A longitudinal study of antibody responses to endemic HCoV and novel SARS-CoV-2 among mother-child pairs in Zambia

Abstract

Background: Seroprevalence estimates of endemic human coronaviruses (HCoV) and novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are limited in Zambia. Information on development of acquired immunity to endemic HCoV in early life is also scarce and the potential cross-protective effect of HCoV immunity on SARS-CoV-2 remains debatable. We investigated seroprevalence of endemic HCoV in mother-child dyads and SARS-CoV-2 in children and explored the association between HCoV and SARS-CoV-2 antibodies in children to elucidate coronavirus seroepidemiology in Zambia.

Methods: We measured endemic HCoV NL63, 229E, OC43 and HKU1 and SARS-CoV-2 Spike protein subunit 1 (S1) specific immunoglobulin G (IgG) using an immunoassay. We tested plasma samples collected from Zambian mother-child dyads before the coronavirus disease 2019 pandemic in 2018 and 2019, and during the pandemic in 2020 and 2021. We determined HCoV S1 IgG seropositivity in mothers and children and SARS-CoV-2 S1 IgG seropositivity in children. We correlated HCoV antibodies in the mother-child pairs and longitudinally profiled HCoV antibodies in children to investigate development of HCoV immunity and contribution of maternal immunity. We compared child HCoV S1 IgG and SARS-CoV-2 S1 IgG antibodies before and during the pandemic to explore cross-reactivity.

Results: HCoV and SARS-CoV-2 S1 IgG antibodies were detected among mothers and children. Child HCoV seroconversion occurred following waning of maternal immunity but there was no significant correlation between HCoV and SARS-CoV-2 S1 IgG before and during the pandemic. A rise in SARS-CoV-2 S1 IgG seroprevalence among children was observed following the second and third epidemic waves of the COVID-19 pandemic in Zambia.

Conclusions: Endemic HCoV NL63, 229E, OC43 and HKU1 widely circulated and are acquired early in Zambia. SARS-CoV-2 seroprevalence in children speaks to the susceptibility of this population to infection that necessitates their inclusion in control measures.

Keywords: Antibody; Child; Coronavirus; HCoV; SARS-CoV-2; Zambia.

Fig. 1

Study sampling schema. Illustration of the timepoints of plasma sampling from mothers and children under the parent rotavirus trial that were utilised for the nested longitudinal study. Created with BioRender.com

Fig. 2

Participant flow chart. Illustration of the selection process for participants included in the study and plasma used in the laboratory analysis from a population of mother-child pairs enrolled in the parent rotavirus vaccine clinical trial

Fig. 3

Seroprevalence of endemic HCoV. Percentage of S1 IgG seropositivity against HCoV-NL63, HCoV-229E, HCoV-OC43 and HCoV-HKU1 in mothers at baseline and among children (n = 134) at ages 6–12 weeks (baseline), 14–20 weeks, 9 months, 12 months and 24 months. The percentage of S1 IgG seropositive individuals out of total number tested at each timepoint are plotted as bars for each HCoV type

Fig. 4

Association of HCoV S1 IgG antibody titres in mothers and children at baseline. Spearman correlation coefficient (r_s) and statistical significance of the relationship between mother and child HCoV-NL63 (A), HCoV-229E (B), HCoV-OC43 (C) and HCoV-HKU1 (D) S1 IgG titres at baseline are shown. Each datapoint represents the HCoV specific S1 IgG titre in relative absorbance units in mother-child pairs

Fig. 5

Trajectory of S1 IgG titres against the endemic HCoV in children. Individual level trends of S1 IgG titres against HCoV-NL63 (A), HCoV-229E (B), HCoV-OC43 (C) and HCoV-HKU1 (D) in children within the first two years of life. Connected datapoints represent the trajectory of HCoV-specific S1 IgG antibody titres measured in relative absorbance units (rAU) for a single child among children that had data available at all five sampling timepoints (n = 134). Horizontal line at each timepoint indicates calculated cut-off value for seropositivity

Fig. 6

Correlation between HCoV and SARS-CoV-2 S1 IgG titres. Correlation matrix and Spearman correlation coefficients of HCoV and SARS-CoV-2 S1 IgG titres measured in relative absorbance units among children at 6–12 weeks old before the pandemic (A, n = 148) and at 24 months old during the pandemic (B, n = 146)