Comparative analyses of all FDA EUA-approved rapid antigen tests and RT-PCR for COVID-19 quarantine and surveillance-based isolation (preprint)

Rapid antigen (RA) tests are being increasingly employed to detect COVID-19 infections in quarantine and surveillance. We conducted a comparative analysis of quarantine durations, testing frequencies, and false-positive rates for all of the 18 RA tests with emergency use authorization (EUA) from the FDA, and an RT-PCR test. For each test, we employed a mathematical model of imminent infections to calculate the effective reproductive number in the context of the test used for quarantine or serial testing. We informed the model with data on test specificity, temporal diagnostic sensitivity, and COVID-19 infectiousness. Our results demonstrate that the relative effectiveness of RA and RT-PCR tests in reducing post-quarantine transmission depends on the quarantine duration and the turnaround time of testing results. For quarantines shorter than five days, RA test on entry to and on exit from quarantine reduced onward transmission more than a single RT-PCR test conducted upon exit. Conducting surveillance via serial RT-PCR testing with a 24-h turnaround time, the minimum testing frequency paired with isolation of positives that is required to suppress the effective reproduction number (RE) below one was found to be every six days. RA tests reduce RE below one when conducted at a minimum frequency that ranges from every six days to every eight days. Our analysis also highlights that the risk of onward transmission during serial testing increases with the delay in obtaining the results. These RA test-specific results are an important component of the tool set for policy decision-making, and demonstrate that judicious selection of an appropriate RA test can supply a viable alternative to RT-PCR in efforts to control the spread of disease.

The impact of vaccination on COVID-19 outbreaks in the United States (preprint)

BackgroundGlobal vaccine development efforts have been accelerated in response to the devastating COVID-19 pandemic. We evaluated the impact of a 2-dose COVID-19 vaccination campaign on reducing incidence, hospitalizations, and deaths in the United States (US). MethodsWe developed an agent-based model of SARS-CoV-2 transmission and parameterized it with US demographics and age-specific COVID-19 outcomes. Healthcare workers and high-risk individuals were prioritized for vaccination, while children under 18 years of age were not vaccinated. We considered a vaccine efficacy of 95% against disease following 2 doses administered 21 days apart achieving 40% vaccine coverage of the overall population within 284 days. We varied vaccine efficacy against infection, and specified 10% pre-existing population immunity for the base-case scenario. The model was calibrated to an effective reproduction number of 1.2, accounting for current non-pharmaceutical interventions in the US. ResultsVaccination reduced the overall attack rate to 4.6% (95% CrI: 4.3% - 5.0%) from 9.0% (95% CrI: 8.4% - 9.4%) without vaccination, over 300 days. The highest relative reduction (54-62%) was observed among individuals aged 65 and older. Vaccination markedly reduced adverse outcomes, with non-ICU hospitalizations, ICU hospitalizations, and deaths decreasing by 63.5% (95% CrI: 60.3% - 66.7%), 65.6% (95% CrI: 62.2% - 68.6%), and 69.3% (95% CrI: 65.5% - 73.1%), respectively, across the same period. ConclusionsOur results indicate that vaccination can have a substantial impact on mitigating COVID-19 outbreaks, even with limited protection against infection. However, continued compliance with non-pharmaceutical interventions is essential to achieve this impact. Key pointsVaccination with a 95% efficacy against disease could substantially mitigate future attack rates, hospitalizations, and deaths, even if only adults are vaccinated. Non-pharmaceutical interventions remain an important part of outbreak response as vaccines are distributed over time.

Optimal COVID-19 quarantine and testing strategies (preprint)

As economic woes of the COVID-19 pandemic deepen, strategies are being formulated to avoid the need for prolonged stay-at-home orders, while implementing risk-based quarantine, testing, contact tracing and surveillance protocols. Given limited resources and the significant economic, public health and operational challenges of the current 14-day quarantine recommendation, it is vital to understand if more efficient but equally effective quarantine and testing strategies can be deployed. To this end, we developed a mathematical model to quantify the probability of post-quarantine transmission that varied across a range of possible quarantine durations, timings of molecular testing, and estimated incubation periods. We found that a 13-day quarantine with testing on entry, a nine-day quarantine with testing on exit, and an eight-day quarantine with testing on both entry and exit each provide equivalent or lower probability of post-quarantine transmission compared to a 14-day quarantine with no testing. We found that testing on exit from quarantine is more effective in reducing probability of post-quarantine transmission than testing upon entry. When conducting a single test, testing on exit was most effective for quarantines of six days or shorter, while testing on day six or seven is optimal for longer quarantines. Optimal timing of testing during quarantine will reduce the probability of post-quarantine transmission, as false-positive results become less likely, enabling case isolation. Based on 4,040 SARS CoV-2 RT-PCR tests, an exit test 96 hours after the start of quarantine for an offshore oil rig population was demonstrated to identify all known asymptomatic cases that previously tested negative at entry, and-moreover-successfully prevented an expected seven or more offshore transmission events, each a serious concern for initiating rapid spread and a disabling outbreak in the close quarters of an offshore rig. This successful outcome highlights the importance of context-specific guidelines for the duration of quarantine and timing of testing that can minimize economic impacts, disruptions to operational integrity, and COVID-related public health risks.

Regional COVID-19 spread despite expected declines: how mitigation is hindered by spatio-temporal variation in local control measures. (preprint)

Successful public health regimes for COVID-19 push below unity long-term global Rt -- the average number of secondary cases caused by an infectious individual. Most assessments use local information. Populations differ in Rt, amongst themselves and over time. We use a SIR model for two populations to make the conceptual point that even if each locality averages Rt < 1, the overall epidemic can still grow, provided these populations have asynchronous variation in transmission, and are coupled by movement of infectious individuals. This emergent effect in pandemic dynamics instantiates "Parrondo's Paradox," -- an entity comprised of distinct but interacting units can behave qualitatively differently than each part on its own. For effective COVID-19 disease mitigation strategies, it is critical that infectious individuals moving among locations be identified and quarantined. This does not warrant indiscriminate prevention of movement, but rather rational, targeted testing and national coordination.