Estimating measures to reduce the transmission of SARS-CoV-2 in Australia to guide a 'National Plan' to reopening

BackgroundIn mid-2021, widespread availability of COVID-19 vaccines with demonstrated impacts on transmission promised relief from the strict public health and social measures (PHSMs) imposed in many countries to limit spread and burden. We were asked to define vaccine coverage thresholds for transition through the stages of Australias National Plan to easing restrictions and reopening international borders. MethodsUsing available evidence of vaccine effectiveness against the then-circulating Delta variant, we used a mathematical model to determine vaccine coverage targets. The absence of any COVID-19 infections in many sub-national jurisdictions in Australia posed particular methodological challenges for modelling in this setting. We used a novel metric called Transmission Potential (TP) as a proxy measure of the population-level effective reproduction number. We estimated TP of the Delta variant under a range of PHSMs, test-trace-isolate-quarantine (TTIQ) efficiencies, vaccination coverage thresholds, and age-based vaccine allocation strategies. FindingsWe found that high coverage of vaccination across all age groups ([≤] 70%) combined with ongoing TTIQ and minimal PHSMs was sufficient to avoid strict lockdowns. At lesser coverage ([≤] 60%) rapid case escalation risked overwhelming of the health sector and would prompt a need to reimpose strict restrictions, with substantive economic impacts in order to achieve the goals of the National Plan. Maintaining low case numbers was the most beneficial strategy for health and the economy, and at higher coverage levels ([≥] 80%) further easing of restrictions was deemed possible. InterpretationThese results reinforced recommendations from other modelling groups that some level of PHSMs should be continued to minimise the burden of the Delta variant following achievement of high population vaccine coverage. They directly informed easing of COVID-19 restrictions in Australia. FundingThis study was supported by the Australian Government Department of Health and Ageing, and the National Health and Medical Research Councils Centre of Research Excellence scheme (GNT1170960).

COVID-19 vaccine coverage targets to inform reopening plans in a low incidence setting

Since the emergence of SARS-CoV-2 in 2019 through to mid-2021, much of the Australian population lived in a COVID-19 free environment. This followed the broadly successful implementation of a strong suppression strategy, including international border closures. With the availability of COVID-19 vaccines in early 2021, the national government sought to transition from a state of minimal incidence and strong suppression activities to one of high vaccine coverage and reduced restrictions but with still-manageable transmission. This transition is articulated in the national "re-opening" plan released in July 2021. Here we report on the dynamic modelling study that directly informed policies within the national re-opening plan including the identification of priority age groups for vaccination, target vaccine coverage thresholds and the anticipated requirements for continued public health measures -- assuming circulation of the Delta SARS-CoV-2 variant. Our findings demonstrated that adult vaccine coverage needed to be at least 70% to minimise public health and clinical impacts following the establishment of community transmission. They also supported the need for continued application of test-trace-isolate-quarantine and social measures during the vaccine roll-out phase and beyond.

Forecasting COVID-19 activity in Australia to support pandemic response: May to October 2020

As of January 2021, Australia had effectively controlled local transmission of COVID-19 despite a steady influx of imported cases and several local, but contained, outbreaks in 2020. Throughout 2020, state and territory public health responses were informed by weekly situational reports that included an ensemble forecast for each jurisdiction. We present here an analysis of one forecasting model included in this ensemble across the variety of scenarios experienced by each jurisdiction from May to October 2020. We examine how successfully the forecasts characterised future case incidence, subject to variations in data timeliness and completeness, showcase how we adapted these forecasts to support decisions of public health priority in rapidly-evolving situations, evaluate the impact of key model features on forecast skill, and demonstrate how to assess forecast skill in real-time before the ground truth is known. Conditioning the model on the most recent, but incomplete, data improved the forecast skill, emphasising the importance of developing strong quantitative models of surveillance system characteristics, such as ascertainment delay distributions. Forecast skill was highest when there were at least 10 reported cases per day, the circumstances in which authorities were most in need of forecasts to aid in planning and response.

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.

Estimating the transmissibility of SARS-CoV-2 during periods of high, low and zero case incidence

Against a backdrop of widespread global transmission, a number of countries have successfully brought large outbreaks of COVID-19 under control and maintained near-elimination status. A key element of epidemic response is the tracking of disease transmissibility in near real-time. During major outbreaks, the reproduction rate can be estimated from a time-series of case, hospitalisation or death counts. In low or zero incidence settings, knowing the potential for the virus to spread is a response priority. Absence of case data means that this potential cannot be estimated directly. We present a semi-mechanistic modelling framework that draws on time-series of both behavioural data and case data (when disease activity is present) to estimate the transmissibility of SARS-CoV-2 from periods of high to low - or zero - case incidence, with a coherent transition in interpretation across the changing epidemiological situations. Of note, during periods of epidemic activity, our analysis recovers the effective reproduction number, while during periods of low - or zero - case incidence, it provides an estimate of transmission risk. This enables tracking and planning of progress towards the control of large outbreaks, maintenance of virus suppression, and monitoring the risk posed by re-introduction of the virus. We demonstrate the value of our methods by reporting on their use throughout 2020 in Australia, where they have become a central component of the national COVID-19 response.

