Search

The Omicron (B.1.1.529) variant of SARS-CoV-2 rapidly achieved global dissemination following its emergence in southern Africa in November, 2021.(1,2) Epidemiologic surveillance has revealed changes in COVID-19 case-to-hospitalization and case-to-mortality ratios following Omicron variant emergence,(3–6) although interpretation of these changes presents challenges due to differential protection against Omicron or Delta (B.1.617.2) variant SARS-CoV-2 infections associated with prior vaccine-derived and naturally-acquired immunity, as well as longer-term changes in testing and healthcare practices.(7) Here we report clinical outcomes among 222,688 cases with Omicron variant infections and 23,305 time-matched cases with Delta variant infections within the Kaiser Permanente Southern California healthcare system, who were followed longitudinally following positive outpatient tests between 15 December, 2021 and 17 January, 2022, when Omicron cases were almost exclusively BA.1 or its sublineages. Adjusted hazard ratios of progression to any hospital admission, symptomatic hospital admission, intensive care unit admission, mechanical ventilation, and death were 0.59 (95% confidence interval: 0.51-0.69), 0.59 (0.51-0.68), 0.50 (0.29-0.87), 0.36 (0.18-0.72), and 0.21 (0.10-0.44) respectively, for cases with Omicron versus Delta variant infections. In contrast, among 14,661 Omicron cases ascertained by outpatient testing between 3 February and 17 March, 2022, infection with the BA.2 or BA.1/BA.1.1 subvariants did not show evidence of differential risk of severe outcomes. Lower risk of severe clinical outcomes among cases with Omicron variant infection merits consideration in planning of healthcare capacity needs amid establishment of the Omicron variant as the dominant circulating SARS-CoV-2 lineage globally, and should inform the interpretation of both case- and hospital-based surveillance data.

Nursing homes (NH) were among the first settings to receive COVID-19 vaccines in the United States, but staff vaccination coverage remains low at an average of 64%. Using an agent-based model, we examined the impact of community prevalence, the Delta variant, staff vaccination coverage, and boosters for residents on outbreak dynamics in nursing homes. We found that increased staff primary series coverage and high booster vaccine effectiveness (VE) in residents leads to fewer infections and that the cumulative incidence is highly dependent on community transmission. Despite high VE, high community transmission resulted in continued symptomatic infections in NHs.

Objectives Universities have turned to SARS-CoV-2 models to examine campus reopening strategies. While these studies have explored a variety of modeling techniques, none have used empirical data. Methods In this study, we use an empirical proximity network of college freshmen obtained using smartphone Bluetooth to simulate the spread of the virus. We investigate the role of immunization, testing, isolation, mask wearing, and social distancing in the presence of implementation challenges and imperfect compliance. Results We show that frequent testing could drastically reduce the spread of the virus if levels of immunity are low, but its effects are limited if immunity is more ubiquitous. Furthermore, moderate levels of mask wearing and social distancing could lead to additional reductions in cumulative incidence, but their benefit decreases rapidly as immunity and testing frequency increase. However, if immunity from vaccination is imperfect or declines over time, scenarios not studied here, frequent testing and other interventions may play more central roles. Conclusions Our findings suggest that although regular testing and isolation are powerful tools, they have limited benefit if immunity is high or other interventions are widely adopted. If universities can attain even moderate levels of vaccination, masking, and social distancing, they may be able to relax the frequency of testing to once every four weeks.

Determining policies to end the SARS-CoV-2 pandemic will require an understanding of the efficacy and effectiveness (hereafter, efficacy) of vaccines. Beyond the efficacy against severe disease and symptomatic and asymptomatic infection, understanding vaccine efficacy against virus transmission, including efficacy against transmission of different viral variants, will help model epidemic trajectory and determine appropriate control measures. Recent studies have proposed using random virologic testing in individual randomized controlled trials to improve estimation of vaccine efficacy against infection. We propose to further use the viral load measures from these tests to estimate efficacy against transmission. This estimation requires a model of the relationship between viral load and transmissibility and assumptions about the vaccine effect on transmission and the progress of the epidemic. We describe these key assumptions, potential violations of them, and solutions that can be implemented to mitigate these violations. Assessing these assumptions and implementing this random sampling, with viral load measures, will enable better estimation of the crucial measure of vaccine efficacy against transmission.

