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Published on: August 7, 2017
Blood neutrophils from children with COVID-19 exhibit both inflammatory and anti-inflammatory markers
Vanesa Seery1, Silvina C Raiden2, Silvia C Algieri3
1Instituto de Investigaciones Biomédicas en Retrovirus y SIDA, Facultad de Medicina. UBA-CONICET, Paraguay 2155, C1121ABG CABA, Argentina.
Insights
Pediatric COVID-19 neutrophils show altered immune markers, with CD64 and IgG levels distinguishing disease severity. This may protect children
Area of Science:
- Immunology
- Pediatrics
- Infectious Diseases
Background:
- Limited research exists on pediatric COVID-19 immune responses, as children rarely develop severe respiratory symptoms.
- This study investigates neutrophil phenotype and function in children with COVID-19.
Purpose of the Study:
- To analyze the phenotype and function of circulating neutrophils in children diagnosed with COVID-19.
- To compare these neutrophils against those from children with multisystem inflammatory syndrome (MIS-C) and healthy controls.
Main Methods:
- Observational study of 182 children with COVID-19, 21 with MIS-C, and 40 healthy children.
- Flow cytometry for neutrophil phenotype analysis.
- ELISA for cytokine, anti-SARS-CoV-2 spike protein IgG, and citrullinated histone H3 levels; fluorometry for cell-free DNA.
Main Results:
- COVID-19 neutrophils exhibited lower CD11b, CD66b, L-selectin expression but higher HLA-DR, CD64, PECAM-1, LAIR-1, and PD-L1 expression compared to controls.
- No significant differences in cytokine or neutrophil extracellular trap (NET) production were found.
- Elevated CD64 expression and anti-SARS-CoV-2 spike protein IgG levels correlated with COVID-19 severity, differentiating asymptomatic from mild/moderate cases.
Conclusions:
- Altered neutrophil adhesion molecule expression and increased inhibitory receptors in pediatric COVID-19 may prevent lung tissue infiltration.
- This neutrophil profile might contribute to preserving lung function in children with COVID-19, unlike in adults with severe disease.
Background:
Perhaps reflecting that children with COVID-19 rarely exhibit severe respiratory symptoms and often remain asymptomatic, little attention has been paid to explore the immune response in pediatric COVID-19. Here, we analyzed the phenotype and function of circulating neutrophils from children with COVID-19.
Methods:
An observational study including 182 children with COVID-19, 21 children with multisystem inflammatory syndrome (MIS-C), and 40 healthy children was performed in Buenos Aires, Argentina. Neutrophil phenotype was analyzed by flow cytometry in blood samples. Cytokine production, plasma levels of IgG antibodies directed to the spike protein of SARS-CoV-2 and citrullinated histone H3 were measured by ELISA. Cell-free DNA was quantified by fluorometry.
Findings:
Compared with healthy controls, neutrophils from children with COVID-19 showed a lower expression of CD11b, CD66b, and L-selectin but a higher expression of the activation markers HLA-DR, CD64 and PECAM-1 and the inhibitory receptors LAIR-1 and PD-L1. No differences in the production of cytokines and NETs were observed. Interestingly, the expression of CD64 in neutrophils and the serum concentration of IgG antibodies directed to the spike protein of SARS-CoV-2 distinguished asymptomatic from mild and moderate COVID-19.
Interpretation:
Acute lung injury is a prominent feature of severe COVID-19 in adults. A low expression of adhesion molecules together with a high expression of inhibitory receptors in neutrophils from children with COVID-19 might prevent tissue infiltration by neutrophils preserving lung function.
Funding:
This study was supported by the Ministry of Science and Technology (National Agency for Scientific and Technological Promotion, IP-COVID-19-0277 and PMO BID PICT 2018-2548), and University of Buenos Aires from Argentina (20020170100573BA).
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