Hematological, Inflammatory, Coagulation, and Oxidative/Antioxidant Biomarkers as Predictors for Severity and Mortality in COVID-19: A Prospective Cohort-Study

Abstract

Purpose

Oxidative stress (OS) and inflammation are pivotal points in the pathophysiology of coronavirus disease-2019 (COVID-19). This study aims to use routine laboratory and oxidative stress/antioxidative biomarkers as predictors for the mortality of the disease.

Patients and Methods

This prospective cohort study, made up of 120 COVID-19 patients from emergency units in Erbil, Duhok, Kirkuk, and Sulaymaniyah cities in Iraq, from May the 1^st to May the 30^th, 2021, and 60 healthy controls (HCs) (n = 60). The patients were re-categorized into mild (n = 54), severe (n = 40), and critical (n = 26) groups based on the clinical criteria. Following admission to the hospital, blood was directly collected for measuring routine laboratory biomarkers.

Results

Neutrophils and neutrophil/lymphocyte ratio (NLR) were higher in the critical group, while lymphocytes were lower in the severe and critical groups compared to the mild group. The CRP, ferritin, and D-dimer values were more elevated in severe and critical cases than in mild COVID-19 cases. The levels of malondialdehyde (MDA), nitric oxide (NO), and copper were elevated, while the superoxide dismutase (SOD) activity level and total antioxidant capacity (TAC) level were lower. However, vitamin C, glutathione peroxidase (GPx), and catalase activity levels were not changed in the COVID-19 groups compared to the HCs. NO and ferritin were predictors of ICU hospitalization; D-dimer, MDA, and NLR were predictors of mortality. NO, and NLR were predictors of SpO₂ depression. Moreover, NO, and copper have both good diagnostic values, their cutoffs were 39.01 and 11.93, respectively.

Conclusion

There is an association between immune dysregulation and oxidative imbalance. The biomarkers, that could be considered as predictors for the severity and mortality of COVID-19, are the NLR, NO, ferritin, and D-dimer. The age equal to and older than 50 has a poor prognosis in the Kurdish population.

Graphical Abstract

Keywords:

• COVID-19
• inflammation
• mortality
• oxidative stress
• predictors

Data Sharing Statement

The data used and/or analyzed during the current study are available from the corresponding author upon reasonable request.

Ethics Approval and Consent to Participate

This study was authorized by Salahaddin University-(SUE) Erbil’s ethics committee following the Helsinki Declaration (approval number: R12-021; 96 approved on April 18, 2021). All participants gave their written informed consent before blood withdrawal. For patients who were unable to sign due to life-threatening emergencies, we asked his or her relatives, who had substitute decision-makers, legal guardians, or power of attorney for the patient.

Consent to Publish

The authors affirm that all participants provided informed consent for publication.

Acknowledgments

The authors wish to thank the University of Tabriz for logistical support.

Author Contributions

All authors made a significant contribution to the work reported, whether that was in the conception, study design, execution, acquisition of data, analysis, and interpretation, or in all these areas; they took part in drafting, revising, or critically reviewing the article; they gave final approval of the version to be published; they agreed on the journal to which the article had been submitted; and they agreed to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.

Additional information

Funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.