A poor and delayed anti-SARS-CoV2 IgG response is associated to severe COVID-19 in children.


Journal

EBioMedicine
ISSN: 2352-3964
Titre abrégé: EBioMedicine
Pays: Netherlands
ID NLM: 101647039

Informations de publication

Date de publication:
Oct 2021
Historique:
received: 31 05 2021
revised: 10 09 2021
accepted: 21 09 2021
pubmed: 15 10 2021
medline: 12 11 2021
entrez: 14 10 2021
Statut: ppublish

Résumé

Most children and youth develop mild or asymptomatic disease during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, a very small number of patients suffer severe Coronavirus induced disease 2019 (COVID-19). The reasons underlying these different outcomes remain unknown. We analyzed three different cohorts: children with acute infection (n=550), convalescent children (n=138), and MIS-C (multisystem inflammatory syndrome in children, n=42). IgG and IgM antibodies to the spike protein of SARS-CoV-2, serum-neutralizing activity, plasma cytokine levels, and the frequency of circulating Follicular T helper cells (cTfh) and plasmablasts were analyzed by conventional methods. Fifty-eight percent of the children in the acute phase of infection had no detectable antibodies at the time of sampling while a seronegative status was found in 25% and 12% of convalescent and MIS-C children, respectively. When children in the acute phase of the infection were stratified according disease severity, we found that contrasting with the response of children with asymptomatic, mild and moderate disease, children with severe COVID-19 did not develop any detectable response. A defective antibody response was also observed in the convalescent cohort for children with severe disease at the time of admission. This poor antibody response was associated to both, a low frequency of cTfh and a high plasma concentration of inflammatory cytokines. A weak and delayed kinetic of antibody response to SARS-CoV-2 together with a systemic pro-inflammatory profile characterize pediatric severe COVID-19. Because comorbidities are highly prevalent in children with severe COVID-19, further studies are needed to clarify their contribution in the weak antibody response observed in severe disease. National Agency for Scientific and Technological Promotion from Argentina (IP-COVID-19-0277 and PMO-BID-PICT2018-2548).

Sections du résumé

BACKGROUND BACKGROUND
Most children and youth develop mild or asymptomatic disease during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, a very small number of patients suffer severe Coronavirus induced disease 2019 (COVID-19). The reasons underlying these different outcomes remain unknown.
METHODS METHODS
We analyzed three different cohorts: children with acute infection (n=550), convalescent children (n=138), and MIS-C (multisystem inflammatory syndrome in children, n=42). IgG and IgM antibodies to the spike protein of SARS-CoV-2, serum-neutralizing activity, plasma cytokine levels, and the frequency of circulating Follicular T helper cells (cTfh) and plasmablasts were analyzed by conventional methods.
FINDINGS RESULTS
Fifty-eight percent of the children in the acute phase of infection had no detectable antibodies at the time of sampling while a seronegative status was found in 25% and 12% of convalescent and MIS-C children, respectively. When children in the acute phase of the infection were stratified according disease severity, we found that contrasting with the response of children with asymptomatic, mild and moderate disease, children with severe COVID-19 did not develop any detectable response. A defective antibody response was also observed in the convalescent cohort for children with severe disease at the time of admission. This poor antibody response was associated to both, a low frequency of cTfh and a high plasma concentration of inflammatory cytokines.
INTERPRETATION CONCLUSIONS
A weak and delayed kinetic of antibody response to SARS-CoV-2 together with a systemic pro-inflammatory profile characterize pediatric severe COVID-19. Because comorbidities are highly prevalent in children with severe COVID-19, further studies are needed to clarify their contribution in the weak antibody response observed in severe disease.
FUNDING BACKGROUND
National Agency for Scientific and Technological Promotion from Argentina (IP-COVID-19-0277 and PMO-BID-PICT2018-2548).

Identifiants

pubmed: 34649078
pii: S2352-3964(21)00408-4
doi: 10.1016/j.ebiom.2021.103615
pmc: PMC8502533
pii:
doi:

Substances chimiques

Antibodies, Viral 0
Cytokines 0
Immunoglobulin G 0
Immunoglobulin M 0

Types de publication

Journal Article Observational Study

Langues

eng

Sous-ensembles de citation

IM

Pagination

103615

Informations de copyright

Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest None.

Auteurs

Inés Sananez (I)

Instituto de Investigaciones Biomédicas en Retrovirus y SIDA. Facultad de Medicina. UBA-CONICET. Paraguay 2155, C1121ABG CABA, Argentina.

Silvina C Raiden (SC)

Departamento de Medicina, Hospital General de Niños Pedro de Elizalde. Av. Montes de Oca 40, C1270 CABA, Argentina.

