Robust innate responses to SARS-CoV-2 in children resolve faster than in adults without compromising adaptive immunity

Vono, Maria; Huttner, Angela; Lemeille, Sylvain; Martinez-Murillo, Paola; Meyer, Benjamin; Baggio, Stephanie; Sharma, Shilpee; Thiriard, Anais; Marchant, Arnaud; Godeke, Gert-Jan; Reusken, Chantal; Alvarez, Catia; Perez-Rodriguez, Francisco; Eckerle, Isabella; Kaiser, Laurent; Loevy, Natasha; Eberhardt, Christiane S.; Blanchard-Rohner, Geraldine; Siegrist, Claire-Anne; Didierlaurent, Arnaud M.

SARS-CoV-2 infection in children is less severe than in adults. We perform a longitudinal analysis of the early innate responses in children and adults with mild infection within household clusters. Children display fewer symptoms than adults despite similar initial viral load and mount a robust anti-viral immune signature typical of SARS-CoV-2 infection and characterized by early interferon gene responses, increases in cytokines such as CXCL10 and GM-CSF, and changes in blood cell numbers. When compared to adults, the antiviral response resolves faster (within a week of symptoms); monocytes and dendritic cells are more transiently activated; and genes associated with B-cell activation appear earlier in children. Nonetheless, these differences do not have major effects on the quality of SARS-CoV-2 specific antibody responses. Our findings reveal that better early control of inflammation as observed in children may be key for rapidly controlling infection and limiting disease course.