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. 2023 Nov 21;26(12):108500.
doi: 10.1016/j.isci.2023.108500. eCollection 2023 Dec 15.

Serum HCoV-spike specific antibodies do not protect against subsequent SARS-CoV-2 infection in children and adolescents

Helen Ratcliffe  1 , Karen S Tiley  1 , Stephanie Longet  2 , Claire Tonry  3 , Cathal Roarty  3 , Chris Watson  3 , Gayatri Amirthalingam  4 , Iason Vichos  1 , Ella Morey  1 , Naomi L Douglas  1 , Spyridoula Marinou  1 , Emma Plested  1 , Parvinder K Aley  1 , Eva Galiza  5 , Saul N Faust  6   7 , Stephen Hughes  8 , Clare Murray  8   9 , Marion R Roderick  10 , Fiona Shackley  11 , Sam Oddie  12 , Tim W R Lee  13 , David P J Turner  14   15 , Mala Raman  16 , Stephen Owens  17 , Paul J Turner  18 , Helen Cockerill  18 , Jamie Lopez Bernal  4 , Samreen Ijaz  4 , John Poh  4 , Justin Shute  4 , Ezra Linley  4 , Ray Borrow  4 , Katja Hoschler  4 , Kevin E Brown  4 , Miles W Carroll  2 , Paul Klenerman  19   20 , Susanna J Dunachie  20   21 , Mary Ramsay  4 , Merryn Voysey  1 , Thomas Waterfield  3 , Matthew D Snape  1   7   22
Affiliations

Serum HCoV-spike specific antibodies do not protect against subsequent SARS-CoV-2 infection in children and adolescents

Helen Ratcliffe et al. iScience. .

Abstract

SARS-CoV-2 infections in children are generally asymptomatic or mild and rarely progress to severe disease and hospitalization. Why this is so remains unclear. Here we explore the potential for protection due to pre-existing cross-reactive seasonal coronavirus antibodies and compare the rate of antibody decline for nucleocapsid and spike protein in serum and oral fluid against SARS-CoV-2 within the pediatric population. No differences in seasonal coronaviruses antibody concentrations were found at baseline between cases and controls, suggesting no protective effect from pre-existing immunity against seasonal coronaviruses. Antibodies against seasonal betacoronaviruses were boosted in response to SARS-CoV-2 infection. In serum, anti-nucleocapsid antibodies fell below the threshold of positivity more quickly than anti-spike protein antibodies. These findings add to our understanding of protection against infection with SARS-CoV-2 within the pediatric population, which is important when considering pediatric SARS-CoV-2 immunization policies.

Keywords: Health sciences; Immunology; Medical specialty; Medicine; Virology.

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Conflict of interest statement

M.D.S. acted on behalf of the University of Oxford as an investigator on studies funded or sponsored by vaccine manufacturers, including AstraZeneca, GlaxoSmithKline, Pfizer, Novavax, Janssen, Medimmune, and MCM. He received no personal financial payment for this work. Subsequent to this study MDS is employed by Moderna Biotech UK and holds equity in this company. S.N.F. acts on behalf of University Hospital Southampton National Health Service (NHS) Foundation Trust as an investigator or providing consultative advice, or both, on clinical trials and studies of COVID-19 and other vaccines funded or sponsored by vaccine manufacturers including Janssen, Pfizer, AstraZeneca, GlaxoSmithKline, Novavax, Seqirus, Sanofi, Medimmune, Merck, and Valneva. He receives no personal financial payment for this work. M.R. has provided post-marketing surveillance reports on vaccines for Pfizer and GlaxoSmithKline for which a cost recovery charge is made. All other authors declare no competing interests. M.C. and S.L. are funded by US Food and Drug Administration Medical Countermeasures Initiative, contract 75F40120C00085.

