Post-acute COVID-19 associated with evidence of bystander T-cell activation and a recurring AMR bacterial pneumonia

  1. Michaela Gregorova
  2. Daniel Morse
  3. Tarcisio Brignoli
  4. Joseph Steventon
  5. Fergus Hamilton
  6. Mahableshwar Albur
  7. David Arnold
  8. Matthew Thomas
  9. Alice Halliday
  10. Holly Baum
  11. Christopher Rice
  12. Matthew B Avison
  13. Andrew D Davidson
  14. Marianna Santopaolo
  15. Elizabeth Oliver
  16. Anu Goenka
  17. Adam Finn
  18. Linda Wooldridge
  19. Borko Amulic
  20. Rosemary J Boyton
  21. Daniel M Altmann
  22. David K Butler
  23. Claire McMurray
  24. Joanna Stockton
  25. Sam Nicholls
  26. Charles Cooper
  27. Nicholas Loman
  28. Michael J Cox
  29. Laura Rivino  Is a corresponding author
  30. Ruth C Massey  Is a corresponding author
  1. University of Bristol, United Kingdom
  2. North Bristol NHS Trust, United Kingdom
  3. Bristol Veterinary School in the Faculty of Health Sciences, United Kingdom
  4. Imperial College London, United Kingdom
  5. University of Birmingham, United Kingdom

Abstract

Here we describe the case of a COVID-19 patient who developed recurring ventilator-associated pneumonia caused by Pseudomonas aeruginosa that acquired increasing levels of antimicrobial resistance (AMR) in response to treatment. Metagenomic analysis revealed the AMR genotype, while immunological analysis revealed massive and escalating levels of T-cell activation. These were both SARS-CoV-2 and P. aeruginosa specific, and bystander activated, which may have contributed to this patient's persistent symptoms and radiological changes.

Data availability

Human-filtered sequencing data for this study have been deposited in the European Nucleotide Archive (ENA) at EMBL-EBI under accession PRJEB40239.

The following data sets were generated

Article and author information

Author details

  1. Michaela Gregorova

    School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1605-0558
  2. Daniel Morse

    School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Tarcisio Brignoli

    School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Joseph Steventon

    School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Fergus Hamilton

    Southmead Hospital, North Bristol NHS Trust, Bristol, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Mahableshwar Albur

    Pathology, North Bristol NHS Trust, Bristol, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9792-7280
  7. David Arnold

    Southmead Hospital, North Bristol NHS Trust, Bristol, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3158-7740
  8. Matthew Thomas

    Intensive Care Unit, North Bristol NHS Trust, Bristol, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  9. Alice Halliday

    School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  10. Holly Baum

    School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  11. Christopher Rice

    School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  12. Matthew B Avison

    School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  13. Andrew D Davidson

    School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1136-4008
  14. Marianna Santopaolo

    School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  15. Elizabeth Oliver

    School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  16. Anu Goenka

    School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  17. Adam Finn

    School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  18. Linda Wooldridge

    Bristol Veterinary School in the Faculty of Health Sciences, Bristol, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  19. Borko Amulic

    School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  20. Rosemary J Boyton

    Lung Immunology Group, Section of Infectious Disease and Immunity, Department of Medicine, MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, Centre for Respiratory Infection Imperial College, Imperial College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  21. Daniel M Altmann

    Human Disease Immunogenetics Group, Section of Infectious Disease and Immunity, Department of Medicine, Imperial College London W12 ONN, Imperial College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  22. David K Butler

    Lung Immunology Group, Section of Infectious Disease and Immunity, Department of Medicine, MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, Centre for Respiratory Infection Imperial Coll, Imperial College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  23. Claire McMurray

    Institute of Microbiology and Infection, University of Birmingham, Birmingham, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  24. Joanna Stockton

    Institute of Microbiology and Infection, University of Birmingham, Birmingham, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  25. Sam Nicholls

    Institute of Microbiology and Infection, University of Birmingham, Birmingham, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  26. Charles Cooper

    Institute of Microbiology and Infection, University of Birmingham, Birmingham, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  27. Nicholas Loman

    Institute of Microbiology and Infection, University of Birmingham, Birmingham, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  28. Michael J Cox

    Institute of Microbiology and Infection, University of Birmingham, Birmingham, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  29. Laura Rivino

    School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom
    For correspondence
    laura.rivino@bristol.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
  30. Ruth C Massey

    School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom
    For correspondence
    ruth.massey@bristol.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8154-4039

Funding

Southmead Hospital Charity

  • Fergus Hamilton

Wellcome Trust (212258/Z/18/Z)

  • Ruth C Massey

Elizabeth Blackwell Institute

  • Laura Rivino

UKRI (MR/S019553/1)

  • Rosemary J Boyton

UKRI (MR/R02622X/1)

  • Daniel M Altmann

Cystic Fibrosis Trust (CF Trust SRC 015)

  • David K Butler

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: The patient was enrolled onto the DISCOVER study (Diagnostic and Severity markers of COVID-19 to Enable Rapid triage study), a single centre prospective study recruiting consecutive patients admitted with COVID-19, from 30.03.2020 until present (Ethics approval via South Yorkshire REC: 20/YH/0121, CRN approval no: 45469). Blood/serum samples from pre-pandemic healthy controls and asymptomatic healthy controls were obtained under the Bristol Biobank (NHS Research Ethics Committee approval ref 14/WA/1253).

Reviewing Editor

  1. Anurag Agrawal, CSIR Institute of Genomics and Integrative Biology, India

Publication history

  1. Received: September 24, 2020
  2. Accepted: December 16, 2020
  3. Accepted Manuscript published: December 17, 2020 (version 1)
  4. Version of Record published: December 31, 2020 (version 2)

Copyright

© 2020, Gregorova et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Michaela Gregorova
  2. Daniel Morse
  3. Tarcisio Brignoli
  4. Joseph Steventon
  5. Fergus Hamilton
  6. Mahableshwar Albur
  7. David Arnold
  8. Matthew Thomas
  9. Alice Halliday
  10. Holly Baum
  11. Christopher Rice
  12. Matthew B Avison
  13. Andrew D Davidson
  14. Marianna Santopaolo
  15. Elizabeth Oliver
  16. Anu Goenka
  17. Adam Finn
  18. Linda Wooldridge
  19. Borko Amulic
  20. Rosemary J Boyton
  21. Daniel M Altmann
  22. David K Butler
  23. Claire McMurray
  24. Joanna Stockton
  25. Sam Nicholls
  26. Charles Cooper
  27. Nicholas Loman
  28. Michael J Cox
  29. Laura Rivino
  30. Ruth C Massey
(2020)
Post-acute COVID-19 associated with evidence of bystander T-cell activation and a recurring AMR bacterial pneumonia
eLife 9:e63430.
https://doi.org/10.7554/eLife.63430
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