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As of June 8, 2020, the global reported number of COVID-19 cases had reached more than 7 million with over 400 000 deaths. The household transmissibility of the causative pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains unclear. We aimed to estimate the secondary attack rate of SARS-CoV-2 among household and non-household close contacts in Guangzhou, China, using a statistical transmission model. In this retrospective cohort study, we used a comprehensive contact tracing dataset from the Guangzhou Center for Disease Control and Prevention to estimate the secondary attack rate of COVID-19 (defined as the probability that an infected individual will transmit the disease to a susceptible individual) among household and non-household contacts, using a statistical transmission model. We considered two alternative definitions of household contacts in the analysis: individuals who were either family members or close relatives, such as parents and parents-in-law, regardless of residential address, and individuals living at the same address regardless of relationship. We assessed the demographic determinants of transmissibility and the infectivity of COVID-19 cases during their incubation period. Between Jan 7, 2020, and Feb 18, 2020, we traced 195 unrelated close contact groups (215 primary cases, 134 secondary or tertiary cases, and 1964 uninfected close contacts). By identifying households from these groups, assuming a mean incubation period of 5 days, a maximum infectious period of 13 days, and no case isolation, the estimated secondary attack rate among household contacts was 12·4% (95% CI 9·8–15·4) when household contacts were defined on the basis of close relatives and 17·1% (13·3–21·8) when household contacts were defined on the basis of residential address. Compared with the oldest age group (≥60 years), the risk of household infection was lower in the youngest age group (<20 years; odds ratio [OR] 0·23 [95% CI 0·11–0·46]) and among adults aged 20–59 years (OR 0·64 [95% CI 0·43–0·97]). Our results suggest greater infectivity during the incubation period than during the symptomatic period, although differences were not statistically significant (OR 0·61 [95% CI 0·27–1·38]). The estimated local reproductive number (R) based on observed contact frequencies of primary cases was 0·5 (95% CI 0·41–0·62) in Guangzhou. The projected local R, had there been no isolation of cases or quarantine of their contacts, was 0·6 (95% CI 0·49–0·74) when household was defined on the basis of close relatives. SARS-CoV-2 is more transmissible in households than SARS-CoV and Middle East respiratory syndrome coronavirus. Older individuals (aged ≥60 years) are the most susceptible to household transmission of SARS-CoV-2. In addition to case finding and isolation, timely tracing and quarantine of close contacts should be implemented to prevent onward transmission during the viral incubation period. US National Institutes of Health, Science and Technology Plan Project of Guangzhou, Project for Key Medicine Discipline Construction of Guangzhou Municipality, Key Research and Development Program of China.

The effectiveness of inactivated SARS-CoV-2 vaccines against the Delta variant, which has been associated with greater transmissibility and virulence, remains unclear. We conducted a test-negative case-control study to explore the vaccine effectiveness (VE) in real-world settings. We recruited participants aged 18-59 years who consisted of SARS-CoV-2 test-positive cases (n = 74) and test-negative controls (n = 292) during the outbreak of the Delta variant in May 2021 in Guangzhou city, China. Vaccination status was compared to estimate The VE of SARS-CoV-2 inactivated vaccines. A single dose of inactivated SARS-CoV-2 vaccine yielded the VE of only 13.8%. After adjusting for age and sex, the overall VE for two-dose vaccination was 59.0% (95% confidence interval: 16.0% to 81.6%) against coronavirus disease 2019 (COVID-19) and 70.2% (95% confidence interval: 29.6-89.3%) against moderate COVID-19 and 100% against severe COVID-19 which might be overestimated due to the small sample size. The VE of two-dose vaccination against COVID-19 reached 72.5% among participants aged 40-59 years, and was higher in females than in males against COVID-19 and moderate diseases. While single dose vaccination was not sufficiently protective, the two-dose dosing scheme of the inactivated vaccines was effective against the Delta variant infection in real-world settings, with the estimated efficacy exceeding the World Health Organization minimal threshold of 50%.

Background The high prevalence of hepatitis B weighs heavily on public health in China. In 2009, a catch-up vaccination program for children aged 8–15y was implemented to curb hepatitis B, while the effectiveness of this intervention has not been investigated. We aimed to evaluate the effectiveness of catch-up vaccination on the incidence of hepatitis B in Guangzhou, China. Methods We obtained individual data of all hepatitis B cases from 2005 to 2019 in Guangzhou from Guangzhou Center for Diseases Control and Prevention. Based on daily reported number of cases, we constructed generalized linear models to estimate the effectiveness of the intervention on the incidence of hepatitis B in each age group from 11 to 25 years. We further estimated the age-standardized effectiveness. Finally, we examined the effectiveness in different subgroups by sex and clinical types of hepatitis B. Results A total of 58,204 hepatitis B cases among individuals aged 11–25y were reported in Guangzhou from 2005 to 2019, with an average annual age-standardized incidence of 117.30 cases per 100,000 individuals. The catch-up vaccination contributed to an age-standardized 20.02% (95% confidence interval: 15.97%, 23.87%) decrease in the hepatitis B incidence among individuals aged 11–25y and prevented an annual age-standardized average of 17.40 (95% empirical confidence interval [eCI]: 9.24, 23.78) cases per 100,000 individuals from hepatitis B during the study period. The intervention could better protect males (excess incidence rate [EIR]: -21.82 [95% eCI: -30.51, -10.15] cases per 100,000 individuals), and prevent chronic cases (EIR: -24.27 [95% eCI: -30.62, -16.09] cases per 100,000 individuals). Conclusions The massive catch-up vaccination against hepatitis B among children plays an important role in alleviating the burden of hepatitis B.

