Specific COVID-19 Symptoms Correlate with High Antibody Levels against SARS-CoV-2

  1. Maya F Amjadi
  2. Sarah E O’Connell
  3. Tammy Armbrust
  4. Aisha M Mergaert
  5. Sandeep R Narpala
  6. Peter J Halfmann
  7. S Janna Bashar
  8. Christopher R Glover
  9. Anna S Heffron
  10. Alison Taylor
  11. Britta Flach
  12. David H O’Connor
  13. Yoshihiro Kawaoka
  14. Adrian B McDermott
  15. Ajay K Sethi
  16. Miriam A Shelef

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Abstract

Lasting immunity will be critical for overcoming COVID-19. However, the factors associated with the development of high titers of anti–SARS-CoV-2 Abs and how long those Abs persist remain incompletely defined. In particular, an understanding of the relationship between COVID-19 symptoms and anti–SARS-CoV-2 Abs is limited. To address these unknowns, we quantified serum anti–SARS- CoV-2 Abs in clinically diverse COVID-19 convalescent human subjects 5 wk (n = 113) and 3 mo (n = 79) after symptom resolution with three methods: a novel multiplex assay to quantify IgG against four SARS-CoV-2 Ags, a new SARS-CoV-2 receptor binding domain-angiotensin converting enzyme 2 inhibition assay, and a SARS-CoV-2 neutralizing assay. We then identified clinical and demographic factors, including never-before-assessed COVID-19 symptoms, that consistently correlate with high anti–SARS-CoV-2 Ab levels. We detected anti–SARS-CoV-2 Abs in 98% of COVID-19 convalescent subjects 5 wk after symptom resolution, and Ab levels did not decline at 3 mo. Greater disease severity, older age, male sex, higher body mass index, and higher Charlson Comorbidity Index score correlated with increased anti–SARS-CoV-2 Ab levels. Moreover, we report for the first time (to our knowledge) that COVID-19 symptoms, most consistently fever, body aches, and low appetite, correlate with higher anti–SARS-CoV-2 Ab levels. Our results provide robust and new insights into the development and persistence of anti–SARS-CoV-2 Abs.

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  1. Version published to 10.4049/immunohorizons.2100022
  2. ScreenIT

    SciScore for 10.1101/2021.01.05.21249240: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementConsent: All subjects provided informed consent.
    IRB: Study approval: Human studies were performed according to the Declaration of Helsinki and were approved by the Institutional Review Board at the UW-Madison.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Serum anti-SARS-CoV-2 antibody levels at five weeks and three months post symptom resolution in the same subjects were compared using paired t tests.
    anti-SARS-CoV-2
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Culture supernatant was aspirated from Vero E6/TMPRSS2 cells plated in 96 well dishes and replaced with the mixtures of serially diluted sera and virus (100µl/well, in duplicate) followed by incubation at 37°C with 5% CO2 for 3 days.
    Vero E6/TMPRSS2
    suggested: None
    Software and Algorithms
    SentencesResources
    Analyses were performed using GraphPad Prism software (San Diego, USA) and STATA version 16 (College Station, USA).
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    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:
    There are a few caveats to our studies. First, COVID-19 symptoms were self-reported up to a month after symptom resolution, which could lead to recall error. Additionally, some of the medical records were incomplete with no recent primary care or admission note in the charts of 19% of subjects and 14% missing BMI data. This gap would be biased toward non-hospitalized patients. Also, our population was relatively homogeneous with regard to race and ethnicity. However, our study is strong in that it includes a wide breadth of COVID-19 severity in 113 subjects with consistent time points and multiple types of antibody tests. In sum, we report that antibody-based immunity against SARS-CoV-2 lasts at least three months post-symptom resolution and that antibody titers consistently correlate with specific COVID-19 symptoms (fever, low appetite, abdominal pain, and diarrhea) and clinical and demographic features (older age, male sex, higher COVID-19 severity, higher BMI, and higher Charlson Comorbidity Index score). Future work is needed to determine which antibody titers are protective against re-infection and how long those titers last.

    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

    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 10.1101/2021.01.05.21249240v1 on medRxiv