Multimodeling approach to evaluating the efficacy of layering pharmaceutical and nonpharmaceutical interventions for influenza pandemics.

When an influenza pandemic emerges, temporary school closures and antiviral treatment may slow virus spread, reduce the overall disease burden, and provide time for vaccine development, distribution, and administration while keeping a larger portion of the general population infection free. The impact of such measures will depend on the transmissibility and severity of the virus and the timing and extent of their implementation. To provide robust assessments of layered pandemic intervention strategies, the Centers for Disease Control and Prevention (CDC) funded a network of academic groups to build a framework for the development and comparison of multiple pandemic influenza models. Research teams from Columbia University, Imperial College London/Princeton University, Northeastern University, the University of Texas at Austin/Yale University, and the University of Virginia independently modeled three prescribed sets of pandemic influenza scenarios developed collaboratively by the CDC and network members. Results provided by the groups were aggregated into a mean-based ensemble. The ensemble and most component models agreed on the ranking of the most and least effective intervention strategies by impact but not on the magnitude of those impacts. In the scenarios evaluated, vaccination alone, due to the time needed for development, approval, and deployment, would not be expected to substantially reduce the numbers of illnesses, hospitalizations, and deaths that would occur. Only strategies that included early implementation of school closure were found to substantially mitigate early spread and allow time for vaccines to be developed and administered, especially under a highly transmissible pandemic scenario.

Point Prevalence Estimates of Activity-Limiting Long-term Symptoms Among United States Adults ≥1 Month After Reported Severe Acute Respiratory Syndrome Coronavirus 2 Infection, 1 November 2021.

BACKGROUND: Although most adults infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) fully recover, a proportion have ongoing symptoms, or post-COVID conditions (PCC), after infection. The objective of this analysis was to estimate the number of United States (US) adults with activity-limiting PCC on 1 November 2021. METHODS: We modeled the prevalence of PCC using reported infections occurring from 1 February 2020 to 30 September 2021, and population-based, household survey data on new activity-limiting symptoms ≥1 month following SARS-CoV-2 infection. From these data sources, we estimated the number and proportion of US adults with activity-limiting PCC on 1 November 2021 as 95% uncertainty intervals, stratified by sex and age. Sensitivity analyses adjusted for underascertainment of infections and uncertainty about symptom duration. RESULTS: On 1 November 2021, at least 3.0-5.0 million US adults, or 1.2%-1.9% of the US adult population, were estimated to have activity-limiting PCC of ≥1 month's duration. Population prevalence was higher in females (1.4%-2.2%) than males. The estimated prevalence after adjusting for underascertainment of infections was 1.7%-3.8%. CONCLUSIONS: Millions of US adults were estimated to have activity-limiting PCC. These estimates can support future efforts to address the impact of PCC on the US population.

Genomic Surveillance for SARS-CoV-2 Variants: Predominance of the Delta (B.1.617.2) and Omicron (B.1.1.529) Variants - United States, June 2021-January 2022.

Genomic surveillance is a critical tool for tracking emerging variants of SARS-CoV-2 (the virus that causes COVID-19), which can exhibit characteristics that potentially affect public health and clinical interventions, including increased transmissibility, illness severity, and capacity for immune escape. During June 2021-January 2022, CDC expanded genomic surveillance data sources to incorporate sequence data from public repositories to produce weighted estimates of variant proportions at the jurisdiction level and refined analytic methods to enhance the timeliness and accuracy of national and regional variant proportion estimates. These changes also allowed for more comprehensive variant proportion estimation at the jurisdictional level (i.e., U.S. state, district, territory, and freely associated state). The data in this report are a summary of findings of recent proportions of circulating variants that are updated weekly on CDC's COVID Data Tracker website to enable timely public health action.† The SARS-CoV-2 Delta (B.1.617.2 and AY sublineages) variant rose from 1% to >50% of viral lineages circulating nationally during 8 weeks, from May 1-June 26, 2021. Delta-associated infections remained predominant until being rapidly overtaken by infections associated with the Omicron (B.1.1.529 and BA sublineages) variant in December 2021, when Omicron increased from 1% to >50% of circulating viral lineages during a 2-week period. As of the week ending January 22, 2022, Omicron was estimated to account for 99.2% (95% CI = 99.0%-99.5%) of SARS-CoV-2 infections nationwide, and Delta for 0.7% (95% CI = 0.5%-1.0%). The dynamic landscape of SARS-CoV-2 variants in 2021, including Delta- and Omicron-driven resurgences of SARS-CoV-2 transmission across the United States, underscores the importance of robust genomic surveillance efforts to inform public health planning and practice.

