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

BackgroundWhile 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. MethodsWe 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. FindingsGlobal 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. InterpretationScaling 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

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

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 12 scenarios: combinations of three viral infectiousness levels (reflecting wild-type virus, alpha variant, and delta variant) and four student vaccination levels (0%, 25%, 50% and 70% coverage). 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) average increase in total infections among students, educators/staff, and their household members associated with moving from more to less intensive mitigation measures. ResultsOver 30 days in the simulated elementary school, the probability of at least one in-school SARS-CoV-2 transmission and the number of estimated additional infections in the immediate school community associated with changes in mitigation measures 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 2/100,000/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 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.

COVID-19 deaths and hospitalizations averted by rapid vaccination rollout in the United States

ImportanceRandomized clinical trials have shown that the COVID-19 vaccines currently approved in the US are highly efficacious. However, more evidence is needed to understand the population-level impact of the US vaccination rollout in the face of the changing landscape of COVID-19 pandemic in the US, including variants with higher transmissibility and immune escape. ObjectiveTo quantify the population-level impact of the US vaccination campaign in averting cases, hospitalizations and deaths from December 12, 2020 to June 28, 2021. DesignAge-stratified agent-based model which included transmission dynamics of the Alpha, Gamma and Delta variants in addition to the original Wuhan-1 variant. SettingOur model was calibrated to COVID-19 outbreak and vaccine rollout in the US. Model predictions were made at the country level. ParticipantsSimulated age-stratified population representing US demographics. Main Outcomes and MeasuresCases, hospitalizations and deaths averted by vaccination against COVID-19 in the US, compared to the counterfactuals of no vaccination and vaccination administered at half the actual pace. ResultsThe swift vaccine rollout in the US curbed a potential resurgence of cases in April 2021, which would have been otherwise fuelled by the Alpha variant. Compared to the scenario without vaccines, we estimated that the actual vaccination program averted more than 26 million cases, 1.2 million hospitalizations and saved 279,000 lives. A vaccination campaign with half the actual rollout rate would have led to an additional 460,000 hospitalizations and 121,000 deaths. Conclusions and RelevanceThe COVID-19 vaccination campaign in the US has had an extraordinary impact on reducing disease burden despite the emergence of highly transmissible variants. These findings highlight that the pace of vaccination was essential for mitigating COVID-19 in the US, and underscore the urgent need to close the vaccine coverage gaps in communities across the country. Key PointsO_ST_ABSQuestionC_ST_ABSHow effective was the United States (US) vaccination campaign in suppressing COVID-19 burden? FindingsThe vaccination campaign was highly effective in curbing the COVID-19 outbreak in the US. We estimated that the vaccine rollout saved over 275,000 lives and averted 1.2 million hospitalizations. MeaningThe swift vaccine rollout in the US averted a remarkable number of cases, hospitalizations and deaths despite the emergence of highly transmissible variants.

Quantifying the potential for dominant spread of SARS-CoV-2 variant B.1.351 in the United States

Recent evidence suggests that some new SARS-CoV-2 variants with spike mutations, such as P.1 (Gamma) and B.1.617.2 (Delta), exhibit partial immune evasion to antibodies generated by natural infection or vaccination. By considering the Gamma and Delta variants in a multi-variant transmission dynamic model, we evaluated the dominance of these variants in the United States (US) despite mounting vaccination coverage and other circulating variants. Our results suggest that while the dominance of the Gamma variant is improbable, the Delta variant would become the most prevalent variant in the US, driving a surge in infections and hospitalizations. Our study highlights the urgency for accelerated vaccination and continued adherence to non-pharmaceutical measures until viral circulation is driven low.

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

ImportanceSeveral 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. ObjectiveTo 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 ParticipantsThis 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 MeasuresThe increase in incidence, hospitalizations, and deaths if mask mandates are lifted on March 14 compared to lifting on June 12. ResultsIf 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. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=126 SRC="FIGDIR/small/21254646v1_fig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@49cbbforg.highwire.dtl.DTLVardef@df7928org.highwire.dtl.DTLVardef@18b5885org.highwire.dtl.DTLVardef@160b6d1_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure 1:C_FLOATNO Cumulative number of infections, hospitalizations, and deaths for (A) Texas and (B) Mississippi through 2021 if NPI were lifted on March 14 (red) or June 12 (blue). C_FIG Conclusions and RelevanceRemoval 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

Two of the 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 a deadly wave of COVID-19 from November 2020 to January 2021 and the emergence of highly contagious SARS-CoV-2 variants, 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 following the first dose and the level of pre-existing immunity in the population. Our results show that for Moderna vaccines, a delay of at least 9 weeks could maximize vaccination program effectiveness and avert at least an additional 17.3 (95% CrI: 7.8 - 29.7) infections, 0.71 (95% CrI: 0.52 - 0.97) hospitalizations, and 0.34 (95% CrI: 0.25 - 0.44) deaths per 10,000 population compared to the recommended 4-week interval between the two doses. Pfizer-BioNTech vaccines also averted an additional 0.61 (95% CrI: 0.37 - 0.89) hospitalizations and 0.31 (95% CrI: 0.23 - 0.45) deaths per 10,000 population in a 9-week delayed second dose strategy compared to the 3-week recommended schedule between doses. However, there was no clear advantage of delaying the second dose with Pfizer-BioNTech vaccines in reducing infections, unless the efficacy of the first dose did not wane over time. Our findings underscore the importance of quantifying the characteristics and durability of vaccine-induced protection after the first dose 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

ImportanceA 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 the current COVID-19 vaccination campaigns. ObjectiveTo investigate the benefits of identifying silent infections among children as a proxy for their vaccination. DesignThis study used an age-structured disease transmission model, parameterized with census data and estimates from published literature, to simulate the synergistic effect of interventions in reducing attack rates over the course of one year. SettingA synthetic population representative of the United States (US) demographics. ParticipantsSix age groups of 0-4, 5-10, 11-18, 19-49, 50-64, 65+ years based on US census data. InterventionsIn addition to the isolation of symptomatic cases within 24 hours of symptom onset, vaccination of adults was implemented to reach a 40%-60% coverage over the course of one year with an efficacy of 95% against symptomatic and severe COVID-19. Main Outcomes and MeasuresThe combinations of proportion and speed for detecting silent infections among children which would suppress future attack rates below 5%. ResultsIn the base-case scenarios with an effective reproduction number Re = 1.2, a targeted approach that identifies 11% and 14% of silent infections among children within 2 or 3 days post-infection, respectively, would bring attack rates under 5% with 40% vaccination coverage of adults. If silent infections among children remained undetected, achieving the same attack rates would require an unrealistically high vaccination coverage (at least 81%) of this age group, in addition to 40% vaccination coverage of adults. The effect of identifying silent infections was robust in sensitivity analyses with respect to vaccine efficacy against infection and reduced susceptibility of children to infection. Conclusions and RelevanceIn this simulation modeling study of a synthetic US population, in the absence of vaccine availability for children, a targeted approach to rapidly identify silent COVID-19 infections in this age group was estimated to 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. Key PointsO_ST_ABSQuestionC_ST_ABSWhat is the effect of a targeted strategy for identification of silent COVID-19 infections among children in the absence of their vaccination? FindingsIn this simulation modeling study, it was found that identifying 10-20% of silent infections among children within three days post-infection would bring attack rates below 5% if only adults were vaccinated. If silent infections among children remained undetected, achieving the same attack rate would require an unrealistically high vaccination coverage (over 80%) of this age group, in addition to vaccination of adults. MeaningRapid identification of silent infections among children can achieve comparable effects as would their vaccination.

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.

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

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.