A post-acute pandemic phase systematic review and meta-analysis of first few X cases (FFX) and household transmission investigations (HHTIs) indicates a need for better standardization in how these investigations are planned, conducted and reported to guide evidence-based pandemic preparedness and response efforts for SARS-CoV-2, the next influenza pandemic and future novel respiratory viruses.
Standardized protocols for SARS-CoV-2 sero-epidemiological investigations, including for first few X cases (FFX) and household transmission investigations (HHTI), are provided by the Unity Studies as part of Pandemic Special Studies (PSS) for pan-respiratory viruses. Developed by WHO and partners, these protocols can be adapted to any resource setting to collect robust data on a pandemic and inform an evidence-based response.
In April 2022, the WHO in partnership with the University of Melbourne and the Unity Studies Collaborator Group published a systematic review and meta-analysis of FFX and HHTIs for SARS-CoV-2. It was designed to estimate the household secondary attack rate (hSAR) of SARS-CoV-2 in studies published between January 2020 and July 2021 that align with the Unity Studies HHTI protocol.
We found hSAR estimates vary substantially between investigations (2%–90% (95% prediction interval: 3%–71%; I2=99.7%). This was expected given that settings also vary, for example in epidemic phase, local response, and differences in what a household represents in different cultural settings . But further sub-group analyses of likely sources of variability could not explain the differences and therefore pooled estimates were not reported.
This large and unexplained variance in hSAR estimates indicates a need for improved standardization in how HHTIs for SARS-CoV- are planned, conducted and analysed. Clearer and more comprehensive reporting of HHTIs, and the context in which they are conducted, is also required to enable a more nuanced analysis of the sources of variability in results.
Standardized FFX and HHTIs provide critical epidemiological tools for monitoring transmission dynamics, infection-severity, and population immunity to novel infectious pathogens, including influenza and other respiratory viruses and including the emergence of new genetic variants or lineages.. The data generated are crucial to inform ongoing and future responses across resource settings, including the use of different public health and social measures and the allocation of pandemic resources like vaccines.
As part of Pandemic Special Studies (PSS), the FFX and HHTI protocols will be updated for pandemic influenza and other novel respiratory viruses. Other planned next steps include developing a reporting guideline and checklist for FFX/HHTIs and a toolkit to support better standardisation and quality of studies, and to enable the timley sharing of results. WHO will continue to advocate for long-term investment in resilient surveillance systems including the design of country-specific pre-planned “sleeping” FFX and HHTIs which are exercised in inter-pandemic periods. In this way, countries will be better prepared to undertake special investigations and operational research to guide evidence-based response efforts when the next pandemic strikes.