Virological and immunological features of SARS-CoV-2-infected children who develop neutralizing antibodies

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...

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Veröffentlicht in:Cell reports (Cambridge) 2021-03, Vol.34 (11), p.108852-108852, Article 108852
Hauptverfasser: Cotugno, Nicola, Ruggiero, Alessandra, Bonfante, Francesco, Petrara, Maria Raffaella, Zicari, Sonia, Pascucci, Giuseppe Rubens, Zangari, Paola, De Ioris, Maria Antonietta, Santilli, Veronica, Manno, E.C., Amodio, Donato, Bortolami, Alessio, Pagliari, Matteo, Concato, Carlo, Linardos, Giulia, Campana, Andrea, Donà, Daniele, Giaquinto, Carlo, Bernardi, Stefania, Romani, Lorenza, Pansa, Paola, Chiurchiú, Sara, Finocchi, Andrea, Cancrini, Caterina, Lancella, Laura, Cursi, Laura, De Luca, Maia, Cutrera, Renato, Sessa, Libera, Morrocchi, Elena, Medri, Chiara, Putignani, Lorenza, Calò Carducci, F.I., D’Argenio, Patrizia, Ciofi degli Atti, Marta, D’Amore, Carmen, Piccioni, Livia, Di Giuseppe, Martina, Jenkner, Alessandro, Giancotta, Carmela, Krzysztofiak, Andrzej, Brodin, Petter, Rossi, Paolo, De Rossi, Anita, Palma, Paolo
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container_issue 11
container_start_page 108852
container_title Cell reports (Cambridge)
container_volume 34
creator Cotugno, Nicola
Ruggiero, Alessandra
Bonfante, Francesco
Petrara, Maria Raffaella
Zicari, Sonia
Pascucci, Giuseppe Rubens
Zangari, Paola
De Ioris, Maria Antonietta
Santilli, Veronica
Manno, E.C.
Amodio, Donato
Bortolami, Alessio
Pagliari, Matteo
Concato, Carlo
Linardos, Giulia
Campana, Andrea
Donà, Daniele
Giaquinto, Carlo
Bernardi, Stefania
Romani, Lorenza
Pansa, Paola
Chiurchiú, Sara
Finocchi, Andrea
Cancrini, Caterina
Lancella, Laura
Cursi, Laura
De Luca, Maia
Cutrera, Renato
Sessa, Libera
Morrocchi, Elena
Medri, Chiara
Putignani, Lorenza
Calò Carducci, F.I.
D’Argenio, Patrizia
Ciofi degli Atti, Marta
D’Amore, Carmen
Piccioni, Livia
Di Giuseppe, Martina
Jenkner, Alessandro
Giancotta, Carmela
Krzysztofiak, Andrzej
Brodin, Petter
Rossi, Paolo
De Rossi, Anita
Palma, Paolo
description 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. [Display omitted] •Antibody neutralization is inversely associated with SARS-CoV-2 in nasopharyngeal swabs•Antigen-specific B cells positively associate with anti-SARS-CoV-2 humoral immunity•SARS-CoV-2 neutralizing antibodies are present in patients with higher specific T cells•Antigen-specific B and T cells are features of SARS-CoV-2 immunity in children Cotugno et al. show that neutralizing antibodies affect SARS-CoV-2 viral load in infected children. Antigen-specific B and T cells are positively associated with virus neutralization. This information provides a basis for defining SARS-CoV-2 adaptive responses in children.
