Plasma IgG binding to SARS-CoV-2 peptides spanning the SARS-CoV-2 spike protein (( B) S1 and ( C) S2 subunits 12-mer overlapping peptides). The numbers above each antigen are the numbers of individuals above the determined threshold. The dashed line indicates a threshold determined by the sum of the mean and standard deviation for the negative control (beads without antigen). Each dot represents an individual in three groups: SARS-CoV-2 convalescent adults (left, n = 44), adults with no prior SARS-CoV-2 infection (middle, n = 44), and pediatric individuals with no prior SARS-CoV-2 (right, n = 866). The median fluorescence intensity (MFI) is shown, and background well subtraction was used to remove nonspecific signals. ( A) Multiplex bead-based antibody binding assay to measure the IgG antibody response to four SARS-CoV-2 viral antigens (S1, S2, RBD, and NP). Levels of SARS-CoV-2 antibodies in adults and children without prior infection were, on average, an order of magnitude lower than those soon after natural infection. Preexisting immunity to the S1 antigen was rarely detectable (1 adult and 3 children Fig. Forty-one of the 44 adults and 57 of the 86 children without prior SARS-CoV-2 infection had detectable IgG antibodies against the SARS-CoV-2 spike S2 subunit 41 and 46 adults and children had detectable antibodies targeting NP (Fig. 5, 6 Therefore, we also determined IgG antibody responses to SARS-CoV-2 in individuals not previously exposed to SARS-CoV-2 using 44 healthy adults recruited in early 2019 and 86 children recruited in 20 prior to the COVID-19 outbreak (Table S2). It has been reported that a subset of children and adults without previous exposure had higher levels of humoral and cellular immunity to SARS-CoV-2, which may influence disease severity. All 44 individuals had detectable IgG antibody responses to the S2 and RBD proteins 38 and 41 of the individuals also had responses to the NP and S1 proteins, respectively (Fig. We defined a detection threshold of 230 MFI (sum of the average and standard deviation of the highest negative control beads without antigen). None of the individuals experienced severe COVID-19 that required hospitalization. We determined IgG antibody responses using a multiplexed fluorescent bead assay that detects levels of antibodies against the SARS-CoV-2 nucleocapsid protein (NP) and three spike protein subunits (S1, S2, and receptor-binding domain (RBD)). First, we used peripheral blood from 44 adults of diverse age, sex, and race/ethnicity who had a positive SARS-CoV-2 PCR test 2–133 days prior to blood sampling (Table S1). Moreover, we mapped antibody epitopes elicited after infection, and cross-reactive antibody epitopes without prior SARS-CoV-2 infection, at high resolution using SARS-CoV-2 spike protein peptide arrays. In this study, we determined antibody responses to SARS-CoV-2 in adults after infection and compared these responses in both children and adults with no prior exposure to SARS-CoV-2. 9 These findings raise the hypothesis that children may have a higher degree of preexisting cross-reactive immunity that provides some level of protection from severe COVID-19. 5, 6, 7, 8 Another study found that children who had never been exposed to SARS-CoV-2 had higher levels of cross-reactive antibodies to the spike glycoprotein subunit S2 of SARS-CoV-2 than adults. 3, 4 It has been reported that a subset of children and adults without previous infection had higher levels of humoral and cellular immunity to SARS-CoV-2, which may influence disease severity. 1, 2 Clinical manifestations of COVID-19 are age dependent, with children appearing to be less vulnerable than adults to severe disease. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel beta-coronavirus that has emerged and caused a global pandemic of coronavirus disease 2019 (COVID-19).
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