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.
Highlights
The coronavirus disease 2019 (COVID-19) pandemic affects societies and healthcare systems worldwide
The prevalence of chronic respiratory and cardiometabolic diseases was similar for study participants who developed severe pneumonia and those who contracted COVID-19 and required hospitalisation, with the exception of COPD
We developed a multi-biomarker score for increased susceptibility to a severe infectious disease course, and demonstrated that this biomarker score captures an increased risk for COVID-19 hospitalisation a decade after the blood sampling
Summary
The coronavirus disease 2019 (COVID-19) pandemic affects societies and healthcare systems worldwide. Protection of those individuals who are most susceptible to a severe and potentially fatal COVID-19 disease course is a prime component of national policies, with stricter social distancing and other preventative means recommended mainly for elderly people and individuals with pre-existing disease conditions. Large numbers of seemingly healthy middle-aged individuals suffer from severe COVID-19 (Zhou et al 2020, Atkins et al 2020, Williamson et al 2020); this could partly be due to similar molecular processes related to impaired immunity. A better understanding of the molecular factors predisposing to severe COVID-19 outcomes may help to explain the risk elevation ascribed to pre-existing disease conditions. From a translational point of view, this might complement the identification of highly susceptible individuals in general population settings beyond current risk factor assessment
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