key: cord-0973338-cqyvr4w5 authors: He, Guanhao; Zeng, Fangfang; Xiao, Jianpeng; Zhao, Jianguo; Liu, Tao; Hu, Jianxiong; Zhang, Sicong; Lin, Ziqiang; Zhu, Huaiping; Liu, Dan; Kang, Min; Zhong, Haojie; Li, Yan; Sun, Limei; Yang, Yuwei; Li, Zhixing; Rong, Zuhua; Zeng, Weilin; Li, Xing; Zhu, Zhihua; Liang, Xiaofeng; Ma, Wenjun title: When and How to Adjust Non-Pharmacological Interventions Concurrent with Booster Vaccinations Against COVID-19 — Guangdong, China, 2022 date: 2022-03-11 journal: China CDC Wkly DOI: 10.46234/ccdcw2022.048 sha: 38161477b289cac73c7535ba155d27df01c02762 doc_id: 973338 cord_uid: cqyvr4w5 INTRODUCTION: With the large-scale roll-out of the coronavirus disease 2019 (COVID-19) booster vaccination effort (a vaccine dose given 6 months after completing primary vaccination) in China, we explore when and how China could lift non-pharmacological interventions (NPIs) against COVID-19 in 2022. METHODS: Using a modified susceptible-infectious-recovered (SIR) mathematical model, we projected the COVID-19 epidemic situation and required medical resources in Guangdong Province, China. RESULTS: If the number of people entering from overseas recovers to 20% of the number in 2019, the epidemic in 2022 could be controlled at a low level by a containment (215 local cases) or suppression strategy (1,397 local cases). A mitigation strategy would lead to 21,722 local cases. A coexistence strategy would lead to a large epidemic with 6,850,083 local cases that would overwhelm Guangdong’s medical system. With 50% or 100% recovery of the 2019 level of travelers from overseas, the epidemic could also be controlled with containment or suppression, but enormous resources, including more hotel rooms for border quarantine, will be required. However, coexistence would lead to an uncontrollable epidemic with 12,922,032 local cases. DISCUSSION: With booster vaccinations, the number of travelers from overseas could increase slightly in 2022, but a suppression strategy would need to be maintained to ensure a controllable epidemic. Non-pharmacological interventions (NPIs) have contributed substantially to the control of coronavirus disease 2019 (COVID-19) (1-2) and have bought time for vaccine development and promotion. With increasing vaccine coverage, some countries have relaxed NPIs. However, breakthrough infections, especially from viral variants, caused significant rebounds of COVID-19 epidemics (3) that were unable to be controlled without re-tightening NPIs (4) . Despite the effectiveness of NPIs, they negatively impact daily life and the economy (5) . Given the welldocumented high efficacy of COVID-19 booster doses (a dose of COVID-19 vaccine 6 months after completing a primary series) (6) , China initiated a booster vaccination campaign, with an expectation to return to normal life and lift NPIs (7) . With booster vaccinations, it is a concern that when and how NPIs could be lifted without devastating the healthcare system. This includes questions of how many medical resources, such as hospital beds, intensive care unit (ICU) beds, and hotel rooms for border quarantine, are necessary as different levels of NPIs are lifted. To address these critical questions, we used realworld data from multiple sources as input to a susceptible-infectious-recovered (SIR) model that we augmented with additional compartments to more accurately represent COVID-19 epidemiology and control policy in China. For 2022, we projected the magnitude of the COVID-19 epidemic in Guangdong Province under different NPI lifting policies, booster dose uptake, and overseas importation pressures. We estimated the number of infected people entering Guangdong from overseas as follow: where Passenger t denotes the number of passengers from overseas at date t, which was obtained from flight data in VariFlight (https://www.variflight.com/en/). We used flight data from 2019 -the pre-pandemic level of passengers -to project flights in 2022 under various levels of restriction. We used the prevalence of COVID-19 cases imported from overseas to Guangdong from August 7, 2021 to November 14, 2021 (0.98%) to estimate the number of imported infections each day projected onto 2022 travel levels. Two scenarios for booster vaccination in 2022 were used for modeling. The first scenario was 60% of the population receiving a booster by June 30 and 85% receiving a booster by December 31. The second scenario was 50% and 75% booster vaccination by June 30 and December 31. Rationale for the scenarios is in the Supplementary Material (available in http://weekly.chinacdc.cn). Inactivated COVID-19 vaccines have been the most widely used vaccines in China; their effectiveness against infection is 65.70% for fully vaccination (8) . With a booster dose, vaccine effectiveness (VE) is 88.00% (6) . Therefore, we used 65.70% and 88.00% for the VE parameters, P protect2 and P protect3 . Vaccination reduces hospital admission, severe illness, and death. Based on previous studies (6, (8) (9) (10) , we set the hospital admission rate, ICU admission rate, and fatality rate to 4.30%, 0.39%, and 0.80%, respectively, for fully vaccinated but infected individuals, and 0.30%, 0.03%, and 0.15%, respectively, for booster-vaccinated infected individuals. Border Quarantine: We developed five scenarios of border quarantine of people coming from overseas to