Antibody Level Predicts the Clinical Course of Breakthrough Infection of COVID-19 Caused by Delta and Omicron Variants: A Prospective Cross-Sectional Study

  1. Min Hyung Kim
  2. Yooju Nam
  3. Nak Hoon Son
  4. Namwoo Heo
  5. Bongyoung Kim
  6. Eawha Kang
  7. Areum Shin
  8. Andrew Jihoon Yang
  9. Yoon Soo Park
  10. Heejung Kim
  11. Taeyoung Kyong
  12. Yong Chan Kim

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Abstract

Background

Omicron variant viruses spread rapidly, even in individuals with high vaccination rates. This study aimed to determine the utility of the antibody against spike protein level as a predictor of the disease course of coronavirus disease 2019 (COVID-19) in vaccinated patients.

Methods

Between December 11, 2021, and February 10, 2022, we performed a prospective observational cohort study in South Korea, which included patients infected with Delta and Omicron variants. A multivariable logistic regression analysis to determine the association between antibody levels and outcomes was conducted. The relationship between antibody levels and cycle threshold (Ct) values was confirmed using a generalized linear model.

Results

From 106 vaccinated patients (39 Delta and 67 Omicron), the geometric mean titers of antibodies in patients with fever (≥37.5°C), hypoxia (≤94% of SpO2), pneumonia, C-reactive protein (CRP) elevation (>8 mg/L), or lymphopenia (<1100 cells/μL) were 1201.5 U/mL, 98.8 U/mL, 774.1 U/mL, 1335.1 U/mL, and 1032.2 U/mL, respectively. Increased antibody levels were associated with a decrease in the occurrence of fever (adjusted odds ratio [aOR], 0.23; 95% CI, 0.12–0.51), hypoxia (aOR, 0.23; 95% CI, 0.08–0.7), CRP elevation (aOR, 0.52; 95% CI, 0.29–0.0.94), and lymphopenia (aOR, 0.57; 95% CI, 0.33–0.98). Ct values showed a positive correlation between antibody levels (P = .02).

Conclusions

Antibody levels are predictive of the clinical course of COVID-19 in vaccinated patients with Delta and Omicron variant infections. Our data highlight the need for concentrated efforts to monitor patients with severe acute respiratory syndrome coronavirus 2 infection who are at risk of low antibody levels.

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  1. Version published to 10.1093/ofid/ofac262
  2. ScreenIT

    SciScore for 10.1101/2022.03.09.22272171: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: This study was approved by the Institutional Review Board of Yonsei University Health System Clinical Trial Centre, and the study protocol adhered to the Declaration of Helsinki guidelines.
    Consent: Written informed consent was obtained from all the participants.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Patients who agreed to undergo PCR tests for the SARS-CoV-2 variant type and anti-SARS-CoV-2 antibody tests were eligible for enrolment in this study.
    anti-SARS-CoV-2
    suggested: None
    Software and Algorithms
    SentencesResources
    Statistical analyses were performed using SAS (version 9.4; SAS Institute) and R (version 4.1.1; R Foundation for Statistical Computing).
    SAS Institute
    suggested: (Statistical Analysis System, RRID:SCR_008567)

    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 had several limitations. First, we could not exclude the effects of previous or current infections on antibody levels. However, none of the participants had a previous infection, although it relied on self-reporting. Furthermore, our findings were robust in a sensitivity analysis involving patients who tested antibody levels within 3 or 5 days of symptom onset or diagnosis. Second, since our study hospital has specific criteria for admission, which allowed only patients with mild to moderate severity to be admitted, we could not investigate the effects of antibody levels on outcomes such as moving to the severe phase (n=2) or death (n=0). Therefore, further studies involving a larger number of patients with a wide range of disease severity are warranted. Third, the diagnosis of pneumonia in this study was based on chest radiographic findings. Chest radiography is limited in its ability to detect subtle pneumonia. Furthermore, we did not routinely perform follow-up chest radiography if the initial test did not report abnormal findings and if the patient’s condition did not change. Therefore, the results associated with pneumonia should be cautiously interpreted. Fourth, we did not consider the type of vaccine (e.g. adenoviral vector-based, mRNA-based) when analysing antibody levels. Most previous studies have demonstrated the effectiveness of vaccines based on homologous vaccination data. However, the real-world population receives heterologous vaccines from differen...

    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 10.1101/2022.03.09.22272171 on medRxiv