COVID-19雙價疫苗對群體免疫的影響：數理模式研究

Abstract

背景及研究目的：因應SARS-CoV-2 Omicron BA.1, BA.2, BA.4, BA.5變異株陸續出現，疫苗廠研發同時針對原始株及Omicron變異株的COVID-19雙價疫苗。最初的雙價疫苗為針對Omicron BA.1/2變異株，在全球Omicron BA.5大流行後，雙價疫苗也演進至針對BA.4/5變異株。然而，COVID-19雙價疫苗是否能有效強化群體免疫，降低SARS-CoV-2在人群中的有效再生數（Effective reproductive number, Rt值），進而降低中重症流行趨勢，目前尚未有基於流行病學實證資料的傳染病數理模式研究。有學者提倡透過打完三劑疫苗後不斷自然感染產生的混和免疫（Hybrid immunity）以終結COVID-19疫情。目前尚不清楚積極追加施打COVID-19雙價疫苗是否能夠產生優於混和免疫的防疫效果。 方法：本研究以系統性文獻回顧彙整COVID-19雙價疫苗保護力實證數據，建立考量免疫衰退（Waning of immunity）、混和免疫、重症率及死亡率之SEIRS SARS-CoV-2傳播動態模型。根據臺灣在2022年至2023年經歷四波主流變異株（BA.2、BA.5、BQ.1及XBB），本研究依序建立四個主要架構相似的數理模型，並依據臺灣2022年及2023年疫苗接種數，以數理模型擬合2022/4/1至2023/6/25 疾病管制署公布之每日新增通報確診人數、中重症人數及死亡人數，估計全臺灣曝險人口平均口罩配戴率、輕症確診於指數爆發期的起始人數、易感族群曝險比例、染疫後重症率、重症致死率、以及自然免疫平均衰退的時間，以此為基礎，進一步推估 2023/1/1至2023/12/31 Rt值、重症及死亡的變化趨勢，估計相較於混和免疫策略（不再追加雙價疫苗，僅憑自然感染維持免疫力），不同強度的雙價疫苗施打率（維持臺灣疫苗施打現況、疫苗施打速率提升為10倍、50倍或100倍）對Rt值及重症人數變化趨勢的影響。敏感度分析考慮雙價疫苗對新變異株保護力之不確定性（預防接種者感染及重症的效果各增減10%）對主分析結果的影響。 結果：藉由模型擬合，推估而得本土流行病學參數：（1）曝險人口平均口罩配戴率為77% (未曝險人口口罩配戴率為100%)；（2） BA.2時期染疫後中重症率為0.66%；（3）中重症死亡率為29.17%；（4）BA.2變異株之自染免疫衰退期約為76天； （5） BQ.1時期染疫後中重症率為0.32%；（6）BQ.1變異株之自染免疫衰退期約為68天。若維持臺灣目前疫苗接種現狀至2023年底，則2023年全年平均每日約有190人重症，累計約63309人重症；將施打速率提升至臺灣目前施打疫苗現況之 50倍，則平均每日重症人數可降至約132人，累計約49640人重症；而若施打速率大幅提升至臺灣施打疫苗現況之 100倍，則平均每日重症人數則可降至約102人，累計約41948人重症。相較於停止施打次世代疫苗或臺灣目前接種疫苗之現況，若將施打速率提升至臺灣目前施打疫苗現況之 50倍，將可降低約 21.6% 的重症人數以及 21.4% 的死亡人數；若將施打速率提升至臺灣目前施打疫苗現況之100倍，則可以降低約 33.47% 之重症及死亡人數。在停止施打次世代疫苗、臺灣目前接種疫苗現況，以及提升至臺灣目前疫苗施打速率10倍的三種情境中，Rt值雖能短暫降至0.86 (2023/1/1 - 2023/1/13)，但隨著免疫衰退，Rt值會持續上升，並在2023年四月初，上升至1.0，至年底皆持續維持在0.96至0.98左右，降不下來。而在提升至臺灣施打疫苗速率50倍及100倍的情境中，Rt值在2023年皆未突破1.0，雖在年初至5月中有上升趨勢，從0.83提升至0.88，但接下來會持續下降，至年底皆維持在0.8左右。敏感度分析的結果發現，若疫苗預防感染及重症效果皆增加10%，相較於停止施打次世代疫苗以及臺灣目前接種疫苗現況，大幅提升疫苗接種速率至現狀之100倍的策略，可降低32.4%的重症人數以及37.5%的死亡人數，而若疫苗防感染及重症效果均降低10%，則可降低約30.4%的重症人數及30.1%的死亡人數。 結論：相較於混和免疫的防疫策略，積極追加疫苗可有效降低約22% - 33%的重症及死亡人數，並降低Rt值。

