiratory Pathways of Infection as Key for the COVID-19 Pandemic

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • https://compsysbio.ornl.gov/covid-19/covid-19-structome/

  • https://compsysbio.ornl.gov/sars-cov-2-mechanisms-of-infection/

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Posted April 12, 2020.
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Functional Immune Deficiency Syndrome via Intestinal Infection in COVID-19
Erica T. Prates, Michael R. Garvin, Mirko Pavicic, Piet Jones, Manesh Shah, Christiane Alvarez, David Kainer, Omar Demerdash, B Kirtley Amos, Armin Geiger, John Pestian, Kang Jin, Alexis Mitelpunkt, Eric Bardes, Bruce Aronow, Daniel Jacobson
bioRxiv 2020.04.06.028712; doi: https://doi.org/10.1101/2020.04.06.028712
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Functional Immune Deficiency Syndrome via Intestinal Infection in COVID-19
Erica T. Prates, Michael R. Garvin, Mirko Pavicic, Piet Jones, Manesh Shah, Christiane Alvarez, David Kainer, Omar Demerdash, B Kirtley Amos, Armin Geiger, John Pestian, Kang Jin, Alexis Mitelpunkt, Eric Bardes, Bruce Aronow, Daniel Jacobson
bioRxiv 2020.04.06.028712; doi: https://doi.org/10.1101/2020.04.06.028712

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