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Virology and immune dynamics reveal high household transmission of ancestral SARS-CoV-2 strain
  • +28
  • Shidan Tosif,
  • Ebene R. Haycroft,
  • Sohinee Sarkar,
  • Zheng Quan Toh,
  • Do Lien Anh-ha,
  • Celeste M. Donato,
  • Kevin J. Selva,
  • Monsurul Hoq,
  • Isabella Overmars,
  • Jill Nguyen,
  • Lai-Yang Lee,
  • Vanessa Clifford,
  • Andrew Daley,
  • Francesa L. Mordant,
  • Jodie McVernon,
  • Kim Mulholland,
  • Adrian Marcato,
  • Miranda Smith,
  • Nigel Curtis,
  • Sarah McNab,
  • Richard Saffery,
  • Katherine Kedzierska,
  • Kanta Subarrao,
  • David Burgner,
  • Andrew Steer,
  • Julie E. Bines,
  • Philip Sutton,
  • Paul Licciardi,
  • Amy W. Chung,
  • Melanie Neeland,
  • Nigel W. Crawford
Shidan Tosif
Department of Paediatrics The University of Melbourne

Corresponding Author:shidan.tosif@rch.org.au

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Ebene R. Haycroft
The Peter Doherty Institute for Infection and Immunity
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Sohinee Sarkar
Department of Paediatrics The University of Melbourne
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Zheng Quan Toh
Department of Paediatrics The University of Melbourne
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Do Lien Anh-ha
Department of Paediatrics The University of Melbourne
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Celeste M. Donato
Department of Paediatrics The University of Melbourne
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Kevin J. Selva
The Peter Doherty Institute for Infection and Immunity
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Monsurul Hoq
Murdoch Children's Research Institute
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Isabella Overmars
Murdoch Children's Research Institute
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Jill Nguyen
Murdoch Children's Research Institute
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Lai-Yang Lee
The Royal Children's Hospital Melbourne
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Vanessa Clifford
Department of Paediatrics The University of Melbourne
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Andrew Daley
The Royal Children's Hospital Melbourne
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Francesa L. Mordant
The Peter Doherty Institute for Infection and Immunity
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Jodie McVernon
The Peter Doherty Institute for Infection and Immunity
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Kim Mulholland
Department of Paediatrics The University of Melbourne
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Adrian Marcato
The Peter Doherty Institute for Infection and Immunity
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Miranda Smith
The Peter Doherty Institute for Infection and Immunity
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Nigel Curtis
Department of Paediatrics The University of Melbourne
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Sarah McNab
Department of Paediatrics The University of Melbourne
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Richard Saffery
Department of Paediatrics The University of Melbourne
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Katherine Kedzierska
The Peter Doherty Institute for Infection and Immunity
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Kanta Subarrao
The Peter Doherty Institute for Infection and Immunity
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David Burgner
Department of Paediatrics The University of Melbourne
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Andrew Steer
Department of Paediatrics The University of Melbourne
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Julie E. Bines
Department of Paediatrics The University of Melbourne
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Philip Sutton
Department of Paediatrics The University of Melbourne
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Paul Licciardi
Department of Paediatrics The University of Melbourne
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Amy W. Chung
The Peter Doherty Institute for Infection and Immunity
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Melanie Neeland
Department of Paediatrics The University of Melbourne
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Nigel W. Crawford
Department of Paediatrics The University of Melbourne
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Abstract

Background Household studies are crucial for understanding the transmission of SARS-CoV-2 infection, which may be underestimated from PCR testing of respiratory samples alone. We aim to combine assessment of household mitigation measures; nasopharyngeal, saliva and stool PCR testing; along with mucosal and systemic SARS-CoV-2 specific antibodies, to comprehensively characterise SARS-CoV-2 infection and transmission in households. Methods Between March and September 2020, we obtained samples from 92 participants in 26 households in Melbourne, Australia, in a 4-week period following onset of infection with ancestral SARS-CoV-2 variants. Results The secondary attack rate was 36% (24/66) when using nasopharyngeal swab (NPS) PCR positivity alone. However, when respiratory and non-respiratory samples were combined with antibody responses in blood and saliva, the secondary attack rate was 76% (50/66). SARS-CoV-2 viral load of the index case and household isolation measures were key factors that determine secondary transmission. In 27% (7/26) of households, all family members tested positive by NPS for SARS-CoV-2 and were characterised by lower respiratory Ct-values than low transmission families (Median 22.62 vs 32.91; IQR 17.06 to 28.67 vs 30.37 to 34.24). High transmission families were associated with enhanced plasma antibody responses to multiple SARS-CoV-2 antigens and the presence of neutralising antibodies. Three distinguishing saliva SARS-CoV-2 antibody features were identified according to age (IgA1 to Spike 1, IgA1 to nucleocapsid protein (NP), suggesting that adults and children generate distinct mucosal antibody responses during the acute phase of infection. Conclusion Utilising respiratory and non-respiratory PCR testing, along with measurement of SARS-CoV-2 specific local and systemic antibodies, provides a more accurate assessment of infection within households and highlights some of the immunological differences in response between children and adults.
01 Apr 2022Submitted to Pediatric Allergy and Immunology
04 Apr 2022Reviewer(s) Assigned
19 Apr 2022Review(s) Completed, Editorial Evaluation Pending
21 Apr 2022Editorial Decision: Revise Major
30 May 20221st Revision Received
02 Jun 2022Review(s) Completed, Editorial Evaluation Pending
07 Jun 2022Editorial Decision: Accept
Jul 2022Published in Pediatric Allergy and Immunology volume 33 issue 7. 10.1111/pai.13824