Effectiveness of chatbots on COVID vaccine confidence and acceptance in Thailand, Hong Kong, and Singapore.

Chatbots have become an increasingly popular tool in the field of health services and communications. Despite chatbots' significance amid the COVID-19 pandemic, few studies have performed a rigorous evaluation of the effectiveness of chatbots in improving vaccine confidence and acceptance. In Thailand, Hong Kong, and Singapore, from February 11th to June 30th, 2022, we conducted multisite randomised controlled trials (RCT) on 2,045 adult guardians of children and seniors who were unvaccinated or had delayed vaccinations. After a week of using COVID-19 vaccine chatbots, the differences in vaccine confidence and acceptance were compared between the intervention and control groups. Compared to non-users, fewer chatbot users reported decreased confidence in vaccine effectiveness in the Thailand child group [Intervention: 4.3 % vs. Control: 17%, P = 0.023]. However, more chatbot users reported decreased vaccine acceptance [26% vs. 12%, P = 0.028] in Hong Kong child group and decreased vaccine confidence in safety [29% vs. 10%, P = 0.041] in Singapore child group. There was no statistically significant change in vaccine confidence or acceptance in the Hong Kong senior group. Employing the RE-AIM framework, process evaluation indicated strong acceptance and implementation support for vaccine chatbots from stakeholders, with high levels of sustainability and scalability. This multisite, parallel RCT study on vaccine chatbots found mixed success in improving vaccine confidence and acceptance among unvaccinated Asian subpopulations. Further studies that link chatbot usage and real-world vaccine uptake are needed to augment evidence for employing vaccine chatbots to advance vaccine confidence and acceptance.

Effect of a mobile app chatbot and an interactive small-group webinar on COVID-19 vaccine intention and confidence in Japan: a randomised controlled trial.

INTRODUCTION: We investigated the effect of social media-based interventions on COVID-19 vaccine intention (VI) and confidence in Japan. METHODS: We conducted a three-arm randomised controlled trial between 5 November 2021 and 9 January 2022 during a low incidence (<1000/day) of COVID-19 in Japan in the midst of the second and the third waves. Japanese citizens aged ≥20 who had not received any COVID-19 vaccine and did not intend to be vaccinated were randomly assigned to one of the following three groups: (1) a control group, (2) a group using a mobile app chatbot providing information on COVID-19 vaccines and (3) a group using interactive webinars with health professionals. VI and predefined Vaccine Confidence Index (VCI) measuring confidence in the importance, safety and effectiveness were compared before and after the interventions under intention-to-treat principle. Logistic regression models were used to investigate the effect of each intervention on postintervention VI and changes of VCI compared with control. RESULTS: Among 386 participants in each group, 359 (93.0%), 231 (59.8%) and 207 (53.6%) completed the postsurvey for the control, chatbot and webinar groups, respectively. The average duration between the intervention and the postsurvey was 32 days in chatbot group and 27 days in webinar group. VI increased from 0% to 18.5% (95% CI 14.5%, 22.5%) in control group, 15.4% (95% CI 10.8%, 20.1%) in chatbot group and 19.7% (95% CI 14.5%, 24.9%) in webinar group without significant difference (OR for improvement=0.8 (95% CI 0.5, 1.3), p=0.33 between chatbot and control, OR=1.1 (95% CI 0.7, 1.6), p=0.73 between webinar and control). VCI change tended to be larger in chatbot group compared with control group without significant difference (3.3% vs -2.5% in importance, OR for improvement=1.3 (95% CI 0.9, 2.0), p=0.18; 2.5% vs 1.9% in safety, OR=1.1 (95% CI 0.7, 1.9), p=0.62; -2.4% vs -7.6% in effectiveness, OR=1.4 (95% CI 0.9, 2.1), p=0.09). Improvement in VCI was larger in webinar group compared with control group for importance (7.8% vs -2.5%, OR=1.8 (95% CI 1.2, 2.8), p<0.01), effectiveness (6.4% vs -7.6%, OR=2.2 (95% CI 1.4, 3.4), p<0.01) and safety (6.0% vs 1.9%, OR=1.6 (95% CI 1.0, 2.6), p=0.08). CONCLUSION: This study demonstrated that neither the chatbot nor the webinar changed VI importantly compared with control. Interactive webinars could be an effective tool to change vaccine confidence. Further study is needed to identify risk factors associated with decreased vaccine confidence and investigate what intervention can increase VI and vaccine confidence for COVID-19 vaccines. TRIAL REGISTRATION NUMBER: UMIN000045747.

