Clinical laboratory parameters associated with severe or critical novel coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of observational prognostic studies
PubMed 33002041 · doi:10.1371/journal.pone.0239802
What was done
A systematic review and meta-analysis of hospital-based observational studies indexed in MEDLINE, Embase, Web of Science, CINAHL, Google Scholar, and medRxiv through April 18, 2020. The review evaluated clinical laboratory parameters in confirmed COVID-19 cases comparing severe or critical disease to non-severe disease, excluding studies with >10% children or pregnant women. Screening, data extraction, and quality assessment were conducted independently in duplicate. Random-effects meta-analyses estimated meta-median differences (MMD) with 95% confidence intervals (CI) across 45 studies from 6 countries.
What was found
Compared to non-severe COVID-19 cases, severe or critical disease exhibited significantly elevated markers of innate inflammation and tissue damage: - Neutrophil count: MMD 1.23 (95% CI: 0.58 to 1.88) ×10^9 cells/L - C-reactive protein: MMD 36.97 (95% CI: 27.58 to 46.35) mg/L - Interleukin-6: MMD 17.37 (95% CI: 4.74 to 30.00) pg/ml - Troponin I: MMD 0.01 (95% CI: 0.00 to 0.02) ng/ml - D-dimer: MMD 0.65 (95% CI: 0.45 to 0.85) mg/ml Severe or critical cases also showed marked reduction in adaptive immune cell counts: - Lymphocytes: MMD -0.39 (95% CI: -0.47 to -0.31) ×10^9 cells/L - CD4+ T cells: MMD -204.9 (95% CI: -302.6 to -107.1) cells/μl - CD8+ T cells: MMD -123.6 (95% CI: -170.6 to -76.6) cells/μl
Why it matters
These findings delineate the biological signature of severe COVID-19—marked by hyperinflammation, tissue damage, and adaptive immune exhaustion—and identify routine laboratory markers for clinical monitoring and risk stratification.
Limits
The review included early-pandemic studies up to April 2020, including un-peer-reviewed preprints. All underlying studies were observational, which introduces risk of bias and heterogeneity in severity definitions and sampling timepoints. Findings exclude pediatric and obstetric populations, and total patient n is not stated in the abstract.
Cited by
- contradicts Common clinical features in COVID-19 patients include low albumin levels, low lymphocyte numbers, low neutrophil numbers, and decreased percentages of CD8-positive T cells.