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

被引：20

作者：

Sananez, Ines ^{[1
]}

Raiden, Silvina C. ^{[2
]}

Algieri, Silvia C. ^{[3
]}

Uranga, Macarena ^{[4
]}

Grisolia, Nicolas A. ^{[2
]}

Filippo, Daniela ^{[5
]}

De Carli, Norberto ^{[6
]}

Di Lalla, Sandra ^{[7
]}

Cairoli, Hector ^{[2
]}

Chiolo, Maria J. ^{[8
]}

Meregalli, Claudia N. ^{[9
]}

Cohen, Emilia ^{[10
]}

Mosquera, Graciela ^{[10
]}

Marco del Pont, Maria ^{[4
]}

Gimenez, Lorena, I ^{[5
]}

Gregorio, Gabriela ^{[3
]}

Sarli, Mariam ^{[11
]}

Alcalde, Ana L. ^{[3
]}

Davenport, Carolina ^{[2
]}

Bruera, Maria J. ^{[11
]}

Simaz, Nancy ^{[3
]}

Perez, Mariela F. ^{[3
]}

Nivela, Valeria ^{[12
]}

Bayle, Carola ^{[12
]}

Alvarez, Laura ^{[13
]}

Revetria, Maria ^{[13
]}

Tuccillo, Patricia ^{[14
,15
]}

Agosta, Maria T. ^{[14
,15
]}

Perez, Hernan ^{[14
,15
]}

Villa Nova, Susana ^{[14
,15
]}

Suarez, Patricia ^{[14
,15
]}

Takata, Eugenia M. ^{[14
,15
]}

Garcia, Mariela ^{[14
,15
]}

Lattner, Jorge ^{[16
]}

Rolon, Maria J. ^{[17
]}

Coll, Patricia ^{[17
]}

Salvatori, Melina ^{[1
]}

Piccardo, Claudio ^{[1
]}

Russo, Constanza ^{[1
]}

Varese, Augusto ^{[1
]}

Seery, Vanesa ^{[1
]}

Holgado, Maria P. ^{[1
]}

Polo, Maria L. ^{[1
]}

Ceballos, Ana ^{[1
]}

Nunez, Myriam ^{[18
]}

Gomez Penedo, Juan Martin ^{[19
]}

Ferrero, Fernando ^{[2
]}

Geffner, Jorge ^{[1
]}

Arruvito, Lourdes ^{[1
]}

机构：

[1] UBA CONICET, Fac Med, Inst Invest Biomed Retrovirus & SIDA, C1121ABG CABA, Caba, Argentina

[2] Hosp Gen Ninos Pedro de Elizalde, Dept Med, Av Montes Oca 40,C1270, Caba, Argentina

[3] Hosp Nacl Prof Alejandro Posadas, Serv Pediat, Marconi Moron 386,B1684, Buenos Aires, DF, Argentina

[4] Hosp Univ Austral, Dept Materno Infantil, Sect Infectol Infantil, Av Juan Domingo Peron 1500,B1629, Buenos Aires, DF, Argentina

[5] Hosp Municipal Diego Thompson, Serv Pediat, Avellaneda 33,B1650, Buenos Aires, DF, Argentina

[6] Clin Nino Quilmes, Serv Pediat, Av Lamadrid 444,B1878, Buenos Aires, DF, Argentina

[7] Hosp Gen Ninos Pedro de Elizalde, Dept Consultorios Externos, Av Montes Oca 40,C1270, Caba, Argentina

[8] Hosp Gen Ninos Pedro de Elizalde, Dept Cirugia, Av Montes Oca 40,C1270, Caba, Argentina

[9] Hosp Gen Ninos Pedro de Elizalde, Dept Urgencias, Unidad Terapia Intens Pediat, Av Montes Oca 40,C1270, Caba, Argentina

[10] Hosp HIGA Eva Peron, Serv Pediat, Av Dr Ricardo Balbin 3200,B1650, Buenos Aires, DF, Argentina

[11] Hosp Nacl Prof Alejandro Posadas, Unidad Terapia Intens Pediat, Marconi Moron 386,B1684, Buenos Aires, DF, Argentina

[12] Hosp Nacl Prof Alejandro Posadas, Dept Emergencias Pediat, Marconi Moron 386,B1684, Buenos Aires, DF, Argentina

[13] Hosp Univ Austral, Dept Lab, Av Juan Domingo Peron 1500,B1629, Buenos Aires, DF, Argentina

[14] Hosp Naval Cirujano Mayor Dr Pedro Mallo, Serv Pediat, Av Patricias Argentinas 351,C1405, Caba, Argentina

[15] Hosp Gen Agudos Dr Juan A Fernandez, Serv Pediat, Av Cervino 3356,C1425, Caba, Argentina

[16] Hosp Naval Cirujano Mayor Dr Pedro Mallo, Serv Infectol Pediat, Av Patricias Argentinas 351,C1405, Caba, Argentina

[17] Hosp Gen Agudos Dr Juan A Fernandez, Div Infectol, Av Cervino 3356,C1425, Caba, Argentina

[18] UBA, Fac Farm & Bioquim, Catedra Matemat, Junin 954,C1113 AAD, Caba, Argentina

[19] UBA CONICET, Lab Anal Estadist, Secretaria Invest, Fac Psicol, Av Hipolito Yrigoyen 3242,C1207 ABR, Caba, Argentina

来源：

EBIOMEDICINE | 2021年 / 72卷

关键词：

Pediatric COVID-19; Disease severity; antibodies; T cells;

D O I：

10.1016/j.ebiom.2021.103615

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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: 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: 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: 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. (C) 2021 The Author(s). Published by Elsevier B.V.

