Emergence of multiple SARS-CoV-2 mutations in an immunocompromised host

  1. Elham Khatamzas
  2. Alexandra Rehn
  3. Maximilian Muenchhoff
  4. Johannes Hellmuth
  5. Erik Gaitzsch
  6. Tobias Weiglein
  7. Enrico Georgi
  8. Clemens Scherer
  9. Stephanie Stecher
  10. Oliver Weigert
  11. Philipp Girl
  12. Sabine Zange
  13. Oliver T. Keppler
  14. Joachim Stemmler
  15. Michael von Bergwelt-Baildon
  16. Roman Wölfel
  17. Markus Antwerpen

Reviewed by

Read the full article

Discuss this preprint

Start a discussion What are Sciety discussions?

Listed in

Log in to save this article

Abstract

Prolonged shedding of infectious SARS-CoV-2 has recently been reported in a number of immunosuppressed individuals with COVID-19. Here, we describe the detection of high levels of replication-competent SARS-CoV-2 in specimens taken from the respiratory tract of a B-cell depleted patient up to 154 days after initial COVID-19 diagnosis concomitant with the development of high mutation rate. In this patient, a total of 11 nonsynonymous mutations were detected in addition to the Y144 deletion in the spike protein of SARS-CoV-2.

Virus evolution studies revealed a dramatic diversification in viral population coinciding with treatment with convalescent plasma and clinical respiratory deterioration. Our findings highlight the urgent need for continuous real-time surveillance of genetic changes of SARS-CoV-2 adaptation alongside immunological investigations in patients with severely compromised humoral responses who may shed infectious virus over prolonged periods of time.

Article activity feed

  1. ScreenIT

    SciScore for 10.1101/2021.01.10.20248871: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    No key resources detected.

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Our data have a number of limitations. They are based on an unusually long course of chronic infection with SARS-CoV-2 in a single individual, to our knowledge the longest published duration of infectious viral shedding since the start of the pandemic. Further we have no data on the neutralizing capacity of SARS-CoV-2-specific antibodies, including the applied convalescent plasma therapy, on the isolated viral populations. We assume little effect based on unaltered detectable viral concentrations measured from respiratory tract specimens throughout the course of infection. We also have no data on potential higher transmission capabilities conferred by the observed mutations. Enhanced appropriate infection control precautions during the prolonged care of this patient on our intensive care unit were sufficient and no nosocomial transmissions were observed. In conclusion, we find that detailed characterization of the interaction between SARS-CoV-2 and the host in immunocompromised, particularly B-cell-depleted patients, provides a rare opportunity to follow viral adaptive evolution during the course of chronic infection. This will be crucial to understand the role of host-specific factors and help in the development of preventive and therapeutic agents. Further studies should therefore also specifically investigate the therapeutic efficacy of convalescent plasma therapy and protective effect of SARS-CoV-2 vaccines in immunocompromised individuals at increased risk of severe COVI...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  2. Version published to 10.1101/2021.01.10.20248871 on medRxiv