Figures

None
Graphical abstract
Figure 1
Figure 1
Timeline of SARS-CoV-2 variants circulating within the UK up until July 2021, adapted to show recruitment periods for “STORY” and “COVID Warrior” studies This figure was produced by my world data and licensed under CC BY.
Figure 2
Figure 2
A comparison of seropositive (red), seronegative (blue), and pre-pandemic (black) samples (positivity defined by the original study assays) tested using the MSD platform Mann–Whitney U test was used to compare between groups. A value of p<0.01 were considered statistically significant. The threshold of positivity is shown by a solid line (adult cut-off) and dashed line (pediatric cut-off).
Figure 3
Figure 3
A matched case-control analysis (positivity defined by original study assays) tested on the MSD platform Mann–Whitney U test was used to compare between groups. A value of p < 0.01 were considered statistically significant. The threshold of positivity is shown by a solid line (adult cut-off) and dashed line (pediatric cut-off).
Figure 4
Figure 4
IgG serum antibody concentrations over time Figure shows results of serological testing for (A) Roche Elecsys® Anti-SARS-CoV-2 IgG spike antibody persistence over time. (B) Roche Elecsys® Anti-SARS-CoV-2 IgG nucleocapsid antibody persistence over time. Time-point 0 is defined as the participant’s first positive result (A and B). (C) Roche Elecsys® Anti-SARS-CoV-2 IgG spike antibody persistence over time d. Roche Elecsys® Anti-SARS-CoV-2 IgG nucleocapsid antibody persistence over time. Time-point 0 is defined as the participant’s highest positive result (C and D). Figures (A–D) are broken down into age groups. Figures (E and F) show a mixed regression model predicting the adjusted means with time point 0 being the highest positive result with individual participant's serum antibody concentrations over time marked with (x) for Roche Elecsys® Anti-SARS-CoV-2 IgG spike antibodies (A) and Roche Elecsys® Anti-SARS-CoV-2 IgG nucleocapsid antibodies (B). 95% confidence intervals are shown. The threshold of positivity is indicated by the red line on each plot.
Figure 5
Figure 5
A comparison of IgG antibody concentration in oral fluid and serum samples over time (A–D) Shows both oral fluid (red) and corresponding serum samples where available (blue). (A and B) Where timepoint 0 is defined as the first positive oral fluid result for spike protein (A) and nucleocapsid (B). (C and D) Define time-point 0 as the highest positive oral fluid result for spike protein (C) and nucleocapsid (D). The threshold of positivity is marked by the dashed line (OF) and solid line (serum). These thresholds overlap on nucleocapsid plots. (E and F) Shows a mixed regression model for oral fluid predicting the adjustment means with time point 0 being highest positive result with individual participants antibody concentrations over time marked with (x) for anti-spike protein (E) and anti-nucleocapsid antibodies (F). 95% confidence intervals shown. The threshold of positivity indicated by the red line on each plot.
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References

    1. Warner S., Richter A., Stamataki Z., Kelly D. Understanding COVID-19: are children the key? BMJ Paediatr. Open. 2021;5 - PMC - PubMed
    1. Kang C.K., Shin H.M., Park W.B., Kim H.R. Why are children less affected than adults by severe acute respiratory syndrome coronavirus 2 infection? Cell. Mol. Immunol. 2022;19:555–557. - PMC - PubMed
    1. Balasubramanian S., Rao N.M., Goenka A., Roderick M., Ramanan A.V. Coronavirus Disease 2019 (COVID-19) in Children - What We Know So Far and What We Do Not. Indian Pediatr. 2020;57:435–442. - PMC - PubMed
    1. Dowell A.C., Butler M.S., Jinks E., Tut G., Lancaster T., Sylla P., Begum J., Bruton R., Pearce H., Verma K., et al. Children develop robust and sustained cross-reactive spike-specific immune responses to SARS-CoV-2 infection. Nat. Immunol. 2022;23:40–49. - PMC - PubMed
    1. Edridge A.W.D., Kaczorowska J., Hoste A.C.R., Bakker M., Klein M., Loens K., Jebbink M.F., Matser A., Kinsella C.M., Rueda P., et al. Seasonal coronavirus protective immunity is short-lasting. Nat. Med. 2020;26:1691–1693. - PubMed

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