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

Abstract

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 Children’s 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 (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. Key points Question What proportion of children with non-hospitalized (mild) SARS-CoV-2 infection seroconvert compared to adults? Findings In this cohort study conducted in 2020, we found the proportion of children who seroconverted to SARS-CoV-2 was half that in adults despite similar viral load. Meaning Serology is a less reliable marker of prior SARS-CoV-2 infection in children. SARS-CoV-2-infected children who do not seroconvert may be susceptible to reinfection. Our findings support strategies to protect children against COVID-19 including vaccination.