Data from Prolonged SARS-CoV-2 Infection in Patients with Lymphoid Malignancies

  1. Christina Y. Lee
  2. Monika K. Shah
  3. David Hoyos
  4. Alexander Solovyov
  5. Melanie Douglas
  6. Ying Taur
  7. Peter Maslak
  8. N. Esther Babady
  9. Benjamin Greenbaum
  10. Mini Kamboj
  11. Santosha A. Vardhana

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Abstract

<div>Abstract<p>Coronavirus disease 2019 (COVID-19) infection results in both acute mortality and persistent and/or recurrent disease in patients with hematologic malignancies, but the drivers of persistent infection in this population are unknown. We found that B-cell lymphomas were at particularly high risk for persistent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positivity. Further analysis of these patients identified discrete risk factors for initial disease severity compared with disease chronicity. Active therapy and diminished T-cell counts were drivers of acute mortality in COVID-19–infected patients with lymphoma. Conversely, B cell–depleting therapy was the primary driver of rehospitalization for COVID-19. In patients with persistent SARS-CoV-2 positivity, we observed high levels of viral entropy consistent with intrahost viral evolution, particularly in patients with impaired CD8<sup>+</sup> T-cell immunity. These results suggest that persistent COVID-19 infection is likely to remain a risk in patients with impaired adaptive immunity and that additional therapeutic strategies are needed to enable viral clearance in this high-risk population.</p>Significance:<p>We describe the largest cohort of persistent symptomatic COVID-19 infection in patients with lymphoid malignancies and identify B-cell depletion as the key immunologic driver of persistent infection. Furthermore, we demonstrate ongoing intrahost viral evolution in patients with persistent COVID-19 infection, particularly in patients with impaired CD8<sup>+</sup> T-cell immunity.</p><p><i>This article is highlighted in the In This Issue feature, p. 1</i></p></div>

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  20. ScreenIT

    SciScore for 10.1101/2021.08.25.21262417: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: The Memorial Sloan Kettering Cancer Center Institutional Review Board granted a Health Insurance Portability and Accountability Act waiver of authorization to conduct this study.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    SARS-CoV-2 Whole Genome Sequencing (WGS): WGS was performed on all samples with high enough viral load (i.e. Ct value < 30).
    WGS
    suggested: None
    We mapped the reads using STAR (version 2.7.7a) to the combined human (hg38 p.13, gencode release 36) and reference SARS-CoV-2 (NC_045512) genome35.
    STAR
    suggested: (STAR, RRID:SCR_004463)
    The immune phenotypes were based on NIH vaccine consensus panels and the Human Immunology Project.
    Human Immunology Project
    suggested: (Human Immunology Project Consortium, RRID:SCR_001491)
    Samples were acquired on a BD Facs Canto using FACSDiva software.
    FACSDiva
    suggested: (BD FACSDiva Software, RRID:SCR_001456)
    Analyses were performed with the use of SPSS software, version 26 and R version 4.0 (R Development Core Team, Vienna, Austria).
    SPSS
    suggested: (SPSS, RRID:SCR_002865)
    R Development Core
    suggested: (R Project for Statistical Computing, RRID:SCR_001905)

    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:
    There are several limitations in our present study. Laboratory markers, including flow cytometry data and viral sampling, were ordered at the discretion of the treating physician and were therefore not uniformly available across patients. Additionally, viral viability was not assessed in patients with persistent COVID-19 PCR positivity. Finally, the management of these patients was heterogeneous and physician dependent with rapidly emerging evidence. Despite this, the high volume of patients with hematologic malignancy and immune-depleting therapies at our institution enabled the identification of this novel syndrome. In summary, the results of this work have significant implications for devising effective preventive and treatment strategies for COVID-infected patients with lymphoid malignancies. The high risk for adverse outcomes with acute COVID-19 in patients with lymphoid cancers is well recognized in multiple previous reports.7,29 We corroborate this finding among our large study cohort. Most importantly, we demonstrate the substantial morbidity and mortality associated with the long-term effects of chronic COVID-19 infection in lymphoma patients unable to attain adequate viral clearance and potentially posing a transmission risk to others. Future studies should elucidate the immunologic defects associated with this clinical phenomenon beyond the recent anti-CD20 treatment risk identified in our report. When taken in conjunction with emerging evidence on suboptimal COVID...

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04374461Active, not recruitingA Study of N-acetylcysteine in Patients With COVID-19 Infect…

    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.
    • Thank you for including a protocol registration statement.

    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.

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