Virology and immune dynamics reveal high household transmission of ancestral SARS-CoV-2 strain

Shidan Tosif; Ebene R Haycroft; Sohinee Sarkar; Zheng Quan Toh; Lien Anh Ha Do; 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 J Marcato; Miranda Z Smith; Nigel Curtis; Sarah McNab; Richard Saffery; Katherine Kedzierska; Kanta Subarrao; David Burgner; Andrew Steer; Julie E Bines; Philip Sutton; Paul V Licciardi; Amy W Chung; Melanie R Neeland; Nigel W Crawford

doi:10.1111/pai.13824

Virology and immune dynamics reveal high household transmission of ancestral SARS-CoV-2 strain

Pediatr Allergy Immunol. 2022 Jul;33(7):10.1111/pai.13824. doi: 10.1111/pai.13824.

Authors

Shidan Tosif^{1

2

3}, Ebene R Haycroft⁴, Sohinee Sarkar^{1

2}, Zheng Quan Toh^{1

2}, Lien Anh Ha Do^{1

2}, Celeste M Donato^{1

2}, Kevin J Selva⁴, Monsurul Hoq⁵, Isabella Overmars², Jill Nguyen², Lai-Yang Lee⁶, Vanessa Clifford^{1

2

6

7}, Andrew Daley⁶, Francesa L Mordant⁴, Jodie McVernon⁸, Kim Mulholland^{1

2}, Adrian J Marcato⁸, Miranda Z Smith⁸, Nigel Curtis^{1

2

7}, Sarah McNab^{1

2

3}, Richard Saffery^{1

2}, Katherine Kedzierska⁴, Kanta Subarrao^{4

9}, David Burgner^{1

2

7}, Andrew Steer^{1

2

7}, Julie E Bines^{1

2

10}, Philip Sutton^{1

2}, Paul V Licciardi^{1

2}, Amy W Chung⁴, Melanie R Neeland^{1

2}, Nigel W Crawford^{1

2

3}

Affiliations

¹ Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia.
² Infection and Immunity, Murdoch Children's Research Institute, Parkville, Victoria, Australia.
³ Department of General Medicine, The Royal Children's Hospital Melbourne, Parkville, Victoria, Australia.
⁴ Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, Victoria, Australia.
⁵ Clinical Epidemiology and Biostatistics Unit, Murdoch Children's Research Institute, Parkville, Victoria, Australia.
⁶ Department of Microbiology, The Royal Children's Hospital Melbourne, Parkville, Victoria, Australia.
⁷ Infectious Diseases Unit, The Royal Children's Hospital Melbourne, Melbourne, Victoria, Australia.
⁸ Department of Infectious Diseases, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria, Australia.
⁹ The Peter Doherty Institute for Infection and Immunity, WHO Collaborating Centre for Reference and Research on Influenza, Melbourne, Victoria, Australia.
¹⁰ Department of Gastroenterology and Clinical Nutrition, RCH, Parkville, Victoria, Australia.

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 the assessment of household mitigation measures; nasopharyngeal, saliva, and stool PCR testing; along with mucosal and systemic SARS-CoV-2-specific antibodies, to comprehensively characterize 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 the 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 nonrespiratory 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 characterized by lower respiratory Ct values than low transmission families (Median 22.62 vs. 32.91; IQR 17.06-28.67 vs. 30.37-34.24). High transmission families were associated with enhanced plasma antibody responses to multiple SARS-CoV-2 antigens and the presence of neutralizing 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: Utilizing respiratory and nonrespiratory PCR testing, along with the 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.

Keywords: COVID-19; SARS-CoV-2, household transmission; children; immunology; novel coronavirus.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Antibodies, Viral
COVID-19* / diagnosis
Child
Humans
Immunoglobulin A
SARS-CoV-2*

Substances

Antibodies, Viral
Immunoglobulin A

Supplementary concepts

SARS-CoV-2 variants

Grants and funding

HHSN272201400008C/AI/NIAID NIH HHS/United States