tetano
Editor, Senior Moderator
J Infect Dis
. 2021 Aug 16;224(4):575-585.
doi: 10.1093/infdis/jiab174.
Immunoglobulin G Immune Complexes May Contribute to Neutrophil Activation in the Course of Severe Coronavirus Disease 2019
Ignacio Mazzitelli[SUP] 1 [/SUP], Lucia Bleichmar[SUP] 1 [/SUP], María Guillermina Ludueña[SUP] 2 [/SUP], Andrea Pisarevsky[SUP] 2 [/SUP], Mariana Labato[SUP] 2 [/SUP], Verónica Chiaradia[SUP] 2 [/SUP], Paola Finocchieto[SUP] 2 [/SUP], Francisco Paulin[SUP] 3 [/SUP], Macarena Hormanstorfer[SUP] 3 [/SUP], María Constanza Baretto[SUP] 3 [/SUP], Santiago Piombi Adanza[SUP] 3 [/SUP], María Noel Parodi[SUP] 3 [/SUP], Martín Ragusa[SUP] 3 [/SUP], Claudia Melucci[SUP] 1 [/SUP], Fernando Erra Díaz[SUP] 1 [/SUP], Ana Paletta[SUP] 1 [/SUP], Facundo Di Diego[SUP] 1 [/SUP], Ana Ceballos[SUP] 1 [/SUP], Jorge Geffner[SUP] 1 [/SUP]
Affiliations
Abstract
Severe coronavirus disease 2019 (COVID-19) is associated with an overactive inflammatory response mediated by macrophages. Here, we analyzed the phenotype and function of neutrophils in patients with COVID-19. We found that neutrophils from patients with severe COVID-19 express high levels of CD11b and CD66b, spontaneously produce CXCL8 and CCL2, and show a strong association with platelets. Production of CXCL8 correlated with plasma concentrations of lactate dehydrogenase and D-dimer. Whole blood assays revealed that neutrophils from patients with severe COVID-19 show a clear association with immunoglobulin G (IgG) immune complexes. Moreover, we found that sera from patients with severe disease contain high levels of immune complexes and activate neutrophils through a mechanism partially dependent on FcγRII (CD32). Interestingly, when integrated in immune complexes, anti-severe acute respiratory syndrome coronavirus 2 IgG antibodies from patients with severe COVID-19 displayed a higher proinflammatory profile compared with antibodies from patients with mild disease. Our study suggests that IgG immune complexes might promote the acquisition of an inflammatory signature by neutrophils, worsening the course of COVID-19.
Keywords: CD32; COVID-19; CXCL8; SARS-CoV-2; immune complexes; inflammation; neutrophils.
. 2021 Aug 16;224(4):575-585.
doi: 10.1093/infdis/jiab174.
Immunoglobulin G Immune Complexes May Contribute to Neutrophil Activation in the Course of Severe Coronavirus Disease 2019
Ignacio Mazzitelli[SUP] 1 [/SUP], Lucia Bleichmar[SUP] 1 [/SUP], María Guillermina Ludueña[SUP] 2 [/SUP], Andrea Pisarevsky[SUP] 2 [/SUP], Mariana Labato[SUP] 2 [/SUP], Verónica Chiaradia[SUP] 2 [/SUP], Paola Finocchieto[SUP] 2 [/SUP], Francisco Paulin[SUP] 3 [/SUP], Macarena Hormanstorfer[SUP] 3 [/SUP], María Constanza Baretto[SUP] 3 [/SUP], Santiago Piombi Adanza[SUP] 3 [/SUP], María Noel Parodi[SUP] 3 [/SUP], Martín Ragusa[SUP] 3 [/SUP], Claudia Melucci[SUP] 1 [/SUP], Fernando Erra Díaz[SUP] 1 [/SUP], Ana Paletta[SUP] 1 [/SUP], Facundo Di Diego[SUP] 1 [/SUP], Ana Ceballos[SUP] 1 [/SUP], Jorge Geffner[SUP] 1 [/SUP]
Affiliations
- PMID: 34398243
- DOI: 10.1093/infdis/jiab174
Abstract
Severe coronavirus disease 2019 (COVID-19) is associated with an overactive inflammatory response mediated by macrophages. Here, we analyzed the phenotype and function of neutrophils in patients with COVID-19. We found that neutrophils from patients with severe COVID-19 express high levels of CD11b and CD66b, spontaneously produce CXCL8 and CCL2, and show a strong association with platelets. Production of CXCL8 correlated with plasma concentrations of lactate dehydrogenase and D-dimer. Whole blood assays revealed that neutrophils from patients with severe COVID-19 show a clear association with immunoglobulin G (IgG) immune complexes. Moreover, we found that sera from patients with severe disease contain high levels of immune complexes and activate neutrophils through a mechanism partially dependent on FcγRII (CD32). Interestingly, when integrated in immune complexes, anti-severe acute respiratory syndrome coronavirus 2 IgG antibodies from patients with severe COVID-19 displayed a higher proinflammatory profile compared with antibodies from patients with mild disease. Our study suggests that IgG immune complexes might promote the acquisition of an inflammatory signature by neutrophils, worsening the course of COVID-19.
Keywords: CD32; COVID-19; CXCL8; SARS-CoV-2; immune complexes; inflammation; neutrophils.