Immune-Inflammatory Parameters in COVID-19 Cases: A Systematic Review and Meta-Analysis

Abstract

Background: The recent outbreak of coronavirus disease 2019 (COVID-19) has been rapidly spreading on a global scale and poses a great threat to human health. Acute respiratory distress syndrome, characterized by a rapid onset of generalized inflammation, is the leading cause of mortality in patients with COVID-19. We thus aimed to explore the effect of risk factors on the severity of the disease, focusing on immune-inflammatory parameters, which represent the immune status of patients. Methods: A comprehensive systematic search for relevant studies published up to April 2020 was performed by using the PubMed, Web of Science, EMBASE, and China National Knowledge Internet (CNKI) databases. After extracting all available data of immune-inflammatory indicators, we statistically analyzed the risk factors of severe and non-severe COVID-19 patients with a meta-analysis. Results: A total of 4,911 patients from 29 studies were included in the final meta-analysis. The results demonstrated that severe patients tend to present with increased white blood cell (WBC) and neutrophil counts, neutrophil-lymphocyte ratio (NLR), procalcitonin (PCT), C-reaction protein (CRP), erythrocyte sedimentation rate (ESR), and Interleukin-6 (IL-6) and a decreased number of total lymphocyte and lymphocyte subtypes, such as CD4+ T lymphocyte and CD8+ T lymphocyte, compared to the non-severe patients. In addition, the WBC count>10 × 10⁹/L, lymphocyte count<1 × 10⁹/L, PCT>0.5 ng/mL, and CRP>10 mg/L were risk factors for disease progression in patients with COVID-19 (WBC count>10 × 10⁹/L: OR = 2.92, 95% CI: 1.96-4.35; lymphocyte count<1 × 10⁹/L: OR = 4.97, 95% CI: 3.53-6.99; PCT>0.5 ng/mL: OR = 6.33, 95% CI: 3.97-10.10; CRP>10 mg/L: OR = 3.51, 95% CI: 2.38-5.16). Furthermore, we found that NLR, as a novel marker of systemic inflammatory response, can also help predict clinical severity in patients with COVID-19 (OR = 2.50, 95% CI: 2.04-3.06). Conclusions: Immune-inflammatory parameters, such as WBC, lymphocyte, PCT, CRP, and NLR, could imply the progression of COVID-19. NLR has taken both the levels of neutrophil and lymphocyte into account, indicating a more complete, accurate, and reliable inspection efficiency; surveillance of NLR may help clinicians identify high-risk COVID-19 patients at an early stage.

Keywords: COVID-19; immune-inflammatory parameters; meta-analysis; neutrophil-lymphocyte ratio; risk factor.

Figure 1

PRISMA flow chart of the study selection procedure.

Figure 2

Correlation between WBC and disease severity of COVID-19. (A) Forest plot of mean difference in WBC count. (B) Forest plot of OR for the association of elevated WBC with disease severity.

Figure 3

Correlation between lymphocyte and disease severity of COVID-19. (A) Forest plot of mean difference in lymphocyte count. (B) Forest plot of OR for the association of lymphopenia with disease severity.

Figure 4

Meta-analysis for NLR in COVID-19 cases. (A) Forest plot of mean difference in NLR. (B) Forest plot of OR for the correlation of elevated NLR with disease severity.

Figure 5

Meta-analysis for PCT in COVID-19 cases. (A) Forest plot of comparison of the included studies. (B) Forest plot of OR for the correlation of elevated PCT with disease severity.

Figure 6

Correlation between CRP and disease severity of COVID-19. (A) Forest plot of mean difference in CRP. (B) Forest plot of OR for the association of increased CRP with disease severity.

Figure 7

Funnel plots of comparison of the included studies. (A,B) Funnel plot and adjusted funnel plot of mean difference in WBC count. (C,D) Funnel plot and adjusted funnel plot of mean difference in neutrophil count. (E) Funnel plot of mean difference in lymphocyte count. (F) Funnel plot of Std. mean difference in PCT. (G,H) Funnel plot and adjusted funnel plot of mean difference in CRP.