key: cord-0734088-qfsl6zsm
authors: Kraay, A. N. M.; Gallagher, M. E.; Ge, Y.; Han, P.; Baker, J. M.; Koelle, K.; Handel, A.; Lopman, B. A.
title: Modeling the use of SARS-CoV-2 vaccination to safely relax non-pharmaceutical interventions
date: 2021-03-13
journal: nan
DOI: 10.1101/2021.03.12.21253481
sha: 4170f1bc3ff3590d6c7687fc87dd2523711cd60a
doc_id: 734088
cord_uid: qfsl6zsm

In response to the COVID-19 pandemic, widespread non-pharmaceutical interventions (NPIs), including physical distancing, mask wearing, and enhanced hygiene, have been implemented. As of March 2021, three effective vaccines have been approved for emergency use in the United States, with several other vaccines in the pipeline. We use a transmission model to study when and how NPIs could be relaxed in the United States with relative safety as vaccination becomes more widespread. We compare different relaxation scenarios where NPIs begin to relax 0-9 months after vaccination begins for both a one dose and two dose strategy, with historical levels of social interactions being reached within 1 month to 1 year. In our model, vaccination can allow widespread relaxation of NPIs to begin safely within 2 to 9 months, greatly reducing deaths and peak health system burden compared to relaxing NPIs without vaccination. Vaccinated individuals can safely begin to relax NPIs sooner than unvaccinated individuals. The extent of delay needed to safely reopen depends primarily on the rate of vaccine rollout, with the degree of protection against asymptomatic infection playing a secondary role. If a vaccination rate of 3 million doses/day can be achieved, similar to the typical rollout speed of seasonal influenza vaccination, NPIs could begin to be safely relaxed in 2-3 months. With a vaccination rate of 1 million doses/day, a 6-9-month delay is needed. A one dose strategy is preferred if relative efficacy is similar to a two-dose series, but the relative benefit of this strategy is minimal when vaccine rollout is fast. Due to the urgent need to pursue strategies that enable safe relaxation of NPIs, we recommend a two-dose strategy with an initial delay of at least 3 months in relaxing restrictions further, and that the speed of vaccine rollout be given immediate priority.

The COVID-19 pandemic has caused catastrophic loss of life and health system strain in the United Figure 1 : Schematic of the base transmission model with vaccination. Individuals are classified as susceptible, S, exposed E, infectious and asymptomatic, A, infectious and symptomatic, I, hospitalized, H, recovered, R, or deceased, D. We assume that recovered individuals are equally as likely as susceptible individuals to receive the vaccine, effectively resulting in wasted doses (red arrows). Vaccinated individuals enter a reduced risk state, in which they are less likely to become infected and may also be less likely to develop symptoms, depending on the modeled mechanism of action.

The rate of vaccination was calculated by assuming that vaccines will preferentially be dis-125 tributed to high risk groups and to the elderly based on the prioritization scheme proposed by the 126 National Academy of Sciences and the CDC [20, 24] . In our framework, elderly individuals with 127 underlying health conditions have the highest priority followed by low-risk elderly, high risk adults, 128 and low risk adults. Given that children were not included in the initial trials, we do not model CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted March 13, 2021. ; https://doi.org/10.1101/2021.03.12.21253481 doi: medRxiv preprint initial low rate of vaccine distribution in this age group, and for simplicity. Because identification of high risk groups is likely to be difficult to achieve in real time, we assumed that vaccines would 134 be distributed to all four of these groups (high risk elderly, low risk elderly, high risk adults, low 135 risk adults), with more doses initially being allocated to the higher risk groups. Once vaccine cov-136 erage reached 80% in a given group, the remaining doses were redistributed among the remaining 137 vaccine-eligible groups. This 80% coverage threshold is consistent with vaccine acceptance from 138 recent surveys in the United States [25, 26] . Parameter values for the model are shown in Tables S2 139 and S1. 140 We model a vaccine that reduces symptomatic infection by 90% (approximately in line with vac- These two rates were converted to the number of complete two dose series available each month, 160 (dividing by two for a two-dose series). The number of doses was then converted to a time-varying 161 rate of vaccination for each age and risk group. We assume that all individuals age 20 and older will 162 eventually have access to vaccination, such that vaccine coverage will eventually reach 80% in both 163 strategies, but that a one dose strategy can achieve this coverage level more quickly. The efficacy 164 of a one dose vaccine has not been tested at large scale in Phase III clinical trials, so we varied 165 this quantity, assuming the relative efficacy (RE) of 1 dose compared with 2 doses was 100%, 80%, 166 or 60%. We focus on results for an 80% RE vaccine in the main text, as this value is similar to 167 the relative efficacy of the Johnson and Johnson vaccine compared with the two mRNA vaccines 168 ( 63 90 = 0.73) and because preliminary trial data have suggested that the 80% threshold is most 169 6 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) have a quicker relaxation process (see Figure 2 ).

