Long-Term Course of Humoral and Cellular Immune Responses in Outpatients After SARS-CoV-2 Infection

  1. Julia Schiffner
  2. Insa Backhaus
  3. Jens Rimmele
  4. Sören Schulz
  5. Till Möhlenkamp
  6. Julia Maria Klemens
  7. Dorinja Zapf
  8. Werner Solbach
  9. Alexander Mischnik

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Abstract

Characterization of the naturally acquired B and T cell immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is important for the development of public health and vaccination strategies to manage the burden of COVID-19 disease. We conducted a prospective, cross-sectional analysis in COVID-19 recovered patients at various time points over a 10-month period in order to investigate how circulating antibody levels and interferon-gamma (IFN-γ) release by peripheral blood cells change over time following natural infection. From March 2020 till January 2021, we enrolled 412 adults mostly with mild or moderate disease course. At each study visit, subjects donated peripheral blood for testing of anti-SARS-CoV-2 IgG antibodies and IFN-γ release after SARS-CoV-2 S-protein stimulation. Anti-SARS-CoV-2 immunoglobulin G (IgG) antibodies were positive in 316 of 412 (76.7%) and borderline in 31 of 412 (7.5%) patients. Our confirmation assay for the presence of neutralizing antibodies was positive in 215 of 412 (52.2%) and borderline in 88 of 412 (21.4%) patients. Likewise, in 274 of 412 (66.5%) positive IFN-γ release and IgG antibodies were detected. With respect to time after infection, both IgG antibody levels and IFN-γ concentrations decreased by about half within 300 days. Statistically, production of IgG and IFN-γ were closely associated, but on an individual basis, we observed patients with high-antibody titres but low IFN-γ levels and vice versa. Our data suggest that immunological reaction is acquired in most individuals after natural infection with SARS-CoV-2 and is sustained in the majority of patients for at least 10 months after infection after a mild or moderate disease course. Since, so far, no robust marker for protection against COVID-19 exists, we recommend utilizing both, IgG and IFN-γ release for an individual assessment of the immunity status.

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  1. Version published to 10.3389/fpubh.2021.732787
  2. ScreenIT

    SciScore for 10.1101/2021.06.24.21259218: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: From the invited patients, 436 responded to the invitation and, finally, 412 of them donated blood for analysis after having given written informed consent (see flowchart).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Detection of anti-SARS-CoV-2 S1-Protein IgG antibodies: Serum Anti-SARS-CoV-2 IgG were detected by automated Enzyme-linked Immunosorbent Assay (product EI 2606-9601 G; EUROIMMUN; https://www.euroimmun.com) according to the manufacturer’s instructions.
    anti-SARS-CoV-2 S1-Protein IgG
    suggested: None
    Anti-SARS-CoV-2 IgG
    suggested: None
    Detection of neutralizing antibodies: For detection of neutralizing antibodies, a semi-quantitative surrogate virus neutralization test (NeutraLISA from Euroimmun, Product No. 2606-4) was applied, through which the binding of SARS-CoV-2 S1/receptor-binding-domain RBD to ACE2 receptors of the recombinant human host cells is determined.
    ACE2
    suggested: None
    Detection of T-cell-activity: Besides B cells and antibodies, T lymphocytes and cytokines are instrumental for the shaping of the specific acute and memory immune response to SARS-CoV-210.
    SARS-CoV-210
    suggested: None
    Software and Algorithms
    SentencesResources
    To identify potential factors associated with SARS-CoV-2 seropositivity (yes/no), a binary logistic regression analysis using the logitem command in Stata (StataCorp, College Station, TX, version 15) to correct for the test’s specificity and sensitivity was performed.
    StataCorp
    suggested: (Stata, RRID:SCR_012763)

    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:
    Strengths and limitations: The current study has few limitations. Longitudinal data for each subject, with at least three time points per subject, would be required for more precise understanding of the kinetics of durability of SARS-CoV-2–specific antibodies. Nevertheless, the current cross-sectional data describe well the dynamics of spike-specific antibodies over 10 months and IFN-γ release by blood T-lymphocytes at one study point. This study was not sufficiently powered to control for many variables simultaneously.

    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

    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.

  3. Version published to 10.1101/2021.06.24.21259218v1 on medRxiv