Analysis of All-Cause Hospitalization and Death Among Nonhospitalized Patients With Type 2 Diabetes and SARS-CoV-2 Infection Treated With Molnupiravir or Nirmatrelvir-Ritonavir During the Omicron Wave in Hong Kong.

Importance: Diabetes and COVID-19 are both global pandemics, and type 2 diabetes is a common comorbidity in patients with acute COVID-19 and is proven to be a key determinant of COVID-19 prognosis. Molnupiravir and nirmatrelvir-ritonavir are oral antiviral medications recently approved for nonhospitalized patients with mild to moderate COVID-19, following demonstration of their efficacies in reducing adverse outcomes of the disease; it is crucial to clarify whether both oral antiviral medications are efficacious in a population consisting exclusively of patients with type 2 diabetes. Objective: To evaluate the effectiveness of molnupiravir and nirmatrelvir-ritonavir in a contemporary population-based cohort comprising exclusively nonhospitalized patients with type 2 diabetes and SARS-CoV-2 infection. Design, Setting, and Participants: This retrospective cohort study was performed using population-based electronic medical record data for patients in Hong Kong with type 2 diabetes and confirmed SARS-CoV-2 infection between February 26 and October 23, 2022. Each patient was followed up until death, outcome event, crossover of oral antiviral treatment, or end of the observational period (October 30, 2022), whichever came first. Outpatient oral antiviral users were divided into molnupiravir and nirmatrelvir-ritonavir treatment groups, respectively, and nontreated control participants were matched through 1:1 propensity score matching. Data analysis was performed on March 22, 2023. Exposures: Molnupiravir (800 mg twice daily for 5 days) or nirmatrelvir-ritonavir (300 mg nirmatrelvir and 100 mg ritonavir twice daily for 5 days, or 150 mg nirmatrelvir and 100 mg ritonavir for patients with an estimated glomerular filtration rate of 30-59 mL/min per 1.73 m2). Main Outcomes and Measures: The primary outcome was a composite of all-cause mortality and/or hospitalization. The secondary outcome was in-hospital disease progression. Hazard ratios (HRs) were estimated with Cox regression. Results: This study identified 22 098 patients with type 2 diabetes and COVID-19. A total of 3390 patients received molnupiravir and 2877 received nirmatrelvir-ritonavir in the community setting. After application of exclusion criteria followed by 1:1 propensity score matching, this study comprised 2 groups. One group included 921 molnupiravir users (487 men [52.9%]), with a mean (SD) age of 76.7 (10.8) years, and 921 control participants (482 men [52.3%]), with a mean (SD) age of 76.6 (11.7) years. The other group included 793 nirmatrelvir-ritonavir users (401 men [50.6%]), with a mean (SD) age of 71.7 (11.5) years, and 793 control participants (395 men [49.8%]), with a mean (SD) age of 71.9 (11.6) years. At a median follow-up of 102 days (IQR, 56-225 days), molnupiravir use was associated with a lower risk of all-cause mortality and/or hospitalization (HR, 0.71 [95% CI, 0.64-0.79]; P < .001) and in-hospital disease progression (HR, 0.49 [95% CI, 0.35-0.69]; P < .001) compared with nonuse. At a median follow-up of 85 days (IQR, 56-216 days), nirmatrelvir-ritonavir use was associated with a lower risk of all-cause mortality and/or hospitalization (HR, 0.71 [95% CI, 0.63-0.80]; P < .001) and a nonsignificantly lower risk of in-hospital disease progression (HR, 0.92 [95% CI, 0.59-1.44]; P = .73) compared with nonuse. Conclusions and Relevance: These findings suggest that both molnupiravir and nirmatrelvir-ritonavir oral antiviral medications were associated with a lower risk of all-cause mortality and hospitalization among patients with COVID-19 and type 2 diabetes. Further studies in specific populations, such as individuals in residential care homes and individuals with chronic kidney disease, are suggested.

Real-time assessment of COVID-19 epidemic in Guangdong Province, China using mathematical models.