Nursing homes (NH) were among the first settings to receive COVID-19 vaccines in the United States, but staff vaccination coverage remains low at an average of 64%. Using an agent-based model, we examined the impact of community prevalence, the Delta variant, staff vaccination coverage, and boosters for residents on outbreak dynamics in nursing homes. We found that increased staff primary series coverage and high booster vaccine effectiveness (VE) in residents leads to fewer infections and that the cumulative incidence is highly dependent on community transmission. Despite high VE, high community transmission resulted in continued symptomatic infections in NHs.

SARS-CoV-2 variants of concern exhibit varying degrees of transmissibility and, in some cases, escape from acquired immunity. Much effort has been devoted to measuring these phenotypes, but understanding their impact on the course of the pandemic – especially that of immune escape – has remained a challenge. Here, we use a mathematical model to simulate the dynamics of wildtype and variant strains of SARS-CoV-2 in the context of vaccine rollout and nonpharmaceutical interventions. We show that variants with enhanced transmissibility frequently increase epidemic severity, whereas those with partial immune escape either fail to spread widely, or primarily cause reinfections and breakthrough infections. However, when these phenotypes are combined, a variant can continue spreading even as immunity builds up in the population, limiting the impact of vaccination and exacerbating the epidemic. These findings help explain the trajectories of past and present SARS-CoV-2 variants and may inform variant assessment and response in the future., A modeling approach looking at the impact of SARS-CoV-2 variants based on escape from immunity or different degrees of transmissibility in the context of vaccination as well as pharmaceutical interventions suggests that epidemic severity is linked more strongly to variants with enhanced transmissibility.

BackgroundIn clinical trials, several SARS-CoV-2 vaccines were shown to reduce risk of severe COVID-19 illness. Local, population-level, real-world evidence of vaccine effectiveness is accumulating. We assessed vaccine effectiveness for community-dwelling New York City (NYC) residents using a quasi-experimental, regression discontinuity design, leveraging a period (January 12–March 9, 2021) when ≥65-year-olds were vaccine-eligible but younger persons, excluding essential workers, were not.MethodsWe constructed segmented, negative binomial regression models of age-specific COVID-19 hospitalization rates among 45–84-year-old NYC residents during a post-vaccination program implementation period (February 21–April 17, 2021), with a discontinuity at age 65 years. The relationship between age and hospitalization rates in an unvaccinated population was incorporated using a pre-implementation period (December 20, 2020–February 13, 2021). We calculated the rate ratio (RR) and 95% confidence interval (CI) for the interaction between implementation period (pre or post) and age-based eligibility (45–64 or 65–84 years). Analyses were stratified by race/ethnicity and borough of residence. Similar analyses were conducted for COVID-19 deaths.ResultsHospitalization rates among 65–84-year-olds decreased from pre- to post-implementation periods (RR 0.85, 95% CI: 0.74–0.97), controlling for trends among 45–64-year-olds. Accordingly, an estimated 721 (95% CI: 126–1,241) hospitalizations were averted. Residents just above the eligibility threshold (65–66-year-olds) had lower hospitalization rates than those below (63–64-year-olds). Racial/ethnic groups and boroughs with higher vaccine coverage generally experienced greater reductions in RR point estimates. Uncertainty was greater for the decrease in COVID-19 death rates (RR 0.85, 95% CI: 0.66–1.10).ConclusionThe vaccination program in NYC reduced COVID-19 hospitalizations among the initially age-eligible ≥65-year-old population by approximately 15%. The real-world evidence of vaccine effectiveness makes it more imperative to improve vaccine access and uptake to reduce inequities in COVID-19 outcomes.

A statistical framework was developed to jointly estimate the distribution of generation time and incubation period from human-to-human transmission pairs of COVID-19, accounting for sampling biases due to exponential growth of the epidemic during the data collection period., Background Coronavirus disease 2019 (COVID-19) has caused a heavy disease burden globally. The impact of process and timing of data collection on the accuracy of estimation of key epidemiological distributions are unclear. Because infection times are typically unobserved, there are relatively few estimates of generation time distribution. Methods We developed a statistical framework to jointly estimate generation time and incubation period from human-to-human transmission pairs, accounting for sampling biases. We applied the framework on 80 laboratory-confirmed human-to-human transmission pairs in China. We further inferred the infectiousness profile, serial interval distribution, proportions of presymptomatic transmission, and basic reproduction number (R0) for COVID-19. Results The estimated mean incubation period was 4.8 days (95% confidence interval [CI], 4.1–5.6), and mean generation time was 5.7 days (95% CI, 4.8–6.5). The estimated R0 based on the estimated generation time was 2.2 (95% CI, 1.9–2.4). A simulation study suggested that our approach could provide unbiased estimates, insensitive to the width of exposure windows. Conclusions Properly accounting for the timing and process of data collection is critical to have correct estimates of generation time and incubation period. R0 can be biased when it is derived based on serial interval as the proxy of generation time.