Model calibration 195 We parameterized the model's reporting rate for symptomatic cases reported and the baseline level 196 of social distancing against US hospitalization data in early February. We found that a reporting 197 rate of 75% combined with a 55% baseline reduction in social contacts closely matched the observed 198 hospitalization data. See Figure S1 for comparisons of incidence between modeled and observed 199 hospitalizations. 7 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted March 13, 2021. ; Figure 2 : An illustrative example of contact levels over time while relaxing social contacts. Under this scenario, pre-pandemic social contact rates are regained after 150 days for everyone, but the rate of relaxation varies by vaccine status and age. Vaccinated adults (solid line) begin to relax as vaccination begins but unvaccinated individuals and the elderly begin to relax 90 days after vaccination starts (dashed line). Model scenarios considered ranged in both the time at which social contacts were restored to pre-pandemic levels (t = 30 to 365) and the initial time at which NPIs started to be relaxed for both vaccinated and unvaccinated individuals (0-240 days).

. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. Figure S4 ), necessitating a slower relaxation to allow more of the population to be vaccinated.

Moreover, speed is less of a benefit if rapid vaccine rollout can be achieved at 3 million doses/day.

While waiting for adequate coverage to be achieved before widespread NPI relaxation begins, 225 we found that allowing vaccinated individuals to begin to relax immediately does not substantially The extent of delay and speed of reopening needed to safely relax NPIs for unvaccinated individ-233 uals and the elderly depends primarily on the rate of vaccine rollout and the dosing strategy (one 234 or two doses) (Figure 3 ). If a two dose strategy is used with a rollout rate of 3 million doses/day, 235 a three month delay in reopening provides the most benefit, with a return to normal interactions 236 9 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted March 13, 2021. ; Figure 3 : Interaction between time to regain pre-pandemic social interactions and the start time of relaxation by vaccine strategy and rollout speed. The x-axis shows the number of days between February 1, 2021 and the start of further NPI relaxation and the y-axis shows when normal interactions are restored after reopening begins (corresponding to the speed of relaxation). Colors show expected deaths for each reopening strategy. For these simulations, vaccinated individuals are assumed to begin relaxing immediately and a susceptibility only vaccine is modeled. See Figure S4 for expected impacts at lower relative efficacy.

. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted March 13, 2021. 

. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted March 13, 2021. ; Figure 5 : Expected deaths after one year if vaccinated individuals begin to relax immediately (black line) or wait to relax with the general population (yellow line) by the rate of vaccine rollout (solid=1 million doses/day, dashed=3 million doses/day). The top row (A and B) shows impacts for a two dose vaccine and the bottom row (C and D) shows impacts for a one dose vaccine with 80% relative efficacy. Column 1 shows impacts for a susceptibility only vaccine (A and C) and column shows impacts for a susceptibility and severity vaccine (B and D). In panel (A), the black and yellow lines overlap.

12 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted March 13, 2021. ; https://doi.org/10.1101/2021.03.12.21253481 doi: medRxiv preprint immediately after 3 months resulting in 84,200 deaths, similar to if NPIs were sustained at their 237 current level of the duration of the epidemic. At this rapid rollout rate, any potential benefit from 238 a one dose strategy is minimal. This three month delay roughly corresponds to the estimated time 239 required to vaccinate 40% of the eligible population, allowing herd immunity to be achieved through 240 a combination of natural and vaccine derived immunity. In contrast, with a slower vaccination rate 241 of 1 million doses/day, the epidemic would not be shortened and NPIs would need to be sustained 242 for the duration of the epidemic, with relaxation not beginning until 7 months after vaccine rollout.

A one dose strategy allows high levels of vaccine coverage to be achieved more quickly, but this 244 strategy could be a liability if relative efficacy is low and NPIs are relaxed too quickly ( Figure S4 ).

