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

Khinda, Jaskaran; Janjua, Naveed Z.; Cheng, Shannon; van den Heuvel, Edwin R.; Bhatti, Parveen; Darvishian, Maryam

To determine the utility of admission laboratory markers in the assessment and prognostication of COVID‐19, a systematic review and meta‐analysis was conducted on the association between admission laboratory values in hospitalized COVID‐19 patients and subsequent disease severity and mortality. Searches were conducted in MEDLINE, Pubmed, Embase, and the WHO Global Research Database from Dec 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. In total, 64 studies met inclusion criteria. The most marked WMDs were for neutrophils (ANC) at 3.82x10(9)/L (2.76, 4.87), lymphocytes (ALC) at ‐0.34x10(9)/L (‐0.45, ‐0.23), interleukin‐6 (IL‐6) at 32.59pg/mL (23.99, 41.19), ferritin at 814.14ng/mL (551.48, 1076.81), C‐reactive protein (CRP) at 66.11mg/L (52.16, 80.06), Ddimer at 5.74mg/L (3.91, 7.58), LDH at 232.41U/L (178.31, 286.52), and high sensitivity troponin I at 90.47pg/mL (47.79, 133.14) when comparing fatal to non‐fatal 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. The results highlight that hyperinflammation, 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. This article is protected by copyright. All rights reserved.