Model-based estimates of deaths averted and cost per life saved by scaling-up mRNA COVID-19 vaccination in low and lower-middle income countries in the COVID-19 Omicron variant era (preprint)

Background: While almost 60% of the world has received at least one dose of COVID-19 vaccine, the global distribution of vaccination has not been equitable. Only 4% of the population of low-income countries has received a full primary vaccine series, compared to over 70% of the population of high-income nations. Methods: We used economic and epidemiologic models, parameterized with public data on global vaccination and COVID-19 deaths, to estimate the potential benefits of scaling up vaccination programs in low and lower-middle income countries (LIC/LMIC) in 2022 in the context of global spread of the Omicron variant of SARS-CoV2. Outcomes were expressed as number of avertable deaths through vaccination, costs of scale-up, and cost per death averted. We conducted sensitivity analyses over a wide range of parameter estimates to account for uncertainty around key inputs. Findings: Global scale up of vaccination to provide two doses of mRNA vaccine to everyone in LIC/LMIC would cost $35.5 billion and avert 1.3 million deaths from COVID-19, at a cost of $26,900 per death averted. Scaling up vaccination to provide three doses of mRNA vaccine to everyone in LIC/LMIC would cost $61.2 billion and avert 1.5 million deaths from COVID-19 at a cost of $40,800 per death averted. Lower estimated infection fatality ratios, higher cost-per-dose, and lower vaccine effectiveness or uptake lead to higher cost-per-death averted estimates in the analysis. Interpretation: Scaling up COVID-19 global vaccination would avert millions of COVID-19 deaths and represents a reasonable investment in the context of the value of a statistical life (VSL). Given the magnitude of expected mortality facing LIC/LMIC without vaccination, this effort should be an urgent priority.

Impact of accelerating booster vaccination amidst Omicron surge in the United States (preprint)

COVID-19 infections driven by the Omicron variant are sweeping across the United States. Although early evidence suggests that the Omicron variant may cause less severe disease than previous variants, the explosive spread of infections threatens to drive hospitalizations and deaths to unprecedented high levels, swamping already overburdened hospitals. Booster vaccination appears to be effective at preventing severe illness and hospitalization. However, the pace of booster vaccination in the US has been slow despite the available infrastructure to administer doses at a much higher rate. We used an age-stratified, multi-variant agent-based model to project the reduction in COVID-related deaths and hospitalizations that could be achieved by accelerating the current daily pace of booster vaccination in the US. We found that doubling the rate of booster vaccination would prevent over 400,000 hospitalizations and 48,000 deaths. Tripling the booster vaccination rate would avert over 600,000 hospitalizations and save 70,000 lives during the first four months of 2022.

When do elementary students need masks in school? Model-estimated risk of in-school SARS-CoV-2 transmission and related infections among household members before and after student vaccination (preprint)

BackgroundWhile CDC guidance for K-12 schools recommends indoor masking regardless of vaccination status, final decisions about masking in schools will be made at the local and state level. The impact of the removal of mask restrictions, however, on COVID-19 outcomes for elementary students, educators/staff, and their households is not well known. MethodsWe used a previously published agent-based dynamic transmission model of SARS-CoV-2 in K-12 schools to simulate an elementary school with 638 students across 6 scenarios: combinations of three viral infectiousness levels (reflecting wild-type virus, alpha variant, and delta variant) and two student vaccination levels (0% and 50% coverage to reflect potential authorization in this age group). For each scenario, we varied observed community COVID-19 incidence (0 to 50 cases/100,000 people/day) and mitigation effectiveness (0-100% reduction to in-school secondary attack rate), and evaluated two outcomes over a 30 day period: (1) the probability of at least one in-school transmission, and (2) the increase in total cases among students, educators/staff, and their household members between in-person and remote instruction. ResultsOver 30 days in the simulated elementary school, the probability of at least one in-school SARS-CoV-2 transmission and the number of projected infections in the immediate school community varied widely. In one scenario with the delta variant and no student vaccination, assuming that baseline mitigation measures of simple ventilation and handwashing reduce the secondary attack rate by 40%, if decision-makers seek to keep the monthly probability of an in-school transmission below 50%, additional mitigation (e.g., masking) would need to be added at a community incidence of approximately 4/100,000/day. Once students are vaccinated, thresholds shift substantially higher. LimitationsThe interpretation of model results should be limited by the uncertainty in many of the parameters, including the effectiveness of individual mitigation interventions and vaccine efficacy against the delta variant, and the limited scope of the model beyond the school community. Additionally, the assumed case detection rate (33% of cases detected) may be too high in areas with decreased testing capacity. ConclusionDespite the assumption of high adult vaccination, the risks of both in-school SARS-CoV-2 transmission and resulting infections among students, educators/staff, and their household members remain high when the delta variant predominates and students are unvaccinated. Mitigation measures or vaccinations for students when available can substantially reduce these risks. These findings underscore the potential role for responsive plans, where mitigation is deployed based on local COVID-19 incidence and vaccine uptake.

