TY - JOUR
T1 - Virological and immunological features of SARS-CoV-2-infected children who develop neutralizing antibodies
AU - The CACTUS Study Team
AU - Cotugno, Nicola
AU - Ruggiero, Alessandra
AU - Bonfante, Francesco
AU - Petrara, Maria Raffaella
AU - Zicari, Sonia
AU - Pascucci, Giuseppe Rubens
AU - Zangari, Paola
AU - De Ioris, Maria Antonietta
AU - Santilli, Veronica
AU - Manno, E. C.
AU - Amodio, Donato
AU - Bortolami, Alessio
AU - Pagliari, Matteo
AU - Concato, Carlo
AU - Linardos, Giulia
AU - Campana, Andrea
AU - Donà, Daniele
AU - Giaquinto, Carlo
AU - Bernardi, Stefania
AU - Romani, Lorenza
AU - Pansa, Paola
AU - Chiurchiú, Sara
AU - Finocchi, Andrea
AU - Cancrini, Caterina
AU - Lancella, Laura
AU - Cursi, Laura
AU - De Luca, Maia
AU - Cutrera, Renato
AU - Sessa, Libera
AU - Morrocchi, Elena
AU - Medri, Chiara
AU - Putignani, Lorenza
AU - Calò Carducci, F. I.
AU - D'Argenio, Patrizia
AU - Ciofi degli Atti, Marta
AU - D'Amore, Carmen
AU - Piccioni, Livia
AU - Di Giuseppe, Martina
AU - Jenkner, Alessandro
AU - Giancotta, Carmela
AU - Krzysztofiak, Andrzej
AU - Brodin, Petter
AU - Rossi, Paolo
AU - De Rossi, Anita
AU - Palma, Paolo
N1 - Funding Information:
We would like to thank all of the patients and guardians who participated in the study and all of the CACTUS study nurses team of the COVID-19 Center of Bambino Gesù Children’s Hospital. We would like to particularly thank all of the nurses of the Academic Department of Pediatrics who made this study possible. We also thank Jennifer Faudella and Gulia Neccia for their administrative assistance. We thank Francesco Carmona (IOV-IRCCS, Padova, Italy) for help in the preparation of the samples. This work was made possible by support from Ministry of Health ( RRC-2020-23669481 to N.C. and P.P.) and Fondazione Cassa di Risparmio di Padova e Rovigo, Progetti di Ricerca Covid-19 (ADR participant). We also thank Dr. Riccardo Truono for providing graphical support.
Publisher Copyright:
© 2021 The Author(s)
PY - 2021/3/16
Y1 - 2021/3/16
N2 - As the global COVID-19 pandemic progresses, it is paramount to gain knowledge on adaptive immunity to SARS-CoV-2 in children to define immune correlates of protection upon immunization or infection. We analyzed anti-SARS-CoV-2 antibodies and their neutralizing activity (PRNT) in 66 COVID-19-infected children at 7 (±2) days after symptom onset. Individuals with specific humoral responses presented faster virus clearance and lower viral load associated with a reduced in vitro infectivity. We demonstrated that the frequencies of SARS-CoV-2-specific CD4+CD40L+ T cells and Spike-specific B cells were associated with the anti-SARS-CoV-2 antibodies and the magnitude of neutralizing activity. The plasma proteome confirmed the association between cellular and humoral SARS-CoV-2 immunity, and PRNT+ patients show higher viral signal transduction molecules (SLAMF1, CD244, CLEC4G). This work sheds lights on cellular and humoral anti-SARS-CoV-2 responses in children, which may drive future vaccination trial endpoints and quarantine measures policies.
AB - As the global COVID-19 pandemic progresses, it is paramount to gain knowledge on adaptive immunity to SARS-CoV-2 in children to define immune correlates of protection upon immunization or infection. We analyzed anti-SARS-CoV-2 antibodies and their neutralizing activity (PRNT) in 66 COVID-19-infected children at 7 (±2) days after symptom onset. Individuals with specific humoral responses presented faster virus clearance and lower viral load associated with a reduced in vitro infectivity. We demonstrated that the frequencies of SARS-CoV-2-specific CD4+CD40L+ T cells and Spike-specific B cells were associated with the anti-SARS-CoV-2 antibodies and the magnitude of neutralizing activity. The plasma proteome confirmed the association between cellular and humoral SARS-CoV-2 immunity, and PRNT+ patients show higher viral signal transduction molecules (SLAMF1, CD244, CLEC4G). This work sheds lights on cellular and humoral anti-SARS-CoV-2 responses in children, which may drive future vaccination trial endpoints and quarantine measures policies.
KW - Ab-mediated neutralization activity
KW - anti-SARS-CoV-2 antibodies
KW - antigen-specific B cells
KW - antigen-specific CD4 T cells
KW - COVID-19
KW - pediatric COVID-19
KW - proteomic profiling
KW - SARS-CoV-2
UR - http://www.scopus.com/inward/record.url?scp=85102596808&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85102596808&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2021.108852
DO - 10.1016/j.celrep.2021.108852
M3 - Article
C2 - 33730580
AN - SCOPUS:85102596808
SN - 2211-1247
VL - 34
JO - Cell Reports
JF - Cell Reports
IS - 11
M1 - 108852
ER -