The asymptomatic proportion of SARS-CoV-2 Omicron-variant infections in households: A systematic review (preprint)

Background Understanding the clinical spectrum of SARS-CoV-2 infection, including the asymptomatic fraction, is important as asymptomatic individuals are still able to infect other individuals and contribute to ongoing transmission. The WHO Unity Household transmission investigation (HHTI) protocol provides a platform for the prospective and systematic collection of high-quality clinical, epidemiological, serological, and virological data from SARS-CoV-2 confirmed cases and their household contacts. These data can be used to understand key severity and transmissibility parameters - including the asymptomatic proportion - in relation to local epidemic context and help inform public health response. Methods We aimed to estimate the asymptomatic proportion of SARS-CoV-2 Omicron-variant infections in Unity-aligned HHTIs. We conducted a systematic review and meta-analysis in alignment with the PRISMA 2020 guidelines and registered our systematic review on PROSPERO (CRD42022378648). We searched EMBASE, Web of Science, MEDLINE, and bioRxiv and medRxiv from 1 November 2021 to 22 August 2023. Results We identified 8,368 records, of which 98 underwent full text review. We identified only three studies for data extraction, with substantial variation in study design and corresponding estimates of the asymptomatic proportion. As a result, we did not generate a pooled estimate or I2 metric. Conclusions The limited number of quality studies that we identified highlights the need for improved preparedness and response capabilities to facilitate robust HHTI implementation, analysis and reporting, to better inform national, regional and global risk assessments and policy making.

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

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.