Projecting the seasonality of endemic COVID-19

ImportanceSuccessive waves of infection by SARS-CoV-2 have left little doubt that COVID-19 will transition to an endemic disease, yet the future seasonality of COVID-19 remains one of its most consequential unknowns. Foreknowledge of spatiotemporal surges would have immediate and long-term consequences for medical and public health decision-making. ObjectiveTo estimate the impending endemic seasonality of COVID-19 in temperate population centers via a phylogenetic ancestral and descendent states approach that leverages long-term data on the incidence of circulating coronaviruses. DesignWe performed a comparative evolutionary analysis on literature-based monthly verified cases of HCoV-NL63, HCoV-229E, HCoV-HKU1, and HCoV-OC43 infection within populations across the Northern Hemisphere. Ancestral and descendent states analyses on human-infecting coronaviruses provided projections of the impending seasonality of endemic COVID-19. SettingQuantitative projections of the endemic seasonality of COVID-19 were based on human endemic coronavirus infection incidence data from New York City (USA); Denver (USA); Tampere (Finland); Trondelag (Norway); Gothenburg (Sweden); Stockholm (Sweden); Amsterdam (Netherlands); Beijing (China); South Korea (Nationwide); Yamagata (Japan); Hong Kong; Nakon Si Thammarat (Thailand); Guangzhou (China); and Sarlahi (Nepal). Main Outcome(s) and Measure(s)The primary projection was the monthly relative frequency of SARS-CoV-2 infections in each geographic locale. Four secondary outcomes consisted of empirical monthly relative frequencies of the endemic human-infecting coronaviruses HCoV-NL63, -229E, -HKU1, and -OC43. ResultsWe project asynchronous surges of SARS-CoV-2 across locales in the Northern Hemisphere. In New York City, SARS-CoV-2 incidence is projected in late fall and winter months (Nov.-Jan.), In Tampere, Finland; Yamagata, Japan; and Sarlahi, Nepal incidence peaks in February. Gothenburg and Stockholm in Sweden reach peak incidence between November and February. Guangzhou, China; and South Korea. In Denver, incidence peaks in early Spring (Mar.). In Amsterdam, incidence rises in late fall (Dec.), and declines in late spring (Apr.). In Hong Kong, the projected apex of infection is in late fall (Nov.-Dec.), yet variation in incidence is muted across other seasons. Seasonal projections for Nakhon Si Thammarat, Thailand and for Beijing, China are muted compared to other locations. Conclusions and RelevanceThis knowledge of likely spatiotemporal surges of COVID-19 is fundamental to medical preparedness and expansions of public health interventions that anticipate the impending endemicity of this disease and mitigate COVID-19 transmission. These results provide crucial guidance for adaptive public health responses to this disease, and are vital to the long-term mitigation of COVID-19 transmission. Key Points QuestionUnder endemic conditions, what are the projected spatiotemporal seasonal surges of COVID-19? FindingsWe applied a phylogenetic ancestral and descendent states approach, leveraging long-term data on the incidence of circulating coronaviruses. We found that seasonal surges are expected in or near the winter months; dependent on the specific population center, infections are forecasted to surge in the late fall, winter, or early spring. MeaningGlobally, endemic COVID-19 surges should be expected to occur asynchronously, often coincident with local expected surges of other human-infecting respiratory viruses.

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.

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.