引用

页数：10

共 37 条

[1]

Anderson Elizabeth M, 2020, medRxiv, DOI 10.1101/2020.08.17.20176552

[2] Assessment of 135 794 Pediatric Patients Tested for Severe Acute Respiratory Syndrome Coronavirus 2 Across the United States [J].

Bailey, L. Charles ;

Razzaghi, Hanieh ;

Burrows, Evanette K. ;

Bunnell, H. Timothy ;

Camacho, Peter E. F. ;

Christakis, Dimitri A. ;

Eckrich, Daniel ;

Kitzmiller, Melody ;

Lin, Simon M. ;

Magnusen, Brianna C. ;

Newland, Jason ;

Pajor, Nathan M. ;

Ranade, Daksha ;

Rao, Suchitra ;

Sofela, Olamiji ;

Zahner, Janet ;

Bruno, Cortney ;

Forrest, Christopher B. .

JAMA PEDIATRICS, 2021, 175 (02) :176-184

[3]

Bellon M, CLIN INFECT DIS OFFI

[4] CD4+ T Follicular Helper Cells in Human Tonsils and Blood Are Clonally Convergent but Divergent from Non-Tfh CD4+ Cells [J].

Brenna, Elena ;

Davydov, Alexey N. ;

Ladell, Kristin ;

McLaren, James E. ;

Bonaiuti, Paolo ;

Metsger, Maria ;

Ramsden, James D. ;

Gilbert, Sarah C. ;

Lambe, Teresa ;

Price, David A. ;

Campion, Suzanne L. ;

Chudakov, Dmitriy M. ;

Borrow, Persephone ;

McMichael, Andrew J. .

CELL REPORTS, 2020, 30 (01) :137-+

[5] Nasal Gene Expression of Angiotensin-Converting Enzyme 2 in Children and Adults [J].

Bunyavanich, Supinda ;

Do, Anh ;

Vicencio, Alfin .

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2020, 323 (23) :2427-2429

[6] The Immunology of Multisystem Inflammatory Syndrome in Children with COVID-19 [J].

Consiglio, Camila Rosat ;

Cotugno, Nicola ;

Sardh, Fabian ;

Pou, Christian ;

Amodio, Donato ;

Rodriguez, Lucie ;

Tan, Ziyang ;

Zicari, Sonia ;

Ruggiero, Alessandra ;

Pascucci, Giuseppe Rubens ;

Santilli, Veronica ;

Campbell, Tessa ;

Bryceson, Yenan ;

Eriksson, Daniel ;

Wang, Jun ;

Marchesi, Alessandra ;

Lakshmikanth, Tadepally ;

Campana, Andrea ;

Villani, Alberto ;

Rossi, Paolo ;

Landegren, Nils ;

Palma, Paolo ;

Brodin, Petter .

CELL, 2020, 183 (04) :968-+

[7]

Del Valle DM, 2020, NAT MED, V26, P1636, DOI [10.1038/s41591-020-1051-9, 10.1101/2020.05.28.20115758]

[8] Multisystem inflammatory syndrome in children and COVID-19 are distinct presentations of SARS CoV-2 [J].

Diorio, Caroline ;

Henrickson, Sarah E. ;

Vella, Laura A. ;

McNerney, Kevin O. ;

Chase, Julie ;

Burudpakdee, Chakkapong ;

Lee, Jessica H. ;

Jasen, Cristina ;

Balamuth, Fran ;

Barrett, David M. ;

Banwell, Brenda L. ;

Bernt, Kathrin M. ;

Blatz, Allison M. ;

Chiotos, Kathleen ;

Fisher, Brian T. ;

Fitzgerald, Julie C. ;

Gerber, Jeffrey S. ;

Gollomp, Kandace ;

Gray, Christopher ;

Grupp, Stephan A. ;

Harris, Rebecca M. ;

Kilbaugh, Todd J. ;

John, Audrey R. Odom ;

Lambert, Michele ;

Liebling, Emily J. ;

Paessler, Michele E. ;

Petrosa, Whitney ;

Phillips, Charles ;

Reilly, Anne F. ;

Romberg, Neil D. ;

Seif, Alix ;

Sesok-Pizzini, Deborah A. ;

Sullivan, Kathleen E. ;

Vardaro, Julie ;

Behrens, Edward M. ;

Teachey, David T. ;

Bassiri, Hamid .

JOURNAL OF CLINICAL INVESTIGATION, 2020, 130 (11) :5967-5975

[9] Epidemiology of COVID-19 Among Children in China [J].

Dong, Yuanyuan ;

Mo, Xi ;

Hu, Yabin ;

Qi, Xin ;

Jiang, Fan ;

Jiang, Zhongyi ;

Tong, Shilu .

PEDIATRICS, 2020, 145 (06)

[10] COVID-19-neutralizing antibodies predict disease severity and survival [J].

Garcia-Beltran, Wilfredo F. ;

Lam, Evan C. ;

Astudillo, Michael G. ;

Yang, Diane ;

Miller, Tyler E. ;

Feldman, Jared ;

Hauser, Blake M. ;

Caradonna, Timothy M. ;

Clayton, Kiera L. ;

Nitido, Adam D. ;

Murali, Mandakolathur R. ;

Alter, Galit ;

Charles, Richelle C. ;

Dighe, Anand ;

Branda, John A. ;

Lennerz, Jochen K. ;

Lingwood, Daniel ;

Schmidt, Aaron G. ;

Iafrate, A. John ;

Balazs, Alejandro B. .

CELL, 2021, 184 (02) :476-+

← 1 2 3 4 →