Preschool-age children maintain a distinct memory CD4 <sup>+</sup> T cell and memory B cell response after SARS-CoV-2 infection
Benoît Manfroi, Bui Thi Cuc, Aurélien Sokal, Alexis Vandenberghe, Sarah Temmam, Mikaël Attia, Mohamed El Behi, Francesco Camaglia, Ngan Thu Nguyen, Jelka Pohar, Layale Salem-Wehbe, Valentine Pottez-Jouatte, S. Borzakian, Narcisse Elenga, Caroline Galeotti, Guillaume Morelle, Camille de Truchis de Lays, Michaëla Semeraro, Anne‐Sophie Romain, Mélodie Aubart, Naïm Ouldali, Florence Mahuteau‐Betzer, Claire Beauvineau, Elsa Amouyal, Romain Berthaud, Célia Cretolle, Marc Duval Arnould, Albert Faye, Mathie Lorrot, Grégoire Benoist, Nelly Briand, Marie Courbebaisse, Roland Martinꝉ, Peter Van Endert, Jean‐Sébastien Hulot, Anne Blanchard, Éric Tartour, Maria Leite‐de‐Moraes, Guillaume Lezmi, Mickaël Ménager, Marine Luka, Claude–Agnès Reynaud, Jean–Claude Weill, Laetitia Languille, Marc Michel, Pascal Chappert, Thierry Mora, Aleksandra M. Walczak, Marc Éloit, Petra Bächer, Alexander Scheffold, Matthieu Mahévas, Isabelle Sermet‐Gaudelus, Simon Fillatreau
Abstract
The development of the human immune system lasts for several years after birth. The impact of this maturation phase on the quality of adaptive immunity and the acquisition of immunological memory after infection at a young age remains incompletely defined. Here, using an antigen-reactive T cell (ARTE) assay and multidimensional flow cytometry, we profiled circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–reactive CD3 + CD4 + CD154 + T cells in children and adults before infection, during infection, and 11 months after infection, stratifying children into separate age groups and adults according to disease severity. During SARS-CoV-2 infection, children younger than 5 years old displayed a lower antiviral CD4 + T cell response, whereas children older than 5 years and adults with mild disease had, quantitatively and phenotypically, comparable virus-reactive CD4 + T cell responses. Adults with severe disease mounted a response characterized by higher frequencies of virus-reactive proinflammatory and cytotoxic T cells. After SARS-CoV-2 infection, preschool-age children not only maintained neutralizing SARS-CoV-2–reactive antibodies postinfection comparable to adults but also had phenotypically distinct memory T cells displaying high inflammatory features and properties associated with migration toward inflamed sites. Moreover, preschool-age children had markedly fewer circulating virus-reactive memory B cells compared with the other cohorts. Collectively, our results reveal unique facets of antiviral immunity in humans at a young age and indicate that the maturation of adaptive responses against SARS-CoV-2 toward an adult-like profile occurs in a progressive manner.