Differential antibody production by symptomatology in SARS-CoV-2 convalescent individuals

  1. Sharada Saraf
  2. Xianming Zhu
  3. Ruchee Shrestha
  4. Tania S. Bonny
  5. Owen R. Baker
  6. Evan J. Beck
  7. Reinaldo E. Fernandez
  8. Yolanda Eby
  9. Olivia Akinde
  10. Jessica E. Ruff
  11. Patrizio Caturegli
  12. Andrew D. Redd
  13. Evan M. Bloch
  14. Thomas C. Quinn
  15. Aaron A. R. Tobian
  16. Oliver Laeyendecker

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Abstract

The association between COVID-19 symptoms and antibody responses against SARS-CoV-2 is poorly characterized. We analyzed antibody levels in individuals with known SARS-CoV-2 infection to identify potential antibody-symptom associations. Convalescent plasma from 216 SARS-CoV-2 RNA+ individuals with symptomatology information were tested for the presence of IgG to the spike S1 subunit (Euroimmun ELISA), IgG to receptor binding domain (RBD, CoronaCHEK rapid test), and for IgG, IgA, and IgM to nucleocapsid (N, Bio-Rad ELISA). Logistic regression was used to estimate the odds of having a COVID-19 symptom from the antibody response, adjusting for sex and age. Cough strongly associated with antibodies against S1 (adjusted odds ratio [aOR] = 5.33; 95% CI from 1.51 to 18.86) and RBD (aOR = 4.36; CI 1.49, 12.78). In contrast, sore throat significantly associated with the absence of antibodies to S1 and N (aOR = 0.25; CI 0.08, 0.80 and aOR = 0.31; 0.11, 0.91). Similarly, lack of symptoms associated with the absence of antibodies to N and RBD (aOR = 0.16; CI 0.03, 0.97 and aOR = 0.16; CI 0.03, 1.01). Cough appeared to be correlated with a seropositive result, suggesting that SARS-CoV-2 infected individuals exhibiting lower respiratory symptoms generate a robust antibody response. Conversely, those without symptoms or limited to a sore throat while infected with SARS-CoV-2 were likely to lack a detectable antibody response. These findings strongly support the notion that severity of infection correlates with robust antibody response.

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  1. Version published to 10.1371/journal.pone.0264298
  2. ScreenIT

    SciScore for 10.1101/2022.02.09.22270718: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Study Participants: This study used stored samples and data from studies that were approved by The Johns Hopkins University School of Medicine Institutional Review Board.
    Consent: All study participants provided written informed consent and were de-identified prior to laboratory testing.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Samples were analyzed using three commercially available serologic assays: Euroimmun Anti-SARS-CoV-2 ELISA (Mountain Lakes, NJ), the CoronaCHEK™ COVID-19 IgG/IgM Rapid Test Cassette (Hangzhou Biotest Biotech Co Ltd), and the Bio-Rad Platelia SARS-CoV-2 Total Antibody ELISA (Marnes-la-Coquette, France).
    Anti-SARS-CoV-2 ELISA (Mountain Lakes, NJ)
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    17 Analytes with ≥80% overall detectability were evaluated for cytokine level differences between symptom groups and included Eotaxin, Eotaxin-3, IFN-y, IL-12/IL23p40, IL-15, IL-16, IL-17A, IL-18, IL-1RA, IL-6, IL-7, IL-8, IP-10, MCP-1, MCP-4, MDC, MIP-1B, TARC, TNF-a, and VEGF-A.
    MCP-1
    suggested: None
    Software and Algorithms
    SentencesResources
    All analysis were performed in STATA v.
    STATA
    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:
    Our study had several limitations. First, capture of clinical symptoms was based on self-reporting rather than review of the patients’ medical records. Individuals reporting a certain symptom may have experienced a more severe presentation than others reporting the same symptom, which was not captured by this dataset and may have influenced antibody production. Second, samples were obtained a median of 49 days after participants had PCR positive results and 30 days post symptom resolution. Antibody levels may have declined at the time of sample collection; furthermore, samples were collected at only one timepoint and inferences about persistently high titers of antibodies based on symptom cannot be made. In this cohort of known SARS-CoV-2 infected individuals, we found a strong association between cough and antibody response. Conversely, a sore throat was strongly associated with a lack of antibody response to SARS-CoV-2 infection. Future studies could test for IgA levels in nasal or throat samples to evaluate whether a robust mucosal IgA response is associated with certain clinical presentations of COVID-19. Immune factors other than antibodies and our panel of human cytokines may also be evaluated to better characterize the immune responses generated by individuals exhibiting particular symptomatology.

    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.
    • Thank you for including a protocol registration statement.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

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  3. Version published to 10.1101/2022.02.09.22270718 on medRxiv