DISCUSSION
This study provides a detailed virological and immunological profile of families exposed to SARS-CoV-2 ‘Alpha’ variants in 2020-2021 in a low COVID-19 incidence country, Australia. A key finding was detection of widespread infection with higher secondary attack rates when a comprehensive set of biological specimens were analysed compared with NPS alone. Enhanced plasma antibody levels were observed in individuals from high transmission families compared to low transmission families. We show that SARS-CoV-2 specific salivary antibodies were detected in a high proportion of participants and that antibody features in blood and saliva differ between children and adults.
Whilst new VOC, such as the Delta and Omicron variants, are associated with higher reproductive numbers compared with the ancestral strain16, our data suggests that high levels of household transmission of the ancestral virus are detected when extensive virology and immune assessments are collected. This highlights that dense sampling protocols are more likely to identify infected household members and could be used as a more accurate assessment of secondary attack rate17. With emergence of new VOC, determining the true extent of infection will be important in comparing virulence and transmission dynamics associated with each variant.
In this study, IgA responses in saliva, especially to the SARS-CoV-2 NP antigen, were identified during the acute phase of infection in adults but not in children. Interestingly, elevated antibody responses to NP were observed in both adult saliva and plasma. Previous studies have demonstrated that SARS-CoV-2 NP is highly cross-reactive with NP from other human coronaviruses, thus cross-reactive antibodies are more rapidly induced upon SARS-CoV-2 exposure within the blood, especially amongst adults and elderly in comparison to children due to pre-existing memory18, 19, 20. Our study suggests that this cross-reactive antibody priming occurs for both mucosal and systemic antibody responses.
Like other studies, we identified prolonged faecal shedding beyond respiratory sample detection 21, 22, 23. Fifteen out of 22 patients in an Italian paediatric cohort had RNA detected in stool at diagnosis, independently from gastrointestinal symptoms. Similarly, prolonged SARS-CoV-2 positivity was detected in a study by Xu et al ., 8 out of 10 children persistently tested positive on rectal swabs even after nasopharyngeal testing was negative24. Stool specimens in this study remained positive when NPS were negative, with a median duration of 14 days (range 10-15) from onset of symptoms compared with 8 days (range 2-17) for NPS, providing an opportunity for diagnosing SARS-CoV-2 beyond the period of acute infection25.
This study has some limitations. Transmission to household contacts was assumed to have occurred within the household, and not due to infections acquired outside the household. This assumption was made due to quarantine rules restricting movement from identification of first positive case, however, a family may have had a shared external exposure. This study includes lineages D.2 and B.1.338, and the applicability of our findings following the emergence of the Delta and Omicron strains with higher transmission rates16 is unclear. Comparative analyses between our data and VOC in the future will be important.