Quantifying the effect of government interventions and virus mutations on transmission advantage during COVID-19 pandemic.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has become a major public health threat. This study aims to evaluate the effect of virus mutation activities and policy interventions on COVID-19 transmissibility in Hong Kong. METHODS: In this study, we integrated the genetic activities of multiple proteins, and quantified the effect of government interventions and mutation activities against the time-varying effective reproduction number Rt. FINDINGS: We found a significantly positive relationship between Rt and mutation activities and a significantly negative relationship between Rt and government interventions. The results showed that the mutations that contributed most to the increase of Rt were from the spike, nucleocapsid and ORF1b genes. Policy of prohibition on group gathering was estimated to have the largest impact on mitigating virus transmissibility. The model explained 63.2% of the Rt variability with the R2. CONCLUSION: Our study provided a convenient framework to estimate the effect of genetic contribution and government interventions on pathogen transmissibility. We showed that the S, N and ORF1b protein had significant contribution to the increase of transmissibility of SARS-CoV-2 in Hong Kong, while restrictions of public gathering and suspension of face-to-face class are the most effective government interventions strategies.

Characterization of key amino acid substitutions and dynamics of the influenza virus H3N2 hemagglutinin.

The annual epidemics of seasonal influenza is partly attributed to the continued virus evolution. It is challenging to evaluate the effect of influenza virus mutations on evading population immunity. In this study, we introduce a novel statistical and computational approach to measure the dynamic molecular determinants underlying epidemics using effective mutations (EMs), and account for the time of waning mutation advantage against herd immunity by measuring the effective mutation periods (EMPs). Extensive analysis is performed on the sequencing and epidemiology data of H3N2 epidemics in ten regions from season to season. We systematically identified 46 EMs in the hemagglutinin (HA) gene, in which the majority were antigenic sites. Eight EMs were located in immunosubdominant stalk domain, an important target for developing broadly reactive antibodies. The EMs might provide timely information on key substitutions for influenza vaccines antigen design. The EMP suggested that major genetic variants of H3N2 circulated in Southeast Asia for an average duration of 4.5 years (SD 2.4) compared to a significantly shorter 2.0 years (SD 1.0) in temperate regions. The proposed method bridges population epidemics and molecular characteristics of infectious diseases, and would find broad applications in various pathogens mutation estimations.

Transmissibility of coronavirus disease 2019 in Chinese cities with different dynamics of imported cases.

BACKGROUND: Monitoring the reproduction number (Rt ) of the disease could help determine whether there is sustained transmission in a population, but areas with similar epidemic trends could have different transmission dynamics given the risk from imported cases varied across regions. In this study, we examined the Rt of coronavirus disease 2019 (COVID-19) by taking different dynamics of imported cases into account and compared the transmissibility of COVID-19 at different intervention periods in Hangzhou and Shenzhen. METHODS: We obtained the daily aggregated counts of laboratory-confirmed imported and local cases of COVID-19 infections in Hangzhou and Shenzhen from January 1 to March 13, 2020. Daily Rt and piecewise Rt before and after Wuhan lockdown were estimated, accounting for imported cases. RESULTS: Since the epidemic of COVID-19 in Shenzhen was dominated by imported cases, Rt was around 0.1 to 0.7 before the Wuhan lockdown. After the lockdown of Wuhan and the initialization of measures in response to the outbreak, local transmission was well-controlled as indicated by a low estimated value of piecewise Rt , 0.15 (95% CI [0.09-0.21]). On the contrary, Rt obtained for Hangzhou ranged from 1.2 to 4.9 with a piecewise Rt of 2.55 (95% CI [2.13-2.97]) before the lockdown of Wuhan due to the surge in local cases. Because of the Wuhan lockdown and other outbreak response measures, Rt dropped below unity in mid-February. CONCLUSIONS: Even though Shenzhen had more cases than Hangzhou, local transmission did not sustain probably due to limited transmission from imported cases owing to the reduction in local susceptibles as residents left the city during Chunyun. The lockdown measures and local outbreak responses helped reduce the local transmissibility.

Risk factors and natural history of breast cancer in younger Chinese women.

AIM: To investigate the age differences in the risk factors, clinicopathological characteristics and patterns of treatment of female breast cancer patients. METHODS: Seven thousand one hundred and fifty-two women with primary breast cancer from the Hong Kong Breast Cancer Registry were recruited after receiving patients' consent, they were asked to complete standardized questionnaires which captured their sociodemographic characteristics and risk factors associated with breast cancer development. Among them, clinicopathological data and patterns of treatment were further collected from medical records of 5523 patients with invasive breast cancers. Patients were divided into two groups according to the age at diagnosis: younger (< 40 years old) vs older patients (≥ 40 years old) for subsequent analyses. RESULTS: Analysis on the sociodemographic characteristics and exposure to risk factors were performed on 7152 women with primary breast cancer and the results revealed that younger patients were more likely to have unhealthy lifestyles; these include a lack of exercise (85.4% vs 73.2%, P < 0.001), having high stress in life (46.1% vs 35.5%, P < 0.001), having dairy/meat-rich diets (20.2% vs 12.9%, P < 0.001), having alcohol drinking habit (7.7% vs 5.2%, P = 0.002). Younger patients were also more likely to have hormone-related risk factors including nulliparity (43.3% vs 17.8%, P < 0.001) and an early age at menarche (20.7% vs 13.2%, P < 0.001). Analyses on clinicopathological characteristics and patterns of treatment were performed on 5523 women diagnosed with invasive breast cancer. The invasive tumours in younger patients showed more aggressive pathological features such as having a higher percentage of grade 3 histology (45.7% vs 36.5%, P < 0.001), having a higher proportion of tumours with lymphovascular invasion (39.6% vs 33.2%, P = 0.003), and having multifocal disease (15.7% vs 10.3%, P < 0.001); they received different patterns of treatment than their older counterparts. CONCLUSION: Younger patients in Hong Kong are more likely to encounter risk factors associated with breast cancer development and have more aggressive tumours than their older counterparts.