Guangdong in 2022: 1) no border quarantine; 2) 7 days of quarantine; 3) 14 days of quarantine; 4) 7 days of quarantine for those entering before July, but no quarantine for those entering after July; and 5) 14 days of quarantine before July but 7 days for those entering after July. A certain proportion of cases from overseas may not be detected during quarantine. Based on real-world data from Guangdong, 1.04% and 0.16% of cases from overseas were not detected during 7-and 14-day quarantines. We used these values to represent residual importation risk after testing negative during quarantine. Infection Detection Measures: In our model, μ denotes the rate of infected people being detected and quarantined. For different infection detection measures, the interval from infection to quarantine was obtained from real-world data in Guangdong (Supplementary Table S1 , available in http://weekly. chinacdc.cn/). Personal Protection and Social Distancing: A metaanalysis indicated that relative risk (RR) reduction from masks and social distancing were 0.47 and 0.75, respectively (2) . Given that the combined effect of personal protection and social distancing was rarely reported, we used the lowest RR (0.47) to represent this combined effectiveness. We modeled 4 strategies that differed by combination of NPIs: 1) containment: 14 days of border quarantine of incoming travelers; use of personal protection, social distancing, and use of sensitive measures for infection detection (fever monitoring and contact tracing); 2) suppression: 7 days border quarantine; use of personal protection, social distancing, and sensitive measures for infection detection; 3) mitigation: no border quarantine; use of personal protection, social distancing, and routine measures for infection detection (fever monitoring but no contact tracing); and 4) coexistence: no border quarantine, no personal protection, no social distancing, and only routine measures for infection detection. The transmission coefficient, β, was estimated using real-world data from a local epidemic triggered by imported cases from Africa in first half of 2020. The data indicated that the β with best fit was 0.14 (R 2 =84.71%, Root Mean Square Error=3.61). During that outbreak, vaccination was unavailable, and therefore this β represents transmission with local NPIs and no vaccination. Given viral variants can have higher transmission rates (transmissibility of variants can reach 1.97 times non-variant transmission) (11), we set β as 0.14×1.97=0.27 to represent the transmission rate in 2022. We also set β as 0.27/0.47=0.57 to represent transmission without personal protection and social distancing. Detailed definitions and values of compartments and parameters are presented in Supplementary Table S2 and Supplementary Table S3 (available in http://weekly.chinacdc.cn/). Statistical analyses were conducted with R software (version 3.6.2, R Foundation for Statistical Computing, Vienna, Austria). We used the R package "deSolve" for numerical treatment of our model's system of differential equations in transmission dynamics analyses. From January 1 to November 14, 2021, 3,768 flights carried 349,987 people into Guangdong from overseas; 2,702 (0.77%) were infected. The percent was higher near the end of 2021 (0.98%). Using the percent infected as a multiplier, Figure 2 shows projected overseas travelers and numbers infected in 2022 under assumptions of 20%, 50%, and 100% of travelers from overseas compared with 2019. Modeling results were based on the percent of 2019 travel into Guangdong that occurs using the percent infected from real world data near the end of 2021 -20%, 50%, and 100% of 2019 travel into Guangdong, called travel recovery. Containment: With 2022 incoming travel at a 20% recovery of 2019 travel, a containment strategy controls the maximum number daily infections at low level ( Figure 3) , with annual cases and deaths of 215 and 2 ( Figure 4 ). As booster dose coverage increases, daily cases become lower ( Figure 3 ). With higher percentages recovery of 2019 travel, the epidemic is still controlled by containment. Suppression: With 20% recovery of travel, a suppression strategy controls the maximum daily infections at 7 (Figure 3 ), with 1,397 total cases and 13 deaths ( Figure 4 ). If booster dose uptake is 85%, the maximum daily number of local infections decreases to 2. With 50% and 100% of travel recovery, the cumulative number of cases is projected to become 3,547 and 7,277. Mitigation: With 20% recovery of travel, a mitigation strategy results in a maximum of 63 infections per day, with 21,722 total cases and 205 deaths. A booster dose coverage of 85% reduces the maximum daily infections to 22. However, 50% and 100% travel recovery yields 55,205 and 113,519 total cases in Guangdong. Coexistence: If most NPIs are lifted, 20% travel recovery brings the projected daily maximum of cases to 75,716, with annual cases and deaths of 6,850,083 and 64,626. With 50% and 100% travel recovery, Guangdong would suffer 10,081,389 or 12,922,032 cases in 2022. Containment: At 20% travel recovery, at the peak of epidemic, 1,398 infected people, including locals and incoming travelers, will require quarantine and isolated treatment. Infected individuals are always hospitalized in China, implying the need for 1,398 hospital beds at epidemic