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

Citation

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

Pediatric Allergy and Immunology, published online 11 July 2022, 33:e13824. DOI: https://doi.org/10.1111/pai.13824

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.

Key Message

When respiratory and nonrespiratory samples were combined with antibody responses in blood and saliva, a much higher secondary attack rate of SARS-CoV-2 in households was identified. Lower viral load and mitigation measures reduced transmission. Saliva and serum antibody analyses show differences in immune responses between adults and children.

Related Research Areas

  • Public health research