China government has relaxed the response measures of COVID-19 in early December 2022. In this report, we assessed the number of infections, the number of severe cases based on the current epidemic trend (October 22, 2022 to November 30, 2022) using a transmission dynamics model, called modified susceptible-exposed-infectious-removed (SEIR) to provide valuable information to ensure the medical operation of the healthcare system under the new situation. Our model showed that the present outbreak in Guangdong Province peaked during December 21, 2022 to December 25, 2022 with about 14.98 million new infections (95% CI: 14.23-15.73 million). The cumulative number of infections will reach about 70% of the province's population from December 24, 2022 to December 26, 2022. The number of existing severe cases is expected to peak during January 1, 2023 to January 5, 2023 with a peak number of approximately 101.45 thousand (95% CI: 96.38-106.52 thousand). In addition, the epidemic in Guangzhou which is the capital city of Guangdong Province is expected to have peaked around December 22, 2022 to December 23, 2022 with the number of new infections at the peak being about 2.45 million (95% CI: 2.33-2.57 million). The cumulative number of infected people will reach about 70% of the city's population from December 24, 2022 to December 25, 2022 and the number of existing severe cases is expected to peak around January 4, 2023 to January 6, 2023 with the number of existing severe cases at the peak being about 6.32 thousand (95% CI: 6.00-6.64 thousand). Predicted results enable the government to prepare medically and plan for potential risks in advance.

Residential clustering of COVID-19 cases and efficiency of building-wide compulsory testing notices as a transmission control measure in Hong Kong.

We described the frequency of residential case clusters and the efficiency of compulsory testing in identifying cases using buildings targeted in compulsory testing and locally infected COVID-19 cases matched by residence in Hong Kong. Most of the buildings (4246/7688, 55.2%) with COVID-19 cases identified had only one reported case and 13% of the daily reported cases were detected through compulsory testing. Compulsory testing notices could be essential in attempting to eliminate infections ('zero covid') and impactful early in an epidemic but appears to be relatively inefficient in response to sustained community transmission.

Reproduction number of SARS-CoV-2 omicron variants, China, December 2022-January 2023.

China adjusted the zero-COVID strategy in late 2022, triggering an unprecedented Omicron wave. We estimated the time-varying reproduction numbers of 32 provincial-level administrative divisions from December 2022 to January 2023. We found that the pooled estimate of initial reproduction numbers is 4.74 (95% CI: 4.41, 5.07).

Within-host dynamics of SARS-CoV-2 infection: A systematic review and meta-analysis.

Within-host model specified by viral dynamic parameters is a mainstream tool to understand SARS-CoV-2 replication cycle in infected patients. The parameter uncertainty further affects the output of the model, such as the efficacy of potential antiviral drugs. However, gathering empirical data on these parameters is challenging. Here, we aim to conduct a systematic review of viral dynamic parameters used in within-host models by calibrating the model to the viral load data measured from upper respiratory specimens. We searched the PubMed, Embase and Web of Science databases (between 1 December 2019 and 10 February 2022) for within-host modelling studies. We identified seven independent within-host models from the above nine studies, including Type I interferon, innate response, humoral immune response or cell-mediated immune response. From these models, we extracted and analyse seven widely used viral dynamic parameters including the viral load at the point of infection or symptom onset, the rate of viral particles infecting susceptible cells, the rate of infected cells releasing virus, the rate of virus particles cleared, the rate of infected cells cleared and the rate of cells in the eclipse phase can become productively infected. We identified seven independent within-host models from nine eligible studies. The viral load at symptom onset is 4.78 (95% CI:2.93, 6.62) log(copies/ml), and the viral load at the point of infection is -1.00 (95% CI:-1.94, -0.05) log(copies/ml). The rate of viral particles infecting susceptible cells and the rate of infected cells cleared have the pooled estimates as -6.96 (95% CI:-7.66, -6.25) log([copies/ml]-1 day-1 ) and 0.92 (95% CI:-0.09, 1.93) day-1 , respectively. We found that the rate of infected cells cleared was associated with the reported model in the meta-analysis by including the model type as a categorical variable (p < .01). Joint viral dynamic parameters estimates when parameterizing within-host models have been published for SARS-CoV-2. The reviewed viral dynamic parameters can be used in the same within-host model to understand SARS-CoV-2 replication cycle in infected patients and assess the impact of pharmaceutical interventions.

Pandemic fatigue impedes mitigation of COVID-19 in Hong Kong.

