Prognostic value of serum/plasma neurofilament light chain for COVID ‐19‐associated mortality

  1. Ruturaj R. Masvekar
  2. Peter Kosa
  3. Kimberly Jin
  4. Kerry Dobbs
  5. Michael A. Stack
  6. Riccardo Castagnoli
  7. Virginia Quaresima
  8. Helen C. Su
  9. Luisa Imberti
  10. Luigi D. Notarangelo
  11. Bibiana Bielekova

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Abstract

Objective

Given the continued spread of coronavirus 2, the early predictors of coronavirus disease 19 (COVID‐19) associated mortality might improve patients' outcomes. Increased levels of circulating neurofilament light chain (NfL), a biomarker of neuronal injury, have been observed in severe COVID‐19 patients. We investigated whether NfL provides non‐redundant clinical value to previously identified predictors of COVID‐19 mortality.

Methods

We measured serum or plasma NfL concentrations in a blinded fashion in 3 cohorts totaling 338 COVID‐19 patients.

Results

In cohort 1, we found significantly elevated NfL levels only in critically ill COVID‐19 patients. Longitudinal cohort 2 data showed that NfL is elevated late in the course of the disease, following the two other prognostic markers of COVID‐19: decrease in absolute lymphocyte count (ALC) and increase in lactate dehydrogenase (LDH). Significant correlations between ALC and LDH abnormalities and subsequent rise of NfL implicate that the multi‐organ failure is the most likely cause of neuronal injury in severe COVID‐19 patients. The addition of NfL to age and gender in cohort 1 significantly improved the accuracy of mortality prediction and these improvements were validated in cohorts 2 and 3.

Interpretation

A substantial increase in serum/plasma NfL reproducibly enhanced COVID‐19 mortality prediction. Combined with other prognostic markers, such as ALC and LDH that are routinely measured in ICU patients, NfL measurements might be useful to identify the patients at a high risk of COVID‐19‐associated mortality, who might still benefit from escalated care.

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  1. Version published to 10.1002/acn3.51542
  2. ScreenIT

    SciScore for 10.1101/2022.01.13.22269244: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Research subjects and cohorts: Serum or plasma samples from COVID-19 patients admitted at ASST Spedali Civili (Brescia, Italy) were obtained through Laboratory of Clinical Immunology and Microbiology (LCIM), National Institute of Allergy and Infectious Diseases (NIAID), under Institutional Review Board (IRB)-approved protocols (Comitato Etico Provinciale: NP 4000 - Studio CORONAlab and NP 4408 - Studio CORONAlab and ClinicalTrials.gov: NCT04582903).
    Consent: Serum and plasma samples from healthy controls (HC) and multiple sclerosis (MS) subjects were collected at Neuroimmunological Diseases Section (NDS), NIAID after informed consent under IRB-approved protocol (ClinicalTrials.gov: NCT00794352).
    Sex as a biological variablenot detected.
    RandomizationSamples were diluted 1:4 and randomly distributed on 96-well plates.
    BlindingAll samples were analyzed blindly under alpha-numeric codes.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Prediction models of COVID-19 associated mortality were developed in R Studio Version 1.1.463 (R version 4.0.2) using logistic regression (glm function of the “stat” package) (R: The R Project for Statistical Computing).
    R Project for Statistical
    suggested: (R Project for Statistical Computing, RRID:SCR_001905)

    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: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04582903RecruitingSend-In Sample Collection for Comprehensive Analyses of Inna…
    NCT00794352RecruitingComprehensive Multimodal Analysis of Neuroimmunological Dise…

    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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  3. Version published to 10.1101/2022.01.13.22269244v1 on medRxiv