In response to the SARS-CoV-2 pandemic, unprecedented travel restrictions and stay-at-home orders were enacted around the world. Ultimately, the public’s response to announcements of lockdowns—defined as restrictions on both local movement or long distance travel—will determine how effective these kinds of interventions are. Here, we evaluate the effects of lockdowns on human mobility and simulate how these changes may affect epidemic spread by analyzing aggregated mobility data from mobile phones. We show that in 2020 following lockdown announcements but prior to their implementation, both local and long distance movement increased in multiple locations, and urban-to-rural migration was observed around the world. To examine how these behavioral responses to lockdown policies may contribute to epidemic spread, we developed a simple agent-based spatial model. Our model shows that this increased movement has the potential to increase seeding of the epidemic in less urban areas, which could undermine the goal of the lockdown in preventing disease spread. Lockdowns play a key role in reducing contacts and controlling outbreaks, but appropriate messaging surrounding their announcement and careful evaluation of changes in mobility are needed to mitigate the possible unintended consequences.

Randomized controlled trials (RCTs) have shown high efficacy of multiple vaccines against SARS-CoV-2 disease (COVID-19), and recent studies have shown the vaccines are also effective against infection. Evidence for the effect of each of these vaccines on ability to transmit the virus is also beginning to emerge. We describe an approach to estimate these vaccines’ effects on viral positivity, a prevalence measure which under the reasonable assumption that vaccinated individuals who become infected are no more infectious than unvaccinated individuals forms a lower bound on efficacy against transmission. Specifically, we recommend separate analysis of positive tests triggered by symptoms (usually the primary outcome) and cross-sectional prevalence of positive tests obtained regardless of symptoms. The odds ratio of carriage for vaccine vs. placebo provides an unbiased estimate of vaccine effectiveness against viral positivity, under certain assumptions, and we show through simulations that likely departures from these assumptions will only modestly bias this estimate. Applying this approach to published data from the RCT of the Moderna vaccine, we estimate that one dose of vaccine reduces the potential for transmission by at least 61%, possibly considerably more. We describe how these approaches can be translated into observational studies of vaccine effectiveness.HighlightsSARS-CoV-2 vaccine trials did not directly estimate vaccine efficacy against transmission.We describe an approach to estimate a lower bound of vaccine efficacy against transmission.We estimate one dose of the Moderna vaccine reduces the potential for transmission by at least 61%.We recommend separate analysis of tests triggered by symptoms vs. cross-sectional tests.

Abstract Background As COVID-19 continues to spread around the world, understanding how patterns of human mobility and connectivity affect outbreak dynamics, especially before outbreaks establish locally, is critical for informing response efforts. In Taiwan, most cases to date were imported or linked to imported cases. Methods In collaboration with Facebook Data for Good, we characterized changes in movement patterns in Taiwan since February 2020, and built metapopulation models that incorporate human movement data to identify the high risk areas of disease spread and assess the potential effects of local travel restrictions in Taiwan. Results We found that mobility changed with the number of local cases in Taiwan in the past few months. For each city, we identified the most highly connected areas that may serve as sources of importation during an outbreak. We showed that the risk of an outbreak in Taiwan is enhanced if initial infections occur around holidays. Intracity travel reductions have a higher impact on the risk of an outbreak than intercity travel reductions, while intercity travel reductions can narrow the scope of the outbreak and help target resources. The timing, duration, and level of travel reduction together determine the impact of travel reductions on the number of infections, and multiple combinations of these can result in similar impact. Conclusions To prepare for the potential spread within Taiwan, we utilized Facebook’s aggregated and anonymized movement and colocation data to identify cities with higher risk of infection and regional importation. We developed an interactive application that allows users to vary inputs and assumptions and shows the spatial spread of the disease and the impact of intercity and intracity travel reduction under different initial conditions. Our results can be used readily if local transmission occurs in Taiwan after relaxation of border control, providing important insights into future disease surveillance and policies for travel restrictions.

