The association between SARS-CoV-2 infection and neuronal damage: A population-based nested case-control study

  1. N. Ahmad Aziz
  2. Marina L.S. Santos
  3. Monique M.B. Breteler

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Abstract

Objective

To assess whether severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is associated with changes in plasma levels of neurofilament light chain (NfL), an extremely sensitive marker of neuroaxonal damage, in community-dwelling individuals.

Setting

This study was embedded within the Rhineland Study, an ongoing community-based cohort study in Bonn, Germany

Design

Cross-sectional nested case-control study.

Participants

Participants were selected based on results from a previously conducted seroprevalence survey within the framework of the Rhineland Study. Cases were defined as those individuals who had had two positive confirmatory test results, including a recombinant spike-based immunofluorescence assay and a plaque reduction neutralization test (N=21). As controls, a random sample of individuals with a negative ELISA test result (Controls I, N=1117), and those with a borderline or positive ELISA test result who failed confirmatory testing (Controls II, N=68), were selected.

Outcome measures

Plasma levels of NfL at the time of measurement, as well as change in plasma NfL levels compared to previously measured pre-pandemic levels

Results

After adjustment for age, sex and batch effects, serologically confirmed SARS-CoV-2 infection was neither associated with cross-sectional NfL levels, nor with the magnitude of change from pre-pandemic levels, compared to either of the two control groups. Similarly, after adjustment for age, sex and batch effects, self-reported neurological symptoms – including altered sense of smell or taste, headache, myalgia and fever – were not associated with changes in NfL levels in participants with a serologically confirmed SARS-CoV-2 infection (all p ≥ 0.56).

Conclusions

Our findings indicate that mild-to-moderate coronavirus disease-19 is unlikely to be associated with a clinically relevant degree of neuroaxonal damage, even in those cases associated with neurological symptoms.

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  1. ScreenIT

    SciScore for 10.1101/2021.09.02.21263019: (What is this?)

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

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    RandomizationAs controls we selected a random sample of individuals with a negative ELISA (Controls I, N=1117), and those with a borderline or positive ELISA who failed confirmatory testing (Controls II, N=68).
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    No key resources detected.

    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:
    Potential limitations of our study include the relatively small number of cases with a serologically confirmed SARS-CoV-2 infection and lack of data on the exact timing of the infection in seropositive individuals. However, given that the samples were collected shortly after the start of the pandemic in Germany, and the relatively long half-life of NfL that is estimated to be up to a few weeks,13 it is unlikely that we would have missed any substantial or progressive post-infectious elevations of serum NfL levels. Our findings indicate that mild-to-moderate COVID-19 is unlikely to be associated with a clinically relevant degree of neuroaxonal damage, even in those cases associated with neurological symptoms like olfactory and gustatory dysfunction, headache and myalgia.

    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

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  2. Version published to 10.1101/2021.09.02.21263019v1 on medRxiv