Modeling Effectiveness of Testing Strategies to Prevent Coronavirus Disease 2019 (COVID-19) in Nursing Homes-United States, 2020.

BACKGROUND: Identifying asymptomatic individuals early through serial testing is recommended to control coronavirus disease 2019 (COVID-19) in nursing homes, both in response to an outbreak ("outbreak testing" of residents and healthcare personnel) and in facilities without outbreaks ("nonoutbreak testing" of healthcare personnel). The effectiveness of outbreak testing and isolation with or without nonoutbreak testing was evaluated. METHODS: Using published SARS-CoV-2 transmission parameters, the fraction of SARS-CoV-2 transmissions prevented through serial testing (weekly, every 3 days, or daily) and isolation of asymptomatic persons compared with symptom-based testing and isolation was evaluated through mathematical modeling using a Reed-Frost model to estimate the percentage of cases prevented (ie, "effectiveness") through either outbreak testing alone or outbreak plus nonoutbreak testing. The potential effect of simultaneous decreases (by 10%) in the effectiveness of isolating infected individuals when instituting testing strategies was also evaluated. RESULTS: Modeling suggests that outbreak testing could prevent 54% (weekly testing with 48-hour test turnaround) to 92% (daily testing with immediate results and 50% relative sensitivity) of SARS-CoV-2 infections. Adding nonoutbreak testing could prevent up to an additional 8% of SARS-CoV-2 infections (depending on test frequency and turnaround time). However, added benefits of nonoutbreak testing were mostly negated if accompanied by decreases in infection control practice. CONCLUSIONS: When combined with high-quality infection control practices, outbreak testing could be an effective approach to preventing COVID-19 in nursing homes, particularly if optimized through increased test frequency and use of tests with rapid turnaround.

Characterizing Norovirus Transmission from Outbreak Data, United States.

Norovirus is the leading cause of acute gastroenteritis outbreaks in the United States. We estimated the basic (R0) and effective (Re) reproduction numbers for 7,094 norovirus outbreaks reported to the National Outbreak Reporting System (NORS) during 2009-2017 and used regression models to assess whether transmission varied by outbreak setting. The median R0 was 2.75 (interquartile range [IQR] 2.38-3.65), and median Re was 1.29 (IQR 1.12-1.74). Long-term care and assisted living facilities had an R0 of 3.35 (95% CI 3.26-3.45), but R0 did not differ substantially for outbreaks in other settings, except for outbreaks in schools, colleges, and universities, which had an R0 of 2.92 (95% CI 2.82-3.03). Seasonally, R0 was lowest (3.11 [95% CI 2.97-3.25]) in summer and peaked in fall and winter. Overall, we saw little variability in transmission across different outbreaks settings in the United States.

Estimated Number of COVID-19 Infections, Hospitalizations, and Deaths Prevented Among Vaccinated Persons in the US, December 2020 to September 2021.

Importance: The number of SARS-CoV-2 infections and COVID-19-associated hospitalizations and deaths prevented among vaccinated persons, independent of the effect of reduced transmission, is a key measure of vaccine impact. Objective: To estimate the number of SARS-CoV-2 infections and COVID-19-associated hospitalizations and deaths prevented among vaccinated adults in the US. Design, Setting, and Participants: In this modeling study, a multiplier model was used to extrapolate the number of SARS-CoV-2 infections and COVID-19-associated deaths from data on the number of COVID-19-associated hospitalizations stratified by state, month, and age group (18-49, 50-64, and ≥65 years) in the US from December 1, 2020, to September 30, 2021. These estimates were combined with data on vaccine coverage and effectiveness to estimate the risks of infections, hospitalizations, and deaths. Risks were applied to the US population 18 years or older to estimate the expected burden in that population without vaccination. The estimated burden in the US population 18 years or older given observed levels of vaccination was subtracted from the expected burden in the US population 18 years or older without vaccination (ie, counterfactual) to estimate the impact of vaccination among vaccinated persons. Exposures: Completion of the COVID-19 vaccination course, defined as 2 doses of messenger RNA (BNT162b2 or mRNA-1273) vaccines or 1 dose of JNJ-78436735 vaccine. Main Outcomes and Measures: Monthly numbers and percentages of SARS-CoV-2 infections and COVID-19-associated hospitalizations and deaths prevented were estimated among those who have been vaccinated in the US. Results: COVID-19 vaccination was estimated to prevent approximately 27 million (95% uncertainty interval [UI], 22 million to 34 million) infections, 1.6 million (95% UI, 1.4 million to 1.8 million) hospitalizations, and 235 000 (95% UI, 175 000-305 000) deaths in the US from December 1, 2020, to September 30, 2021, among vaccinated adults 18 years or older. From September 1 to September 30, 2021, vaccination was estimated to prevent 52% (95% UI, 45%-62%) of expected infections, 56% (95% UI, 52%-62%) of expected hospitalizations, and 58% (95% UI, 53%-63%) of expected deaths in adults 18 years or older. Conclusions and Relevance: These findings indicate that the US COVID-19 vaccination program prevented a substantial burden of morbidity and mortality through direct protection of vaccinated individuals.

