Blood Cytokine Analysis Suggests That SARS-CoV-2 Infection Results in a Sustained Tumour Promoting Environment in Cancer Patients

  1. Fien H. R. De Winter
  2. An Hotterbeekx
  3. Manon T. Huizing
  4. Angelina Konnova
  5. Erik Fransen
  6. Bart ’s Jongers
  7. Ravi Kumar Jairam
  8. Vincent Van averbeke
  9. Pieter Moons
  10. Ella Roelant
  11. Debbie Le Blon
  12. Wim Vanden Berghe
  13. Annelies Janssens
  14. Willem Lybaert
  15. Lieselot Croes
  16. Christof Vulsteke
  17. Surbhi Malhotra-Kumar
  18. Herman Goossens
  19. Zwi Berneman
  20. Marc Peeters
  21. Peter A. van Dam
  22. Samir Kumar-Singh

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Abstract

Cytokines, chemokines, and (angiogenic) growth factors (CCGs) have been shown to play an intricate role in the progression of both solid and haematological malignancies. Recent studies have shown that SARS-CoV-2 infection leads to a worse outcome in cancer patients, especially in haematological malignancy patients. Here, we investigated how SARS-CoV-2 infection impacts the already altered CCG levels in solid or haematological malignancies, specifically, whether there is a protective effect or rather a potentially higher risk for major COVID-19 complications in cancer patients due to elevated CCGs linked to cancer progression. Serially analysing immune responses with 55 CCGs in cancer patients under active treatment with or without SARS-CoV-2 infection, we first showed that cancer patients without SARS-CoV-2 infection (n = 54) demonstrate elevated levels of 35 CCGs compared to the non-cancer, non-infected control group of health care workers (n = 42). Of the 35 CCGs, 19 were common to both the solid and haematological malignancy groups and comprised previously described cytokines such as IL-6, TNF-α, IL-1Ra, IL-17A, and VEGF, but also several less well described cytokines/chemokines such as Fractalkine, Tie-2, and T cell chemokine CTACK. Importantly, we show here that 7 CCGs are significantly altered in SARS-CoV-2 exposed cancer patients (n = 52). Of these, TNF-α, IFN-β, TSLP, and sVCAM-1, identified to be elevated in haematological cancers, are also known tumour-promoting factors. Longitudinal analysis conducted over 3 months showed persistence of several tumour-promoting CCGs in SARS-CoV-2 exposed cancer patients. These data demonstrate a need for increased vigilance for haematological malignancy patients as a part of long COVID follow-up.

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  1. Version published to 10.3390/cancers13225718
  2. ScreenIT

    SciScore for 10.1101/2021.10.29.21265511: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: In addition, health care workers (HCWs; n = 92) from these units donated similar blood samples during the study period at time points 0, 1, 2 and 3 months after written informed consent.
    IRB: The study was approved by the ethics committee of the Antwerp University hospital (EC number 20/13/156, internal EDGE 001070).
    Sex as a biological variablenot detected.
    RandomizationMeasurements were performed in randomized batches.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Anti-SARS-CoV-2 immunoglobins (Ig) in blood were tested by three commercial tests, namely, Liaison SARS-CoV-2 S1/S2 IgG (DiaSorin, Saluggia, Italy), Alinity SARS-CoV-2 IgG (Abbott, Chicago, IL, USA), and Elecsys Anti-SARS-CoV-2 (Roche, Basel, Switzerland), as described [26].
    Abbott
    suggested: (Abbott, RRID:SCR_010477)
    Statistics: All data were analysed using SPSS v27, R (version R4.0.4) and Metaboanalyst 5.0 (https://www.metabo-analyst.ca/).
    SPSS
    suggested: (SPSS, RRID:SCR_002865)
    Group differences in CCG profiles were explored by Partial Least-Squares Discriminant Analysis (PLS-DA) using Metaboanalyst.
    Metaboanalyst
    suggested: (MetaboAnalyst, RRID:SCR_015539)

    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:
    As limitations, this study is a case-control study and prospective data collection especially for patients who were not positive for SARS-CoV-2 was not possible. Secondly, although older healthy controls were enrolled for this study, this group remained younger and had fewer co-morbidities compared to the cancer groups. And lastly, as the study was conducted in an oncology unit setting, cancer patients that were immediately transferred to the COVID-19 wards and had succumbed to the infection, were not included.

    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

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  3. Version published to 10.1101/2021.10.29.21265511v1 on medRxiv