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

Marisol Perez-Toledo; Sian E Faustini; Sian E Jossi; Adrian M Shields; Hari Krishnan Kanthimathinathan; Joel D Allen; Yasunori Watanabe; Margaret Goodall; David C Wraith; Tonny V Veenith; Mark T Drayson; Deepthi Jyothish; Eslam Al-Abadi; Ashish Chikermane; Steven B Welch; Kavitha Masilamani; Scott Hackett; Max Crispin; Barnaby R Scholefield; Adam F Cunningham; Alex G Richter

doi:10.1101/2020.06.05.20123117

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

Marisol Perez-Toledo, Sian E Faustini, Sian E Jossi, Adrian M Shields, Hari Krishnan Kanthimathinathan, Joel D Allen, Yasunori Watanabe, Margaret Goodall, David C Wraith, Tonny V Veenith, Mark T Drayson, Deepthi Jyothish, Eslam Al-Abadi, Ashish Chikermane, Steven B Welch, Kavitha Masilamani, Scott Hackett, Max Crispin, Barnaby R Scholefield, Adam F CunninghamAlex G Richter

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Journal	medRxiv
DOIs	https://doi.org/10.1101/2020.06.05.20123117
Publication status	Published - 7 Jun 2020

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Perez-Toledo, M., Faustini, S. E., Jossi, S. E., Shields, A. M., Kanthimathinathan, H. K., Allen, J. D., Watanabe, Y., Goodall, M., Wraith, D. C., Veenith, T. V., Drayson, M. T., Jyothish, D., Al-Abadi, E., Chikermane, A., Welch, S. B., Masilamani, K., Hackett, S., Crispin, M., Scholefield, B. R., ... Richter, A. G. (2020). Serology confirms SARS-CoV-2 infection in PCR-negative children presenting with Paediatric Inflammatory Multi-System Syndrome. medRxiv. https://doi.org/10.1101/2020.06.05.20123117

@article{9017b3c7442946fca02276559fb4bbee,

title = "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.",

author = "Marisol Perez-Toledo and Faustini, {Sian E} and Jossi, {Sian E} and Shields, {Adrian M} and Kanthimathinathan, {Hari Krishnan} and Allen, {Joel D} and Yasunori Watanabe and Margaret Goodall and Wraith, {David C} and Veenith, {Tonny V} and Drayson, {Mark T} and Deepthi Jyothish and Eslam Al-Abadi and Ashish Chikermane and Welch, {Steven B} and Kavitha Masilamani and Scott Hackett and Max Crispin and Scholefield, {Barnaby R} and Cunningham, {Adam F} and Richter, {Alex G}",

year = "2020",

month = jun,

day = "7",

doi = "10.1101/2020.06.05.20123117",

language = "English",

journal = "medRxiv",

publisher = "Cold Spring Harbor Laboratory Press",

}

Perez-Toledo, M , Faustini, SE, Jossi, SE, Shields, AM, Kanthimathinathan, HK, Allen, JD, Watanabe, Y, Goodall, M, Wraith, DC, Veenith, TV, Drayson, MT, Jyothish, D, Al-Abadi, E, Chikermane, A, Welch, SB, Masilamani, K, Hackett, S, Crispin, M, Scholefield, BR , Cunningham, AF & Richter, AG 2020, 'Serology confirms SARS-CoV-2 infection in PCR-negative children presenting with Paediatric Inflammatory Multi-System Syndrome', medRxiv. https://doi.org/10.1101/2020.06.05.20123117

TY - JOUR

T1 - Serology confirms SARS-CoV-2 infection in PCR-negative children presenting with Paediatric Inflammatory Multi-System Syndrome

AU - Perez-Toledo, Marisol

AU - Faustini, Sian E

AU - Jossi, Sian E

AU - Shields, Adrian M

AU - Kanthimathinathan, Hari Krishnan

AU - Allen, Joel D

AU - Watanabe, Yasunori

AU - Goodall, Margaret

AU - Wraith, David C

AU - Veenith, Tonny V

AU - Drayson, Mark T

AU - Jyothish, Deepthi

AU - Al-Abadi, Eslam

AU - Chikermane, Ashish

AU - Welch, Steven B

AU - Masilamani, Kavitha

AU - Hackett, Scott

AU - Crispin, Max

AU - Scholefield, Barnaby R

AU - Cunningham, Adam F

AU - Richter, Alex G

PY - 2020/6/7

Y1 - 2020/6/7

N2 - 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.

AB - 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.

U2 - 10.1101/2020.06.05.20123117

DO - 10.1101/2020.06.05.20123117

M3 - Article

C2 - 32577677

JO - medRxiv

JF - medRxiv

ER -

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

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