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

BackgroundRapid antigen (RA) tests are being increasingly employed to detect SARS-CoV-2 infections in quarantine and surveillance. Prior research has focused on RT-PCR testing, a single RA test, or generic diagnostic characteristics of RA tests in assessing testing strategies. MethodsFor 18 RA tests with emergency use authorization from the United States of America FDA and an RT-PCR test, we conducted a comparative analysis of the post-quarantine transmission, the effective reproduction number during serial testing, and the false-positive rates. To quantify the extent of transmission, we developed an analytical mathematical framework informed by COVID-19 infectiousness, test specificity, and temporal diagnostic sensitivity data. ResultsWe 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 of two days or shorter, conducting a RA test on exit from quarantine reduces onward transmission more than a single RT-PCR test (with a 24-h delay) conducted upon exit. Applied to a complementary approach of performing serial testing at a specified frequency paired with isolation of positives, we have shown that RA tests outperform RT-PCR with a 24-h delay. The results from our modeling framework are consistent with quarantine and serial testing data collected from a remote industry setting. ConclusionsThese 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. Plain language summaryPrevious research has determined optimal timing for testing in quarantine and the utility of different frequencies of testing for disease surveillance using RT-PCR and generalized rapid antigen tests. However, these strategies can depend on the specific rapid antigen test used. By examining 18 rapid antigen tests, we demonstrate that a single rapid antigen test performs better than RT-PCR when quarantines are two days or less in duration. In the context of disease surveillance, the ability of a rapid antigen test to provide results quickly counteracts its lower sensitivity with potentially more false positives. These analytical results based on highly controlled test validation were consistent with real-world data obtained from quarantine and serial testing in an industrial setting.

Racial disparities in COVID-19 mortality across Michigan, United States

Black populations in the US are disproportionately affected by the COVID-19 pandemic, but the increased mortality burden after accounting for health and demographic characteristics is not well understood. We evaluated COVID-19 mortality in Michigan using individual-level death certificate and surveillance data from the Michigan Department of Health and Human Services from March 16 to October 26, 2020. Among the 6,065 COVID-19-related deaths, Black individuals experienced 3.6 times the mortality rate as White individuals. Black individuals under 65 years without comorbidities had a mortality rate 12.6 times that of their White counterparts. After accounting for age, sex, and comorbidities, we found that Black individuals in all strata are at higher risk of COVID-19 mortality than their White peers. We demonstrate that inequities in mortality are driven by ongoing systemic racism, as opposed to comorbidity burden or older age, and further highlight how underlying disparities across the race are compounded in crises.

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

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

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 shorter but equally effective quarantine and testing strategies can be deployed. To quantify the probability of post-quarantine transmission upon isolation of a positive test, we developed a mathematical model in which we varied quarantine duration and the timing of molecular tests for three scenarios of entry into quarantine. Specifically, we consider travel quarantine, quarantine of traced contacts with an unknown time if infection, and quarantine of cases with a known time of exposure. With a one-day delay between test and result, we found that testing on exit (or entry and exit) can reduce the duration of a 14-day quarantine by 50%, while testing on entry shortened quarantine by at most one day. Testing on exit more effectively reduces post-quarantine transmission than testing upon entry. Furthermore, we identified the optimal testing date within quarantines of varying duration, finding that testing on exit was most effective for quarantines lasting up to seven days. As a real-world validation of these principles, we analyzed the results of 4,040 SARS CoV-2 RT-PCR tests administered to offshore oil rig employees. Among the 47 positives obtained with a testing on entry and exit strategy, 16 cases that previously tested negative at entry were identified, with no further cases detected among employees following quarantine exit. Moreover, this strategy successfully prevented an expected nine offshore transmission events stemming from cases who had tested negative on the entry test, each one a serious concern for initiating rapid spread and a disabling outbreak in the close quarters of an offshore rig. This successful outcome highlights that appropriately timed testing can make shorter quarantines more effective, thereby minimizing economic impacts, disruptions to operational integrity, and COVID-related public health risks.