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

Nicola Cotugno; Alessandra Ruggiero; Francesco Bonfante; Maria Raffaella Petrara; Sonia Zicari; Giuseppe Rubens Pascucci; Paola Zangari; Maria Antonietta De Ioris; Veronica Santilli; E C Manno; Donato Amodio; Alessio Bortolami; Matteo Pagliari; Carlo Concato; Giulia Linardos; Andrea Campana; Daniele Donà; Carlo Giaquinto; CACTUS Study Team; Petter Brodin; Paolo Rossi; Anita De Rossi; Paolo Palma

doi:10.1016/j.celrep.2021.108852

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

Cell Rep. 2021 Mar 16;34(11):108852. doi: 10.1016/j.celrep.2021.108852.

Authors

Nicola Cotugno¹, Alessandra Ruggiero², Francesco Bonfante³, Maria Raffaella Petrara⁴, Sonia Zicari², Giuseppe Rubens Pascucci², Paola Zangari², Maria Antonietta De Ioris⁵, Veronica Santilli², E C Manno², Donato Amodio¹, Alessio Bortolami³, Matteo Pagliari³, Carlo Concato⁶, Giulia Linardos⁶, Andrea Campana⁵, Daniele Donà⁷, Carlo Giaquinto⁷; CACTUS Study Team; Petter Brodin⁸, Paolo Rossi¹, Anita De Rossi⁹, Paolo Palma¹⁰

Affiliations

¹ Academic Department of Pediatrics (DPUO), Research Unit of Clinical Immunology and Vaccinology, Bambino Gesù Children's Hospital, IRCCS, 00165 Rome, Italy; Chair of Pediatrics, Department of Systems Medicine, University of Rome "Tor Vergata," 00185 Rome, Italy.
² Academic Department of Pediatrics (DPUO), Research Unit of Clinical Immunology and Vaccinology, Bambino Gesù Children's Hospital, IRCCS, 00165 Rome, Italy.
³ Laboratory of Experimental Animal Models, Division of Comparative Biomedical Sciences, Istituto Zooprofilattico Sperimentale delle Venezie, 35020 Legnaro, Italy.
⁴ Section of Oncology and Immunology, Department of Surgery, Oncology, and Gastroenterology, Unit of Viral Oncology and AIDS Reference Center, University of Padova, 35128 Padova, Italy.
⁵ Academic Department of Pediatrics, Bambino Gesù Children's Hospital, IRCCS, 00165 Rome, Italy.
⁶ Department of Laboratories, Division of Virology, Bambino Gesù Children's Hospital, IRCCS, 00165 Rome, Italy.
⁷ Department of Mother and Child Health, University of Padova, 35128 Padova, Italy.
⁸ Pediatric Rheumatology, Karolinska University Hospital, 17177 Stockholm, Sweden.
⁹ Section of Oncology and Immunology, Department of Surgery, Oncology, and Gastroenterology, Unit of Viral Oncology and AIDS Reference Center, University of Padova, 35128 Padova, Italy; Istituto Oncologico Veneto (IOV)-IRCCS, 35128 Padova, Italy.
¹⁰ Academic Department of Pediatrics (DPUO), Research Unit of Clinical Immunology and Vaccinology, Bambino Gesù Children's Hospital, IRCCS, 00165 Rome, Italy; Chair of Pediatrics, Department of Systems Medicine, University of Rome "Tor Vergata," 00185 Rome, Italy. Electronic address: [email protected].

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.

Keywords: Ab-mediated neutralization activity; COVID-19; SARS-CoV-2; anti-SARS-CoV-2 antibodies; antigen-specific B cells; antigen-specific CD4 T cells; pediatric COVID-19; proteomic profiling.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptive Immunity / immunology
Antibodies, Neutralizing / immunology*
Antibodies, Viral / immunology*
B-Lymphocytes / immunology
CD4-Positive T-Lymphocytes / immunology
COVID-19 / immunology*
COVID-19 / virology
Child
Humans
Immunity, Humoral / immunology
Proteome / immunology
SARS-CoV-2 / immunology
Signal Transduction / immunology
Viral Load / immunology

Substances

Antibodies, Neutralizing
Antibodies, Viral
Proteome