Delaying relaxation also allows NPIs to be relaxed more quickly without increasing population CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted March 13, 2021. coverage might need to be higher before restrictions can be safely relaxed. Some have cautioned 317 that pursuing a one-dose strategy might increase the risk of evolution of vaccine-resistant strains, 318 but this concern remains speculative [36] . As of early March 2021, at least three new variants of 319 concern have emerged, including the UK strain, the South African strain, and the Brazilian strain.

At present, all three vaccines approved for emergency use appear to be protective against these and potentially future variants of concern. However, immune escape is still a distinct possibility.

Second, due to a lack of data and the short time scale of our simulations, we did not account for In conclusion, we have found that widespread vaccination has the potential to reduce deaths 331 from COVID-19, lessen health system strain, and shorten the length of the COVID-19 pandemic, 332 even as non-pharmaceutical interventions continue to be relaxed. Based on currently available 333 data, we find that using the full recommended series for approved vaccines is likely to make a 334 substantial impact. A one dose series could outperform a two dose series, but if vaccine rollout can 335 be achieved at 3 million doses/day, the additional benefit of a one dose strategy is minimal and the 336 potential risk is high, particularly if VE is low. Using this strategy, a three month delay in further 337 reopening followed by gradual relaxation provides the best opportunity to minimize deaths, with CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted March 13, 2021. 

17 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted March 13, 2021. 18 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

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The relative size of each age group was estimated using the US Census data. Within each age group, 357 the fraction of the population considered occupationally exposed was estimated based on the NAP by assuming that all high susceptibility individuals are also occupationally exposed. There is no 363 difference between these two assumptions for the elderly or for children (because neither age group 364 is occupationally exposed). Overall, the modeled hospitalizations were consistent with observed data in late February. For 367 model calibration, we assumed the higher bound of baseline immunity (32%) and one million doses 368 of vaccine per day. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted March 13, 2021. ; Figure S1 : Consistency between modeled hospitalizations (black line) and observed data (points) from the Covid Tracking Project [1] 20 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted March 13, 2021. ; Figure S2 : Deaths between February 1, 2021 and February 1, 2022 for different vaccination strategies and relative performance with no relaxation of NPIs. This figure shows performance for a susceptibility only vaccine, but results for a susceptibility and severity vaccine were similar.

We then solved for the value of a that satisfied the equation to get the appropriate V E values.

In the main text, we focus on a one dose vaccine with an 80% relative efficacy, as this is similar to 376 initial data for Pfizer [16] . Without delaying reopening, the model predicts that the US healthcare system would quickly 389 surpass levels seen in early January 2021 at the peak health system load unless vaccination can be 390 rolled out at 3 million doses/day or relaxation occurred gradually over a 6-12 month period. infection is less pronounced, the US healthcare system would quickly surpass levels seen in early 394 January at the peak health system load unless vaccination can be rolled out at 3 million doses/day 395 or relaxation occurred gradually over a 6-12 month period.

. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted March 13, 2021. ; Figure S4 : Relaxation tradeoff for varying levels of relative efficacy and rollout speeds for a susceptibility only vaccine.

. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) Figure S5 : Number of hospitalized cases over time if non-pharmaceutical interventions begin to be relaxed for everyone of February 1, 2021 based on dosing strategy and speed of reopening for a susceptibility only vaccine. The black line shows the number of individuals hospitalized on January 12, 2021 (131,326), which was the peak of US hospitalizations.

. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) Figure S6 : Number of hospitalized cases over time if non-pharmaceutical interventions begin to be relaxed for unvaccinated individuals after 90 days based on dosing strategy and speed of reopening for a susceptibility and severity vaccine. Vaccinated individuals relax as soon as they complete their vaccine series. The black line shows the number of individuals hospitalized on January 12, 2021 (131,326), which was the peak of US hospitalizations.

. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted March 13, 2021. ; https://doi.org/10.1101/2021.03.12.21253481 doi: medRxiv preprint Figure S7 : Relaxation tradeoff for deaths for varying relaxation speeds for a susceptibility only vaccine assuming baseline immunity is 16%.

1.6.4 Lower baseline immunity (16%) 397 With a lower level of baseline immunity, the delay needed to minimize deaths is slightly longer, and 398 expected deaths are higher. 399 1 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

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