Background: In response to the emergence of SARS-CoV-2 Omicron BA.1, BA.2, BA.4, and BA.5 variants, vaccine manufacturers have been developing bivalent COVID-19 vaccines that target both the original strain and the Omicron variant strains. However, whether mass vaccination can reduce the effective reproductive number (Rt value) and consequently mitigate the trends of severe and critical cases still remains unclear. Some scholars advocate terminating COVID-19 pandemic through hybrid immunity, which is achieved by continuous natural infections after completing three doses of vaccination. Currently, it is unclear whether actively administering additional doses of COVID-19 bivalent vaccines can generate superior protection compared to hybrid immunity. Methods:This study conducted a systematic literature review to consolidate empirical data on the effectiveness of bivalent COVID-19 vaccines, subsequently, established an SEIRS SARS-CoV-2 transmission dynamic model that considered waning of immunity, hybrid immunity, severity rate, and mortality rate. Based on four major variant waves (BA.2, BA.5, BQ.1, and XBB) between 2022 and 2023 in Taiwan, the study sequentially constructed four similar mathematical models. Using vaccination data from 2022 and 2023 in Taiwan, the models were fitted to the daily reported numbers of new confirmed cases, severe cases, and deaths announced by the Taiwan Centers for Disease Control from April 1, 2022, to June 25, 2023. The study estimated parameters including the mask-wearing rate among the population, initial number of infected people during the exponential growth phase, susceptible-exposed ratio of the population, post-infection severity rate, severe case fatality rate, and average duration of natural immunity. Based on these estimations, the study further predicted the effective reproductive number (Rt value), severe cases, and deaths from January 1, 2023, to December 31, 2023. The study compared different intensities of bivalent vaccine administration (maintaining the current vaccination rate, increasing vaccination rate by 10 times, 50 times, or 100 times) to the hybrid immunity strategy (no further administration of bivalent vaccines, relying solely on natural infections to maintain immunity) in terms of their impacts on Rt value, severe cases, and death. In the sensitivity analysis, the study considered the uncertainty of bivalent vaccine effectiveness against new Omicron variant (with ±10% of vaccine effectiveness against both infection and severe disease) and assessed its impact on the main outcomes. Results: Based on the model fitting procedures, the study estimated several parameters as follows: (1) mask-wearing rate among the population was 77%, (2) severity rate after infection with the BA.2 variant was 0.66%, (3) fatality rate for severe cases was 29.17%, (4) mean duration of natural immunity for the BA.2 variant was approximately 76 days, (5) severity rate after infection with the BQ.1 variant was 0.32%. (6) mean duration of natural immunity for the BQ.1 variant was approximately 68 days. If Taiwan remains the vaccination rate as status quo until the end of 2023, daily severe cases would be approximately 190, with a cumulative total of around 63,309 severe cases. Increasing the vaccination rate to 50 times the current rate would reduce the daily severe cases to approximately 132 individuals, with a cumulative total of around 49,640. Further, if the vaccination rate is dramatically increased to 100 times the current rate, the daily number of severe cases would be approximately 102 individuals, with a cumulative total of around 41,948. Comparing the scenario to a situation where no further doses of bivalent vaccine are administered, increasing the vaccination rate to 50 times the current rate could reduce severe cases and deaths by approximately 21.6% and 21.4%, respectively. Similarly, increasing the vaccination rate to 100 times the current rate could lead to reductions of approximately 33.47% in severe cases and deaths. In the scenarios of no further doses of bivalent vaccines, the Rt value could briefly decrease to 0.86 (from January 1 to January 13, 2023). However, with the waning of immunity, the Rt value would continue to rise and reach 1.0 on April 9, 2023, remaining around 0.96 – 0.98 until the end of the year. On the other hand, in the scenarios of increasing the vaccination rate to 50 times and 100 times the current rate, the Rt value would not exceed 1.0 throughout 2023, instead, the Rt value would remain around 0.8 until the end of the year. The sensitivity analysis revealed that if the vaccine effectiveness against infection and severity are increased by 10%, dramatically increasing the vaccination rate to 100 times the current rate can reduce severe cases and deaths by 32.4% and 37.5%, respectively. Conversely, if the vaccine effectiveness is decreased by 10%, it could still reduce severe cases by approximately 30.4% and deaths by 30.1% compared to the scenarios of no further boosting. Conclusion:Compared to the hybrid immunity strategy, actively administering additional vaccines can effectively reduce severe cases and deaths by approximately 22% to 33% and reduce the Rt value.