In response to the coronavirus disease (COVID-19) pandemic, public health scientists have produced a large and rapidly expanding body of literature that aims to answer critical questions, such as the proportion of the population in a geographic area that has been infected; the transmissibility of the virus and factors associated with high infectiousness or susceptibility to infection; which groups are the most at risk of infection, morbidity and mortality; and the degree to which antibodies confer protection to re-infection. Observational studies are subject to a number of different biases, including confounding, selection bias, and measurement error, that may threaten their validity or influence the interpretation of their results. To assist in the critical evaluation of a vast body of literature and contribute to future study design, we outline and propose solutions to biases that can occur across different categories of observational studies of COVID-19. We consider potential biases that could occur in five categories of studies: (1) cross-sectional seroprevalence, (2) longitudinal seroprotection, (3) risk factor studies to inform interventions, (4) studies to estimate the secondary attack rate, and (5) studies that use secondary attack rates to make inferences about infectiousness and susceptibility. Supplementary Information The online version of this article (10.1007/s10654-021-00727-7) contains supplementary material, which is available to authorized users.

Background Nowcasting approaches enhance the utility of reportable disease data for trend monitoring by correcting for delays, but implementation details affect accuracy. Objective To support real-time COVID-19 situational awareness, the New York City Department of Health and Mental Hygiene used nowcasting to account for testing and reporting delays. We conducted an evaluation to determine which implementation details would yield the most accurate estimated case counts. Methods A time-correlated Bayesian approach called Nowcasting by Bayesian Smoothing (NobBS) was applied in real time to line lists of reportable disease surveillance data, accounting for the delay from diagnosis to reporting and the shape of the epidemic curve. We retrospectively evaluated nowcasting performance for confirmed case counts among residents diagnosed during the period from March to May 2020, a period when the median reporting delay was 2 days. Results Nowcasts with a 2-week moving window and a negative binomial distribution had lower mean absolute error, lower relative root mean square error, and higher 95% prediction interval coverage than nowcasts conducted with a 3-week moving window or with a Poisson distribution. Nowcasts conducted toward the end of the week outperformed nowcasts performed earlier in the week, given fewer patients diagnosed on weekends and lack of day-of-week adjustments. When estimating case counts for weekdays only, metrics were similar across days when the nowcasts were conducted, with Mondays having the lowest mean absolute error of 183 cases in the context of an average daily weekday case count of 2914. Conclusions Nowcasting using NobBS can effectively support COVID-19 trend monitoring. Accounting for overdispersion, shortening the moving window, and suppressing diagnoses on weekends—when fewer patients submitted specimens for testing—improved the accuracy of estimated case counts. Nowcasting ensured that recent decreases in observed case counts were not overinterpreted as true declines and supported officials in anticipating the magnitude and timing of hospitalizations and deaths and allocating resources geographically.

To rapidly evaluate the safety and efficacy of COVID-19 vaccine candidates, prioritizing vaccine trial sites in areas with high expected disease incidence can speed endpoint accrual and shorten trial duration. Mathematical and statistical forecast models can inform the process of site selection, integrating available data sources and facilitating comparisons across locations. We recommend the use of ensemble forecast modeling - combining projections from independent modeling groups - to guide investigators identifying suitable sites for COVID-19 vaccine efficacy trials. We describe an appropriate structure for this process, including minimum requirements, suggested output, and a user-friendly tool for displaying results. Importantly, we advise that this process be repeated regularly throughout the trial, to inform decisions about enrolling new participants at existing sites with waning incidence versus adding entirely new sites. These types of data-driven models can support the implementation of flexible efficacy trials tailored to the outbreak setting.

