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

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.

Learnings from the Australian First Few X Household Transmission Project for COVID-19

BackgroundFirst Few "X" (FFX) studies provide a platform to collect the required epidemiological, clinical and virological data to help address emerging information needs about the COVID-19 pandemic. MethodsWe adapted the WHO FFX protocol for COVID-19 to understand severity and household transmission dynamics in the early stages of the pandemic in Australia. Implementation strategies were developed for participating sites; all household members provided baseline epidemiological data and were followed for 14 days from case identification. Household contacts completed symptom diaries and had respiratory swabs taken at baseline, day 7 and day 14, and day 28 where applicable. We modelled the spread of COVID-19 within households using a susceptible-exposed-infectious-recovered-type model, and calculated the household secondary attack rate and key epidemiological parameters. Findings96 households with 101 cases and 286 household contacts were recruited into the study between April-October 2020. Forty household contacts tested positive for SARS-CoV-2 in the study follow-up period. Our model estimated the household secondary attack rate to be 15% (95% CI 8-25%), which scaled up with increasing household size. Children were less infectious than their adult counterparts but were also more susceptible to infection. InterpretationOur study provides important baseline data characterising the transmission of early SARS-CoV-2 strains from children and adults in Australia, against which properties of variants of concern can be benchmarked. We encountered many challenges with respect to logistics, ethics, governance and data management that may have led to biases in our study. Continued efforts to invest in preparedness research will help to test, refine and further develop Australian FFX study protocols in advance of future outbreaks. FundingAustralian Government Department of Health Research in contextO_ST_ABSEvidence before this studyC_ST_ABSThe emergence of SARS-CoV-2 was initially characterised by uncertainty over key epidemiological, clinical and virological characteristics of the pathogen. We conducted a prospective household transmission study of confirmed cases of COVID-19 and their household contacts to collect data to understand severity and household transmission dynamics in Australia and add to the emerging evidence base for decision making. Large systematic reviews and meta-analyses of severity and transmission dynamics of SARS-CoV-2 in households have since been published, although estimates vary by setting. Added value of this studyThis is the first multi-jurisdictional prospective household transmission study of its kind for SARS-CoV-2 in Australia. Australia experienced low epidemic activity during the study period in 2020 due to robust public health and social measures including extensive PCR testing of symptomatic persons and isolation of all known contacts of confirmed cases. Hence, we describe the transmission dynamics in our cohort, i.e. in a low incidence setting and provide estimates of the household secondary attack rate, the relative susceptibility of children compared to adults, and transmission from children compared to adults. Implications of all the available evidenceOur findings describe the epidemiology of COVID-19 in Australian households in 2020, and demonstrate the effectiveness of public health measures to limit transmission in this setting. Comparisons to other household transmission studies must be interpreted in light of the local epidemiology and context including study design, and sampling methods. Additional research is needed to incorporate genomic and serological data to further study transmission dynamics in our cohort. Continued development of the FFX study platform in Australia will enable integration into surveillance systems and help inform targetted public health responses to future infectious disease emergencies.