Persistent SARS-CoV-2 infection and intra-host evolution in association with advanced HIV infection

  1. F Karim
  2. MYS Moosa
  3. BI Gosnell
  4. S Cele
  5. J Giandhari
  6. S Pillay
  7. H Tegally
  8. E Wilkinson
  9. JE San
  10. N Msomi
  11. K Mlisana
  12. K Khan
  13. M Bernstein
  14. N Manickchund
  15. L Singh
  16. U Ramphal
  17. COMMIT-KZN Team
  18. W Hanekom
  19. RJ Lessells
  20. A Sigal
  21. T de Oliveira

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Abstract

While most people effectively clear SARS-CoV-2, there are several reports of prolonged infection in immunosuppressed individuals. Here we present a case of prolonged infection of greater than 6 months with shedding of high titter SARS-CoV-2 in an individual with advanced HIV and antiretroviral treatment failure. Through whole genome sequencing at multiple time-points, we demonstrate the early emergence of the E484K substitution associated with escape from neutralizing antibodies, followed by other escape mutations and the N501Y substitution found in most variants of concern. This provides support to the hypothesis of intra-host evolution as one mechanism for the emergence of SARS-CoV-2 variants with immune evasion properties.

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  1. Rapid Reviews Infectious Diseases

    Alix Augusto Armero

    Review 1: "Persistent SARS-CoV-2 infection and intra-host evolution in association with advanced HIV infection"

    Reviewer: Alix Augusto Armero (Institut Pasteur of Shanghai Chinese Academy of Sciences) | 📘📘📘📘📘

  2. Rapid Reviews Infectious Diseases

    Alix Augusto Armero

    Review of "Persistent SARS-CoV-2 infection and intra-host evolution in association with advanced HIV infection"

    Reviewer: Alix Augusto Armero (Institut Pasteur of Shanghai Chinese Academy of Sciences) | 📘📘📘📘📘

  3. ScreenIT

    SciScore for 10.1101/2021.06.03.21258228: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Ethical considerations: The protocol for the prospective cohort study exploring the effect of HIV and TB on the natural history and immune response to SARS-CoV-2 infection was approved by the Biomedical Research Ethics Committee of the University of KwaZulu-Natal (ref.
    Consent: We obtained written informed consent from all participants.
    Field Sample Permit: Specimen collection and laboratory testing: We collected nasopharyngeal swabs and blood specimens on day 6 (day of study enrolment), day 20, day 34, day 71, day 106, day 190, day 204, day 216 and day 233.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power AnalysisSample analysis was performed using an Agilent High Pressure Liquid Chromatography (HPLC) system (Agilent Technologies, Santa Clara, CA) coupled to the AB Sciex 5500 (AB Sciex, Framingham, MA), triple quadrupole mass spectrometer equipped with an electrospray ionization (ESI) TurboIonSpray source.

    Table 2: Resources

    Antibodies
    SentencesResources
    Anti-SARS-CoV-2 antibodies in the blood were measured using the Test-it CoV-2 IgM/IgG test kit (Lifeassay Diagnostics, Cape Town, South Africa), which detects IgM and IgG against the S1 subunit of spike.
    Anti-SARS-CoV-2
    suggested: None
    Software and Algorithms
    SentencesResources
    HIV-1 viral load was measured using the Abbott m2000 RealTime assay (Abbott Laboratories, Abbott Park, IL) and CD4+ count using the BD FACSCantoâ„¢ (BD Biosciences, San Jose, CA).
    Abbott
    suggested: (Abbott, RRID:SCR_010477)
    Abbott Laboratories
    suggested: None
    BD FACSCantoâ„¢
    suggested: None
    All mutations were confirmed visually with BAM files using Geneious software (Biomatters, Auckland, New Zealand).
    Geneious
    suggested: (Geneious, RRID:SCR_010519)
    For analysis of low frequency mutations, we used LoFreq v.
    LoFreq
    suggested: (LoFreq, RRID:SCR_013054)
    We annotated the variants using snpEff v4.523 and extracted them for additional processing and visualizing using SnpSift v.
    snpEff
    suggested: (SnpEff, RRID:SCR_005191)
    SnpSift
    suggested: (SnpSift, RRID:SCR_015624)

    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: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    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.

    Results from scite Reference Check: We found no unreliable references.

    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.

  4. Version published to 10.1101/2021.06.03.21258228v1 on medRxiv