Hong Kong has implemented stringent public health and social measures (PHSMs) to curb each of the four COVID-19 epidemic waves since January 2020. The third wave between July and September 2020 was brought under control within 2 m, while the fourth wave starting from the end of October 2020 has taken longer to bring under control and lasted at least 5 mo. Here, we report the pandemic fatigue as one of the potential reasons for the reduced impact of PHSMs on transmission in the fourth wave. We contacted either 500 or 1,000 local residents through weekly random-digit dialing of landlines and mobile telephones from May 2020 to February 2021. We analyze the epidemiological impact of pandemic fatigue by using the large and detailed cross-sectional telephone surveys to quantify risk perception and self-reported protective behaviors and mathematical models to incorporate population protective behaviors. Our retrospective prediction suggests that an increase of 100 daily new reported cases would lead to 6.60% (95% CI: 4.03, 9.17) more people worrying about being infected, increase 3.77% (95% CI: 2.46, 5.09) more people to avoid social gatherings, and reduce the weekly mean reproduction number by 0.32 (95% CI: 0.20, 0.44). Accordingly, the fourth wave would have been 14% (95% CI%: -53%, 81%) smaller if not for pandemic fatigue. This indicates the important role of mitigating pandemic fatigue in maintaining population protective behaviors for controlling COVID-19.

Cost-effectiveness of fractional doses of COVID-19 vaccine boosters in India

Background Coronavirus disease 2019 (COVID-19) continues to be a major global public health crisis in 2022 that exacts significant human and economic costs. Booster vaccination of individuals can improve waning immunity and reduce the impact of community epidemics. Methods Using an epidemiological model that incorporates population-level SARS-CoV-2 transmission and waning of vaccine-derived immunity, we identify the hypothetical potential of mass vaccination with fractionated vaccine doses specific to ChAdOx1 nCoV-19 (AZD1222 [Covishield];AstraZeneca) as an optimal and cost-effective strategy in India's Omicron outbreak. Findings We find that the optimal strategy is 1/8 fractional dosing under mild (Re ∼ 1.2) and rapid (Re ∼ 5) transmission scenarios, leading to an estimated $6 (95% CI: -13, 26) billion and $2 (95% CI:-26, 30) billion in health-related net monetary benefit over 200 days, respectively. Rapid and broad use of fractional dosing for boosters, together with delivery costs divided by fractionation, could substantially gain more net monetary benefit by $11 (95% CI: -10, 33) and $2 (95% CI: -23, 28) billion, respectively, under the mild and rapid transmission scenarios. Conclusions Mass vaccination with fractional doses of COVID-19 vaccines to boost immunity in a vaccinated population could be a cost effective strategy for mitigating the public health costs of resurgences caused by vaccine-evasive variants and fractional dosing deserves further clinical and regulatory evaluation. Funding Financial support was provided by the AIR@InnoHK Programme from Innovation and Technology Commission of the Government of the Hong Kong Special Administrative Region. Graphical This analysis demonstrated that the use of fractional dose could offer greater net monetary benefit in both moderate and rapid transmission scenarios given the epidemiological and socioeconomic conditions in India in 2022. In the face of a vaccine shortage, fractional dosage of vaccinations would have additional beneficial public health benefits.

Viral burden rebound in hospitalised patients with COVID-19 receiving oral antivirals in Hong Kong: a population-wide retrospective cohort study.

