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.

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.

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.

Projecting the impact of a two-dose COVID-19 vaccination campaign in Ontario, Canada

BackgroundA number of highly effective COVID-19 vaccines have been developed and approved for mass vaccination. We evaluated the impact of vaccination on COVID-19 outbreak and disease outcomes in Ontario, Canada. MethodsWe used an agent-based transmission model and parameterized it with COVID-19 characteristics, demographics of Ontario, and age-specific clinical outcomes. We implemented a two-dose vaccination program according to tested schedules in clinical trials for Pfizer-BioNTech and Moderna vaccines, prioritizing healthcare workers, individuals with comorbidities, and those aged 65 and older. Daily vaccination rate was parameterized based on vaccine administration data. Using estimates of vaccine efficacy, we projected the impact of vaccination on the overall attack rate, hospitalizations, and deaths. We further investigated the effect of increased daily contacts at different stages during vaccination campaigns on outbreak control. ResultsMaintaining non-pharmaceutical interventions (NPIs) with an average of 74% reduction in daily contacts, vaccination with Pfizer-BioNTech and Moderna vaccines was projected to reduce hospitalizations by 27.3% (95% CrI: 22.3% - 32.4%) and 27.0% (95% CrI: 21.9% - 32.6%), respectively, over a one-year time horizon. The largest benefits of vaccination were observed in preventing deaths with reductions of 31.5% (95% CrI: 22.5% - 39.7%) and 31.9% (95% CrI: 22.0% - 41.4%) for Pfizer-BioNTech and Moderna vaccines, respectively, compared to no vaccination. We found that an increase of only 10% in daily contacts at the end of lockdown, when vaccination coverage with only one dose was 6%, would trigger a surge in the outbreak. Early relaxation of population-wide measures could lead to a substantial increase in the number of infections, potentially reaching levels observed during the peak of the second wave in Ontario. ConclusionsVaccination can substantially mitigate ongoing COVID-19 outbreaks. Sustaining population-wide NPIs, to allow for a sufficient increase in population-level immunity through vaccination, is essential to prevent future outbreaks.

Multifaceted strategies for the control of COVID-19 outbreaks in long-term care facilities in Ontario, Canada

The novel coronavirus disease 2019 (COVID-19) has caused severe outbreaks in Canadian long-term care facilities (LTCFs). In Canada, over 80% of COVID-19 deaths during the first pandemic wave occurred in LTCFs. We sought to evaluate the effect of mitigation measures in LTCFs including frequent testing of staff, and vaccination of staff and residents. We developed an agent-based transmission model and parameterized it with disease-specific estimates, temporal sensitivity of nasopharyngeal and saliva testing, results of vaccine efficacy trials, and data from initial COVID-19 outbreaks in LTCFs in Ontario, Canada. Characteristics of staff and residents, including contact patterns, were integrated into the model with age-dependent risk of hospitalization and death. Estimates of infection and outcomes were obtained and 95% credible intervals were generated using a bias-corrected and accelerated bootstrap method. Weekly routine testing of staff with 2-day turnaround time reduced infections among residents by at least 25.9% (95% CrI: 23.3% - 28.3%), compared to baseline measures of mask-wearing, symptom screening, and staff cohorting alone. A similar reduction of hospitalizations and deaths was achieved in residents. Vaccination averted 2-4 times more infections in both staff and residents as compared to routine testing, and markedly reduced hospitalizations and deaths among residents by 95.9% (95% CrI: 95.4% - 96.3%) and 95.8% (95% CrI: 95.5% - 96.1%), respectively, over 200 days from the start of vaccination. Vaccination could have a substantial impact on mitigating disease burden among residents, but may not eliminate the need for other measures before population-level control of COVID-19 is achieved.

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.

Rapid disappearance of influenza following the implementation of COVID-19 mitigation measures in Hamilton, Ontario

BackgroundPublic health measures, such as social distancing and closure of schools and non-essential services, were rapidly implemented in Canada to interrupt the spread of the novel coronavirus disease 2019 (COVID-19). ObjectiveWe sought to investigate the impact of mitigation measures during the spring wave of COVID-19 on the incidence of other laboratory-confirmed respiratory viruses in Hamilton, Ontario. MethodsAll nasopharyngeal swab specimens (n = 57,503) submitted for routine respiratory virus testing at a regional laboratory serving all acute-care hospitals in Hamilton, Ontario between January 2010 and June 2020 were reviewed. Testing for influenza A/B, respiratory syncytial virus, human metapneumovirus, parainfluenza I-III, adenovirus and rhinovirus/enterovirus was done routinely using a laboratory-developed polymerase chain reaction multiplex respiratory viral panel. A Bayesian linear regression model was used to determine the trend of positivity rates of all influenza samples for the first 26 weeks of each year from 2010 to 2019. The mean positivity rate of Bayesian inference was compared with the weekly reported positivity rate of influenza samples in 2020. ResultsThe positivity rate of influenza in 2020 diminished sharply following the population-wide implementation of COVID-19 interventions. Weeks 12-26 reported 0% positivity for influenza, with the exception of 0.1% reported in week 13. ConclusionsPublic health measures implemented during the COVID-19 pandemic were associated with a reduced incidence of other respiratory viruses and should be considered to mitigate severe seasonal influenza and other respiratory virus pandemics.

Routine saliva testing for the identification of silent COVID-19 infections in healthcare workers

ObjectiveCurrent COVID-19 guidelines recommend symptom-based screening and regular nasopharyngeal (NP) testing for healthcare personnel in high-risk settings. We sought to estimate case detection percentages with various routine NP and saliva testing frequencies. DesignSimulation modelling study. MethodsWe constructed a sensitivity function based on the average infectiousness profile of symptomatic COVID-19 cases to determine the probability of being identified at the time of testing. This function was fitted to reported data on the percent positivity of symptomatic COVID-19 patients using NP testing. We then simulated a routine testing program with different NP and saliva testing frequencies to determine case detection percentages during the infectious period, as well as the pre-symptomatic stage. ResultsRoutine bi-weekly NP testing, once every two weeks, identified an average of 90.7% (SD: 0.18) of cases during the infectious period and 19.7% (SD: 0.98) during the pre-symptomatic stage. With a weekly NP testing frequency, the corresponding case detection percentages were 95.9% (SD: 0.18) and 32.9% (SD: 1.23), respectively. A 5-day saliva testing schedule had a similar case detection percentage as weekly NP testing during the infectious period, but identified about 10% more cases (mean: 42.5%; SD: 1.10) during the pre-symptomatic stage. ConclusionOur findings highlight the utility of routine non-invasive saliva testing for frontline healthcare workers to protect vulnerable patient populations. A 5-day saliva testing schedule should be considered to help identify silent infections and prevent outbreaks in nursing homes and healthcare facilities.

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.