Robust SARS-CoV-2-specific and heterologous immune responses in vaccine-naïve residents of long-term care facilities who survive natural infection

  1. Gokhan Tut
  2. Tara Lancaster
  3. Megan S. Butler
  4. Panagiota Sylla
  5. Eliska Spalkova
  6. David Bone
  7. Nayandeep Kaur
  8. Christopher Bentley
  9. Umayr Amin
  10. Azar T. Jadir
  11. Samuel Hulme
  12. Morenike Ayodel
  13. Alexander C. Dowell
  14. Hayden Pearce
  15. Jianmin Zuo
  16. Sandra Margielewska-Davies
  17. Kriti Verma
  18. Samantha Nicol
  19. Jusnara Begum
  20. Elizabeth Jinks
  21. Elif Tut
  22. Rachel Bruton
  23. Maria Krutikov
  24. Madhumita Shrotri
  25. Rebecca Giddings
  26. Borscha Azmi
  27. Chris Fuller
  28. Aidan Irwin-Singer
  29. Andrew Hayward
  30. Andrew Copas
  31. Laura Shallcross
  32. Paul Moss

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Abstract

We studied humoral and cellular immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 152 long-term care facility staff and 124 residents over a prospective 4-month period shortly after the first wave of infection in England. We show that residents of long-term care facilities developed high and stable levels of antibodies against spike protein and receptor-binding domain. Nucleocapsid-specific responses were also elevated but waned over time. Antibodies showed stable and equivalent levels of functional inhibition against spike-angiotensin-converting enzyme 2 binding in all age groups with comparable activity against viral variants of concern. SARS-CoV-2 seropositive donors showed high levels of antibodies to other beta-coronaviruses but serostatus did not impact humoral immunity to influenza or other respiratory syncytial viruses. SARS-CoV-2-specific cellular responses were similar across all ages but virus-specific populations showed elevated levels of activation in older donors. Thus, survivors of SARS-CoV-2 infection show a robust and stable immunity against the virus that does not negatively impact responses to other seasonal viruses.

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  1. Version published to 10.1038/s43587-022-00224-w
  2. ScreenIT

    SciScore for 10.1101/2021.08.13.21261889: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: All participants provided written informed consent for blood sample collection or if residents lacked the capacity to consent, a personal or nominated consultee was identified to act on their behalf.
    IRB: Ethical approval for this study was obtained from the South Central - Hampshire B Research Ethics Committee, REC Ref: 20/SC/0238.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Data linkage: Abbott antibody test results were submitted to the COVID-19 datastore (https://data.england.nhs.uk/covid-19/) and linked to routinely held data on age, sex, LTCF, role (staff or resident) obtained through the national SARS-CoV-2 testing programme and to vaccination status (date and vaccine type) derived from the National Immunisations Management System (NIMS).
    https://data.england.nhs.uk/covid-19/
    suggested: None
    After incubation, plates were washed and anti-IgG detection antibodies were added.
    anti-IgG
    suggested: None
    An index value cut-off of 0.8 was used to classify samples as antibody-positive (≥ 0.8)(25, 26).
    antibody-positive
    suggested: None
    Purified anti-CD40 antibody was added to the cell suspension at final concentration 1μg/ml.
    anti-CD40
    suggested: None
    Software and Algorithms
    SentencesResources
    Presented data were adjusted for any sample dilutions For assessment of serological response against the SARS-CoV-2 nucleocapsid, blood samples were tested for the presence of IgG antibodies specific for nucleocapsid (N) protein using the Abbott ARCHITECT system (Abbott, Maidenhead, UK), a semi-quantitative chemiluminescent microparticle immunoassay.
    Abbott
    suggested: (Abbott, RRID:SCR_010477)
    Cells were washed and run on a BD Symphony A3 flow cytometer (BD Biosciences) and analysis was carried out using FlowJo v10.7.1 and Cytobank 2021.
    FlowJo
    suggested: (FlowJo, RRID:SCR_008520)
    Cytobank
    suggested: (Cytobank, RRID:SCR_014043)

    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:
    Potential limitations of our study include the fact that all seropositive donors clearly represent survivors of acute SARS-CoV-2 infection and, as mortality rates were high within the LTCF resident age group, there may have been potential selection bias for donors with the most effective underlying immune function. Additionally, we did not have access to the exact time or severity of primary infection or history of patient co-morbidities. These findings indicate that immune responses to SARS-CoV-2 infection within the elderly and potentially frail resident LTCF population appear robust and comparable to those seen within younger people. These findings are consistent with similar levels of protection against reinfection within this cohort and provide insight into the potent influence of previous infection on the magnitude of the immune response to Covid-19 vaccination. It will now be important to assess how infection status acts to support the longeity of vaccine-induced immune responses and if this should be used as a determinant of the need for vaccine boosters.

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

    IdentifierStatusTitle
    ISRCTN14447421NANA

    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 10.1101/2021.08.13.21261889v1 on medRxiv