In 2019, dengue incidences increased dramatically in many countries. However, the prospective growth in dengue incidence did not occur in Guangzhou, China. We examined the effectiveness of early start of Grade III response to dengue in Guangzhou. We extracted the data on daily number of dengue cases during 2017-2019 in Guangzhou and weekly data for Foshan and Zhongshan from the China National Notifiable Disease Reporting System, while the data on weekly number of positive ovitraps for adult and larval Aedes albopictus were obtained from Guangzhou Center for Disease Control and Prevention. We estimated the number of dengue cases prevented by bringing forward the starting time of Grade III response from September in 2017-2018 to August in 2019 in Guangzhou using a quasi-Poisson regression model and applied the Baron and Kenny's approach to explore whether mosquito vector density was a mediator of the protective benefit. In Guangzhou, early start of Grade III response was associated with a decline in dengue incidence (relative risk [RR]: 0.54, 95% confidence interval [CI]: 0.43-0.70), with 987 (95% CI: 521-1,593) cases averted in 2019. The rate of positive ovitraps also significantly declined (RR: 0.64, 95% CI: 0.53-0.77). Moreover, both mosquito vector density and early start of Grade III response was significantly associated with dengue incidence after adjustment for each other. By comparing with the incidence in Foshan and Zhongshan where the Grade III response has not been taken, benefits from the response starting in August were confirmed but not if starting from September. Early start of Grade III response has effectively mitigated the dengue burden in Guangzhou, China, which might be partially through reducing the mosquito vector density. Our findings have important public health implications for development and implementation of dengue control interventions for Guangzhou and other locations with dengue epidemics.

The composition of influenza vaccines is updated annually. To ensure vaccine safety, the coverage and adverse events following immunization (AEFI) of 6 manufacturers of trivalent inactivated influenza vaccine (TIV3) need to be evaluated. In January 2022, we analyzed data from more than 1.59 million children in the Childhood Vaccination Information Management System and the AEFI Surveillance Information Management System and evaluated influenza vaccines for children aged 6 to 35 months in Guangzhou from 2016/17 to 2019/20 Vaccination rates and AEFI reporting rates. From 2016/17 to 2019/20, the 1-dose influenza vaccination rate was 25.0% (range: 20.7%-30.2%), and the 2-dose (full course) influenza vaccination rate was 21.6% (range: 17.7%-26.4%). The full vaccination coverage rate has trended down since 2017/2018 (2017/18: 26.0%; 2018/19: 8.3; 2019/20: 17.7%). Fifty-two cases (13.1/100 000) and 24 cases (6.9/100 000) received AEFI reports for 1 dose and 2 doses, respectively, mainly due to fever ≥38.6°C (39 cases for 1 dose, 9.8/100 000; 15 cases for 2 dose, 4.3/100 000) and allergic rash (9 cases with 1 dose, 2.3/100 000; 5 cases with 2 doses, 1.4/100 000). Patients who received A and F manufacturers were more likely to report side effects. The safety of influenza vaccines from 6 manufacturers is good, and it is necessary to improve the recommended information on influenza vaccines to dispel people’s concerns and increase the vaccination rate.

The national Expanded Program on Immunization (EPI) in China has covered vaccines for measles, mumps, and rubella, among children aged 18–24 months since September 2008. However, no previous studies have quantified the effectiveness of the EPI on mumps incidence. There are methodological challenges in assessing the effect of an intervention that targets a subpopulation but finally influences the whole population. In this study, monthly data on mumps incidence were collected in Guangzhou, China, during 2005–2019. We proposed a multi-age-group interrupted time-series design, setting the starting time of exerting effect separately for 14 different age groups. A mixed-effects quasi-Poisson regression was applied to analyze the effectiveness of the EPI on mumps incidence, after controlling for long-term and seasonal trends, and meteorological factors. The model also accounted for the first-order autocorrelation within each age group. Between-age-group correlations were expressed using the contact matrix of age groups. We found that 70,682 mumps cases were reported during 2005–2019, with an annual incidence rate of 37.91 cases per 100,000 population. The effect of EPI strengthened over time, resulting in a decrease in the incidence of mumps by 16.6% (EPI-associated excess risk% = −16.6%, 95% CI: −27.0% to −4.7%) in September 2009 to 40.1% (EPI-associated excess risk% = −40.1%, 95% CI: −46.1% to −33.3%) in September 2019. A reverse U-shape pattern was found in age-specific effect estimates, with the largest reduction of 129 cases per 100,000 population (95% CI: 14 to 1173) in those aged 4–5 years. The EPI is effective in reducing the mumps incidence in Guangzhou. The proposed modeling strategy can be applied for simultaneous assessment of the effectiveness of public health interventions across different age groups, with adequate adjustment for within- and between-group correlations.

