Test-trace-isolate-quarantine (TTIQ) intervention strategies after symptomatic COVID-19 case identification.

The test-trace-isolate-quarantine (TTIQ) strategy, where confirmed-positive pathogen carriers are isolated from the community and their recent close contacts are identified and pre-emptively quarantined, is used to break chains of transmission during a disease outbreak. The protocol is frequently followed after an individual presents with disease symptoms, at which point they will be tested for the pathogen. This TTIQ strategy, along with hygiene and social distancing measures, make up the non-pharmaceutical interventions that are utilised to suppress the ongoing COVID-19 pandemic. Here we develop a tractable mathematical model of disease transmission and the TTIQ intervention to quantify how the probability of detecting and isolating a case following symptom onset, the fraction of contacts that are identified and quarantined, and the delays inherent to these processes impact epidemic growth. In the model, the timing of disease transmission and symptom onset, as well as the frequency of asymptomatic cases, is based on empirical distributions of SARS-CoV-2 infection dynamics, while the isolation of confirmed cases and quarantine of their contacts is implemented by truncating their respective infectious periods. We find that a successful TTIQ strategy requires intensive testing: the majority of transmission is prevented by isolating symptomatic individuals and doing so in a short amount of time. Despite the lesser impact, additional contact tracing and quarantine increases the parameter space in which an epidemic is controllable and is necessary to control epidemics with a high reproductive number. TTIQ could remain an important intervention for the foreseeable future of the COVID-19 pandemic due to slow vaccine rollout and highly-transmissible variants with the potential for vaccine escape. Our results can be used to assess how TTIQ can be improved and optimised, and the methodology represents an improvement over previous quantification methods that is applicable to future epidemic scenarios.

On the relationship between serial interval, infectiousness profile and generation time.

The timing of transmission plays a key role in the dynamics and controllability of an epidemic. However, observing generation times-the time interval between the infection of an infector and an infectee in a transmission pair-requires data on infection times, which are generally unknown. The timing of symptom onset is more easily observed; generation times are therefore often estimated based on serial intervals-the time interval between symptom onset of an infector and an infectee. This estimation follows one of two approaches: (i) approximating the generation time distribution by the serial interval distribution or (ii) deriving the generation time distribution from the serial interval and incubation period-the time interval between infection and symptom onset in a single individual-distributions. These two approaches make different-and not always explicitly stated-assumptions about the relationship between infectiousness and symptoms, resulting in different generation time distributions with the same mean but unequal variances. Here, we clarify the assumptions that each approach makes and show that neither set of assumptions is plausible for most pathogens. However, the variances of the generation time distribution derived under each assumption can reasonably be considered as upper (approximation with serial interval) and lower (derivation from serial interval) bounds. Thus, we suggest a pragmatic solution is to use both approaches and treat these as edge cases in downstream analysis. We discuss the impact of the variance of the generation time distribution on the controllability of an epidemic through strategies based on contact tracing, and we show that underestimating this variance is likely to overestimate controllability.

Quantifying the impact of quarantine duration on COVID-19 transmission.

The large number of individuals placed into quarantine because of possible severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) exposure has high societal and economic costs. There is ongoing debate about the appropriate duration of quarantine, particularly since the fraction of individuals who eventually test positive is perceived as being low. We use empirically determined distributions of incubation period, infectivity, and generation time to quantify how the duration of quarantine affects onward transmission from traced contacts of confirmed SARS-CoV-2 cases and from returning travellers. We also consider the roles of testing followed by release if negative (test-and-release), reinforced hygiene, adherence, and symptoms in calculating quarantine efficacy. We show that there are quarantine strategies based on a test-and-release protocol that, from an epidemiological viewpoint, perform almost as well as a 10-day quarantine, but with fewer person-days spent in quarantine. The findings apply to both travellers and contacts, but the specifics depend on the context.

The COVID-19 pandemic has led many countries to impose quarantines, ensuring that people who may have been exposed to the SARS-CoV-2 virus or who return from abroad are isolated for a specific period to prevent the spread of the disease. These measures have crippled travel, taken a large economic toll, and affected the wellbeing of those needing to self-isolate. However, there is no consensus on how long COVID-19 quarantines should be. Reducing the duration of quarantines could significantly decrease the costs of COVID-19 to the overall economy and to individuals, so Ashcroft et al. decided to examine how shorter isolation periods and test-and-release schemes affected transmission. Existing data on how SARS-CoV-2 behaves in a population were used to generate a model that would predict how changing quarantine length impacts transmission for both travellers and people who may have been exposed to the virus. The analysis predicted that shortening quarantines from ten to seven days would result in almost no increased risk of transmission, if paired with PCR testing on day five of isolation (with people testing positive being confined for longer). The quarantine could be cut further to six days if rapid antigen tests were used. Ashcroft et al.'s findings suggest that it may be possible to shorten COVID-19 quarantines if good testing approaches are implemented, leading to better economic, social and individual outcomes.