ObjectivesTo illustrate the intersections of, and intercounty variation in, individual, household and community factors that influence the impact of COVID-19 on US counties and their ability to respond.DesignWe identified key individual, household and community characteristics influencing COVID-19 risks of infection and survival, guided by international experiences and consideration of epidemiological parameters of importance. Using publicly available data, we developed an open-access online tool that allows county-specific querying and mapping of risk factors. As an illustrative example, we assess the pairwise intersections of age (individual level), poverty (household level) and prevalence of group homes (community-level) in US counties. We also examine how these factors intersect with the proportion of the population that is people of colour (ie, not non-Hispanic white), a metric that reflects histories of US race relations. We defined ‘high’ risk counties as those above the 75th percentile. This threshold can be changed using the online tool.SettingUS counties.ParticipantsAnalyses are based on publicly available county-level data from the Area Health Resources Files, American Community Survey, Centers for Disease Control and Prevention Atlas file, National Center for Health Statistic and RWJF Community Health Rankings.ResultsOur findings demonstrate significant intercounty variation in the distribution of individual, household and community characteristics that affect risks of infection, severe disease or mortality from COVID-19. About 9% of counties, affecting 10 million residents, are in higher risk categories for both age and group quarters. About 14% of counties, affecting 31 million residents, have both high levels of poverty and a high proportion of people of colour.ConclusionFederal and state governments will benefit from recognising high intrastate, intercounty variation in population risks and response capacity. Equitable responses to the pandemic require strategies to protect those in counties at highest risk of adverse COVID-19 outcomes and their social and economic impacts.

Estimation of the effective reproductive number Rt is important for detecting changes in disease transmission over time. During the Coronavirus Disease 2019 (COVID-19) pandemic, policy makers and public health officials are using Rt to assess the effectiveness of interventions and to inform policy. However, estimation of Rt from available data presents several challenges, with critical implications for the interpretation of the course of the pandemic. The purpose of this document is to summarize these challenges, illustrate them with examples from synthetic data, and, where possible, make recommendations. For near real-time estimation of Rt, we recommend the approach of Cori and colleagues, which uses data from before time t and empirical estimates of the distribution of time between infections. Methods that require data from after time t, such as Wallinga and Teunis, are conceptually and methodologically less suited for near real-time estimation, but may be appropriate for retrospective analyses of how individuals infected at different time points contributed to the spread. We advise caution when using methods derived from the approach of Bettencourt and Ribeiro, as the resulting Rt estimates may be biased if the underlying structural assumptions are not met. Two key challenges common to all approaches are accurate specification of the generation interval and reconstruction of the time series of new infections from observations occurring long after the moment of transmission. Naive approaches for dealing with observation delays, such as subtracting delays sampled from a distribution, can introduce bias. We provide suggestions for how to mitigate this and other technical challenges and highlight open problems in Rt estimation., PLoS Computational Biology, 16 (12), ISSN:1553-734X, ISSN:1553-7358

The extent and duration of immunity following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are critical outstanding questions about the epidemiology of this novel virus, and studies are needed to evaluate the effects of serostatus on reinfection. Understanding the potential sources of bias and methods for alleviating biases in these studies is important for informing their design and analysis. Confounding by individual-level risk factors in observational studies like these is relatively well appreciated. Here, we show how geographic structure and the underlying, natural dynamics of epidemics can also induce noncausal associations. We take the approach of simulating serological studies in the context of an uncontrolled or controlled epidemic, under different assumptions about whether prior infection does or does not protect an individual against subsequent infection, and using various designs and analytical approaches to analyze the simulated data. We find that in studies assessing whether seropositivity confers protection against future infection, comparing seropositive persons with seronegative persons with similar time-dependent patterns of exposure to infection by stratifying or matching on geographic location and time of enrollment is essential in order to prevent bias.

Researchers starting clinical trials of prevention measures for COVID-19 have a unique window of opportunity for collecting blood from the participants, at baseline and at the end of the trial, to be able to incorporate critical data into their analysis once serological tests for the causative coronavirus become available.