BACKGROUND: Viral rebound after nirmatrelvir-ritonavir treatment has implications for the clinical management and isolation of patients with COVID-19. We evaluated an unselected, population-wide cohort to identify the incidence of viral burden rebound and associated risk factors and clinical outcomes. METHODS: We did a retrospective cohort study of hospitalised patients with a confirmed diagnosis of COVID-19 in Hong Kong, China, for an observation period from Feb 26 to July 3, 2022 (during the omicron BA.2.2 variant wave). Adult patients (age ≥18 years) admitted 3 days before or after a positive COVID-19 test were selected from medical records held by the Hospital Authority of Hong Kong. We included patients with non-oxygen-dependent COVID-19 at baseline receiving either molnupiravir (800 mg twice a day for 5 days), nirmatrelvir-ritonavir (nirmatrelvir 300 mg with ritonavir 100 mg twice a day for 5 days), or no oral antiviral treatment (control group). Viral burden rebound was defined as a reduction in cycle threshold (Ct) value (≥3) on quantitative RT-PCR test between two consecutive measurements, with such decrease sustained in an immediately subsequent Ct measurement (for those patients with ≥3 Ct measurements). Logistic regression models were used to identify prognostic factors for viral burden rebound, and to assess associations between viral burden rebound and a composite clinical outcome of mortality, intensive care unit admission, and invasive mechanical ventilation initiation, stratified by treatment group. FINDINGS: We included 4592 hospitalised patients with non-oxygen-dependent COVID-19 (1998 [43·5%] women and 2594 [56·5%] men). During the omicron BA.2.2 wave, viral burden rebound occurred in 16 of 242 patients (6·6% [95% CI 4·1-10·5]) receiving nirmatrelvir-ritonavir, 27 of 563 (4·8% [3·3-6·9]) receiving molnupiravir, and 170 of 3787 (4·5% [3·9-5·2]) in the control group. The incidence of viral burden rebound did not differ significantly across the three groups. Immunocompromised status was associated with increased odds of viral burden rebound, regardless of antiviral treatment (nirmatrelvir-ritonavir: odds ratio [OR] 7·37 [95% CI 2·56-21·26], p=0·0002; molnupiravir: 3·05 [1·28-7·25], p=0·012; control: 2·21 [1·50-3·27], p<0·0001). Among patients receiving nirmatrelvir-ritonavir, the odds of viral burden rebound were higher in those aged 18-65 years (vs >65 years; 3·09 [1·00-9·53], p=0·050), those with high comorbidity burden (score >6 on the Charlson Comorbidity Index; 6·02 [2·09-17·38], p=0·0009), and those concomitantly taking corticosteroids (7·51 [1·67-33·82], p=0·0086); whereas the odds were lower in those who were not fully vaccinated (0·16 [0·04-0·67], p=0·012). In patients receiving molnupiravir, those aged 18-65 years (2·68 [1·09-6·58], p=0·032) or on concomitant corticosteroids (3·11 [1·23-7·82], p=0·016) had increased odds of viral burden rebound. We found no association between viral burden rebound and occurrence of the composite clinical outcome from day 5 of follow-up (nirmatrelvir-ritonavir: adjusted OR 1·90 [0·48-7·59], p=0·36; molnupiravir: 1·05 [0·39-2·84], p=0·92; control: 1·27 [0·89-1·80], p=0·18). INTERPRETATION: Viral burden rebound rates are similar between patients with antiviral treatment and those without. Importantly, viral burden rebound was not associated with adverse clinical outcomes. FUNDING: Health and Medical Research Fund, Health Bureau, The Government of the Hong Kong Special Administrative Region, China. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Characterizing Human Collective Behaviors During COVID-19 - Hong Kong SAR, China, 2020.

What is already known about this topic?: People are likely to engage in collective behaviors online during extreme events, such as the coronavirus disease 2019 (COVID-19) crisis, to express awareness, take action, and work through concerns. What is added by this report?: This study offers a framework for evaluating interactions among individuals' emotions, perceptions, and online behaviors in Hong Kong Special Administrative Region (SAR) during the first two waves of COVID-19 (February to June 2020). Its results indicate a strong correlation between online behaviors, such as Google searches, and the real-time reproduction numbers. To validate the model's output of risk perception, this investigation conducted 10 rounds of cross-sectional telephone surveys on 8,593 local adult residents from February 1 through June 20 in 2020 to quantify risk perception levels over time. What are the implications for public health practice?: Compared to the survey results, the estimates of the risk perception of individuals using our network-based mechanistic model capture 80% of the trend of people's risk perception (individuals who are worried about being infected) during the studied period. We may need to reinvigorate the public by involving people as part of the solution that reduced the risk to their lives.

Cost effectiveness of fractional doses of COVID-19 vaccine boosters in India.

BACKGROUND: Coronavirus disease 2019 (COVID-19) continues to be a major global public health crisis that exacts significant human and economic costs. Booster vaccination of individuals can improve waning immunity and reduce the impact of community epidemics. METHODS: Using an epidemiological model that incorporates population-level severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission and waning of vaccine-derived immunity, we identify the hypothetical potential of mass vaccination with fractionated vaccine doses specific to ChAdOx1 nCoV-19 (AZD1222 [Covishield]; AstraZeneca) as an optimal and cost-effective strategy in India's Omicron outbreak. FINDINGS: We find that the optimal strategy is 1/8 fractional dosing under mild (Re ∼ 1.2) and rapid (Re ∼ 5) transmission scenarios, leading to an estimated $6 (95% confidence interval [CI]: -13, 26) billion and $2 (95% CI: -26, 30) billion in health-related net monetary benefit over 200 days, respectively. Rapid and broad use of fractional dosing for boosters, together with delivery costs divided by fractionation, could substantially gain more net monetary benefit by $11 (95% CI: -10, 33) and $2 (95% CI: -23, 28) billion, respectively, under the mild and rapid transmission scenarios. CONCLUSIONS: Mass vaccination with fractional doses of COVID-19 vaccines to boost immunity in a vaccinated population could be a cost-effective strategy for mitigating the public health costs of resurgences caused by vaccine-evasive variants, and fractional dosing deserves further clinical and regulatory evaluation. FUNDING: Financial support was provided by the AIR@InnoHK Program from Innovation and Technology Commission of the Government of the Hong Kong Special Administrative Region.

