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

Abstract

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.

Impact of vaccination with SCB-2019 COVID-19 vaccine on transmission of SARS-CoV-2 infection: a household contact study in the Philippines

“…Household transmission has played a significant role in the scale of the COVID-19 pandemic [21,24]. There is a lack of conclusive evidence on the impact of vaccines to prevent secondary infections in household contacts; some studies have demonstrated a positive impact of COVID-19 vaccines on reducing household transmission of SARS-CoV-2 [12][13][14][15][16] while others reported limited impact in decreasing the risk of household transmission of COVID-19 especially for contacts of Delta variant index cases [17,18].…”

Household transmission investigation: Design, reporting and critical appraisal

“…During the COVID-19 pandemic in the absence F I G U R E 2 A practical example. In the transmission of SARS-CoV-2 in standardised first few X cases and household transmission investigations: a systematic review and meta-analysis, 8 teams of two investigators critically appraised a total 80 studies eligible to be included in the systematic review. of a fit-for-purpose critical appraisal tool, generic tools for longitudinal studies, 10,11 which do not adequately capture the nuances of HHTIs, were used or partially adapted.…”

“…Further, as stated in the Unity Studies HHTI protocol, investigators may need to adapt HHTIs to local circumstances—including public health mandates, laboratory and health system capacity, financial resources, sociopolitical context, and culture‐specific household practices 5 . Such adaptations lead to heterogeneity in implementation 7,8 . For example, many HHTIs for COVID‐19 conducted throughout 2020 and 2021 8,9 were adapted to local context but not clearly reported 8 .…”

“…5 Such adaptations lead to heterogeneity in implementation. 7,8 For example, many HHTIs for COVID-19 conducted throughout 2020 and 2021 8,9 were adapted to local context but not clearly reported. 8 As a result, the collection, sharing, aggregation, analysis and reporting of epidemiological and biological data may vary in meaning, precision, and accuracy across settings.…”

“…Lewis et al8 conducted a systematic review of the household secondary attack rate (hSAR) of SARS-CoV-2 from investigations aligned with the WHO Unity Studies HHTIs protocol. Investigations included in the systematic review were assessed using the HHTI Critical Appraisal Checklist.…”