Neutrophils from children with acute Covid-19 exhibit an inflammatory signatura with a distinct expression of high affinity receptor for IgG

Abstract

Children can be infected by severe acute respiratorysyndrome coronavirus 2 (SARS-COV-2), being most pediatriccases mild but the reason underlying are still unknown. This studyaddressed the immunopathological characteristics of neutrophilsfrom acute COVID-19 infected children.METHODS: Sixty acute COVID-19 mildly infected children (1-14years-old) and 9 healthy infants were studied. A multiparametric flowcytometry from neutrophils was performed in whole blood. Levels ofIL-1β in supernatant culture from purified neutrophils and serum antiSARS-CoV-2 IgG were quantified by ELISA.RESULTS: A low expression of CD11b (p<0.01), CD66b (p<0.01)and CD62L (p<0.001), three molecules involved in neutrophil migration,was observed in COVID-19 neutrophils (n=33) comparedwith healthy controls (n=9). Interestingly, COVID-19 neutrophilsalso showed a higher expression of two inhibitory receptors LAIR-1(p<0.01) and PECAM-1 (p<0.01). In addition, a higher expressionof two activation markers was also found in COVID-19 respect tohealthy controls: HLA-DR (p<0.0001) and the high affinity receptorfor IgG, CD64 (p<0.01). According to the functional associationbetween the β2 integrin CD11b/CD18 and receptors for IgG, wefound not only that the plasma levels of IgG antibodies directed tothe S protein of SARS-CoV-2 inversely correlated with CD11b MFI(p<0.01, r= -0.43), but also directly correlated with CD64 (p<0.05, r=0.5). CD64 is able to mediate a positive feedback on the activation ofinflammasome. Indeed, we found that neutrophils from children withCOVID-19 spontaneously produced higher concentrations of IL-1βcompared with healthy donors and increase greatly after TLR7/8 agoniststimulation.CONCLUSION: Neutrophils from infants with acute mild COVID-19have a distinct proinflammatory signature that could potentially compromisetheir ability to migrate to peripheral tissues.