Comparison of Seroconversion in Children and 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 nonhospitalized children and adults with mild SARS-CoV-2 infection and identify factors that are associated with seroconversion.

Design, setting, and participants: 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.

Main outcomes and measures: 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.

Results: 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.

Conclusions and relevance: 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.

Figure 1.. SARS-CoV-2 Antibody Response in Children and Adults Measured by 3 Serological Assays

Assays include SARS-CoV-2 S1/S2 immunoglobulin G (DiaSorin), an antibody enzyme-linked immunosorbent assay (ELISA) (Beijing Wantai Biological Pharmacy Enterprise Co, Ltd [Wantai]), and an in-house ELISA. Immunoglobulin G SARS-CoV-2 antibody levels are expressed as means; error bars indicate 95% CIs. Acute levels were measured at a median of 7-12 (IQR, 4-13) days in 14 children and 17 adults. Convalescent levels were measured at a median of 41 (IQR, 31-49) days in 57 children and 51 adults. AU indicates assay units.

Figure 2.. SARS-CoV-2 Immunoglobulin G Seropositivity Rate in Children and Adults at Convalescent Period Measured by 3 Serological Assays

Assays include SARS-CoV-2 S1/S2 immunoglobulin G assay (DiaSorin), an antibody enzyme-linked immunosorbent assay (ELISA) (Beijing Wantai Biological Pharmacy Enterprise Co, Ltd [Wantai]), and an in-house ELISA. Convalescent period was a median of 41 (IQR, 31-49) days.

Figure 3.. Factors Associated With SARS-CoV-2 Antibody Responses Based on In-House Enzyme-Linked Immunosorbent Assay (ELISA)

A, Seropositivity rate in children and adults at convalescent period (median, 41 [IQR, 31-49] days) in 54 children and 42 adults who were seropositive and seronegative by all 3 serological assays. B, Mean (SD) viral load in 42 children and 18 adults with data available. C, Mean (SD) viral load in 42 children and 18 adults stratified by serostatus. D, Proportion of asymptomatic children and adults stratified by serostatus. Ct indicates cycle threshold.

Figure 4.. Ex Vivo Cellular Immune Profile During Convalescence Period

Among children, 14 had positive polymerase chain (PCR-positive)/seronegative findings; 13, PCR-positive/seropositive findings. Among adults, 4 had PCR-positive/seronegative findings; 15, PCR-positive/seropositive findings. An uninfected control group (PCR-negative/seronegative findings) of 11 children and 22 adults was included for comparison. Bars represent the median; error bars represent the range. IgG indicates immunoglobulin G.