Associations of immunological features with COVID-19 severity: a systematic review and meta-analysis

Zhang, Zhicheng; Ai, Guo; Chen, Liping; Liu, Shunfang; Gong, Chen; Zhu, Xiaodong; Zhang, Chunli; Qin, Hua; Hu, Junhui; Huang, Jinjin

BACKGROUND: COVID-19 has spread widely worldwide, causing millions of deaths. We aim to explore the association of immunological features with COVID-19 severity. METHODS: We conducted a meta-analysis to estimate mean difference (MD) of immune cells and cytokines levels with COVID-19 severity in PubMed, Web of Science, Scopus, the Cochrane Library and the grey literature. RESULTS: A total of 21 studies with 2033 COVID-19 patients were included. Compared with mild cases, severe cases showed significantly lower levels of immune cells including CD3(+) T cell (× 10(6), MD, − 413.87; 95%CI, − 611.39 to − 216.34), CD4(+) T cell (× 10(6), MD, − 203.56; 95%CI, − 277.94 to − 129.18), CD8(+) T cell (× 10(6), MD, − 128.88; 95%CI, − 163.97 to − 93.79), B cell (× 10(6)/L; MD, − 23.87; 95%CI, − 43.97 to − 3.78) and NK cell (× 10(6)/L; MD, − 57.12; 95%CI, − 81.18 to − 33.06), and significantly higher levels of cytokines including TNF-α (pg/ml; MD, 0.34; 95%CI, 0.09 to 0.59), IL-5 (pg/ml; MD, 14.2; 95%CI, 3.99 to 24.4), IL-6 (pg/ml; MD, 13.07; 95%CI, 9.80 to 16.35), and IL-10 (pg/ml; MD, 2.04; 95%CI, 1.32 to 2.75), and significantly higher levels of chemokines as MCP-1 (SMD, 3.41; 95%CI, 2.42 to 4.40), IP-10 (SMD, 2.82; 95%CI, 1.20 to 4.45) and eotaxin (SMD, 1.55; 95%CI, 0.05 to 3.05). However, no significant difference was found in other indicators such as Treg cell (× 10(6), MD, − 0.13; 95%CI, − 1.40 to 1.14), CD4(+)/CD8(+) ratio (MD, 0.26; 95%CI, − 0.02 to 0.55), IFN-γ (pg/ml; MD, 0.26; 95%CI, − 0.05 to 0.56), IL-2 (pg/ml; MD, 0.05; 95%CI, − 0.49 to 0.60), IL-4 (pg/ml; MD, − 0.03; 95%CI, − 0.68 to 0.62), GM-CSF (SMD, 0.44; 95%CI, − 0.46 to 1.35), and RANTES (SMD, 0.94; 95%CI, − 2.88 to 4.75). CONCLUSION: Our meta-analysis revealed significantly lower levels of immune cells (CD3(+) T, CD4(+) T, CD8(+) T, B and NK cells), higher levels of cytokines (TNF-α, IL-5, IL-6 and IL-10) and higher levels of chemokines (MCP-1, IP-10 and eotaxin) in severe cases in comparison to mild cases of COVID-19. Measurement of immunological features could help assess disease severity for effective triage of COVID-19 patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12879-021-06457-1.