Accounting for the Potential of Overdispersion in Estimation of the Time-varying Reproduction Number.

BACKGROUND: The time-varying reproduction number, Rt, is commonly used to monitor the transmissibility of an infectious disease during an epidemic, but standard methods for estimating Rt seldom account for the impact of overdispersion on transmission. METHODS: We developed a negative binomial framework to estimate Rt and a time-varying dispersion parameter (kt). We applied the framework to COVID-19 incidence data in Hong Kong in 2020 and 2021. We conducted a simulation study to compare the performance of our model with the conventional Poisson-based approach. RESULTS: Our framework estimated an Rt peaking around 4 (95% credible interval = 3.13, 4.30), similar to that from the Poisson approach but with a better model fit. Our approach further estimated kt <0.5 at the start of both waves, indicating appreciable heterogeneity in transmission. We also found that kt decreased sharply to around 0.4 when a large cluster of infections occurred. CONCLUSIONS: Our proposed approach can contribute to the estimation of Rt and monitoring of the time-varying dispersion parameters to quantify the role of superspreading.

The Structural Identifiability of a Humidity-Driven Epidemiological Model of Influenza Transmission.

Influenza epidemics cause considerable morbidity and mortality every year worldwide. Climate-driven epidemiological models are mainstream tools to understand seasonal transmission dynamics and predict future trends of influenza activity, especially in temperate regions. Testing the structural identifiability of these models is a fundamental prerequisite for the model to be applied in practice, by assessing whether the unknown model parameters can be uniquely determined from epidemic data. In this study, we applied a scaling method to analyse the structural identifiability of four types of commonly used humidity-driven epidemiological models. Specifically, we investigated whether the key epidemiological parameters (i.e., infectious period, the average duration of immunity, the average latency period, and the maximum and minimum daily basic reproductive number) can be uniquely determined simultaneously when prevalence data is observable. We found that each model is identifiable when the prevalence of infection is observable. The structural identifiability of these models will lay the foundation for testing practical identifiability in the future using synthetic prevalence data when considering observation noise. In practice, epidemiological models should be examined with caution before using them to estimate model parameters from epidemic data.

Real-world COVID-19 vaccine effectiveness against the Omicron BA.2 variant in a SARS-CoV-2 infection-naive population.

The SARS-CoV-2 Omicron variant has demonstrated enhanced transmissibility and escape of vaccine-derived immunity. Although first-generation vaccines remain effective against severe disease and death, robust evidence on vaccine effectiveness (VE) against all Omicron infections, irrespective of symptoms, remains sparse. We used a community-wide serosurvey with 5,310 subjects to estimate how vaccination histories modulated risk of infection in infection-naive Hong Kong during a large wave of Omicron BA.2 epidemic in January-July 2022. We estimated that Omicron infected 45% (41-48%) of the local population. Three and four doses of BNT162b2 or CoronaVac were effective against Omicron infection 7 days after vaccination (VE of 48% (95% credible interval 34-64%) and 69% (46-98%) for three and four doses of BNT162b2, respectively; VE of 30% (1-66%) and 56% (6-97%) for three and four doses of CoronaVac, respectively). At 100 days after immunization, VE waned to 26% (7-41%) and 35% (10-71%) for three and four doses of BNT162b2, and to 6% (0-29%) and 11% (0-54%) for three and four doses of CoronaVac. The rapid waning of VE against infection conferred by first-generation vaccines and an increasingly complex viral evolutionary landscape highlight the necessity for rapidly deploying updated vaccines followed by vigilant monitoring of VE.

Estimating the transmission dynamics of SARS-CoV-2 Omicron BF.7 in Beijing after adjustment of the zero-COVID policy in November-December 2022.

