Transmission of SARS-CoV-2 in standardised First Few X cases and household transmission investigations: a systematic review and meta-analysis [preprint]


Hannah C Lewis, Adrian J Marcato, Niamh Meagher, Marta Valenciano, Juan-Pablo Villanueva-Cabezas, Violeta Spirkoska, James E Fielding, Amalia Karahalios, Lorenzo Subissi, Anthony Nardone, Brianna Cheng, Soatiana Rajatonirina, Joseph Okeibunor, Eman A Aly, Amal Barakat, Pernille Jorgensen, Tasnim Azim, Pushpa Ranjan Wijesinghe, Linh-Vi Le, Angel Rodriguez, Andrea Vicari, Maria Van Kerkhove, Jodie McVernon, Richard Pebody, David J Price, Isabel Bergeri, the Unity Studies Collaborator Group

MedRxiv, posted online 15 April 2022. DOI:

We aimed to estimate the household secondary infection attack rate (hSAR) of SARS-CoV-2 in investigations aligned with the WHO Unity Studies Household Transmission Investigations (HHTI) protocol. We conducted a systematic review and meta-analysis according to PRISMA 2020 guidelines.

We searched Medline, Embase, Web of Science, Scopus and medRxiv/bioRxiv for ‘Unity-aligned’ First Few X cases (FFX) and HHTIs 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 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.

FFX and HHTI remain critical epidemiological tools for early and ongoing characterisation of novel infectious pathogens. The large, unexplained variance in hSAR estimates emphasises the need to further support standardisation in planning, conduct and analysis, and for clear and comprehensive reporting of FFX and HHTIs in time and place, to guide evidence-based pandemic preparedness and response efforts for SARS-CoV-2, influenza and future novel respiratory viruses.

Related Broad Research Areas