Observation and research have revealed some significant COVID-19 biomarker patterns, including those that help differentiate between severe and moderate disease.
Literature review reveals that COVID-19 patients with severe disease had significantly lower levels of lymphocytes, natural killer cells, B cells, and CD4+ and CD8+ T cells compared to those with mild or moderate disease. Increases in basophils and neutrophils reflected increased severity as well.[i]
A significant correlation was found between mortality and[ii]
Advanced COVID-19 pattern
|
|
Elevated |
Decreased |
|
AST and ALT Blood urea nitrogen (may be elevated or decreased) C-reactive protein Creatine kinase Creatinine (may be elevated or decreased) Cytokines IL-6, IL-8, IL-10, IL-2R, IL-1β, and TNF-α D-dimer Erythrocyte sedimentation rate (ESR) Ferritin Fibrinogen Glucose LDH Neutrophils NLR Neutrophil to lymphocyte ratio Procalcitonin RDW-CV Thrombin time Total bilirubin |
Albumin Basophils Eosinophils Lymphocytes Monocytes Prealbumin Selenium Super oxide dismutase (SOD) Total protein Total white blood cells Vitamin C Vitamin D Zinc
|
Biomarker |
Relevant ranges |
Background |
|
Albumin |
Below 3.5 mg/dL Associated with severe COVID-19 [xxii] [xxiii] [xxiv] [xxv] 2.9 mg/dL Predicted ICU admission and 1.8 mg/dL or lower Predicted mortality from COVID-19[xxvi] |
Visceral carrier protein, decreases with inflammation, critical illness, prognostic indicator for progression to pneumonia.[xxvii] |
|
LDH |
388 u/L (6.48 ukat/L) Associated with positive PCR test for COVID-19[xxviii] 731 U/L (12.2 ukat/L) and above predicted mortality from COVID-19[xxix] |
Lactate dehydrogenase enzyme is found in many tissues, an increase in serum levels is associated with tissue and organ damage, including lung damage. |
|
NLR |
2.425 cutoff for COVID-19 [xxx] 3.0 Associated with clinical improvement[xxxi] 3.27 Predicted severe disease and 5.72 predicted mortality[xxxii] |
Neutrophil/lymphocyte ratio (NLR) is a marker of inflammation. Elevated levels are associated with critical illness and more severe COVID-19. |
|
Vitamin C |
0.19 mg/dL (11 umol/L) Deficient and 0.41 mg/dL (23 umol/L) insufficient[xxxiii] 1.3-4 mg/dL (73.8-227 umol/L) can be achieved with dietary intake[xxxiv] |
Vitamin C is an important antioxidant that also exerts anti-inflammatory, anti-viral, and immune-modulating effects. [xxxv] It protects epithelium, stimulates lymphocyte proliferation, reduces proinflammatory cytokines, and can reduce the risk of ARDS. Critically ill may need 20-30 times more vitamin C.[xxxvi] |
|
Vitamin D 25(OH)D |
10 ng/mL (25 nmol/L) Severe deficiency 11.1 ng/mL (27.7 nmol/L) more likely to test positive for COVID-19[xxxvii] 20 ng/mL (50 nmol/L) Insufficiency[xxxviii] 30 ng/mL (75 nmol/L) Reduced severity of COVID-19[xxxix] 40-60 ng/mL (100-150 nmol/L) Reduced risk of respiratory infection, COVID-19.[xl] 50-70 ng/mL (125-175 nmol/L) Robust serum Vitamin D for disease prevention[xli] |
Vitamin D is converted to an active hormone with anti-inflammatory, antifibrotic, antioxidant, and immune-modulating functions. [xlii] COVID-19 patients with serum 25(OH)D below 20 ng/mL (50 nmol/L) were more likely to be critically ill versus COVID-19 patients with serum levels above 20 ng/mL who were more likely to be asymptomatic. [xliii] |
|
Selenium |
Below 100 ug/L (1.27 umol/L) Indication for supplementation[xliv] |
Selenium is a trace mineral required for innate immunity, normal T cell function, antibody production, and antioxidant, anti-inflammatory, and antimicrobial actions. [xlv]
|
|
Zinc |
Below 60 ug/dL (9.2 umol/L) Deficient[xlvi] and loss of sense of smell[xlvii] Below 70 ug/dL (10.7 umol/L) Increased risk of pneumonia in elderly[xlviii] 80-120 ug/dL (12.24-18.4 umol/L) Hospital reference range[xlix] |
Zinc is a trace mineral required for antioxidant systems, immunity, activation of T-lymphocytes, and inhibition of viral replication. [l] Both zinc deficiency and excess can compromise immunity.[li] |
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[iii] Deng, Xiaoling et al. “Blood biochemical characteristics of patients with coronavirus disease 2019 (COVID-19): a systemic review and meta-analysis.” Clinical chemistry and laboratory medicine vol. 58,8 (2020): 1172-1181. doi:10.1515/cclm-2020-0338
[iv] Gallo Marin, Benjamin et al. “Predictors of COVID-19 severity: A literature review.” Reviews in medical virology, e2146. 30 Jul. 2020, doi:10.1002/rmv.2146
[v] Li, Jie et al. “Epidemiology of COVID-19: A systematic review and meta-analysis of clinical characteristics, risk factors, and outcomes.” Journal of medical virology, 10.1002/jmv.26424. 13 Aug. 2020, doi:10.1002/jmv.26424
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[xi] Ferrari, Davide et al. “Routine blood tests as a potential diagnostic tool for COVID-19.” Clinical chemistry and laboratory medicine vol. 58,7 (2020): 1095-1099. doi:10.1515/cclm-2020-0398).
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[xxviii] Ferrari, Davide et al. “Routine blood tests as a potential diagnostic tool for COVID-19.” Clinical chemistry and laboratory medicine vol. 58,7 (2020): 1095-1099. doi:10.1515/cclm-2020-0398).
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[xxx] Xie, Guogang et al. “The role of peripheral blood eosinophil counts in COVID-19 patients.” Allergy, 10.1111/all.14465. 20 Jun. 2020, doi:10.1111/all.14465
[xxxi] Ciccullo, Arturo et al. “Neutrophil-to-lymphocyte ratio and clinical outcome in COVID-19: a report from the Italian front line.” International journal of antimicrobial agents vol. 56,2 (2020): 106017. doi:10.1016/j.ijantimicag.2020.106017
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[xli] Zotarelli Filho, Idiberto José, et al. “Major Meta-Analysis, Randomized Clinical Studies, and International Consensus on Serum Levels and Importance of Supplementing Vitamin D:State of the Art.” MedNEXT Journal of Medical and Health Sciences, 2021, pp. 54–66., doi:10.34256/mdnt2129.
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