Association of immunological features with COVID-19 severity: a systematic review and meta-analysis (preprint)

ABSTRACT

Background: 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 some immune cells, CD3+ T cell (×106, MD, -413.87; 95%CI, -611.39 to -216.34), CD4+ T cell (×106, MD, -203.56; 95%CI, -277.94 to -129.18), CD8+ T cell (×106, MD, -128.88; 95%CI, -163.97 to -93.79), B cell (×106/L; MD, -23.87; 95%CI, -43.97 to -3.78) and NK cell (×106/L; MD, -57.12; 95%CI, -81.18 to -33.06), and significantly higher levels of some cytokines, 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 some chemokines, 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 differences were found in other indicators, Treg cell (×106, 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 significant lower levels of immune cells (CD3+ T, CD4+ T, CD8+ T, B and NK cells), significant higher levels of cytokines (TNF-α, IL-5, IL-6 and IL-10) and significant higher levels of chemokines (MCP-1, IP-10 and eotaxin) in severe cases compared with mild cases of COVID-19. Measurement of immunological features could help to assess disease severity for effective triage of COVID-19 patients.