First Few X cases (FFX) investigations and Household transmission investigations (HHTI) are essential epidemiological tools for early characterisation of novel infectious pathogens and their variants. We aimed to estimate the household secondary infection attack rate (hSAR) of SARS-CoV-2 in investigations aligned with the WHO Unity Studies HHTI protocol. We conducted a systematic review and meta-analysis according to PRISMA 2020 guidelines (PROSPERO registration: CRD42021260065).
We searched Medline, Embase, Web of Science, Scopus and medRxiv/bioRxiv for Unity-aligned FFX and HHTI published between 1 December 2019 and 26 July 2021. Standardised early results were shared by WHO Unity Studies Collaborators (to 1 October 2021). We used a bespoke tool to assess investigation methodological quality. Values for hSAR and 95% confidence intervals (CIs) were extracted or calculated from crude data. Heterogeneity was assessed by visually inspecting overlap of CIs on forest plots and quantified in meta-analyses.
Of 9988 records retrieved, 80 articles (64 from databases; 16 provided by WHO Unity Studies collaborators) were retained in the systematic review and 62 were included in the primary meta-analysis.
hSAR point estimates ranged from 2%-90% (95% prediction interval: 3%-71%; I2 = 99.7%); I2 values remained >99% in subgroup analyses, indicating high, unexplained heterogeneity and leading to a decision not to report pooled hSAR estimates.
The large, unexplained variance in hSAR estimates emphasises the need for improved standardisation in planning, conduct and analysis, and for clear and comprehensive reporting of FFX and HHTIs, to guide evidence-based pandemic preparedness and response efforts for SARS-CoV-2, influenza and future novel respiratory viruses.
Household transmission investigations (HHTI) contribute timely epidemiologic knowledge in response to emerging pathogens. HHTIs conducted in the context of the COVID-19 pandemic in 2020-21 reported variable methodological approaches, producing epidemiological estimates that vary in meaning, precision, and accuracy. Since specific tools to assist with the optimal design and critical appraisal of HHTIs are not available, the aggregation and pooling of HHTI to inform policy and interventions may be challenging. In this manuscript, we discuss key aspects of the HHTI design, we provide recommendations for the reporting of these studies, and propose an appraisal tool that contributes to the optimal design and critical appraisal of HHTI studies. The appraisal tool consists of 12 questions that explore 10 aspects of HHTIs and can be answered ‘yes’, ‘no’ or ‘unclear’. The manuscript seeks to fill a gap in the epidemiologic literature and contribute to standardise HHTI approaches across settings, to achieve richer and more informative datasets. The manuscript also calls for a periodic revision of HHTI protocols and critical appraisal tools
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