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.