doi_str_mv 10.1016/j.celrep.2021.108852
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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. [Display omitted] •Antibody neutralization is inversely associated with SARS-CoV-2 in nasopharyngeal swabs•Antigen-specific B cells positively associate with anti-SARS-CoV-2 humoral immunity•SARS-CoV-2 neutralizing antibodies are present in patients with higher specific T cells•Antigen-specific B and T cells are features of SARS-CoV-2 immunity in children Cotugno et al. show that neutralizing antibodies affect SARS-CoV-2 viral load in infected children. Antigen-specific B and T cells are positively associated with virus neutralization. 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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. [Display omitted] •Antibody neutralization is inversely associated with SARS-CoV-2 in nasopharyngeal swabs•Antigen-specific B cells positively associate with anti-SARS-CoV-2 humoral immunity•SARS-CoV-2 neutralizing antibodies are present in patients with higher specific T cells•Antigen-specific B and T cells are features of SARS-CoV-2 immunity in children Cotugno et al. show that neutralizing antibodies affect SARS-CoV-2 viral load in infected children. Antigen-specific B and T cells are positively associated with virus neutralization. This information provides a basis for defining SARS-CoV-2 adaptive responses in children.</description><subject>Ab-mediated neutralization activity</subject><subject>Adaptive Immunity - immunology</subject><subject>anti-SARS-CoV-2 antibodies</subject><subject>Antibodies, Neutralizing - immunology</subject><subject>Antibodies, Viral - immunology</subject><subject>antigen-specific B cells</subject><subject>antigen-specific CD4 T cells</subject><subject>B-Lymphocytes - immunology</subject><subject>CD4-Positive T-Lymphocytes - immunology</subject><subject>Child</subject><subject>COVID-19</subject><subject>COVID-19 - immunology</subject><subject>COVID-19 - virology</subject><subject>Humans</subject><subject>Immunity, Humoral - immunology</subject><subject>pediatric COVID-19</subject><subject>Proteome - immunology</subject><subject>proteomic profiling</subject><subject>SARS-CoV-2</subject><subject>SARS-CoV-2 - immunology</subject><subject>Signal Transduction - immunology</subject><subject>Viral Load - 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immunology</topic><topic>anti-SARS-CoV-2 antibodies</topic><topic>Antibodies, Neutralizing - immunology</topic><topic>Antibodies, Viral - immunology</topic><topic>antigen-specific B cells</topic><topic>antigen-specific CD4 T cells</topic><topic>B-Lymphocytes - immunology</topic><topic>CD4-Positive T-Lymphocytes - immunology</topic><topic>Child</topic><topic>COVID-19</topic><topic>COVID-19 - immunology</topic><topic>COVID-19 - virology</topic><topic>Humans</topic><topic>Immunity, Humoral - immunology</topic><topic>pediatric COVID-19</topic><topic>Proteome - immunology</topic><topic>proteomic profiling</topic><topic>SARS-CoV-2</topic><topic>SARS-CoV-2 - immunology</topic><topic>Signal Transduction - immunology</topic><topic>Viral Load - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cotugno, Nicola</creatorcontrib><creatorcontrib>Ruggiero, Alessandra</creatorcontrib><creatorcontrib>Bonfante, Francesco</creatorcontrib><creatorcontrib>Petrara, Maria Raffaella</creatorcontrib><creatorcontrib>Zicari, Sonia</creatorcontrib><creatorcontrib>Pascucci, Giuseppe Rubens</creatorcontrib><creatorcontrib>Zangari, Paola</creatorcontrib><creatorcontrib>De Ioris, Maria Antonietta</creatorcontrib><creatorcontrib>Santilli, Veronica</creatorcontrib><creatorcontrib>Manno, E.C.</creatorcontrib><creatorcontrib>Amodio, Donato</creatorcontrib><creatorcontrib>Bortolami, Alessio</creatorcontrib><creatorcontrib>Pagliari, Matteo</creatorcontrib><creatorcontrib>Concato, Carlo</creatorcontrib><creatorcontrib>Linardos, Giulia</creatorcontrib><creatorcontrib>Campana, Andrea</creatorcontrib><creatorcontrib>Donà, Daniele</creatorcontrib><creatorcontrib>Giaquinto, Carlo</creatorcontrib><creatorcontrib>Bernardi, Stefania</creatorcontrib><creatorcontrib>Romani, Lorenza</creatorcontrib><creatorcontrib>Pansa, Paola</creatorcontrib><creatorcontrib>Chiurchiú, Sara</creatorcontrib><creatorcontrib>Finocchi, Andrea</creatorcontrib><creatorcontrib>Cancrini, Caterina</creatorcontrib><creatorcontrib>Lancella, Laura</creatorcontrib><creatorcontrib>Cursi, Laura</creatorcontrib><creatorcontrib>De Luca, Maia</creatorcontrib><creatorcontrib>Cutrera, Renato</creatorcontrib><creatorcontrib>Sessa, Libera</creatorcontrib><creatorcontrib>Morrocchi, Elena</creatorcontrib><creatorcontrib>Medri, Chiara</creatorcontrib><creatorcontrib>Putignani, Lorenza</creatorcontrib><creatorcontrib>Calò Carducci, F.I.