Timing is everything: the relationship between COVID outcomes and the date at which mask mandates are relaxed (preprint)

Importance Several states including Texas and Mississippi have lifted their mask mandates, sparking concerns that this policy change could lead to a surge in cases and hospitalizations. Objective To estimate the increase in incidence, hospitalizations, and deaths in Texas and Mississippi following the removal of mask mandates, and to evaluate the relative reduction of these outcomes if policy change is delayed by 90 days. Design, Setting, and Participants This study uses an age-stratified compartmental model parameterized to incidence data in Texas and Mississippi to simulate increased transmission following policy change in March or June 2021, and to estimate the resulting number of incidence, hospitalizations, and deaths. Main Outcomes and Measures The increase in incidence, hospitalizations, and deaths if mask mandates are lifted on March 14 compared to lifting on June 12. Results If transmission is increased by 67% when mask mandates are lifted, we projected 11.39 (CrI: 11.22 - 11.55) million infections, 170,909 (CrI: 167,454 - 174,379) hospitalizations, and 5647 (5511 - 5804) deaths (Figure 1) in Texas from March 14 through the end of 2021. Delaying NPI lift until June reduces the average number of infections, hospitalizations, and deaths by 36%, 65%, and 62%, respectively. Proportionate differences were similar for the state of Mississippi. Peak hospitalization rates would be reduced by 79% and 63% in Texas and Mississippi, respectively. Conclusions and Relevance Removal of mask mandates in March 2021 is premature. Delaying this policy change until June 2021, when a larger fraction of the population has been vaccinated, will avert more than half of the expected COVID-19 hospitalizations and deaths, and avoid an otherwise likely strain on healthcare capacity.

Evaluation of COVID-19 vaccination strategies with a delayed second dose (preprint)

COVID-19 vaccines currently approved in the United States require two doses, administered three to four weeks apart. Constraints in vaccine supply and distribution capacity, together with the rise of COVID-19 cases and hospitalizations, have sparked a policy debate on whether to vaccinate more individuals with the first dose of available vaccines and delay the second dose, or to continue with the recommended two-dose series as tested in clinical trials. We developed an agent-based model of COVID-19 transmission to compare the impact of these two vaccination strategies, while varying the temporal waning of vaccine efficacy against disease following the first dose, vaccine efficacy against infection, and the level of pre-existing immunity in the population. Our results show that for Moderna vaccines with 80% efficacy following the first dose, a delay of 9-12 weeks could enhance the program effectiveness and prevent additional infections, hospitalizations, and deaths, compared to a 4-week interval between the doses. However, for Pfizer-BioNTech vaccines with demonstrated efficacy of 52% after the first dose, there was no clear advantage for delaying the second dose beyond the 3-week tested schedule, unless the efficacy of the first dose did not wane over time. Our findings underscore the importance of quantifying the durability of vaccine-induced protection after the first dose as well as vaccine efficacy against infection in order to determine the optimal time interval between the two doses.

Identifying silent COVID-19 infections among children is critical for controlling the pandemic (preprint)

Importance: A significant proportion of COVID-19 transmission occurs silently during the pre-symptomatic and asymptomatic stages of infection. Children, while being important drivers of silent transmission, are not included in COVID-19 vaccination campaigns given their exclusion from clinical trials thus far. Objective: To investigate the impact of a targeted approach to identifying silent infections among children as a proxy for their vaccination. Design: This study used an age-structured disease transmission model to simulate the synergistic impact of interventions in reducing attack rates over the course of one year. Setting: A synthetic population representative of the demographics of the United States (US). Participants: Six age groups of 0-4, 5-10, 11-18, 19-49, 50-64, 65+ years old, stratified for their population size based on US census data. Exposures: Vaccination of adults, self-isolation of all symptomatic cases within 24 hours of symptom onset, and detection of silent infections. Main Outcomes and Measures: Vaccination of adults was implemented to reach a 40% coverage over the course of one year with a vaccine efficacy of 95% against symptomatic and severe COVID-19. Without vaccination of children, we determined the proportion and speed that would be required for identifying silent infections among this age group to suppress future attack rates below 5%. Results: A targeted approach that identifies 20.6% and 28.6% of silent infections among children within 2 or 3 days post-infection, respectively, would be required to bring attack rates under 5% with vaccination of adults. If silent infections among children remained undetected, achieving the same attack rates would require an unrealistically high vaccination coverage (at least 82%) of this age group, in addition to the base-case 40% vaccination coverage of adults. The results were robust in sensitivity analyses with respect to vaccine efficacy against infection and reduced susceptibility of children to infection. Conclusions and Relevance: In the absence of vaccine availability for children, a targeted approach to rapid identification of silent COVID-19 infections in this age group can significantly mitigate disease burden. Without measures to interrupt transmission chains from silent infections, vaccination of adults is unlikely to contain the outbreaks in the near term.

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

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 (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.

Strict Physical Distancing May Be More Efficient: A Mathematical Argument for Making Lockdowns Count (preprint)

COVID-19 created a global public health and economic emergency. Policymakers acted quickly and decisively to contain the spread of disease through physical distancing measures. However, these measures also impact physical, mental and economic well-being, creating difficult trade-offs. Here we use a simple mathematical model to explore the balance between public health measures and their associated social and economic costs. Across a range of cost-functions and model structures, commitment to intermittent and strict social distancing measures leads to better overall outcomes than temporally consistent implementation of moderate physical distancing measures. With regard to the trade-offs that policymakers may soon face, our results emphasize that economic and health outcomes do not exist in full competition. Compared to consistent moderation, intermittently strict policies can better mitigate the impact of the pandemic on both of these priorities for a range of plausible utility functions.