Silvia C Algieri (SC)

Servicio de Pediatría, Hospital Nacional Profesor Alejandro Posadas. Marconi Morón 386, B1684 Buenos Aires, Argentina.

Macarena Uranga (M)

Sector Infectología infantil, Departamento Materno Infantil, Hospital Universitario Austral. Av. Juan Domingo Perón 1500, B1629 Buenos Aires, Argentina.

Nicolás A Grisolía (NA)

Departamento de Medicina, Hospital General de Niños Pedro de Elizalde. Av. Montes de Oca 40, C1270 CABA, Argentina.

Daniela Filippo (D)

Servicio de Pediatría, Hospital Municipal Diego Thompson. Avellaneda 33, B1650 Buenos Aires, Argentina.

Norberto De Carli (N)

Servicio de Pediatría, Clínica del Niño de Quilmes. Av. Lamadrid 444, B1878 Buenos Aires, Argentina.

Sandra Di Lalla (SD)

Departamento de Consultorios Externos, Hospital General de Niños Pedro de Elizalde. Av. Montes de Oca 40, C1270 CABA, Argentina.

Héctor Cairoli (H)

Departamento de Medicina, Hospital General de Niños Pedro de Elizalde. Av. Montes de Oca 40, C1270 CABA, Argentina.

María J Chiolo (MJ)

Departamento de Cirugía, Hospital General de Niños Pedro de Elizalde. Av. Montes de Oca 40, C1270 CABA, Argentina.

Claudia N Meregalli (CN)

Unidad de Terapia Intensiva Pediátrica, Departamento de Urgencias, Hospital General de Niños Pedro de Elizalde. Av. Montes de Oca 40, C1270 CABA, Argentina.

Emilia Cohen (E)

Servicio de Pediatría, Hospital HIGA Eva Perón. Av. Dr Ricardo Balbín 3200, B1650 Buenos Aires, Argentina.

Graciela Mosquera (G)

Servicio de Pediatría, Hospital HIGA Eva Perón. Av. Dr Ricardo Balbín 3200, B1650 Buenos Aires, Argentina.

María Marcó Del Pont (M)

Sector Infectología infantil, Departamento Materno Infantil, Hospital Universitario Austral. Av. Juan Domingo Perón 1500, B1629 Buenos Aires, Argentina.

Lorena I Giménez (LI)

Servicio de Pediatría, Hospital Municipal Diego Thompson. Avellaneda 33, B1650 Buenos Aires, Argentina.

Gabriela Gregorio (G)

Servicio de Pediatría, Hospital Nacional Profesor Alejandro Posadas. Marconi Morón 386, B1684 Buenos Aires, Argentina.

Mariam Sarli (M)

Unidad de Terapia Intensiva Pediátrica, Hospital Nacional Profesor Alejandro Posadas. Marconi Morón 386, B1684 Buenos Aires, Argentina.

Ana L Alcalde (AL)

Servicio de Pediatría, Hospital Nacional Profesor Alejandro Posadas. Marconi Morón 386, B1684 Buenos Aires, Argentina.

Carolina Davenport (C)

Departamento de Medicina, Hospital General de Niños Pedro de Elizalde. Av. Montes de Oca 40, C1270 CABA, Argentina.

María J Bruera (MJ)

Unidad de Terapia Intensiva Pediátrica, Hospital Nacional Profesor Alejandro Posadas. Marconi Morón 386, B1684 Buenos Aires, Argentina.

Nancy Simaz (N)

Servicio de Pediatría, Hospital Nacional Profesor Alejandro Posadas. Marconi Morón 386, B1684 Buenos Aires, Argentina.

Mariela F Pérez (MF)

Servicio de Pediatría, Hospital Nacional Profesor Alejandro Posadas. Marconi Morón 386, B1684 Buenos Aires, Argentina.

Valeria Nivela (V)

Departamento de Emergencias Pediátrica, Hospital Nacional Profesor Alejandro Posadas. Marconi Morón 386, B1684 Buenos Aires, Argentina.

Carola Bayle (C)

Departamento de Emergencias Pediátrica, Hospital Nacional Profesor Alejandro Posadas. Marconi Morón 386, B1684 Buenos Aires, Argentina.

Laura Alvarez (L)

Departamento Laboratorio, Hospital Universitario Austral. Av. Juan Domingo Perón 1500, B1629 Buenos Aires, Argentina.

María Revetria (M)

Departamento Laboratorio, Hospital Universitario Austral. Av. Juan Domingo Perón 1500, B1629 Buenos Aires, Argentina.

