key: cord-0783030-pjceiq4i authors: León, Tomás M; Vargo, Jason; Pan, Erica S; Jain, Seema; Shete, Priya B title: Nonpharmaceutical Interventions Remain Essential to Reducing Coronavirus Disease 2019 Burden Even in a Well-Vaccinated Society: A Modeling Study date: 2021-08-09 journal: Open Forum Infect Dis DOI: 10.1093/ofid/ofab415 sha: a3ff90b915573a151a387eb9f2595e8d11c94c90 doc_id: 783030 cord_uid: pjceiq4i Vaccination and nonpharmaceutical interventions (NPIs) reduce transmission of severe acute respiratory syndrome coronavirus 2 infection, but their effectiveness depends on coverage and adherence levels. We used scenario modeling to evaluate their effects on cases and deaths averted and herd immunity. NPIs and vaccines worked synergistically in different parts of the pandemic to reduce disease burden. Since the beginning of the pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections led to a reported 2 515 377 cases and 33 205 deaths through 31 December 2020 in California, and 3 718 538 cases and 63 460 deaths through 30 June 2021 (covid19.ca.gov). Amidst the winter surge, a regional stay-at-home order was in effect at the end of 2020 that affected 98% of Californians. Concurrently, starting in December, administration of 2 authorized vaccines began in the state in accordance with recommended prioritization schemes, first targeting the phase 1A priority groups (healthcare personnel and residents of long-term care facilities) [1] [2] [3] [4] [5] [6] . In January, California then relaxed restrictions to allow adults aged ≥65 years, who are at highest risk of coronavirus disease 2019 (COVID-19)-related mortality, to receive the vaccine sooner [6] . The secondary prioritization based on age was due in part to data from studies of the 2 vaccines describing higher efficacy for reducing disease severity as measured by hospitalization and death [2] [3] [4] [5] . The potential synergistic effects of vaccination and nonpharmaceutical interventions (NPIs) to reduce SARS-CoV-2 transmission and consequent disease are not well understood. Considering the complexity of SARS-CoV-2 transmission dynamics and health effects, it is important to estimate the effects of vaccine uptake alongside other interventions using mathematical modeling. We aimed to assess the effects of different levels and strategies of NPIs and vaccination on key epidemiological outcomes in California, specifically cases, deaths, and time until herd immunity. We investigated the impact on projected cases and deaths of an age ≥65 vaccine prioritization strategy compared with vaccinating all adults, and considered the interaction between vaccines that partially reduce transmission with continued NPIs on these outcomes for the population of California. Finally, we examined how these combinations of NPIs and vaccination levels might impact progression to a theoretical herd immunity in 2021. We used a modified, age-stratified compartmental (Susceptible-Exposed-Infectious-Recovered) model based on a previously published model [7] and parameterized for the state of California. We varied adherence to NPIs by scaling of the contact matrix between age groups, including 65-74 and ≥75 years to account for changing age-based prioritization of vaccines. The effects of specific NPIs were not separately estimated, but rather the rescaled contact matrix was used to represent the total effect of different NPIs and adherence levels on contact rates for specified scenarios. Initial conditions corresponded to polymerase chain reaction (PCR)-confirmed cases of COVID-19 and consequent deaths reported to the California Department of Public Health by 1 January 2021. We assumed that cases diagnosed in the preceding 2 weeks were actively infectious and cases diagnosed in the following 2 weeks after 1 January were exposed as of 1 January but not yet infectious. Immunity from prior infection (ie, those considered "recovered") at the start of model simulations was estimated from available statewide seroprevalence data, which suggested that a third of estimated infections became cases confirmed by PCR (https:// www.cdph.ca.gov/programs/CID/DCDC/pages/COVID-19/ sero-prevalence-COVID-19-data.aspx). This estimate is limited by what seroprevalence data represent in terms of immunity. Estimates of the theoretical "herd immunity" threshold to prevent exponential growth vary widely between 50% and 80% based on an estimated R 0 between 2 and 5. To estimate herd immunity, we included all successful vaccinations and natural infections and did not consider waning immunity. We compared 18 different scenarios covering 3 NPI levels (implemented as contact rate reductions of 10%, 25%, and 40%), 3 vaccine coverage levels, and 2 vaccine prioritization strategies to model their interactive effects on COVID-19 cases, deaths, and herd immunity. Vaccination coverage rate varied between 20%, 40%, and 60% of the total California population (40.3 million) over 6 months. Contact rates (ie, the amount of contact between persons and across age strata that could facilitate COVID-19 transmission) varied by scaling the contact matrix for low (corresponding to close to 2019 pre-pandemic rates), moderate (between June and October 2020 when mobility was fairly stable), and high (April 2020, after the first stay-at-home order) NPI scenarios [8] . Vaccination prioritization scenarios considered were either all adults (≥18 years) or adults ≥65 years only, according to the implemented prioritization scheme in California. We assumed that the currently approved vaccines work similarly well and are 90% effective at preventing infection, hospitalization, and death, and 70% effective at reducing transmission [9] [10] [11] . We assumed 20% vaccine hesitancy for adults ≥65 years of age and 25% for the other age strata based on current California trends; in the model, this proportion of each age stratum will never be vaccinated. Vaccine distribution occurred at a constant daily rate according to the level of coverage/ speed specified in each scenario such that distribution was completed over the 6 months from January through June 2021. The vaccines are modeled as providing "all-or-nothing" protection (ie, vaccine efficacy corresponds to the proportion of vaccinated individuals with perfect protection from infection) and with variable transmission blocking as previously described [7] . Scenarios of different NPI levels with different levels of vaccine coverage avert more cases and deaths compared with a base scenario of pre-pandemic contact rates and no vaccination ( Figure 1 ). For cases, NPI adherence had the biggest effect on reducing incidence compared with the vaccinationrelated factors, particularly in the