Humoral response, associated symptoms and profile of patients infected by SARS-CoV-2 with taste or smell disorders in the SAPRIS multicohort study

  1. Julien Ramillon
  2. Xavier de Lamballerie
  3. Olivier Robineau
  4. Helene Blanché
  5. Gianluca Severi
  6. Mathilde Touvier
  7. Marie Zins
  8. Fabrice Carrat
  9. Nathanaël Lapidus
  10. the SAPRIS-SERO study group

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Abstract

Objectives

Taste or smell disorders have been reported as strongly associated with COVID-19 diagnosis. We aimed to identify subject characteristics, symptom associations, and humoral response intensity associated with taste or smell disorders.

Patients and methods

We used data from SAPRIS, a study based on a consortium of five prospective cohorts gathering 279,478 participants in the French general population. In the analysis, we selected participants who were presumably infected by SARS-CoV-2 during the first epidemic wave.

Results

The analysis included 3,439 patients with a positive ELISA-Spike. Sex (OR = 1.28 [95% CI 1.05-1.58] for women), smoking (OR = 1.54 [95% CI 1.13-2.07]), consumption of more than 2 drinks of alcohol a day (OR = 1.37 [95% CI 1.06-1.76]) were associated with a higher probability of taste or smell disorders. The relationship between age and taste or smell disorders was non-linear. Serological titers were associated with taste or smell disorders: OR = 1.31 [95% CI 1.26-1.36], OR = 1.37 [95% CI 1.33-1.42] and OR = 1.34 [95% CI 1.29-1.39] for ELISA-Spike, ELISA-Nucleocapsid and seroneutralization, respectively. Among participants with taste or smell disorders, 90% reported a wide variety of other symptoms whereas 10% reported no other symptom or only rhinorrhea.

Conclusion

Among patients with a positive ELISA-Spike test, women, smokers and people drinking more than 2 drinks a day were more likely to develop taste or smell disorders. This symptom was strongly associated with a humoral response. The overwhelming majority of patients with taste or smell disorders experienced a wide variety of symptoms.

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  1. ScreenIT

    SciScore for 10.1101/2022.02.01.22270250: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: Ethical approval and written or electronic informed consent were obtained from each participant before enrolment in the original cohort.
    IRB: The SAPRIS survey was approved by the Inserm ethics committee (approval #20-672 dated March 30, 2020).
    Sex as a biological variablePatient and public involvement: This study was designed without patient or public involvement. 2.2. Design: We used data from SAPRIS (“Santé, Perception, pratiques Relations et Inégalités Sociales en population générale pendant la crise COVID-19”) based on a consortium of prospective cohort studies involving three general population-based adult cohorts: CONSTANCES, a “general population” cohort including a representative sample of 215,000 adults (including 66,000 followed by internet) aged 18 to 69 years at inclusion and recruited from 2012; E3N / E4N, a multigenerational adult cohort based on a community of families with 113,000 participants (women recruited in 1990 and still actively followed, their offspring and the fathers of this offspring) among whom 90,000 have been invited to an internet follow-up; and NutriNet-Santé a nutritional general population-based internet cohort started in 2009, with 170,000 included participants.
    RandomizationThese data were combined with serological results from the SAPRIS-SERO study, in which a random sample of SAPRIS participants were invited to provide self-sampling dried-blood spot (DBS) aimed at serology testing [6].
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    The ELISA test (Euroimmun®, Lübeck, Germany) was used to detect anti-SARS-CoV-2 antibodies (IgG) directed against the S1 domain of the spike protein of the virus (ELISA-S).
    anti-SARS-CoV-2
    suggested: None
    All samples with an ELISA-S test ≥ 0.7 were also tested with an ELISA test to detect IgG antibodies against the SARS-CoV-2 nucleocapsid protein (Euroimmun®, Lübeck, Germany, ELISA-NP) using the same thresholds as above and with an in-house micro-neutralization assay to detect neutralizing anti-SARS-CoV-2 antibodies (SN), as described elsewhere with a positive SN defined as a titer ≥ 40 (SN titer was determined by iterative dilutions, leading to discrete values for titers, equal to 10, 20, 40, 80 or 160) [8]. 2.5. Variables: The main outcome was the presence of self-reported TSD on either the first or the second questionnaire.
    SARS-CoV-2 nucleocapsid protein
    suggested: None
    Software and Algorithms
    SentencesResources
    A sensitivity analysis with multiple imputation of missing data was conducted to assess robustness of results: 20 imputed datasets were generated with multiple imputation by chained equations (predictive mean matching), among which all estimates were poled using Rubin’s rule. 2.7.
    Rubin’s
    suggested: None

    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: Our study presents numerous strengths. Participants from the SAPRIS study were recruited from the general population, via well-characterized cohorts with a very high participation rate. This design ensured a large sample size and a more comprehensive overview on COVID-19 symptoms than studies focusing only on either outpatients or inpatients. Moreover, our case definition is prospective and does not rely on reported symptoms, hence the important number of asymptomatic or paucisymptomatic patients. Regarding serology, most DBS were collected within 1 to 3 months following a period of intense viral circulation and serological analyses were centralized and performed blinded to subjects and investigators. The combination of several serological analysis methods (ELISA-S, ELISA-NP and seroneutralization) tends to reinforce the robustness of the results regarding the association between humoral response and TSD. Several limitations must also be noted. First, we considered subjects with a positive ELISA-S (i.e. ≥ 1.1) as having been infected by the SARS-CoV-2. This choice may tend to underestimate the number of subjects who have been infected with the COVID 19 virus as (i) indeterminate results (between 0.8 and 1.1) were considered as negative, (ii) there is evidence that the humoral immunity developed in the weeks following infection decreases over time (though this issue was partly controlled as DBS were mostly collected soon after the first epidemic wave...

    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.

  2. Version published to 10.1101/2022.02.01.22270250 on medRxiv