peak. If only severe cases are hospitalized, 55 hospital beds and 5 ICU beds will be needed, but 90,448 hotel rooms will be needed for border quarantine. With 50% and 100% travel recovery, the peak needs for treatment will be 3,496 and 6,995 hospital beds and 226,119 and 452,238 quarantine rooms, respectively. Suppression strategy: At 20% travel recovery, at the peak of the epidemic, 1,454 hospital beds will be needed. If only severe cases are hospitalized, 58 beds will be needed. Compared to containment, suppression requires fewer hotel rooms for imported quarantine (45,458), which is within Guangdong's capacity. With 50% and 100% travel recovery, 3,639 and 7,295 hospital rooms will be needed at epidemic peak, and 113,645 and 227,289 quarantine hotel rooms will be needed, respectively. Mitigation: With 20% travel recovery, 3,498 hospital beds will be needed at peak if all infected individuals are hospitalized; 170 hospital beds will be needed if only severe cases are hospitalized. A peak of 29 ICU beds would be needed. With travel recovery of 50% and 100% levels, 8 100 China CDC Weekly the COVID-19 epidemic under control and utilize affordable levels of medical resources. If incoming international travel recovers to 20% of the level in 2019 and the infection rate of incoming travelers is the same as in 2021 in Guangdong, a suppression strategy may be considered in 2022. Suppression involves reducing incoming quarantine to 7 days, using personal protection and social distancing, and contact tracing during outbreaks. Under this scenario, the required medical resources will be within the current capacity of Guangdong. Our model also indicated that with increasing uptake of booster doses, the number of daily new infections decreased significantly. We project that a high booster dose vaccination rate of 85% will allow more incoming travel and decreased use of NPIs by the end of 2022. Furthermore, several antiviral medicines against COVID-19 are being developed and some have been granted regulatory approval (12-13). Effective antivirals raise the possibility that infected people with mild symptomatic may be able to be safely treated at home, partially alleviating stress on the medical system. This study was subject to several limitations. We assumed that reinfection would not occur. This assumption may cause the model to underestimate the epidemic magnitude and peak. We also did not consider the waning of booster-dose-induced immunity over time and assumed that the prevalence of imported COVID-19 in 2022 will be the same as it was in 2021. Additionally, we were under the assumption that the transmissibility of the virus in 2022 will be the same as the Delta variant. Given that the Omicron variant has higher transmissibility than Delta and that future variants may also have high transmissibility, our results may be underestimates. Our model used an SIR structure rather than an SEIR (susceptible, exposed, infectious, and recovered) structure for simulation. However, given that COVID-19 cases can transmit during the incubation period (14), SIR models have been used successfully (15) and we believe that an SIR structure reasonably simulates COVID-19 epidemics. Finally, our model did not consider vaccination effectiveness against SARS-CoV-2 infectiousness (VEI). As booster vaccination increases in 2022, incoming international travel could increase slightly, but a suppression strategy should be maintained to ensure that the resulting COVID-19 epidemic can be maintained under control. High coverage of booster dose vaccinations along with the use of antiviral medicines and increasing the availability of medical The study used Guangdong Province of China as an example to project the epidemic magnitude of coronavirus disease 2019 (COVID-19) from January 1, 2022, to December 31, 2022. Guangdong Province is located in the southeast coastal area of China and has frequent international exchange. Guangdong is the most populous province in China with 126,012,500 residents and is the most developed province with the highest gross domestic product (GDP) (1) (2) . Guangdong has the highest total export-import volume in China (2) . For these reasons, Guangdong faces considerable risk of COVID-19 in the global pandemic. Based on the susceptible-infectious-recovered (SIR) modeling framework, we introduced several compartments to include import risk from overseas, imported (border) quarantine, vaccination, and exiting population (Figure 1 ). Two compartments were added to describe the imported infectors (I in ) and imported susceptibles (S in ). I in shunts into imported infectors with (Q in,p ) and without quarantine or leaked after quarantine (I in,p ). S in shunts into imported susceptible with (Q in,s ) and without quarantine (S in,s ). We divided the S compartment into 3 sections: susceptible without vaccination (S non-vaccine ); susceptible with full vaccination (S vaccine2 ); susceptible with booster dose vaccination (S vaccine3 ). We further divided S vaccine2 /S vaccine3 into 2 sections: vaccinated susceptible with immunity against COVID-19 (S protect2 , S protect3 ); vaccinated susceptible without immunity against COVID-19 (S non-protect2 , S non-protect3 ). S non-protect , S non-protect2 , and S non-protect3 would gradually become infectors and flow into I non-vaccine , I vaccine2 , and I