Poor Survival in COVID-19 Associated with Lymphopenia and Higher Neutrophile-Lymphocyte Ratio

Isr Med Assoc J. 2021 Mar;23(3):153-159.

Abstract

Background: Immune cell counts in blood in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection may be useful prognostic biomarkers of disease severity, mortality, and response to treatment.

Objectives: To analyze sub-populations of lymphocytes at hospital admission in survivors and deceased from severe pneumonia due to coronavirus disease-2019 (COVID-19).

Methods: We conducted a cross-sectional study of healthcare workers confirmed with SARS-CoV-2 in convalescents (control group) and healthy controls (HC) diagnosed with severe COVID-19. Serum samples were taken at hospital admission and after recovery. Serum samples ≥ 25 days after onset of symptoms were analyzed for lymphocyte subpopulations through flow cytometry. Descriptive statistics, Kruskall-Wallis test, receiver operating characteristic curve, calculation of sensitivity, specificity, predictive values, and Kaplan-Meier analysis were performed.

Results: We included 337 patients: 120 HC, 127 convalescents, and 90 severe COVID-19 disease patients (50 survivors, 40 deceased). For T cells, total lymphocytes ≥ 800/μL, CD3+ ≥ 400/μL, CD4+ ≥ 180/μL, CD8+ ≥ 150/μL, B cells CD19+ ≥ 80/μL, and NK ≥ 34/μL subsets were associated with survival in severe COVID-19 disease patients. All subtypes of lymphocytes had higher concentrations in survivors than deceased, but similar between HC and convalescents. Leukocytes ≥ 10.150/μL or neutrophils ≥ 10,000/μL were associated with increased mortality. The neutrophil-to-lymphocyte ratio (NLR) ≥ 8.5 increased the probability of death in severe COVID-19 (odds ratio 11.68).

Conclusions: Total lymphocytes; NLR; and levels of CD3+, CD4+, CD8+, and NK cells are useful as biomarkers of survival or mortality in severe COVID-19 disease and commonly reach normal levels in convalescents.

MeSH terms

  • Biomarkers / blood
  • CD4-Positive T-Lymphocytes / pathology*
  • CD8-Positive T-Lymphocytes / pathology*
  • COVID-19* / blood
  • COVID-19* / diagnosis
  • COVID-19* / mortality
  • COVID-19* / therapy
  • Correlation of Data
  • Cross-Sectional Studies
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Killer Cells, Natural / pathology
  • Leukocyte Count / methods
  • Lymphopenia* / blood
  • Lymphopenia* / diagnosis
  • Lymphopenia* / etiology
  • Male
  • Mexico / epidemiology
  • Middle Aged
  • Mortality
  • Neutrophils / pathology*
  • Predictive Value of Tests
  • Symptom Assessment / methods

Substances

  • Biomarkers