From 11 March to 6 July 2020, a total of 268 imported cases of COVID-19 from abroad were confirmed in Guangzhou. 74% of the imported cases were detected during customs inspection and 19% under centralized quarantine. We advocate for legally enforced quarantine and monitoring of quarantined persons.

Background Many injection drug users (IDUs) in China have high risk sexual behaviors that contribute to the spread of HIV infection. Although many IDUs in China move through drug rehabilitation centers, this opportunity for sexual health education has largely been overlooked. Methods A convenience sample of 667 drug users from two rehabilitation centers in South China was recruited in the study. Two hundred and forty seven drug users from a single Guangdong Province rehabilitation center received the peer-based education intervention, while 420 drug users from another rehabilitation center received routine HIV/STI education and was used as the control. One hundred and eighty nine (22.1%) individuals refused to participate in the study. HIV/STI behavioral and knowledge domains were assessed at 3 months in rehabilitation centers after the intervention (first follow-up) and at 2-23 months in the community after release (second follow-up). Results Drug users who completed the intervention reported more frequent condom use with casual sex partners (60.0% vs. 12.5% condom use every time, p = 0.011) and less frequent injection (56.7% vs. 26.4% no injection per day, p = 0.008) at the second follow-up compared to those in the routine education group. Loss to follow up was substantial in both control and intervention groups, and was associated with living far from the detention center and having poor HIV knowledge at baseline. Conclusions This study shows that rehabilitation centers may be a useful location for providing behavioral HIV/STI prevention services and referral of individuals to community-based programs upon release. More research is needed on behalf of detained drug users in China who have complex social, medical, and legal needs.

PRKAG2 cardiac syndrome is an autosomal dominant inherited disease resulted from mutations in the PRK- AG2 gene that encodes γ2 regulatory subunit of AMP-activated protein kinase. Affected patients usually develop ventricular tachyarrhythmia and experience progressive heart failure that is refractory to medical treatment and requires cardiac transplantation. In this study, we identify a H530R mutation in PRKAG2 from patients with familial Wolff-Parkinson-White syndrome. By generating H530R PRKAG2 transgenic and knock-in mice, we show that both models recapitulate human symptoms including cardiac hypertrophy and glycogen storage, confirming that the H530R mutation is causally related to PRKAG2 cardiac syndrome. We further combine adeno-associated virus-9 （AAV9） and the CRISPR/Cas9 gene-editing system to disrupt the mutant PRKAG2 allele encoding H530R while leav- ing the wild-type allele intact. A single systemic injection of AAV9-Cas9/sgRNA at postnatal day 4 or day 42 substantially restores the morphology and function of the heart in H530R PRKAG2 transgenic and knock-in mice. Together, our work suggests that in vivo CRISPR/Cas9 genome editing is an effective tool in the treatment of PRKAG2 cardiac syndrome and other dominant inherited cardiac diseases by selectively disrupting disease-causing mutations.

Endocardial fibroelastosis （EFE） refers to the thickening of the ventricular endocardium as a result of de novo deposition of subendocardial fibrous tissue layers during neonatal heart development. The origin of EFE fibroblasts is proposed to be postnatal endocardial cells that undergo an aberrant endothelial-to-mesenchymal transition （End- MT）. Genetic lineage tracing of endocardial cells with the inducible endocardial Cre line Npr3-CreER and the endo- thelial cell tracing line Cdh5-CreER on an EFE-like model did not reveal any contribution of neonatal endocardial cells to fibroblasts in the EFE-like tissues. Instead, lineage tracing of embryonic epicardium by Wtl-CreER suggested that epicardium-derived mesenchymal cells （MCs） served as the major source of EFE fibroblasts. By labeling MCs using Sox9-CreER, we confirmed that MCs of the embryonic heart expand and contribute to the majority of neonatal EFE fibroblasts. During this pathological process, TGFp signaling, the key mediator of fibroblasts activation, was highly upregulated in the EFE-like tissues. Targeting TGFp signaling by administration of its antagonist bone mor- phogenetic protein 7 effectively reduced fibroblast accumulation and tissue fibrosis in the EFE-like model. Our study provides genetic evidence that excessive fibroblasts in the EFE-like tissues mainly originate from the epicardium-de- rived MCs through epicardial to mesenchymal transition （EpiMT）. These EpiMT-derived fibroblasts within the EFE- like tissues could serve as a potential therapeutic target.