Association between markers of immune response at hospital admission and COVID-19 disease severity and mortality: A meta-analysis and meta-regression

Background: To determine the utility of admission laboratory markers in the assessment and prognostication of coronavirus disease-2019 (COVID-19), a systematic review and meta-analysis were conducted on the association between admission laboratory values in hospitalized COVID-19 patients and subsequent disease severity and mortality. Material and Methods: Searches were conducted in MEDLINE, Pubmed, Embase, and the WHO Global Research Database from December 1,2019 to May 1, 2020 for relevant articles. A random effects meta-analysis was used to calculate the weighted mean difference (WMD) and 95% confidence interval (95% CI) for each of 27 laboratory markers. The impact of age and sex on WMDs was estimated using meta-regression techniques for 11 markers. Results: In total, 64 studies met the inclusion criteria. The most marked WMDs were for neutrophils (ANC) at 3.82 × 10⁹/L (2.76, 4.87), lymphocytes (ALC) at −0.34 × 10⁹/L (−0.45, −0.23), interleukin-6 (IL-6) at 32.59 pg/mL (23.99, 41.19), ferritin at 814.14 ng/mL (551.48, 1076.81), C-reactive protein (CRP) at 66.11 mg/L (52.16, 80.06), D-dimer at 5.74 mg/L (3.91, 7.58), LDH at 232.41 U/L (178.31, 286.52), and high sensitivity troponin I at 90.47 pg/mL (47.79, 133.14) when comparing fatal to nonfatal cases. Similar trends were observed comparing severe to non-severe groups. There were no statistically significant associations between age or sex and WMD for any of the markers included in the meta-regression. Conclusion: The results highlight that hyper inflammation, blunted adaptive immune response, and intravascular coagulation play key roles in the pathogenesis of COVID-19. Markers of these processes are good candidates to identify patients for early intervention and, importantly, are likely reliable regardless of age or sex in adult patients.