Immunity response against mild-to-moderate breakthrough COVID-19

  1. Pichanun Mongkolsucharitkul
  2. Apinya Surawit
  3. Nitat Sookrung
  4. Anchalee Tungtrongchitr
  5. Pochamana Phisalprapa
  6. Naruemit Sayabovorn
  7. Weerachai Srivanichakorn
  8. Chaiwat Washirasaksiri
  9. Chonticha Auesomwang
  10. Tullaya Sitasuwan
  11. Thanet Chaisathaphol
  12. Rungsima Tinmanee
  13. Methee Chayakulkeeree
  14. Pakpoom Phoompoung
  15. Watip Tangjittipokin
  16. Sansanee Senawong
  17. Gornmigar Sanpawitayakul
  18. Saipin Muangman
  19. Korapat Mayurasakorn
  20. the SPHERE Investigators

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Abstract

BACKGROUND

The Omicron variant prevails the Delta variant after December 2021 in Thailand. Both variants of concern embody diverse epidemiological trends and immunogenicity, raising enormous public health concerns. We determined whether biological and clinical characteristics and immunogenicity of patients differ between Delta and Omicron during post-coronavirus disease 2019 (COVID-19) stage.

METHODS

A retrospective cohort study involved patients with mild-to-moderate COVID-19 who were under a home isolation (HI) strategy. Clinical outcomes and laboratory data of 2704 and 2477 patients during the Delta and Omicron pandemics were analyzed, respectively. We evaluated anti-receptor binding domain immunoglobulin G (anti-RBD IgG) and surrogate viral neutralizing (sVNT) activity in a subset of 495 individuals post-COVID-19 infection during the Delta pandemic.

RESULTS

Eighty-four percent of all patients received antiviral treatment. The peak cycle threshold (Ct) values, which inversely related to viral load, were lower in the Omicron (19 [IQR=17-22]) compared with the Delta (21 [IQR=18-26]; p<0.001), regardless of vaccination status. Upper respiratory tract symptoms were common signs during the Omicron compared with the Delta pandemic. At least two-dose vaccination reduced the chance of hospital readmissions by 10–30% and death by less than 1%. Furthermore, anti-RBD IgG and sVNT against the Delta variants tended to be higher among the older individuals after post-COVID 19 infections and expressed in the long interval after two-dose vaccination than in other groups.

CONCLUSIONS

Mild-to-moderate Delta and Omicron breakthrough infection with prior full vaccination is limitedly immunogenic; thereby exerting reduced protection against reinfection and infection from novel variants. However, this may be only sufficient to prevent hospitalization and death, particularly in countries where vaccines are limited. ( ClinicalTrials.gov number, NCT05328479 .)

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  1. ScreenIT

    SciScore for 10.1101/2022.05.30.22275050: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: This follow-up study was approved by the Institutional Review Board, Faculty of Medicine Siriraj Hospital, Mahidol University (COA: Si 833/2021, COA: Si 732/2021).
    Sex as a biological variablenot detected.
    RandomizationThe Ct value of ≥30 was shown to correspond to 150 copies per milliliter or less, indicating low viral RNA.15 SEROLOGIC ASSAYS: Patients were randomly invited to test for anti-SARS-CoV-2 receptor binding domain immunoglobulin G (anti-SARS-CoV-2 RBD IgG).
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    A study protocol and guidelines for COVID-19 standard care was based on a standard recommendation of the National and World Health Organization (WHO) (Methods S1).7,14 PATIENT SELECTION AND PROCEDURES: A subset of 495 patients (age≥12 years) from the aforementioned patients were recruited for the reactogenicity and immunogenicity follow-up study after COVID-19 recovery at 21-150 days post COVID-19 onset to test for SARS-CoV-2 antibodies and a surrogate virus neutralization test (sVNT) against SARS-CoV-2 Wuhan and Delta variants (Method S1).
    SARS-CoV-2
    suggested: None
    A chemiluminescent microparticle immunoassay for qualitative detection of IgG against RBD of the SARS-CoV-2 spike protein and SARS-CoV-2 nucleocapsid protein (SARS-CoV-2 IgG II Quant for use with ARCHITECT; Abbott Laboratories, USA) were undertaken.7 Anti-SARS-CoV-2 RBD IgG assay was then converted to the WHO International Standard concentration as binding antibody unit (BAU) per milliliter.
    SARS-CoV-2 nucleocapsid protein (SARS-CoV-2 IgG
    suggested: None
    Anti-SARS-CoV-2 RBD IgG
    suggested: None
    Software and Algorithms
    SentencesResources
    Statistical significance of Ct values, IgG, and sVNT were determined by Kruskal-Wallis and Dunn’s multiple comparisons test by using GraphPad Prism 9 (GraphPad Software, CA, USA).
    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:
    There are several limitations to our study. We only have blood test from a small subset of hospitalized patients and assumed that these findings might be similar to all milder infected cases without hospitalization. At the time of analysis, we didn’t have serology data from patients during the Omicron pandemic and long term follow up data, so we could not determine the antibody levels against the Omicron variants and vaccine efficacy after the COVID-19 infection and its impact on the long COVID-19. Our future COVID-19 direction is to further gain insight into the long-term monitoring of neutralizing antibodies and to study if the breakthrough Omicron infection will have a protective immunity against reinfection of SARS-CoV-2 Omicron sub-lineages BA.4 and BA.5.

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

    IdentifierStatusTitle
    NCT05328479Active, not recruitingPlasma Immunity of Mild SARS-CoV-2 Omicron and Delta Pandemi…

    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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  2. Version published to 10.1101/2022.05.30.22275050v1 on medRxiv