D-Dimer in Viral Respiratory Infections: Established Evidence in COVID-19 and Emerging Evidence in Other Respiratory Viruses.
- 1Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Majmaah 11952, Saudi Arabia.
- 2Department of Botany and Microbiology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.
- 3Research Center, King Fahad Medical City, Riyadh Second Health Cluster, Riyadh 11525, Saudi Arabia.
Abstract
Viral respiratory infections remain a major cause of global morbidity and mortality, with severe disease increasingly recognized to involve profound interactions between inflammation, endothelial dysfunction, coagulation activation, and immunothrombosis. D-dimer, a fibrin degradation product and established biomarker of fibrin turnover, has gained considerable attention because of its strong association with adverse outcomes in coronavirus disease 2019 (COVID-19). This narrative review compares the evidence for D-dimer in COVID-19 with that available for other respiratory viruses and deliberately separates three questions that are frequently conflated: whether D-dimer predicts severity or death (prognostic), whether it identifies or excludes venous thromboembolism (diagnostic), and whether it identifies patients who benefit from anticoagulation (treatment-predictive). In COVID-19, elevated D-dimer is reproducibly associated with disease severity, thromboembolic complications, intensive care unit admission, and mortality, and the association persists after adjustment; however, discrimination is only moderate, incremental value over routine clinical variables has rarely been tested, and randomized trials have not established D-dimer as a treatment-selection biomarker. Outside of COVID-19, the evidence is substantially weaker and uneven: influenza is supported mainly by comparative cohorts, adenovirus by a single unvalidated paediatric prediction model, and the only direct study of D-dimer and clinical severity in bronchiolitis was negative, while for MERS-CoV, parainfluenza, and human metapneumovirus, we identified no study relating D-dimer to a clinical outcome. Moreover, substantial heterogeneity in assay methodology, sampling strategies, and proposed cut-off values restricts standardization and cross-study comparisons. We therefore present COVID-19 as a mechanistic and methodological reference rather than a validated universal rule, and summarize the evidence in a structured table and a visual evidence map. Overall, D-dimer appears to represent an integrated biomarker of coagulation activation, endothelial injury, and systemic inflammation rather than thrombosis alone, supporting its role in risk stratification while underscoring the need for context-specific interpretation. The cross-viral propositions advanced here should be regarded as hypothesis-generating. Future prospective multicentre studies using standardized assays, serial biomarker assessment, and multimarker prediction models are required to establish pathogen-specific prognostic frameworks and define the role of D-dimer in precision medicine for viral respiratory infections.
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BibTeX
@article{madkhali2026ddimer,
title = {{D-Dimer in Viral Respiratory Infections: Established Evidence in COVID-19 and Emerging Evidence in Other Respiratory Viruses.}},
author = {Yahya Madkhali and Ayman Mubarak and Bandar Alosaimi and Wael Alturaiki},
journal = {International journal of molecular sciences},
year = {2026},
month = sep,
doi = {10.3390/ijms27198525},
url = {https://europepmc.org/article/MED/42883774},
note = {CC BY},
}
RIS
TY - JOUR
TI - D-Dimer in Viral Respiratory Infections: Established Evidence in COVID-19 and Emerging Evidence in Other Respiratory Viruses.
AU - Yahya Madkhali
AU - Ayman Mubarak
AU - Bandar Alosaimi
AU - Wael Alturaiki
PY - 2026
DA - 2026/09/24
JO - International journal of molecular sciences
DO - 10.3390/ijms27198525
UR - https://europepmc.org/article/MED/42883774
AB - Viral respiratory infections remain a major cause of global morbidity and mortality, with severe disease increasingly recognized to involve profound interactions between inflammation, endothelial dysfunction, coagulation activation, and immunothrombosis. D-dimer, a fibrin degradation product and established biomarker of fibrin turnover, has gained considerable attention because of its strong association with adverse outcomes in coronavirus disease 2019 (COVID-19). This narrative review compares the evidence for D-dimer in COVID-19 with that available for other respiratory viruses and deliberately separates three questions that are frequently conflated: whether D-dimer predicts severity or death (prognostic), whether it identifies or excludes venous thromboembolism (diagnostic), and whether it identifies patients who benefit from anticoagulation (treatment-predictive). In COVID-19, elevated D-dimer is reproducibly associated with disease severity, thromboembolic complications, intensive care unit admission, and mortality, and the association persists after adjustment; however, discrimination is only moderate, incremental value over routine clinical variables has rarely been tested, and randomized trials have not established D-dimer as a treatment-selection biomarker. Outside of COVID-19, the evidence is substantially weaker and uneven: influenza is supported mainly by comparative cohorts, adenovirus by a single unvalidated paediatric prediction model, and the only direct study of D-dimer and clinical severity in bronchiolitis was negative, while for MERS-CoV, parainfluenza, and human metapneumovirus, we identified no study relating D-dimer to a clinical outcome. Moreover, substantial heterogeneity in assay methodology, sampling strategies, and proposed cut-off values restricts standardization and cross-study comparisons. We therefore present COVID-19 as a mechanistic and methodological reference rather than a validated universal rule, and summarize the evidence in a structured table and a visual evidence map. Overall, D-dimer appears to represent an integrated biomarker of coagulation activation, endothelial injury, and systemic inflammation rather than thrombosis alone, supporting its role in risk stratification while underscoring the need for context-specific interpretation. The cross-viral propositions advanced here should be regarded as hypothesis-generating. Future prospective multicentre studies using standardized assays, serial biomarker assessment, and multimarker prediction models are required to establish pathogen-specific prognostic frameworks and define the role of D-dimer in precision medicine for viral respiratory infections.
SN - 1422-0067
ER -