Patricia Tuccillo (P)

Servicio de Pediatría, Hospital Naval Cirujano Mayor Dr. Pedro Mallo. Av. Patricias Argentinas 351, C1405 CABA, Argentina.

María T Agosta (MT)

Servicio de Pediatría, Hospital Naval Cirujano Mayor Dr. Pedro Mallo. Av. Patricias Argentinas 351, C1405 CABA, Argentina.

Hernán Pérez (H)

Servicio de Pediatría, Hospital Naval Cirujano Mayor Dr. Pedro Mallo. Av. Patricias Argentinas 351, C1405 CABA, Argentina.

Susana Villa Nova (SV)

Servicio de Pediatría, Hospital General de Agudos Dr. Juan A. Fernández. Av. Cerviño 3356, C1425 CABA, Argentina.

Patricia Suárez (P)

Servicio de Pediatría, Hospital General de Agudos Dr. Juan A. Fernández. Av. Cerviño 3356, C1425 CABA, Argentina.

Eugenia M Takata (EM)

Servicio de Pediatría, Hospital General de Agudos Dr. Juan A. Fernández. Av. Cerviño 3356, C1425 CABA, Argentina.

Mariela García (M)

Servicio de Pediatría, Hospital General de Agudos Dr. Juan A. Fernández. Av. Cerviño 3356, C1425 CABA, Argentina.

Jorge Lattner (J)

Servicio de Infectología Pediátrica, Hospital Naval Cirujano Mayor Dr. Pedro Mallo. Av. Patricias Argentinas 351, C1405 CABA, Argentina.

María J Rolón (MJ)

División Infectología, Hospital General de Agudos Dr. Juan A. Fernández. Av. Cerviño 3356, C1425 CABA, Argentina.

Patricia Coll (P)

División Infectología, Hospital General de Agudos Dr. Juan A. Fernández. Av. Cerviño 3356, C1425 CABA, Argentina.

Melina Salvatori (M)

Instituto de Investigaciones Biomédicas en Retrovirus y SIDA. Facultad de Medicina. UBA-CONICET. Paraguay 2155, C1121ABG CABA, Argentina.

Claudio Piccardo (C)

Instituto de Investigaciones Biomédicas en Retrovirus y SIDA. Facultad de Medicina. UBA-CONICET. Paraguay 2155, C1121ABG CABA, Argentina.

Constanza Russo (C)

Instituto de Investigaciones Biomédicas en Retrovirus y SIDA. Facultad de Medicina. UBA-CONICET. Paraguay 2155, C1121ABG CABA, Argentina.

Augusto Varese (A)

Instituto de Investigaciones Biomédicas en Retrovirus y SIDA. Facultad de Medicina. UBA-CONICET. Paraguay 2155, C1121ABG CABA, Argentina.

Vanesa Seery (V)

Instituto de Investigaciones Biomédicas en Retrovirus y SIDA. Facultad de Medicina. UBA-CONICET. Paraguay 2155, C1121ABG CABA, Argentina.

María P Holgado (MP)

Instituto de Investigaciones Biomédicas en Retrovirus y SIDA. Facultad de Medicina. UBA-CONICET. Paraguay 2155, C1121ABG CABA, Argentina.

María L Polo (ML)

Instituto de Investigaciones Biomédicas en Retrovirus y SIDA. Facultad de Medicina. UBA-CONICET. Paraguay 2155, C1121ABG CABA, Argentina.

Ana Ceballos (A)

Instituto de Investigaciones Biomédicas en Retrovirus y SIDA. Facultad de Medicina. UBA-CONICET. Paraguay 2155, C1121ABG CABA, Argentina.

Myriam Nuñez (M)

Cátedra de Matemática. Facultad de Farmacia y Bioquímica. UBA. Junín 954, C1113 AAD CABA, Argentina.

Juan Martín Gómez Penedo (JMG)

Laboratorio de Análisis Estadísticos, Secretaría de Investigaciones. Facultad de Psicología. UBA- CONICET. Av. Hipólito Yrigoyen 3242, C1207 ABR CABA, Argentina.

Fernando Ferrero (F)

Departamento de Medicina, Hospital General de Niños Pedro de Elizalde. Av. Montes de Oca 40, C1270 CABA, Argentina.

Jorge Geffner (J)

Instituto de Investigaciones Biomédicas en Retrovirus y SIDA. Facultad de Medicina. UBA-CONICET. Paraguay 2155, C1121ABG CABA, Argentina.

Lourdes Arruvito (L)

Instituto de Investigaciones Biomédicas en Retrovirus y SIDA. Facultad de Medicina. UBA-CONICET. Paraguay 2155, C1121ABG CABA, Argentina. Electronic address: arruvitol@gmail.com.

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