Metabolic biomarker profiling for identification of susceptibility to severe pneumonia and COVID-19 in the general population

  1. Nightingale Health UK Biobank Initiative
  2. Heli Julkunen
  3. Anna Cichońska
  4. P Eline Slagboom
  5. Peter Würtz  Is a corresponding author
  1. Nightingale Health Ltd, Finland
  2. Leiden University Medical Center, Netherlands

Abstract

Biomarkers of low-grade inflammation have been associated with susceptibility to a severe infectious disease course, even when measured prior to disease onset. We investigated whether metabolic biomarkers measured by nuclear magnetic resonance (NMR) spectroscopy could be associated with susceptibility to severe pneumonia (2507 hospitalised or fatal cases) and severe COVID-19 (652 hospitalised cases) in 105,146 generally healthy individuals from UK Biobank, with blood samples collected 2007–2010. The overall signature of metabolic biomarker associations was similar for the risk of severe pneumonia and severe COVID-19. A multi-biomarker score, comprised of 25 proteins, fatty acids, amino acids and lipids, was associated equally strongly with enhanced susceptibility to severe COVID-19 (odds ratio 2.9 [95%CI 2.1–3.8] for highest vs lowest quintile) and severe pneumonia events occurring 7–11 years after blood sampling (2.6 [1.7–3.9]). However, the risk for severe pneumonia occurring during the first 2 years after blood sampling for people with elevated levels of the multi-biomarker score was over four times higher than for long-term risk (8.0 [4.1–15.6]). If these hypothesis generating findings on increased susceptibility to severe pneumonia during the first few years after blood sampling extend to severe COVID-19, metabolic biomarker profiling could potentially complement existing tools for identifying individuals at high risk. These results provide novel molecular understanding on how metabolic biomarkers reflect the susceptibility to severe COVID-19 and other infections in the general population.

Data availability

The data are available for approved researchers from UK Biobank. The metabolic biomarker data has been released to the UK Biobank resource in March 2021.

The following previously published data sets were used
    1. Sudlow et al
    (2015) UK Biobank
    https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1001779.

Article and author information

Author details

  1. Nightingale Health UK Biobank Initiative

  2. Heli Julkunen

    R&D, Nightingale Health Ltd, Helsinki, Finland
    Competing interests
    Heli Julkunen, HJ is employee of Nightingale Health Ltd..
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4282-0248
  3. Anna Cichońska

    R&D, Nightingale Health Ltd, Helsinki, Finland
    Competing interests
    Anna Cichońska, AC is employee and hold stock options with Nightingale Health Ltd..
  4. P Eline Slagboom

    Leiden University Medical Center, Leiden, Netherlands
    Competing interests
    No competing interests declared.
  5. Peter Würtz

    R&D, Nightingale Health Ltd, Helsinki, Finland
    For correspondence
    peter.wurtz@nightingalehealth.com
    Competing interests
    Peter Würtz, PW is employee and shareholder of Nightingale Health Ltd..
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5832-0221

Funding

The study was funded by Nightingale Health Plc. Three of the study authors are employees of Nightingale Health Plc.

Ethics

Human subjects: The UK Biobank recruited 502 639 participants aged 37-70 years in 22 assessment centres across the UK. All participants provided written informed consent and ethical approval was obtained from the North West Multi-Center Research Ethics Committee. Details of the design of the UK Biobank have been reported previously (Sudlow et al PLOS Medicine 2015). The current analysis was approved under UK Biobank Project 30418.

Reviewing Editor

  1. Edward D Janus, University of Melbourne, Australia

Publication history

  1. Received: September 11, 2020
  2. Accepted: May 2, 2021
  3. Accepted Manuscript published: May 4, 2021 (version 1)
  4. Version of Record published: June 2, 2021 (version 2)

Copyright

© 2021, Julkunen et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 3,076
    Page views
  • 325
    Downloads
  • 20
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Nightingale Health UK Biobank Initiative
  2. Heli Julkunen
  3. Anna Cichońska
  4. P Eline Slagboom
  5. Peter Würtz
(2021)
Metabolic biomarker profiling for identification of susceptibility to severe pneumonia and COVID-19 in the general population
eLife 10:e63033.
https://doi.org/10.7554/eLife.63033
  1. Further reading

Further reading

    1. Epidemiology and Global Health
    2. Evolutionary Biology
    Erin Brintnell, Art Poon
    Insight

    Combining clinical and genetic data can improve the effectiveness of virus tracking with the aim of reducing the number of HIV cases by 2030.

    1. Epidemiology and Global Health
    Catherine Meh, Prabhat Jha
    Research Article

    Preference for sons and smaller families and, in the case of China, a one-child policy, have contributed to missing girl births in India and China over the last few decades due to sex-selective abortions. Selective abortion occurs also among Indian and Chinese diaspora, but their variability and trends over time are unknown. We examined conditional sex ratio (CSR) of girl births per 1000 boy births among second or third births following earlier daughters or sons in India, China, and their diaspora in Australia, Canada, United Kingdom (UK), and United States (US) drawing upon 18.4 million birth records from census and nationally representative surveys from 1999 to 2019. Among Indian women, the CSR in 2016 for second births following a first daughter favoured boys in India (866), similar to those in diaspora in Australia (888) and Canada (882). For third births following two earlier daughters in 2016, CSRs favoured sons in Canada (520) and Australia (653) even more than in India (769). Among women in China outside the one-child restriction, CSRs in 2015 for second order births somewhat favoured more girls after a first son (1154) but more heavily favoured boys after a first daughter (561). Third-birth CSRs generally fell over time among diaspora, except among Chinese diaspora in the UK and US. In the UK, third-birth CSRs fell among Indian but not among other South Asian diasporas. Selective abortion of girls is notable among Indian diaspora, particularly at higher-order births.