Iron status and the risk of sepsis and severe COVID-19: a two-sample Mendelian randomization study
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Abstract
Observational studies have indicated an association between iron status and risk of sepsis and COVID-19. We estimated the effect of genetically-predicted iron biomarkers on risk of sepsis and risk of being hospitalized with COVID-19, performing a two-sample Mendelian randomization study. For risk of sepsis, one standard deviation increase in genetically-predicted serum iron was associated with odds ratio (OR) of 1.14 (95% confidence interval [CI] 1.01–1.29, P = 0.031). The findings were supported in the analyses for transferrin saturation and total iron binding capacity, while the estimate for ferritin was inconclusive. We found a tendency of higher risk of hospitalization with COVID-19 for serum iron; OR 1.29 (CI 0.97–1.72, P = 0.08), whereas sex-stratified analyses showed OR 1.63 (CI 0.94–2.86, P = 0.09) for women and OR 1.21 (CI 0.92–1.62, P = 0.17) for men. Sensitivity analyses supported the main findings and did not suggest bias due to pleiotropy. Our findings suggest a causal effect of genetically-predicted higher iron status and risk of hospitalization due to sepsis and indications of an increased risk of being hospitalized with COVID-19. These findings warrant further studies to assess iron status in relation to severe infections, including the potential of improved management.
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- Authors
- Mohus, R. M., Flatby, H., Liyanarachi, K. V., DeWan, A. T., Solligård, E., Damås, J. K., Åsvold, B. O., Gustad, L. T., & Rogne, T.
- Affiliations
- Norwegian University of Science and Technology (NO)
- Norwegian Institute of Public Health (NO)
- Corresponding author
- Mohus, Randi Marie
- ORCID
- Venue
- Scientific Reports
- Published
- 2022-09-28
- Volume
- 12
- Issue
- 1
- Pages
- 16157-16157
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC9516524
- OpenAlex
- W4297473991
- Cited by
- 28
- References
- 61
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 8 · 2023: 9 · 2022: 1
- FWCI
- 4.55
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- medRxiv (acceptedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- NORA - Norwegian Open Research Archives (submittedVersion, other-oa)
- NORA - Norwegian Open Research Archives (submittedVersion, cc-by)
- Funders
- NTNU Norwegian University of Science and Technology
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
- Keywords
- iron status, sepsis, COVID-19 pandemic, serum iron, transferrin saturation, total iron binding capacity, ferritin, hospitalization risk, sex differences, genetic biomarkers, causal effects
- MeSH terms
- COVID-19, Female, Ferritins, Humans, Iron, Male, Transferrin, Biomarkers, Sepsis, Polymorphism, Single Nucleotide, Genome-Wide Association Study, Mendelian Randomization Analysis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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