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Detection of long SARS-CoV-2 nucleocapsid sequences in peripheral blood monocytes collected soon after hospital admission

Nathan Pagano, Maudry Laurent-Rolle, Jack Chun-Chieh Hsu, the Yale IMPACT research team, Chantal BF Vogels, Nathan D Grubaugh, View ORCID ProfileLaura Manuelidis
doi: https://doi.org/10.1101/2020.12.16.423113
Nathan Pagano
1Section of Neuropathology, Surgery Department, Yale Medical school 333 Cedar Street, New Haven CT 06510
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Maudry Laurent-Rolle
2Section of Infectious Diseases, Yale Medical school 333 Cedar Street, New Haven CT 06510
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Jack Chun-Chieh Hsu
2Section of Infectious Diseases, Yale Medical school 333 Cedar Street, New Haven CT 06510
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Chantal BF Vogels
3Department of immunobiology, Yale Medical school 333 Cedar Street, New Haven CT 06510
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Nathan D Grubaugh
3Department of immunobiology, Yale Medical school 333 Cedar Street, New Haven CT 06510
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Laura Manuelidis
1Section of Neuropathology, Surgery Department, Yale Medical school 333 Cedar Street, New Haven CT 06510
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  • ORCID record for Laura Manuelidis
  • For correspondence: laura.manuelidis@yale.edu
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ABSTRACT

Many different viruses infect circulating mononuclear cells to disseminate infection to diverse organs. Blood mononuclear cells (PBMC) are being intensively studied as immunologic and pathologic responders to the new pandemic SARS-CoV-2 virus (CoV19) but direct evidence showing CoV19 in these cells has not been published. PBMC myeloid cells that take up residence in various organs can harbor viral genomes for many years in lymphatic tissues, skin and brain, and act as a source for re-infection and/or post-viral organ pathology. To test if PBMC from acutely ill hospitalized patients contain viral nucleic acids, we first analyzed a standard short CoV19 nucleocapsid (NC) 72bp sequence. Because NC proteins protect the viral genome, we further analyzed longer (301nt) adjacent NC stretches by RNA/qPCR. In 2 of 11 patient PBMC, but no uninfected controls, longer NC sequences were positive as early as 2-6 days after hospital admission and were validated by sequencing. The presence of longer NC sequences indicates pathogenic fragments, or possibly the complete infectious virus, are carried by a rare population of monocytes, probably a subset of myeloid migratory cells. Predictably, such cells carried CoV19 to heart and brain with consequent late post-viral immune pathologies that are now evident.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted December 16, 2020.
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Detection of long SARS-CoV-2 nucleocapsid sequences in peripheral blood monocytes collected soon after hospital admission
Nathan Pagano, Maudry Laurent-Rolle, Jack Chun-Chieh Hsu, the Yale IMPACT research team, Chantal BF Vogels, Nathan D Grubaugh, Laura Manuelidis
bioRxiv 2020.12.16.423113; doi: https://doi.org/10.1101/2020.12.16.423113
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Detection of long SARS-CoV-2 nucleocapsid sequences in peripheral blood monocytes collected soon after hospital admission
Nathan Pagano, Maudry Laurent-Rolle, Jack Chun-Chieh Hsu, the Yale IMPACT research team, Chantal BF Vogels, Nathan D Grubaugh, Laura Manuelidis
bioRxiv 2020.12.16.423113; doi: https://doi.org/10.1101/2020.12.16.423113

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