Abstract
The immune response in children with SARS-CoV-2 infection is not well understood. To compare seroconversion in nonhospitalized children and adults with mild SARS-CoV-2 infection and identify factors that are associated with seroconversion. This household cohort study of SARS-CoV-2 infection collected weekly nasopharyngeal and throat swabs and blood samples during the acute (median, 7 days for children and 12 days for adults [IQR, 4-13] days) and convalescent (median, 41 [IQR, 31-49] days) periods after polymerase chain reaction (PCR) diagnosis for analysis. Participants were recruited at The Royal Children's Hospital, Melbourne, Australia, from May 10 to October 28, 2020. Participants included patients who had a SARS-CoV-2-positive nasopharyngeal or oropharyngeal swab specimen using PCR analysis. SARS-CoV-2 immunoglobulin G (IgG) and cellular (T cell and B cell) responses in children and adults. Seroconversion was defined by seropositivity in all 3 (an in-house enzyme-linked immunosorbent assay [ELISA] and 2 commercial assays: a SARS-CoV-2 S1/S2 IgG assay and a SARS-CoV-2 antibody ELISA) serological assays. Among 108 participants with SARS-CoV-2-positive PCR findings, 57 were children (35 boys [61.4%]; median age, 4 [IQR, 2-10] years) and 51 were adults (28 women [54.9%]; median age, 37 [IQR, 34-45] years). Using the 3 established serological assays, a lower proportion of children had seroconversion to IgG compared with adults (20 of 54 [37.0%] vs 32 of 42 [76.2%]; P < .001). This result was not associated with viral load, which was similar in children and adults (mean [SD] cycle threshold [Ct] value, 28.58 [6.83] vs 24.14 [8.47]; P = .09). In addition, age and sex were not associated with seroconversion within children (median age, 4 [IQR, 2-14] years for both seropositive and seronegative groups; seroconversion by sex, 10 of 21 girls [47.6%] vs 10 of 33 boys [30.3%]) or adults (median ages, 37 years for seropositive and 40 years for seronegative adults [IQR, 34-39 years]; seroconversion by sex, 18 of 24 women [75.0%] vs 14 of 18 men [77.8%]) (P > .05 for all comparisons between seronegative and seropositive groups). Symptomatic adults had 3-fold higher SARS-CoV-2 IgG levels than asymptomatic adults (median, 227.5 [IQR, 133.7-521.6] vs 75.3 [IQR, 36.9-113.6] IU/mL), whereas no differences were observed in children regardless of symptoms. Moreover, differences in cellular immune responses were observed in adults compared with children with seroconversion. The findings of this cohort study suggest that among patients with mild COVID-19, children may be less likely to have seroconversion than adults despite similar viral loads. This finding has implications for future protection after SARS-CoV-2 infection in children and for interpretation of serosurveys that involve children. Further research to understand why seroconversion and development of symptoms are potentially less likely in children after SARS-CoV-2 infection and to compare vaccine responses may be of clinical and scientific importance.
Highlights
Since the start of the COVID-19 pandemic, most children with COVID-19 either have been asymptomatic or have presented with mild illness, and very few have required hospitalization.[1-3]
Using the 3 established serological assays, a lower proportion of children had seroconversion to immunoglobulin G (IgG) compared with adults (20 of 54 [37.0%] vs 32 of 42 [76.2%]; P < .001)
This result was not associated with viral load, which was similar in children and adults
Summary
Since the start of the COVID-19 pandemic, most children with COVID-19 either have been asymptomatic or have presented with mild illness, and very few have required hospitalization.[1-3]. The severity of COVID-19 generally correlates with the magnitude of host immune responses against SARS-CoV-2,7,8 children and adolescents with mild or asymptomatic SARS-CoV-2 infection can mount robust and durable antibody responses.[9]. Immunity to SARS-CoV-2 induced through natural infection is likely to be mediated by a combination of humoral and cellular immunity.[10-12]. The immune correlates of protection against SARS-CoV-2 have not been identified, neutralizing antibodies are increasingly recognized as the primary mediator of protection.[17-19]. Most adults (>90%) infected with SARS-CoV-2 mount an immunoglobulin G (IgG) response,[20,21] which can persist for at least 12 months.[22]. The proportion of children infected with SARS-CoV-2 with seroconversion is unknown, among those with asymptomatic or mild infection Seropositive recovered adults are estimated to have as much as 89% protection from reinfection against the same strain.[23,24] In contrast, the proportion of children infected with SARS-CoV-2 with seroconversion is unknown, among those with asymptomatic or mild infection
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