Serology confirms SARS-CoV-2 infection in PCR-negative children presenting with Paediatric Inflammatory Multi-System Syndrome

Abstract

Background: During the COVID-19 outbreak, reports have surfaced of children who present with features of a multisystem inflammatory syndrome with overlapping features of Kawasaki disease and toxic shock syndrome - Paediatric Inflammatory Multisystem Syndrome- temporally associated with SARS-CoV-2 pandemic (PIMS-TS). Initial reports find that many of the children are PCR-negative for SARS-CoV-2, so it is difficult to confirm whether this syndrome is a late complication of viral infection in an age group largely spared the worst consequences of this infection, or if this syndrome reflects enhanced surveillance.

Methods: Children hospitalised for symptoms consistent with PIMS-TS between 28 April and 8 May 2020, and who were PCR-negative for SARS-CoV-2, were tested for antibodies to viral spike glycoprotein using an ELISA test.

Results: Eight patients (age range 7-14 years, 63% male) fulfilled case-definition for PIMS-TS during the study period. Six of the eight patients required admission to intensive care. All patients exhibited significant IgG and IgA responses to viral spike glycoprotein. Further assessment showed that the IgG isotypes detected in children with PIMS-TS were of the IgG1 and IgG3 subclasses, a distribution similar to that observed in samples from hospitalised adult COVID-19 patients. In contrast, IgG2 and IgG4 were not detected in children or adults. IgM was not detected in children, which contrasts with adult hospitalised adult COVID-19 patients of whom all had positive IgM responses.

Conclusions: Strong IgG antibody responses can be detected in PCR-negative children with PIMS-TS. The low detection rate of IgM in these patients is consistent with infection having occurred weeks previously and that the syndrome onset occurs well after the control of SARS-CoV-2 viral load. This implies that the disease is largely immune-mediated. Lastly, this indicates that serology can be an appropriate diagnostic tool in select patient groups.

Figure 1.. Detection of anti-SARS-CoV-2 antibody responses in children with PIMS-TS.

Serological responses were detected against purified near-full-length trimeric SARS-CoV-2 viral spike glycoprotein by ELISA. A) Absorbance values of individual sera at a single dilution (1:40) from pre-2019 healthy adult donors (green) or sera from children with PIMS-TS (red), or plasma from adult ITU patients (orange) detected using combined HRP-labelled anti-IgG, IgA and IgM. One symbol represents results for a single serum and the bar shows the median values for each group. B) Absorbance values for individual sera from pre-2019 negative control donors (green), children with PIMS-TS (red), or plasma from adult ITU patients (orange) serially diluted five-fold from 1:50, primary antibodies were detected using HRP-labelled anti-IgG, IgA or IgM individually, or C) HRP-labelled IgG1 or IgG3.