292 - Antibody Seronegativity in COVID-19 RT-PCR-Positive Children

Poster Number: 292
Publication Number: 292.215

Maala Bhatt, University of Ottawa Faculty of Medicine, Ottawa, ON, Canada; Roger Zemek, University of Ottawa, Children's Hospital of Eastern Ontario, Ottawa, ON, Canada; Ken Tang, n/a, Richmond, BC, Canada; Amy C. Plint, University of Ottawa, Ottawa, ON, Canada; Richard Malley, Boston Children's Hospital, Boston, MA, United States; Anne Pham-Huy, University of Ottawa Faculty of Medicine, Ottawa, ON, Canada; jennifer Dawson, Children's Hospital of Eastern Ontario Research Institute, Ottawa, ON, Canada; Candice McGahern, CHEO, Ottawa, ON, Canada; Marc-Andre Langlois, University of Ottawa, Ottawa, ON, Canada; Corey R. Arnold, University of Ottawa, Ottawa, ON, Canada; Kiran Nakka, University of Ottawa Faculty of Medicine, Ottawa, ON, Canada

Background: The gold standard for diagnosing acute symptomatic and asymptomatic COVID-19 infection is SARS-CoV-2 gene detection via nucleic acid amplification testing (e.g. RT-PCR). SARS-CoV-2-specific antibodies (seroconversion) are detectable 5-days post-symptom onset (IgM) and can remain detectable at least 12-months post-infection (IgG). However, not all infected individuals seroconvert; disease severity, symptoms, and viral load may affect antibody response, and the response may differ between children and adults.

Objective:
To determine the frequency of non-seroconversion in SARS-CoV-2 RT-PCR-positive individuals and examine factors associated with non-seroconversion.

Design/Methods: We conducted a secondary analysis of a prospective case-ascertained study of household COVID-19 transmission in Ottawa, Canada, from Sept 2020 to Mar 2021. Participants with a positive COVID-19 RT-PCR test were included in this sub-study; vaccinated individuals were excluded. Participants underwent phlebotomy for SARS-CoV-2-specific antibodies at least 2-weeks after diagnosis. Automated ELISA assays evaluated SARS-CoV-2-specific IgA, IgM and IgG against the spike-trimer (S) and nucleocapsid (N) protein. This validated serology platform has a sensitivity and specificity of >98%. Individual isotopes were considered positive when both anti-S and anti-N antibodies were above cut-off values (S/CO >=1). Samples were defined as SARS-CoV-2-antibody-positive when IgG was positive, or if both IgA and IgM were positive.

Results: 332 RT-PCR-positive participants (161 children, 171 adults) completed blood sampling for SARS-CoV-2 antibodies. 43 (13%, 95%CI:9.7,17.0) individuals did not seroconvert. Seroconversion was less common in children (27/161, 17%) vs. adults (16/171, 9%); p=0.04. All hospitalized participants (10/332, 3%) seroconverted. Seroconversion was not associated with time since infection (≤30d vs >30d) (OR=0.9; 95%CI:0.4,1.8). Children 0-3 years had lower odds of seroconversion than older children and adults (Fig 1). Symptom count was not associated with seroconversion. Fever/chills was associated with increased seroconversion (OR=0.4; 95%CI:0.2,0.9). Rhinorrhea when it was the only symptom trended toward non-seroconversion (OR=3.1; 95%CI:0.6,15.2).Conclusion(s): Overall 17% of children did not seroconvert following COVID-19 infection. Children were less likely to develop antibodies than adults. Apart from fever/chills and rhinorrhea-only, individual symptoms did not strongly predict non-seroconversion. Public health messaging should inform populations that seroconversion is not always detected, even after symptomatic infection.
Figure 1. Risk factors associated with non-seroconversionSlide1.jpeg