Potent anti-SARS-CoV-2 Antibody Responses are Associated with Better Prognosis in Hospital Inpatient COVID-19 Disease

  1. Patrick J. Tighe
  2. Richard A. Urbanowicz
  3. C. Lucy Fairclough
  4. C. Patrick McClure
  5. Brian J. Thomson
  6. Nancy Gomez
  7. Joseph G. Chappell
  8. Theocharis Tsoleridis
  9. Matthew Loose
  10. Matthew Carlile
  11. Christopher Moore
  12. Nadine Holmes
  13. Fei Sang
  14. Divyateja Hrushikesh
  15. Gemma Clark
  16. Nigel Temperton
  17. Tim Brooks
  18. Jonathan K. Ball
  19. William L. Irving
  20. Alexander W. Tarr

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Abstract

COVID-19 continues to cause a pandemic, having infected more than 20 million people globally. Successful elimination of the SARS-CoV-2 virus will require an effective vaccine. However, the immune correlates of infection are currently poorly understood. While neutralizing antibodies are believed to be essential for protection against infection, the contribution of the neutralizing antibody response to resolution of SARS-CoV-2 infection has not yet been defined. In this study the antibody responses to the SARS-CoV-2 spike protein and nucleocapsid proteins were investigated in a UK patient cohort, using optimised immunoassays and a retrovirus-based pseudotype entry assay. It was discovered that in severe COVID-19 infections an early antibody response to both antigens was associated with improved prognosis of infection. While not all SARS-CoV-2-reactive sera were found to possess neutralizing antibodies, neutralizing potency of sera was found to be greater in patients who went on to resolve infection, compared with those that died from COVID-19. Furthermore, viral genetic variation in spike protein was found to influence the production of neutralizing antibodies. Infection with the recently described spike protein variant 614G produced higher levels of neutralizing antibodies when compared to viruses possessing the 614D variant. These findings support the assertion that vaccines targeting generation of neutralizing antibodies may be useful at limiting SARS-CoV-2 infection. Assessment of the antibody responses to SARS-CoV-2 at time of diagnosis will be a useful addition to the diagnostic toolkit, enabling stratification of clinical intervention for severe COVID-19 disease.

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  1. ScreenIT

    SciScore for 10.1101/2020.08.22.20176834: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIACUC: Review by the School of Life Sciences Ethical Review Committee deemed the study to not require full ethical review.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Assay plates were then washed 3 times and 20 µL of pre-diluted serum sample (including SARS-CoV-2 antibody-positive and negative serum controls) added in duplicate wells.
    SARS-CoV-2
    suggested: None
    antibody-positive
    suggested: None
    Commercial anti-S1 and anti-N assays: Detection of antibodies to the S1 protein (Euroimmun) and N Protein (Roche) were performed at the Rare & Imported Pathogens Laboratory at Public Health England using the standard protocol.
    anti-S1
    suggested: None
    anti-N
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Briefly, 1.5 × 106 HEK293T cells were seeded overnight in a 10 cm diameter Primaria-coated dish (Corning).
    HEK293T
    suggested: None
    The following day, SARS-CoV-2 pv-containing supernatants were incubated with sera (pre-treated with 1% Triton X-100/heat-inactivated for 1 hr at RT), before being added to VeroE6 cells for 4 h.
    VeroE6
    suggested: JCRB Cat# JCRB1819, RRID:CVCL_YQ49)
    Software and Algorithms
    SentencesResources
    Data was collected and analysed using RAMPART [19], as previously described [20].
    RAMPART
    suggested: (Rampart, RRID:SCR_016742)
    Statistical analyses: All analyses were performed using GraphPad Prism version 8.4.3.
    GraphPad Prism
    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:
    While there are limitations on interpretation of our data given the retrospective sampling approach we have adopted, further analysis of the potency of neutralizing antibody responses, and the potential for infection enhancement are warranted. The data presented here also supports the rationale for use of optimised vaccines that generate antibodies directed to the spike and nucleocapsid genes and elicit potently neutralizing antibodies. The use of convalescent sera as a therapeutic approach [36] may also provide sufficient potency to contribute to resolution of infection, if potently neutralizing sera are specifically selected.

    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 10.1101/2020.08.22.20176834 on medRxiv