Humoral immune response to SARS-CoV-2 and endemic coronaviruses in urban and indigenous children in Colombia

Abstract

Background: Although anti-SARS-CoV-2 humoral immune responses and epidemiology have been extensively studied, data gaps remain for certain populations such as indigenous people or children especially in low- and middle-income countries. To address this gap, we evaluated SARS-CoV-2 seroprevalence and humoral immunity towards the parental B.1 strain, local SARS-CoV-2 variants, and endemic coronaviruses in children from Colombia from March to April 2021.

Methods: We performed a cross-sectional seroprevalence study with 80 children from Bogotá and expanded our analysis by comparing results with an independent observational study of 82 children from the Wiwa community living in the north-eastern Colombian territories. Antibody IgG titers towards SARS-CoV-2 and the endemic coronaviruses as well as ACE2 binding inhibition as a proxy for neutralization towards several SARS-CoV-2 variants were analyzed using two multiplex-based immunoassays.

Results: While we find seroprevalence estimates of 21.3% in children from Bogotá, seroprevalence is higher with 34.1% in Wiwa children. We observe a robust induction of antibodies towards the surface-exposed spike protein, its S1-, S2- and receptor-binding-subdomains in all SARS-CoV-2 seropositive children. Only nucleocapsid-specific IgG is significantly lower in the indigenous participants. ACE2 binding inhibition is low for all SARS-CoV-2 variants examined. We observe a dominance of NL63 S1 IgG levels in urban and indigenous children which suggests an early exposure to this respiratory virus independent of living conditions and geographic location. SARS-CoV-2 seropositivity does not correlate with antibody levels towards any of the four endemic coronaviruses indicating the absence of cross-protective immunity.

Conclusions: Overall, antibody titers, but in particular ACE2 binding inhibition are low within Colombian samples, requiring further investigation to determine any potential clinical significance.

Fig. 1. Antigenic characterization of SARS-CoV-2 antibody responses in urban and indigenous children.

IgG responses of sera samples collected in March and April 2021 were measured using MULTICOV-AB towards the spike B.1 (a), the RBD B.1 (b), the S1 B.1 subdomain (c), the S2 B.1 subdomain (d), and the nucleocapsid B.1 antigen (e) of SARS-CoV-2. Data is expressed as normalized MFI ratio for seropositive urban children (n = 17, blue) and seropositive indigenous children (n = 28, yellow). Seropositivity is defined as a dual cut-off of spike and RBD S/CO ≥ 1.0. Boxes represent the median and the 25th and 75th percentiles. Whiskers show the largest and smallest non-outliers values. Outliers were identified using upper/lower quartiles 1.5 ± times IQR. Means of two population groups were compared with the Wilcoxon’s ranked sum test. Statistical significance was defined as p < 0.05.

Fig. 2. Humoral immune response towards endemic coronaviruses according to SARS-CoV-2 serostatus in urban and indigenous children.

Humoral IgG responses of urban (n = 80) and indigenous children (n = 82) towards the spike S1 subdomain of OC43 (a), HKU1 (b), NL63 (c), and 229E (d) are split based on SARS-CoV-2 serostatus. Box and whisker plots represent the median, 25th and 75th percentiles. Whiskers show the largest and smallest non-outliers values. Outliers were identified using upper/lower quartile 1.5 ± times IQR. Statistical significance was defined as p < 0.05 using the Wilcoxon’s ranked sum test.

Fig. 3. Correlation of IgG binding and ACE2 binding inhibition for the SARS-CoV-2 B.1 RBD.

Correlation analysis of ACE2 binding inhibition and IgG binding from sera samples of children from urban Bogotá (n = 80, blue) and from the indigenous Wiwa (n = 82, yellow) was performed for the RBD of the B.1 isolate. Correlation analysis was performed across all samples. The resulting Spearman’s coefficient is shown in the upper left quadrant. Dashed lines indicate the ACE2 responder threshold of 20% and the S/CO of 1 for the RBD B.1 antigen.