vaccine3 , respectively, which would be later detected, quarantined, and treated in Q nonvaccine , Q vaccine2 , and Q vaccine3 , respectively. Then the recovered infectors would enter recovery compartment R. We introduced Out to describe the exported population from Guangdong. The system of differential equations in the model is as follows: Guangdong Province has 126,012,500 residents (1). As of November 30, 2021, 86.67% residents in Guangdong were fully vaccinated. We assumed that the full vaccination (2 doses) rate could reach 90% by the beginning of 2022 in Guangdong. In the second half of 2021, full vaccination increased from 46.72% (on June 30) to 86.62% (on November 30). In other words, 46.72% and 86.62% of the population are eligible for booster doses on January 1 and June 1, 2022. In addition, 7.97 million people have received booster doses by November 30, and we predict that 10 million people could receive booster doses by January 1, 2022. As the roll-out of vaccination normally had a "fast, followed by slow, trend," we set high and low vaccination scenarios: 1) 60% population boosted by June 30, 2022 and 85% population boosted by December 31, 2022; 2) 50% population boosted by June 30, 2022 and 75% boosted by December 31, 2022. Inactivated COVID-19 vaccines were widely used in China, and their vaccine efficacy against infection was 65.70% for the fully vaccinated according to a recent meta-analysis (3). According to a recent publication, the efficacy for booster doses was 88.00% (4). Therefore, P protect2 and P protect3 were set to be 65.70% and 88.00%, respectively. Vaccination reduces hospital admission, severe illness, and death. According to US CDC, for unvaccinated and fully vaccinated infected people, hospital admission rates were 9.00% and 3.90%; intensive care unit (ICU) admission rates were 3.12% and 0.36%; and the fatality rates were 1.40% and 0.70% (5) . Given that inactivated vaccines have lower efficacy than mRNA vaccines, we adjusted these rates based on the ratio between the efficacy of inactive and mRNA vaccine (3, 6) . The hospital admission rate, ICU admission rate, and fatality rate were set to SUPPLEMENTARY Association of public health interventions with the epidemiology of the COVID-19 outbreak in Wuhan, China A previous study demonstrated that risk of hospitalization, ICU admission, and death following booster doses were 6.50%, 8.10%, and 19.12% of full vaccination, respectively (4) 2021 China statistical yearbook Real-world effectiveness of COVID-19 vaccines: a literature review and metaanalysis Effectiveness of a third dose of the BNT162b2 mRNA COVID-19 vaccine for preventing severe outcomes in Israel: an observational study Incidence of SARS-CoV-2 infection, emergency department visits, and hospitalizations because of COVID-19 among persons aged ≥12 years, by COVID-19 vaccination status -Oregon and Washington Effectiveness of an inactivated SARS-CoV-2 vaccine in Chile Increased transmissibility and global spread of SARS-CoV-2 variants of concern as at Effectiveness of public health measures in reducing the incidence of COVID-19, SARS-CoV-2 transmission, and covid-19 mortality: systematic review and meta-analysis Three-year action plan for construction of public health prevention and treatment in Guangdong Province In the dynamic transmission model, μ denotes the rate from infected persons to quarantine people. For assessing different local infection detection measures, we obtained information on the interval from infection to quarantine from real-world data in Guangdong Province. We collected real world time series data of imported and local infected persons in a Guangdong epidemic during March 15, 2020 to April 15, 2020. This epidemic was triggered by imported cases from Africa. Based on the realworld data, we conducted an SIR model to calculate a contact transmission coefficient β value with the best fit. Vaccination had not started during or prior to this outbreak. Its β value therefore represents the transmission rate with local non-pharmacological interventions (NPIs) but without vaccine-induced immunity. We found that the β with best fitness was 0.14 (R 2 =84.71%, Root Mean Square Error=3.61).Given viral variants could have higher transmission rates (transmissibility of variants could reach 1.97 times of non-variant) (7), we thus set β as 0.14×1.97=0.27 to represent the transmission rate in 2022.A meta-analysis found that the relative risk (RR) reductions associated with mask wearing and social distancing were 0.47 and 0.75, respectively (8) . Given that the effects of combinations of personal protection and social distancing were rarely reported, in our study we used the lowest risk reduction (RR=0.47) to represent the effectiveness of personal protection together with social distancing. We set β as 0.27/0.47=0.57 to represent the transmission rate without personal protection and social distancing. As of December 28, 2020, 7,091 hospital beds and 156 ICU beds (estimated by the number of total ICU beds multiplying by the proportion of infectious diseases) could be used for infectious disease cases in Guangdong Province (9) . If 50% of these hospital beds could be used for COVID-19 treatment, 3,546 hospital beds and 78 ICU beds would be available. In addition, 419 hotels with 47,636 rooms could be used for quarantine of travelers.