Metabolic biomarker profiling for identification of susceptibility to severe pneumonia and COVID-19 in the general population
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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.
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SciScore for 10.1101/2020.07.02.20143685: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement Consent: All participants provided written informed consent and ethical approval was obtained from the North West Multi-Center Research Ethics Committee.
IRB: All participants provided written informed consent and ethical approval was obtained from the North West Multi-Center Research Ethics Committee.Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not 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 …SciScore for 10.1101/2020.07.02.20143685: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement Consent: All participants provided written informed consent and ethical approval was obtained from the North West Multi-Center Research Ethics Committee.
IRB: All participants provided written informed consent and ethical approval was obtained from the North West Multi-Center Research Ethics Committee.Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not 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:To overcome this limitation, we took advantage of the well-powered biomarker associations with severe pneumonia. We observed prominent risk elevation for severe pneumonia in the extreme tail of the multi-biomarker infectious disease score, whereas the risk elevation was modest for approximately four fifth of the study population. These features could aid establishing high-risk threshold for potential preventative screening applications if results generalise to severe COVID-19. The technical repeatability for measuring the infectious disease score was high, further supporting potential screening applications. The biological stability of the multi-biomarker score measured years apart was similar to that for cholesterol testing, reflecting the modifiable nature of the metabolic biomarkers but still indicating a stronger stability over time than many inflammatory markers. Our study has both strengths and limitations. Strengths include the large sample size, which enabled the analysis of risk for severe COVID-19 based on pre-pandemic blood samples from general population settings. However, the UK Biobank study participants are not fully representative of the whole UK population (Fry et al 2017); although this is generally not a concern for investigating risk associations (Keyes and Westreich 2019), it does limit power to explore effects of ethnicity and old age. We used the widely employed Nightingale metabolomics platform, which enables absolute quantification of biomarker concen...
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.
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SciScore for 10.1101/2020.07.02.20143685: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement All participants provided written informed consent and ethical approval was obtained from the North West Multi-Center Research Ethics Committee. Randomization not detected. Blinding The measurement repeatability was high ( Pearson correlation 0.94 in blind duplicate samples) . Power Analysis Exploiting the strong statistical power and time-resolved information for analyses of severe pneumonia , we showed that the very highest levels of the multi-biomarker infectious disease score are strongly indicative of risk for severe pneumonia . Sex as a biological variable The association was similar across age groups , and also for men and women analysed separately ( … SciScore for 10.1101/2020.07.02.20143685: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement All participants provided written informed consent and ethical approval was obtained from the North West Multi-Center Research Ethics Committee. Randomization not detected. Blinding The measurement repeatability was high ( Pearson correlation 0.94 in blind duplicate samples) . Power Analysis Exploiting the strong statistical power and time-resolved information for analyses of severe pneumonia , we showed that the very highest levels of the multi-biomarker infectious disease score are strongly indicative of risk for severe pneumonia . Sex as a biological variable The association was similar across age groups , and also for men and women analysed separately ( panels 2C and 2D) . Table 2: Resources
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