Streptococcus pneumoniae colonization associates with impaired adaptive immune responses against SARS-CoV-2

  1. Elena Mitsi
  2. Jesús Reiné
  3. Britta C. Urban
  4. Carla Solórzano
  5. Elissavet Nikolaou
  6. Angela D. Hyder-Wright
  7. Sherin Pojar
  8. Ashleigh Howard
  9. Lisa Hitchins
  10. Sharon Glynn
  11. Madlen C. Farrar
  12. Konstantinos Liatsikos
  13. Andrea M. Collins
  14. Naomi F. Walker
  15. Helen C. Hill
  16. Esther L. German
  17. Katerina S. Cheliotis
  18. Rachel L. Byrne
  19. Christopher T. Williams
  20. Ana I. Cubas-Atienzar
  21. Tom E. Fletcher
  22. Emily R. Adams
  23. Simon J. Draper
  24. David Pulido
  25. Rohini Beavon
  26. Christian Theilacker
  27. Elizabeth Begier
  28. Luis Jodar
  29. Bradford D. Gessner
  30. Daniela M. Ferreira

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Abstract

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  1. Version published to 10.1172/jci157124
  2. ScreenIT

    SciScore for 10.1101/2021.07.22.21260837: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: Study exclusion criteria included lack of willingness or ability to provide informed consent, or lack of an appropriate legal guardian or representative to provide informed consent.
    IRB: The two study protocols were reviewed and approved by the NHS Health Service Research Ethics Committees (REF: 20/SC/0147 for SAFER and 20/SC/0169 for FASTER).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Goat anti-human IgG (γ-chain specific, A9544, Sigma-Aldrich) or IgA (α-chain specific, A9669, Sigma-Aldrich) or mouse anti-human IgA1 (Fc-specific, ab99794, Abcam) or IgA2 (Fc-specific, ab99800, Abcam) conjugated to alkaline phosphatase was used as secondary antibody and plates were developed by adding 4-nitrophenyl phosphate in diethanolamine substrate buffer.
    anti-human IgG
    suggested: (GenWay Biotech Inc. Cat# GWB-9C4ADD, RRID:AB_10508694)
    α-chain
    suggested: (Sigma-Aldrich Cat# M8695, RRID:AB_2617179)
    anti-human IgA1
    suggested: None
    IgA2
    suggested: (Abcam Cat# ab99800, RRID:AB_10710695)
    Software and Algorithms
    SentencesResources
    HCWs in a variety of roles were enrolled onto SARS-CoV-2 Acquisition in Frontline Healthcare Workers - Evaluation to inform Response (SAFER) study between 30th March and 9th April 2020 at Royal Liverpool University Hospital (
    Frontline Healthcare
    suggested: None
    For the patient cohort, adults (aged ≥ 18 years) with signs and symptoms of suspected COVID-19 infection attending RLUH, Aintree University and Whiston Hospital in Merseyside between April 2020 to January 2021 were recruited into Facilitating A SARS Cov-2 Test for Rapid Triage (FASTER), regardless of disease severity, race, ethnicity, gender, pregnancy or nursing status, or the presence of other medical conditions.
    FASTER
    suggested: (FASTER, RRID:SCR_009045)
    Blank corrected samples and standard values were plotted using the 4-Parameter logistic model (Gen5 v3.09, BioTek).
    Gen5
    suggested: (Gen5, RRID:SCR_017317)
    SARS-CoV-2 S1 and S2 proteins were conjugated with Biotin (EZ Link conjugation kit, Thermofisher), then directly labelled with Streptavidin-BV785 and PE (Biolegend), respectively.
    Thermofisher
    suggested: (ThermoFisher; SL 8; Centrifuge, RRID:SCR_020809)
    All samples were acquired on an Aurora cytometer (Cytek Biosciences) and analysed using Flowjo software v.10 (Treestar).
    Flowjo
    suggested: (FlowJo, RRID:SCR_008520)
    Statistical Analysis: Statistical analyses were performed using R software (version 4.0.4) or GraphPad Prism (version 9.0).
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    Clinical and demographic data were analysed using GraphPad.
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)

    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 study has limitations. Diagnosis of co-infection was complex amongst patients, as pneumococcus might be carried by the patient before the viral infection or might be picked up later. High use of antibiotics (potentially prescribed at an outpatient visit) and reduced social mixing affected survival, prevalence and transmission dynamics of other respiratory pathogens, such RSV1, 49, and most likely pneumococcal transmission. Hence, we observed decreased prevalence of pneumococcus amongst patients-particularly during periods of national lockdown, which subsequently limited the number of SARS-CoV-2/ pneumococcus co-infected individuals studied here. Thus, despite inclusion of nearly 500 subjects in our study, we were able to evaluate pneumococcal mediated immunomodulatory effects only for a relatively small number of individuals, limiting the ability to do further stratifications. In children, pneumococcal colonisation has been profusely documented. Children however experience an attenuated course of SARS-CoV-2 infection. This emphasises the importance of our findings in adults and indicate the need to conduct future studies aimed at understanding the differential disease course in children, taking this important variable into consideration. In addition, differences in age and underlying disease between the HCW and patient cohorts are some factors that have potentially affected the course and outcome of the disease. Further studies, ideally in the setting of controlled human ...

    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.

  3. Version published to 10.1101/2021.07.22.21260837 on medRxiv