Cost-effectiveness of pediatric norovirus vaccination in daycare settings.

OBJECTIVE: Noroviruses are the leading cause of acute gastroenteritis in the United States and outbreaks frequently occur in daycare settings. Results of norovirus vaccine trials have been promising, however there are open questions as to whether vaccination of daycare children would be cost-effective. We investigated the incremental cost-effectiveness of a hypothetical norovirus vaccination for children in daycare settings compared to no vaccination. METHODS: We conducted a model-based cost-effectiveness analysis using a disease transmission model of children attending daycare. Vaccination with a 90% coverage rate in addition to the observed standard of care (exclusion of symptomatic children from daycare) was compared to the observed standard of care. The main outcomes measures were infections and deaths averted, quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratio (ICER). Cost-effectiveness was analyzed from a societal perspective, including medical costs to children as well as productivity losses of parents, over a two-year time horizon. Data sources included outbreak surveillance data and published literature. RESULTS: A 50% efficacious norovirus vaccine averts 571.83 norovirus cases and 0.003 norovirus-related deaths per 10,000 children compared to the observed standard of care. A $200 norovirus vaccine that is 50% efficacious has a net cost increase of $178.10 per child and 0.025 more QALYs, resulting in an ICER of $7,028/QALY. Based on the probabilistic sensitivity analysis, we estimated that a $200 vaccination with 50% efficacy was 94.0% likely to be cost-effective at a willingness-to-pay of $100,000/QALY threshold and 95.3% likely at a $150,000/QALY threshold. CONCLUSION: Due to the large disease burden associated with norovirus, it is likely that vaccinating children in daycares could be cost-effective, even with modest vaccine efficacy and a high per-child cost of vaccination. Norovirus vaccination of children in daycare has a cost-effectiveness ratio similar to other commonly recommended childhood vaccines.

Targeting pediatric versus elderly populations for norovirus vaccines: a model-based analysis of mass vaccination options.

BACKGROUND: Noroviruses are the leading cause of acute gastroenteritis and foodborne diarrheal disease in the United States. Norovirus vaccine development has progressed in recent years, but critical questions remain regarding which age groups should be vaccinated to maximize population impact. METHODS: We developed a deterministic, age-structured compartmental model of norovirus transmission and immunity in the U.S. POPULATION: The model was fit to age-specific monthly U.S. hospitalizations between 1996 and 2007. We simulated mass immunization of both pediatric and elderly populations assuming realistic coverages of 90% and 65%, respectively. We considered two mechanism of vaccine action, resulting in lower vaccine efficacy (lVE) between 22% and 43% and higher VE (hVE) of 50%. RESULTS: Pediatric vaccination was predicted to avert 33% (95% CI: 27%, 40%) and 60% (95% CI: 49%, 71%) of norovirus episodes among children under five years for lVE and hVE, respectively. Vaccinating the elderly averted 17% (95% CI: 12%, 20%) and 38% (95% CI: 34%, 42%) of cases in 65+ year olds for lVE and hVE, respectively. At a population level, pediatric vaccination was predicted to avert 18-21 times more cases and twice as many deaths per vaccinee compared to elderly vaccination. CONCLUSIONS: The potential benefits are likely greater for a pediatric program, both via direct protection of vaccinated children and indirect protection of unvaccinated individuals, including adults and the elderly. These findings argue for a clinical development plan that will deliver a vaccine with a safety and efficacy profile suitable for use in children.