We tracked the effective reproduction number (Rt) of the predominant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant Omicron BF.7 in Beijing in November-December 2022 by fitting a transmission dynamic model parameterized with real-time mobility data to (i) the daily number of new symptomatic cases on 1-11 November (when China's zero-COVID interventions were still strictly enforced) and (ii) the proportion of individuals who participated in online polls on 10-22 December and self-reported to have been test-positive since 1 November. After China's announcement of 20 measures to transition from zero-COVID, we estimated that Rt increased to 3.44 (95% credible interval (CrI): 2.82-4.14) on 18 November and the infection incidence peaked on 11 December. We estimated that the cumulative infection attack rate (IAR; that is, proportion of the population infected since 1 November) in Beijing was 75.7% (95% CrI: 60.7-84.4) on 22 December 2022 and 92.3% (95% CrI: 91.4-93.1) on 31 January 2023. Surveillance programs should be rapidly set up to monitor the evolving epidemiology and evolution of SARS-CoV-2 across China.

Real-world effectiveness of molnupiravir and nirmatrelvir plus ritonavir against mortality, hospitalisation, and in-hospital outcomes among community-dwelling, ambulatory patients with confirmed SARS-CoV-2 infection during the omicron wave in Hong Kong: an observational study.

BACKGROUND: Little is known about the real-world effectiveness of oral antivirals against the SARS-CoV-2 omicron (B.1.1.529) variant. We aimed to assess the clinical effectiveness of two oral antiviral drugs among community-dwelling COVID-19 outpatients in Hong Kong. METHODS: In this observational study, we used data from the Hong Kong Hospital Authority to identify an unselected, territory-wide cohort of non-hospitalised patients with an officially registered diagnosis of SARS-CoV-2 infection between Feb 26 and June 26, 2022, during the period in which the omicron subvariant BA.2.2 was dominant in Hong Kong. We used a retrospective cohort design as primary analysis, and a case-control design as sensitivity analysis. We identified patients with COVID-19 who received either molnupiravir (800 mg twice daily for 5 days) or nirmatrelvir plus ritonavir (nirmatrelvir 300 mg and ritonavir 100 mg twice daily for 5 days, or nirmatrelvir 150 mg and ritonavir 100 mg if estimated glomerular filtration rate was 30-59 mL/min per 1·73 m2). Outpatient oral antiviral users were matched with controls using propensity score (1:10) according to age, sex, date of SARS-CoV-2 infection diagnosis, Charlson Comorbidity Index score, and vaccination status. Study outcomes were death, COVID-19-related hospitalisation, and in-hospital disease progression (in-hospital death, invasive mechanical ventilation, or intensive care unit admission). Hazard ratios (HRs) were estimated by Cox regression for the primary analysis, and odds ratios in oral antiviral users compared with non-users by logistic regression for the sensitivity analysis. FINDINGS: Among 1 074 856 non-hospitalised patients with COVID-19, 5383 received molnupiravir and 6464 received nirmatrelvir plus ritonavir in the community setting. Patients were followed up for a median of 103 days in the molnupiravir group and 99 days in the nirmatrelvir plus ritonavir group. Compared with nirmatrelvir plus ritonavir users, those on molnupiravir were older (4758 [85·9%] vs 4418 [88.7%] aged >60 years) and less likely to have been fully vaccinated (1850 [33·4%] vs 800 [16·1%]). Molnupiravir use was associated with lower risks of death (HR 0·76 [95% CI 0·61-0·95]) and in-hospital disease progression (0·57 [0·43-0·76]) than non-use was, whereas risk of hospitalisation was similar in both groups (0·98 [0·89-1·06]). Nirmatrelvir plus ritonavir use was associated with lower risks of death (0·34 [0·22-0·52]), hospitalisation (0·76 [0·67-0·86]), and in-hospital disease progression (0·57 [0·38-0·87]) than non-use was. We consistently found reduced risks of mortality and hospitalisation associated with early oral antiviral use among older patients. The findings from the case-control analysis broadly supported those from the primary analysis. INTERPRETATION: During Hong Kong's wave of SARS-CoV-2 omicron subvariant BA.2.2, among non-hospitalised patients with COVID-19, early initiation of novel oral antivirals was associated with reduced risks of mortality and in-hospital disease progression. Nirmatrelvir plus ritonavir use was additionally associated with a reduced risk of hospitalisation. FUNDING: Health and Medical Research Fund, Health Bureau, Government of Hong Kong Special Administrative Region, China. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.