Distinct antibody responses to SARS-CoV-2 in children and adults across the COVID-19 clinical spectrum

Abstract

Clinical manifestations of COVID-19 caused by the new coronavirus SARS-CoV-2 are associated with age 1,2. Adults develop respiratory symptoms, which can progress to acute respiratory distress syndrome (ARDS) in the most severe form, while children are largely spared from respiratory illness but can develop a life-threatening multisystem inflammatory syndrome (MIS-C) 3-5. Here, we show distinct antibody responses in children and adults after SARS-CoV-2 infection. Adult COVID-19 cohorts had anti-spike (S) IgG, IgM and IgA antibodies, as well as anti-nucleocapsid (N) IgG antibody, while children with and without MIS-C had reduced breadth of anti-SARS-CoV-2-specific antibodies, predominantly generating IgG antibodies specific for the S protein but not the N protein. Moreover, children with and without MIS-C had reduced neutralizing activity as compared to both adult COVID-19 cohorts, indicating a reduced protective serological response. These results suggest a distinct infection course and immune response in children independent of whether they develop MIS-C, with implications for developing age-targeted strategies for testing and protecting the population. The clinical manifestations of SARS-CoV-2 infection in children are distinct from adults. Children with COVID-19 rarely exhibit severe respiratory symptoms and often remain asymptomatic 2 , whereas adults experience respiratory symptoms of varying severity; older adults and those with comorbidities such as hypertension and diabetes have substantially higher risks of developing COVID-19-associated ARDS with high mortality 2,6. In children, a rare but severe clinical manifestation of SARS-CoV-2 infection designated MIS-C, exhibits similarities to Kawasaki disease in certain inflammatory features and cardiovascular involvement while generally lacking severe respiratory symptoms 3-5. The nature of the immune response to SARS-CoV-2 in children with different clinical manifestations ranging from asymptomatic to MIS-C relative to the more common respiratory manifestations of COVID-19 in adults is unclear. The generation of virus-specific antibodies that neutralize or block infectivity is the most consistent correlate of protective immunity for multiple infections and vaccines 7,8. Antibodies specific for the major SARS-CoV-2 antigens, including the S protein which binds the cellular receptor for viral entry and the N protein necessary for viral replication, have been detected in actively infected patients and in patients with mild disease who recovered 9-12. Anti-S antibodies, in particular, can exhibit potent neutralizing activity and are currently being pursued as a therapeutic option for infusion into patients during severe disease and for targeted generation in vaccines 13-15. Defining the nature of the antibody response to SARS-CoV-2 infection as a function of age and clinical syndrome can provide essential insights for improved screening and targeted protection for the global population that continues to suffer from this relentless pandemic. In this study, we inves...

Antibody response and therapy in COVID-19 patients: what can be learned for vaccine development?

“…Third, it was observed that children with COVID-19 have milder symptoms and better prognoses than adults (Ludvigsson, 2020), and age is a significant determinant in COVID-19 severity (Cummings et al, 2020;Yang et al, 2020;. Consistent with the above clinical manifestation, adult COVID-19 patients have higher titers of anti-SARS-CoV-2 antibodies than children (Pierce et al, 2020;Weisberg et al, 2020). Together, these features of antibody responses support the hypothesis that rapid and increased induction of antigen-specific IgG upon SARS-CoV-2 infection in adults may result in ADE and contribute to COVID-19 pathogenesis (Fierz and Walz, 2020) ( Figure 1B).…”

“…COVID-19 positive adults developed anti-S IgG, IgM and IgA classes as well as anti-N IgG antibody, while COVID-19 positive children predominantly developed anti-S but not anti-N IgG antibody (Weisberg et al, 2020). Children had reduced breadth of antigen-specific antibodies as well as neutralizing activity, indicating a reduced humoral response (Pierce et al, 2020;Weisberg et al, 2020). These observations may be related to antibody-mediated disease pathology in adult patients.…”

“…Fourth, antibody responses were different in adults and children (Pierce et al, 2020;Weisberg et al, 2020). COVID-19 positive adults developed anti-S IgG, IgM and IgA classes as well as anti-N IgG antibody, while COVID-19 positive children predominantly developed anti-S but not anti-N IgG antibody (Weisberg et al, 2020).…”

“…Fourth, antibody responses were different in adults and children (Pierce et al, 2020;Weisberg et al, 2020). COVID-19 positive adults developed anti-S IgG, IgM and IgA classes as well as anti-N IgG antibody, while COVID-19 positive children predominantly developed anti-S but not anti-N IgG antibody (Weisberg et al, 2020). Children had reduced breadth of antigen-specific antibodies as well as neutralizing activity, indicating a reduced humoral response (Pierce et al, 2020;Weisberg et al, 2020).…”

Antibody response to SARS-CoV-2 infection in humans: A systematic review

“…A recent study has characterised sex differences in the cytokine and cellular response, although identified no differences in anti-S1 IgG or -IgM between male and female cases [171]. With regard to age, recent data published beyond the cut off for this review has shown distinct antibody responses in children and adults, which may inform future understanding of the disease course in different age groups [172]. This is a welcome addition to the literature considering the lack of studies on children included identified for our review.…”