Serum Levels of Proinflammatory Lipid Mediators and Specialized Proresolving Molecules Are Increased in Patients With Severe Acute Respiratory Syndrome Coronavirus 2 and Correlate With Markers of the Adaptive Immune Response

  1. James Turnbull
  2. Rakesh R Jha
  3. Catherine A Ortori
  4. Eleanor Lunt
  5. Patrick J Tighe
  6. William L Irving
  7. Sameer A Gohir
  8. Dong-Hyun Kim
  9. Ana M Valdes
  10. Alexander W Tarr
  11. David A Barrett
  12. Victoria Chapman

Reviewed by

Read the full article See related articles

Listed in

Log in to save this article

Abstract

Background

Specialized proresolution molecules (SPMs) halt the transition to chronic pathogenic inflammation. We aimed to quantify serum levels of pro- and anti-inflammatory bioactive lipids in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients, and to identify potential relationships with innate responses and clinical outcome.

Methods

Serum from 50 hospital admitted inpatients (22 female, 28 male) with confirmed symptomatic SARS-CoV-2 infection and 94 age- and sex-matched controls collected prior to the pandemic (SARS-CoV-2 negative), were processed for quantification of bioactive lipids and anti-nucleocapsid and anti-spike quantitative binding assays.

Results

SARS-CoV-2 serum had significantly higher concentrations of omega-6–derived proinflammatory lipids and omega-6– and omega-3–derived SPMs, compared to the age- and sex-matched SARS-CoV-2–negative group, which were not markedly altered by age or sex. There were significant positive correlations between SPMs, proinflammatory bioactive lipids, and anti-spike antibody binding. Levels of some SPMs were significantly higher in patients with an anti-spike antibody value >0.5. Levels of linoleic acid and 5,6-dihydroxy-8Z,11Z,14Z-eicosatrienoic acid were significantly lower in SARS-CoV-2 patients who died.

Conclusions

SARS-CoV-2 infection was associated with increased levels of SPMs and other pro- and anti-inflammatory bioactive lipids, supporting the future investigation of the underlying enzymatic pathways, which may inform the development of novel treatments.

Article activity feed

  1. Version published to 10.1093/infdis/jiab632
  2. ScreenIT

    SciScore for 10.1101/2021.12.07.21267409: (What is this?)

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

    Table 1: Rigor

    EthicsField Sample Permit: Sample Collection and Preparation: Serum samples obtained from 50 inpatients admitted to Nottingham University Hospitals NHS Trust Queen’s Medical Centre with symptomatic RT-PCR confirmed SARS-CoV-2 infection were collected as diagnostic specimens for clinical chemistry testing, excess sera were provided anonymously for research purposes.
    IACUC: Review by the University of Nottingham’s School of Life Sciences Ethical Review Committee deemed the study to not require full ethical review.
    IRB: Ethical approval was obtained from the Research Ethics Committee (ref: 18/EM/0154) and the Health Research Authority (protocol no: 18021)
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    The median time between sample collection for CRP measurement and collection of serum for the measurement of bioactive lipids, anti-nucleocapsid and anti-spike antibody binding was 5 days.
    anti-nucleocapsid
    suggested: None
    anti-spike
    suggested: None
    Software and Algorithms
    SentencesResources
    Data Analysis: GraphPad Prism (Version 8.2.1) was used.
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)
    Multivariate analysis using Metaboanalyst 4.0 (https://www.metaboanalyst.ca/)[28] including principal component analysis (PCA) was performed.
    Metaboanalyst
    suggested: (MetaboAnalyst, RRID:SCR_015539)

    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 number of study limitations. Serum samples were collected from patients hospitalised with SARS-CoV-2 for clinical diagnostic tests during the first wave of the pandemic in the UK. Due to the clinical pressures within the system at the time some clinical data, such as BMI, was not collected. It is known that levels of SPMs are decreased with increased BMI, which could potentially contribute to SARS-CoV-2 related morbidities and mortalities[40]. Although we have data relating to whether a patient was admitted to intensive care, clinical decision making was related to multiple factors beyond the severity of the infection and therefore further analysis of potential impact has not been performed. Serum samples were collected within the first few days of hospital admission and represent a snapshot of the anti-nucleocapsid and anti-spike response and the lipid levels at a point in time. It is important to note that levels of antibodies change over time, however we do not have matched longitudinal data. The anti-nucleocapsid and anti-spike signal provides an indication of the potency of the adaptive immune response following infection. The viral genome sequencing data available for these patients indicated that the nucleocapsid amino acid sequence was completely conserved between infections. While it is possible that there may be mismatches between the antigen used in our assay and the strain of infecting virus that mean that antibodies are present which are undetected by...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).

    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.

  3. Version published to 10.1101/2021.12.07.21267409v1 on medRxiv