Coronavirus Infections in the Central Nervous System and Respiratory Tract Show Distinct Features in Hospitalized Children

Abstract

Background/aims: Coronavirus (CoV) infections induce respiratory tract illnesses and central nervous system (CNS) diseases. We aimed to explore the cytokine expression profiles in hospitalized children with CoV-CNS and CoV-respiratory tract infections.

Methods: A total of 183 and 236 hospitalized children with acute encephalitis-like syndrome and respiratory tract infection, respectively, were screened for anti-CoV IgM antibodies. The expression profiles of multiple cytokines were determined in CoV-positive patients.

Results: Anti-CoV IgM antibodies were detected in 22/183 (12.02%) and 26/236 (11.02%) patients with acute encephalitis-like syndrome and respiratory tract infection, respectively. Cytokine analysis revealed that the level of serum granulocyte colony-stimulating factor (G-CSF) was significantly higher in both CoV-CNS and CoV-respiratory tract infection compared with healthy controls. Additionally, the serum level of granulocyte macrophage colony-stimulating factor (GM-CSF) was significantly higher in CoV-CNS infection than in CoV-respiratory tract infection. In patients with CoV-CNS infection, the levels of IL-6, IL-8, MCP-1, and GM-CSF were significantly higher in their cerebrospinal fluid samples than in matched serum samples.

Conclusion: To the best of our knowledge, this is the first report showing a high incidence of CoV infection in hospitalized children, especially with CNS illness. The characteristic cytokine expression profiles in CoV infection indicate the importance of host immune response in disease progression.

Fig. 1

Peripheral blood cell counts of lymphocytes (a), eosinophils (b), neutrophils (c), and monocytes (d) among patients with coronavirus infection of the central nervous system (CoV-CNS, n = 22), patients with coronavirus infection of the respiratory tract (CoV-respiratory tract, n = 26), and healthy controls (n = 26). Cell counts are expressed as 10⁹ cells/L. Data are plotted as medians with the 10th-90th percentile ranges. The Student t test or Mann-Whitney U test was performed. p values were derived from a two-tailed test; * p ≥ 0.05.

Fig. 2

Expression levels of serum G-CSF (a) and GM-CSF (b) among patients with coronavirus infection of the central nervous system (CoV-CNS, n = 22), patients with coronavirus infection of the respiratory tract (CoV-respiratory tract, n = 26), and healthy controls (n = 26). Data are expressed as medians with the 10-90th percentile ranges. The Student t test or Mann-Whitney U test was performed. p values were derived from a two-tailed test; * p ≥ 0.05.

Fig. 3

Expression levels of GM-CSF (a), IL-6 (b), IL-8 (c), and MCP-1 (d) levels in matched serum (PLA) and cerebrospinal fluid (CSF) from patients with coronavirus infection (CoV) of the central nervous system (n = 17). Data are expressed as medians with the 10-90th percentile ranges. Student's t tests or Mann-Whitney U tests were performed. p values were derived from a two-tailed test; * p ≥ 0.05, ** p ≥ 0.001.