Modelling testing and response strategies for COVID-19 outbreaks in remote Australian Aboriginal communities

BackgroundRemote Australian Aboriginal and Torres Strait Islander communities have potential to be severely impacted by COVID-19, with multiple factors predisposing to increased transmission and disease severity. Our modelling aims to inform optimal public health responses. MethodsAn individual-based simulation model represented communities ranging from 100 to 3,500 people, comprised of large interconnected households. A range of strategies for case finding, quarantining of contacts, testing, and lockdown were examined, following the silent introduction of a case. ResultsMultiple secondary infections are likely present by the time the first case is identified. Quarantine of close contacts, defined by extended household membership, can reduce peak infection prevalence from 60-70% to around 10%, but subsequent waves may occur when community mixing resumes. Exit testing significantly reduces ongoing transmission. Concurrent lockdown of non-quarantined households for 14 days is highly effective for epidemic control and reduces overall testing requirements; peak prevalence of the initial outbreak can be constrained to less than 5%, and the final community attack rate to less than 10% in modelled scenarios. Lockdown also mitigates the effect of a delay in the initial response. Compliance with lockdown must be at least 80-90%, however, or epidemic control will be lost. ConclusionsA SARS-CoV-2 outbreak will spread rapidly in remote communities. Prompt case detection with quarantining of extended-household contacts and a 14-day lockdown for all other residents, combined with exit testing for all, is the most effective strategy for rapid containment. Compliance is crucial, underscoring the need for community supported, culturally sensitive responses.

INFERRED RESOLUTION THROUGH HERD IMMMUNITY OF FIRST COVID-19 WAVE IN MANAUS, BRAZILIAN AMAZON

INTRODUCTORY PARAGRAPHAs in many other settings, peak excess mortality preceded the officially reported first wave peak of the COVID-19 epidemic in Manaus, Brazil, reflecting delayed case recognition and limited initial access to diagnostic testing. To avoid early information bias, we used detailed age and gender stratified death certificate and hospitalisation data to evaluate the epidemics trajectory and infer the cause of its decline using a stochastic model. Our results are consistent with heterogenous transmission reducing over time due to the development of herd immunity. Relative to a baseline model that assumed homogenous mixing across Manaus, a model that permitted a small, self-isolated population fraction raised the estimated herd-immunity threshold from 28% to 30% and reduced the final attack rate from 86% to 65%. In the latter scenario, a substantial proportion of vulnerable, older individuals remained susceptible to infection. Given uncertainties regarding the distancing behaviours of population subgroups with different social and economic characteristics, and the duration of sterilising or transmission-modifying immunity in exposed individuals, we conclude that the potential for epidemic outbreaks remains, but that future waves of infection are likely to be much less pronounced than that already experienced.

Early analysis of the Australian COVID-19 epidemic

As of 18 April 2020, there had been 6,533 confirmed cases of COVID-19 in Australia [1]. Of these, 67 had died from the disease. The daily count of new confirmed cases was declining. This suggests that the collective actions of the Australian public and government authorities in response to COVID-19 were sufficiently early and assiduous to avert a public health crisis -- for now. Analysing factors, such as the intensity and timing public health interventions, that contribute to individual country experiences of COVID-19 will assist in the next stage of response planning globally. Using data from the Australian national COVID-19 database, we describe how the epidemic and public health response unfolded in Australia up to 13 April 2020. We estimate that the effective reproduction number was likely below 1 (the threshold value for control) in each Australian state since mid-March and forecast that hospital ward and intensive care unit occupancy will remain below capacity thresholds over the next two weeks.

Modelling the impact of COVID-19 in Australia to inform transmission reducing measures and health system preparedness

BackgroundThe ability of global health systems to cope with increasing numbers of COVID-19 cases is of major concern. In readiness for this challenge, Australia has drawn on clinical pathway models developed over many years in preparation for influenza pandemics. These models have been used to estimate health care requirements for COVID-19 patients, in the context of broader public health measures. MethodsAn age and risk stratified transmission model of COVID-19 infection was used to simulate an unmitigated epidemic with parameter ranges reflecting uncertainty in current estimates of transmissibility and severity. Overlaid public health measures included case isolation and quarantine of contacts, and broadly applied social distancing. Clinical presentations and patient flows through the Australian health care system were simulated, including expansion of available intensive care capacity and alternative clinical assessment pathways. FindingsAn unmitigated COVID-19 epidemic would dramatically exceed the capacity of the Australian health system, over a prolonged period. Case isolation and contact quarantine alone will be insufficient to constrain case presentations within a feasible level of expansion of health sector capacity. Overlaid social restrictions will need to be applied at some level over the course of the epidemic to ensure that systems do not become overwhelmed, and that essential health sector functions, including care of COVID-19 patients, can be maintained. Attention to the full pathway of clinical care is needed to ensure access to critical care. InterpretationReducing COVID-19 morbidity and mortality will rely on a combination of measures to strengthen and extend public health and clinical capacity, along with reduction of overall infection transmission in the community. Ongoing attention to maintaining and strengthening the capacity of health care systems and workers to manage cases is needed. FundingAustralian Government Department of Health Office of Health Protection, Australian Government National Health and Medical Research Council