Research Blog

July 26, 2021

COVID-19: Blood Biomarkers - Neutrophils

Neutrophils are not neutral in COVID-19

Dicken Weatherby, N.D. and Beth Ellen DiLuglio, MS, RDN, LDN

Neutrophils are the first white blood cell responders during an infection. Lymphocytes are the white blood cells that become B cells or T cells. Calculating the ratio between them provides important clues to inflammatory state and prognosis in COVID-19.

The ODX COVID-19 Series

  1. COVID-19: The pandemic that has become endemic
  2. COVID-19: Overlapping risk factors and chronic disease
  3. Nutritional status COVID-19: A covert factor in disease susceptibility
  4. COVID-19: Blood chemistry biomarker patterns - Clues and patterns lurking just under the surface
  5. COVID-19: Blood chemistry biomarker patterns - Down the research rabbit hole
  6. COVID-19: Blood Biomarkers - Neutrophils
  7. COVID-19: Blood Biomarkers - Albumin
  8. COVID-19: BloodBiomarkers - Cytokines
  9. COVID-19: Blood Biomarkers - Interleukin-6
  10. COVID-19: Blood Biomarkers - Interleukin-10
  11. COVID-19: Blood Biomarkers - Vitamin C
  12. COVID-19: Blood Biomarkers - Vitamin D
  13. COVID-19: Blood Biomarkers - Zinc
  14. Biomarker characteristics and blood type - help sharpen the COVID-19 clinical picture
  15. COVID-19: Initial indications and conventional interventions
  16. COVID-19: Long-term risk reduction - Naturopathic, functional medicine, and nutrition-based approaches to prevention
  17. A healthy diet is primary prevention for COVID-19
  18. You should have a gut feeling about COVID-19
  19. Beyond dietary food patterns…plant-based compounds may mitigate COVID-19 risk
  20. Targeted nutrition support in the battle against COVID-19
  21. Targeted nutrition support in COVID-19: Armed with vitamin C
  22. Targeted nutrition support in COVID-19: In sync with zinc
  23. Targeted nutrition support in COVID-19: Micronutrients and phytonutrients are important players
  24. Optimal Takeaways for improving immunity and reducing susceptibility to COVID-19
  25. Optimal - The Podcast: Episode 8 -Blood Biomarkers and Risk Factors for COVID-19 and its Comorbidities

Neutrophil:Lymphocyte Ratio (NLR)

The neutrophil-lymphocyte ratio serves as a biomarker of inflammation.

When comparing severe to non-severe COVID-19 cases, a meta-analysis of 15 studies revealed that individuals with severe COVID-19 presented with higher neutrophils and neutrophil:lymphocyte ratios, and lower lymphocyte counts.[i]

Meta-analysis of 13 studies comprising 1579 patients found that NLR provided good predictive value for assessing disease severity and mortality in COVID-19. For disease severity, the positive likelihood ratio was 3.6 (negative likelihood at NLR 0.2) and for mortality, the positive likelihood ratio was 4.8, though some studies established a “high cutoff value” of 6.5 or greater.[ii]

In an Italian cohort of 74 hospitalized COVID-19 patients, a median NLR of 5.6 was associated with severe disease, and an NLR greater than 4 was associated with transfer to the ICU. An NLR below 3 was associated with clinical improvement.[iii]

One study of 81 COVID-19 patients found that an NLR of greater than 9.8 was associated with significantly higher rates of acute respiratory distress syndrome and mechanical ventilation.[iv]

A retrospective study of 139 hospitalized COVID-19 patients considered NLR values to be independent predictors of disease severity and mortality with optimal thresholds of 3.27 and 5.72, respectively. The study also found BUN/Creatinine ratios independently predicted severe disease and mortality with optimal thresholds of 33.5 and 51.7, respectively. A number of lab parameters differed significantly between severe and non-severe disease: [v]

Biomarker Severe Non-severe
BUN 46 23.8 mg/dl
BUN:Creatinine ratio 50.3 24.2
CRP 53.6 14.2 mg/dl
Lymphocyte count 1.16 1.48 10^9/L
Monocyte:Lymphocyte ratio 0.4 0.27
Neutrophil count 6.33 3.99 10^9/L
Neutrophil:Lymphocyte ratio  6.1 2.46
WBC - Total 8.1 6.1 10^9/L

Optimal Takeaway

Assessing and monitoring the neutrophil:lymphocyte ratio is an invaluable tool for gauging severity and potential improvement in COVID-19.

Next Up - COVID-19: Blood Biomarkers - Albumin


[i] Zeng, Furong et al. “Can we predict the severity of coronavirus disease 2019 with a routine blood test?.” Polish archives of internal medicine vol. 130,5 (2020): 400-406. doi:10.20452/pamw.15331

[ii] Li, Xiaoming et al. “Predictive values of neutrophil-to-lymphocyte ratio on disease severity and mortality in COVID-19 patients: a systematic review and meta-analysis.” Critical care (London, England) vol. 24,1 647. 16 Nov. 2020, doi:10.1186/s13054-020-03374-8

[iii] 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

[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] Ok, Fesih et al. “Predictive values of blood urea nitrogen/creatinine ratio and other routine blood parameters on disease severity and survival of COVID-19 patients.” Journal of medical virology, 10.1002/jmv.26300. 14 Jul. 2020, doi:10.1002/jmv.26300

Tag(s): Biomarkers

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