</creatorcontrib><creatorcontrib>D’Argenio, Patrizia</creatorcontrib><creatorcontrib>Ciofi degli Atti, Marta</creatorcontrib><creatorcontrib>D’Amore, Carmen</creatorcontrib><creatorcontrib>Piccioni, Livia</creatorcontrib><creatorcontrib>Di Giuseppe, Martina</creatorcontrib><creatorcontrib>Jenkner, Alessandro</creatorcontrib><creatorcontrib>Giancotta, Carmela</creatorcontrib><creatorcontrib>Krzysztofiak, Andrzej</creatorcontrib><creatorcontrib>Brodin, Petter</creatorcontrib><creatorcontrib>Rossi, Paolo</creatorcontrib><creatorcontrib>De Rossi, Anita</creatorcontrib><creatorcontrib>Palma, Paolo</creatorcontrib><creatorcontrib>The CACTUS Study Team</creatorcontrib><creatorcontrib>CACTUS Study Team</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Freely available online</collection><collection>SwePub Articles full text</collection><jtitle>Cell reports (Cambridge)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cotugno, Nicola</au><au>Ruggiero, Alessandra</au><au>Bonfante, Francesco</au><au>Petrara, Maria Raffaella</au><au>Zicari, Sonia</au><au>Pascucci, Giuseppe Rubens</au><au>Zangari, Paola</au><au>De Ioris, Maria Antonietta</au><au>Santilli, Veronica</au><au>Manno, E.C.</au><au>Amodio, Donato</au><au>Bortolami, Alessio</au><au>Pagliari, Matteo</au><au>Concato, Carlo</au><au>Linardos, Giulia</au><au>Campana, Andrea</au><au>Donà, Daniele</au><au>Giaquinto, Carlo</au><au>Bernardi, Stefania</au><au>Romani, Lorenza</au><au>Pansa, Paola</au><au>Chiurchiú, Sara</au><au>Finocchi, Andrea</au><au>Cancrini, Caterina</au><au>Lancella, Laura</au><au>Cursi, Laura</au><au>De Luca, Maia</au><au>Cutrera, Renato</au><au>Sessa, Libera</au><au>Morrocchi, Elena</au><au>Medri, Chiara</au><au>Putignani, Lorenza</au><au>Calò Carducci, F.I.</au><au>D’Argenio, Patrizia</au><au>Ciofi degli Atti, Marta</au><au>D’Amore, Carmen</au><au>Piccioni, Livia</au><au>Di Giuseppe, Martina</au><au>Jenkner, Alessandro</au><au>Giancotta, Carmela</au><au>Krzysztofiak, Andrzej</au><au>Brodin, Petter</au><au>Rossi, Paolo</au><au>De Rossi, Anita</au><au>Palma, Paolo</au><aucorp>The CACTUS Study Team</aucorp><aucorp>CACTUS Study Team</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Virological and immunological features of SARS-CoV-2-infected children who develop neutralizing antibodies</atitle><jtitle>Cell reports (Cambridge)</jtitle><addtitle>Cell Rep</addtitle><date>2021-03-16</date><risdate>2021</risdate><volume>34</volume><issue>11</issue><spage>108852</spage><epage>108852</epage><pages>108852-108852</pages><artnum>108852</artnum><issn>2211-1247</issn><eissn>2211-1247</eissn><abstract>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. [Display omitted] •Antibody neutralization is inversely associated with SARS-CoV-2 in nasopharyngeal swabs•Antigen-specific B cells positively associate with anti-SARS-CoV-2 humoral immunity•SARS-CoV-2 neutralizing antibodies are present in patients with higher specific T cells•Antigen-specific B and T cells are features of SARS-CoV-2 immunity in children Cotugno et al. show that neutralizing antibodies affect SARS-CoV-2 viral load in infected children. Antigen-specific B and T cells are positively associated with virus neutralization. This information provides a basis for defining SARS-CoV-2 adaptive responses in children.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>33730580</pmid><doi>10.1016/j.celrep.2021.108852</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-5978-1193</orcidid><orcidid>https://orcid.org/0000-0003-4550-3018</orcidid><orcidid>https://orcid.org/0000-0003-1240-8057</orcidid><orcidid>https://orcid.org/0000-0002-1041-7489</orcidid><orcidid>https://orcid.org/0000-0001-6435-7509</orcidid><oa>free_for_read</oa></addata></record>
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subjects Ab-mediated neutralization activity
Adaptive Immunity - immunology
anti-SARS-CoV-2 antibodies
Antibodies, Neutralizing - immunology
Antibodies, Viral - immunology
antigen-specific B cells
antigen-specific CD4 T cells
B-Lymphocytes - immunology
CD4-Positive T-Lymphocytes - immunology
Child
COVID-19
COVID-19 - immunology
COVID-19 - virology
Humans
Immunity, Humoral - immunology
pediatric COVID-19
Proteome - immunology
proteomic profiling
SARS-CoV-2
SARS-CoV-2 - immunology
Signal Transduction - immunology
Viral Load - immunology
title Virological and immunological features of SARS-CoV-2-infected children who develop neutralizing antibodies
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