first half of the simulation (January-April). For cases, scenario results ranged from 540 000 (11%) cases averted (adults aged ≥65 years prioritized, 20% vaccine coverage, low NPIs) to 3 930 000 (80%) cases averted (all adults, 60% vaccine coverage, high NPIs) Table 2 ). Model results for progression toward herd immunity over the course of the projection period vary by scenario (Figure 2 ). With 60% intended vaccination coverage, the upper end of the herd immunity range is reached between May and July 2021 in California. Herd immunity is not reached in any of the scenarios without vaccination. While high levels of NPI adherence delay achievement of herd immunity compared with lower levels of NPI adherence by 2 months at 60% vaccination coverage, this scenario averts 2 540 000 more cases (68%) and 45 800 more deaths (36%). Our results show that even with high vaccination coverage, concomitant NPIs are required to reduce cumulative deaths ( Figure 1A ). NPI adherence figures prominently because NPIs drive total cases down faster than vaccinations alone ( Figure 1B) . Even with no vaccination, a high level of NPI adherence averts 74% of COVID-19 cases and 61% of COVID-19 deaths over the simulation period between January and July 2021 (Supplementary Table 1 ). Our findings demonstrate that continued NPIs are important for preventing additional deaths and cases while vaccine deployment scales up. In a scenario in which 20% of the total population has been vaccinated with age prioritization, a moderate level of physical distancing would still avert 89 000 (47%) deaths compared to low physical distancing, which would avert 38 300 (20%) deaths. COVID-19 case and death trajectories in early 2021 suggested that California was operating at moderate NPI scenario levels with vaccine prioritization for adults aged ≥65 years and total vaccine coverage at 50%. Actual data for cases and deaths fall within the range of the relevant scenarios for these conditions (Supplementary Figure 1) . Our model also describes the relationship between vaccination coverage, NPIs, and "herd immunity, " the level of immunity sufficient to disrupt and prevent sustained disease transmission. A new wave in summer 2021 suggests that herd immunity has not been reached, and a potential transition to becoming a seasonal virus casts doubt on the feasibility at all. Although maintaining NPIs during vaccination scale-up may be challenging, such measures could prevent ≥100 000 additional deaths in California from occurring. Any effect of higher NPI adherence on delaying herd immunity, due to averted infections contributing natural immunity, is outweighed by the effects of increasing vaccination speed and coverage on reducing deaths and incident cases (Figure 2 ). Our results suggest that prioritizing Californians aged ≥65 years reduces cumulative deaths substantially at all levels of vaccine coverage. Based on our findings, we estimate that 40% vaccine coverage in the ≥65 age group has approximately the same reduction in deaths as vaccination coverage of at least 80% among the entire adult population over the same time. While not explicitly modeled, hospitalizations preceding deaths are also likely to be substantially reduced by prioritizing adults aged ≥65 years, which would otherwise strain California's health system. Like all scenario models, ours has limitations, including inherent uncertainty about parameters and scenario conditions and ignoring heterogeneities within California. Additionally, our analyses do not account for increasing prevalence of novel SARS-CoV-2 variants that are more infectious (such as Delta) or immune evasive. Each of these challenges supports maintaining a conservative approach to NPIs. Our analyses provide evidence to support continued disease control and prevention efforts, including masking, social/physical distancing, ventilation, and hand hygiene (ie, NPIs), during initial COVID-19 vaccine implementation. First, the effect of vaccination in low NPI scenarios is attenuated by ongoing transmission while herd immunity is still distant. Second, despite potential accelerated scale-up of vaccinations, the levels of herd immunity required to reduce the need for NPIs would not be reached until summer 2021 or later, absent a major increase in vaccine supply and distribution. Public health stakeholders should continue implementing both vaccines and physical distancing measures (NPIs) simultaneously to reduce transmission, hospitalizations, and deaths as we aspire to pandemic control and until herd immunity, driven by vaccination, reaches a sufficient level to ensure protection for the most vulnerable. Supplementary materials are available at Open Forum Infectious Diseases online. Consisting of data provided by the authors to benefit the reader, the posted materials are not copyedited and are the sole responsibility of the authors, so questions or comments should be addressed to the corresponding author. National Academies of Sciences, Engineering, and Medicine Committee on Equitable Allocation of Vaccine for the Novel Coronavirus. Framework for Equitable Allocation of COVID-19 Vaccine The Advisory Committee on Immunization Practices' interim recommendation for use of Pfizer-BioNTech COVID-19 vaccine-United States The Advisory Committee on Immunization Practices' interim recommendation for use of Moderna COVID-19 vaccine-United States The Advisory Committee on Immunization Practices' updated interim recommendation for allocation of COVID-19 vaccine-United States Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine Updated COVID-19 vaccine eligibility guidelines Model-informed COVID-19 vaccine prioritization strategies by age and serostatus COVE Study Group. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine Interim estimates of vaccine effectiveness of BNT162b2 and mRNA-1273 COVID-19 vaccines in preventing SARS-CoV-2 infection among health care personnel, first responders, and other essential and frontline workers-eight U.S. locations Indirect protection by reducing transmission: ending the pandemic with SARS-CoV-2 vaccination We thank Kate Bubar and Daniel Larremore for helpful comments on this manuscript and Megha Mehrotra for support with seroprevalence estimates.Disclaimer. The views and opinions expressed by the authors are their own and do not necessarily represent the views and opinions of the California Department of Public Health or the California Health and Human Services Agency.Financial support. This work was supported by the California Department of Public Health.Potential conflicts of interest. All authors: No reported conflicts of interest.All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.