Summary Background Voluntary individual quarantine and voluntary active monitoring of contacts are core disease control strategies for emerging infectious diseases such as COVID-19. Given the impact of quarantine on resources and individual liberty, it is vital to assess under what conditions individual quarantine can more effectively control COVID-19 than active monitoring. As an epidemic grows, it is also important to consider when these interventions are no longer feasible and broader mitigation measures must be implemented. Methods To estimate the comparative efficacy of individual quarantine and active monitoring of contacts to control severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we fit a stochastic branching model to reported parameters for the dynamics of the disease. Specifically, we fit a model to the incubation period distribution (mean 5·2 days) and to two estimates of the serial interval distribution: a shorter one with a mean serial interval of 4·8 days and a longer one with a mean of 7·5 days. To assess variable resource settings, we considered two feasibility settings: a high-feasibility setting with 90% of contacts traced, a half-day average delay in tracing and symptom recognition, and 90% effective isolation; and a low-feasibility setting with 50% of contacts traced, a 2-day average delay, and 50% effective isolation. Findings Model fitting by sequential Monte Carlo resulted in a mean time of infectiousness onset before symptom onset of 0·77 days (95% CI −1·98 to 0·29) for the shorter serial interval, and for the longer serial interval it resulted in a mean time of infectiousness onset after symptom onset of 0·51 days (95% CI −0·77 to 1·50). Individual quarantine in high-feasibility settings, where at least 75% of infected contacts are individually quarantined, contains an outbreak of SARS-CoV-2 with a short serial interval (4·8 days) 84% of the time. However, in settings where the outbreak continues to grow (eg, low-feasibility settings), so too will the burden of the number of contacts traced for active monitoring or quarantine, particularly uninfected contacts (who never develop symptoms). When resources are prioritised for scalable interventions such as physical distancing, we show active monitoring or individual quarantine of high-risk contacts can contribute synergistically to mitigation efforts. Even under the shorter serial interval, if physical distancing reduces the reproductive number to 1·25, active monitoring of 50% of contacts can result in overall outbreak control (ie, effective reproductive number

Key Points Question What are the associations of cohorting, staffing, and testing interventions with COVID-19 transmission in nursing homes? Findings In this decision analytical modeling study in a simulated nursing home with 100 residents and 100 staff, routine screening testing and strategies that prioritized pairing recovered staff and recovered residents with susceptible residents were associated with a reduction in transmission of COVID-19 in nursing homes. Meaning These findings suggest that frequent testing and immunity-based staffing interventions may reduce transmission of SARS-CoV-2 in nursing homes and protect this vulnerable population., This decision analytical modeling study examines the associations of cohorting, staffing, and testing interventions with COVID-19 transmission in nursing homes., Importance Nursing homes and other long-term care facilities have been disproportionately impacted by the COVID-19 pandemic. Strategies are urgently needed to reduce transmission in these high-risk populations. Objective To evaluate COVID-19 transmission in nursing homes associated with contact-targeted interventions and testing. Design, Setting, and Participants This decision analytical modeling study developed an agent-based susceptible–exposed–infectious (asymptomatic/symptomatic)–recovered model between July and September 2020 to examine SARS-CoV-2 transmission in nursing homes. Residents and staff of a simulated nursing home with 100 residents and 100 staff split among 3 shifts were modeled individually; residents were split into 2 cohorts based on COVID-19 diagnosis. Data were analyzed from September to October 2020. Exposures In the resident cohorting intervention, residents who had recovered from COVID-19 were moved back from the COVID-19 (ie, infected with SARS-CoV-2) cohort to the non–COVID-19 (ie, susceptible and uninfected with SARS-CoV-2) cohort. In the immunity-based staffing intervention, staff who had recovered from COVID-19 were assumed to have protective immunity and were assigned to work in the non–COVID-19 cohort, while susceptible staff worked in the COVID-19 cohort and were assumed to have high levels of protection from personal protective equipment. These interventions aimed to reduce the fraction of people’s contacts that were presumed susceptible (and therefore potentially infected) and replaced them with recovered (immune) contacts. A secondary aim of was to evaluate cumulative incidence of SARS-CoV-2 infections associated with 2 types of screening tests (ie, rapid antigen testing and polymerase chain reaction [PCR] testing) conducted with varying frequency. Main Outcomes and Measures Estimated cumulative incidence proportion of SARS-CoV-2 infection after 3 months. Results Among the simulated cohort of 100 residents and 100 staff members, frequency and type of testing were associated with smaller outbreaks than the cohorting and staffing interventions. The testing strategy associated with the greatest estimated reduction in infections was daily antigen testing, which reduced the mean cumulative incidence proportion by 49% in absence of contact-targeted interventions. Under all screening testing strategies, the resident cohorting intervention and the immunity-based staffing intervention were associated with reducing the final estimated size of the outbreak among residents, with the immunity-based staffing intervention reducing it more (eg, by 19% in the absence of testing) than the resident cohorting intervention (eg, by 8% in the absence of testing). The estimated reduction in transmission associated with these interventions among staff varied by testing strategy and community prevalence. Conclusions and Relevance These findings suggest that increasing the frequency of screening testing of all residents and staff, or even staff alone, in nursing homes may reduce outbreaks in this high-risk setting. Immunity-based staffing may further reduce spread at little or no additional cost and becomes particularly important when daily testing is not feasible.