Longitudinal Dynamics of the Neutralizing Antibody Response to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection

  1. Kai Wang
  2. Quan-Xin Long
  3. Hai-Jun Deng
  4. Jie Hu
  5. Qing-Zhu Gao
  6. Gui-Ji Zhang
  7. Chang-Long He
  8. Lu-Yi Huang
  9. Jie-Li Hu
  10. Juan Chen
  11. Ni Tang
  12. Ai-Long Huang

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Abstract

Background

Coronavirus disease 2019 (COVID-19) is a global pandemic with no licensed vaccine or specific antiviral agents for therapy. Little is known about the longitudinal dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–specific neutralizing antibodies (NAbs) in patients with COVID-19.

Methods

Blood samples (n = 173) were collected from 30 patients with COVID-19 over a 3-month period after symptom onset and analyzed for SARS-CoV-2–specific NAbs using the lentiviral pseudotype assay, coincident with the levels of IgG and proinflammatory cytokines.

Results

SARS-CoV-2–specific NAb titers were low for the first 7–10 days after symptom onset and increased after 2–3 weeks. The median peak time for NAbs was 33 days (interquartile range [IQR], 24–59 days) after symptom onset. NAb titers in 93.3% (28/30) of the patients declined gradually over the 3-month study period, with a median decrease of 34.8% (IQR, 19.6–42.4%). NAb titers increased over time in parallel with the rise in immunoglobulin G (IgG) antibody levels, correlating well at week 3 (r = 0.41, P < .05). The NAb titers also demonstrated a significant positive correlation with levels of plasma proinflammatory cytokines, including stem cell factor (SCF), TNF-related apoptosis-inducing ligand (TRAIL), and macrophage colony-stimulating factor (M-CSF).

Conclusions

These data provide useful information regarding dynamic changes in NAbs in patients with COVID-19 during the acute and convalescent phases.

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  1. Version published to 10.1093/cid/ciaa1143
  2. ScreenIT

    SciScore for 10.1101/2020.07.14.20151159: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: Ethical approval: The study was approved by the Ethics Commission of Chongqing Medical University (ref. no. 2020003).
    Consent: Written informed consent was waived by the Ethics Commission of the designated hospital for emerging infectious diseases.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    12 Briefly, HEK293T cells (5 × 106) were co-transfected with pNL4-3.
    HEK293T
    suggested: None
    13 Neutralization assays: The 293T-ACE2 cells (2 × 104 cells/well) were seeded in 96-well plates.
    293T-ACE2
    suggested: RRID:CVCL_YZ65)

    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 some limitations to this study, which should be addressed. Due to the small sample size, we could not find any correlation between the dynamics of NAb titers and clinical characteristics contributing to different clinical outcomes. Serological blood samples were collected up to 3 months after symptom onset; data collected over longer follow-up times should be obtained to demonstrate the duration of humoral immunity after SARS-CoV-2 infection. The lack of data to determine an anamnestic immune response, such as tests for SARS-CoV-2-specific memory B cells, memory T cells, and specific cytokine-dependent memory cells, hampered the evaluation of the immune response, especially protective immunity against viral reinfection. These are major issues that should be investigated in future studies. In summary, we determined the dynamics of NAb titers within 3 months after symptom onset in 30 SARS-CoV-2-infected patients and found a positive correlation between NAb titers and IgG antibodies. Our work provides valuable insight into the humoral immunity against SARS-CoV-2 infection. We also described a pseudotype system for measuring NAb titers, which could be expanded to antiviral drug screening and vaccine development.

    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

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  3. Version published to 10.1101/2020.07.14.20151159 on medRxiv