Reduced seroconversion in children compared to adults with mild COVID-19

Toh, Z. Q.; Anderson, J.; Mazarakis, N.; Neeland, M.; Higgins, R. A.; Rautenbacher, K.; Dohle, K.; Nguyen, J.; Overmars, I.; Donato, C.; Sarkar, S.; Clifford, V.; Daley, A.; Nicholson, S.; Mordant, F. L.; Subbarao, K.; Burgner, D.; Curtis, N.; Bines, J. E.; McNab, S.; Steer, A. C.; Mulholland, K.; Tosif, S.; Crawford, N. W.; Pellicci, D. G.; Do, L. A. H.; Licciardi, P.

Importance: The immune response in children with SARS-CoV-2 infection is not well understood. Objective: To compare seroconversion in children and adults with non-hospitalized (mild) SARS-CoV-2 infection and to understand the factors that influence this. Design: Participants were part of a household cohort study of SARS-CoV-2 infection. Weekly nasopharyngeal/throat swabs and blood samples were collected during the acute and convalescent period following PCR diagnosis for analysis. Setting: Participants were recruited at the Royal Childrens Hospital, Melbourne, Australia between May and October 2020. Participants: Those who had a SARS-CoV-2 PCR-positive nasal/throat swab. Main outcomes and measures: SARS-CoV-2 antibody and cellular responses in children and adults. Seroconversion was defined by seropositivity in all three serological assays. Results: Among 108 SARS-CoV-2 PCR-positive participants, 57 were children (median age: 4, IQR 2-10) and 51 were adults (median age: 37, IQR 34-45). Using three established serological assays, a lower proportion of children seroconverted compared with adults [20/54 69 (37.0%) vs 32/42 (76.2%); (p<0.001)]. This was not related to viral load, which was similar in children and adults [mean Ct 28.58 (SD: 6.83) vs 24.14 (SD: 8.47)]. Age and sex also did not influence seroconversion or the magnitude of antibody response within children or adults. Notably, in adults (but not children) symptomatic adults had three-fold higher antibody levels than asymptomatic adults (median 227.5 IU/mL, IQR 133.7-521.6 vs median 75.3 IU/mL, IQR 36.9-113.6). Evidence of cellular immunity was observed in adults who seroconverted but not in children who seroconverted. Conclusion and Relevance: In this non-hospitalized cohort with mild COVID-19, children were less likely to seroconvert than adults despite similar viral loads. This has implications for future protection following COVID-19 infection in children and for interpretation of serosurveys that involve children. Further research to understand why children are less likely to seroconvert and develop symptoms following SARS-CoV-2 infection, and comparison with vaccine responses may be of clinical and scientific importance.