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

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; Brodin, Petter; Rossi, Paolo; De Rossi, Anita; Palma, Paolo

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.