Background: COVID-19 (coronavirus disease 2019) has caused a major epidemic worldwide; however, much is yet to be known about the epidemiology and evolution of the virus partly due to the scarcity of full-length SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) genomes reported. One reason is that the challenges underneath sequencing SARS-CoV-2 directly from clinical samples have not been completely tackled, i.e., sequencing samples with low viral load often results in insufficient viral reads for analyses. Methods: We applied a novel multiplex PCR amplicon (amplicon)-based and hybrid capture (capture)-based sequencing, as well as ultra-high-throughput metatranscriptomic (meta) sequencing in retrieving complete genomes, inter-individual and intra-individual variations of SARS-CoV-2 from serials dilutions of a cultured isolate, and eight clinical samples covering a range of sample types and viral loads. We also examined and compared the sensitivity, accuracy, and other characteristics of these approaches in a comprehensive manner. Results: We demonstrated that both amplicon and capture methods efficiently enriched SARS-CoV-2 content from clinical samples, while the enrichment efficiency of amplicon outran that of capture in more challenging samples. We found that capture was not as accurate as meta and amplicon in identifying between-sample variations, whereas amplicon method was not as accurate as the other two in investigating within-sample variations, suggesting amplicon sequencing was not suitable for studying virus-host interactions and viral transmission that heavily rely on intra-host dynamics. We illustrated that meta uncovered rich genetic information in the clinical samples besides SARS-CoV-2, providing references for clinical diagnostics and therapeutics. Taken all factors above and cost-effectiveness into consideration, we proposed guidance for how to choose sequencing strategy for SARS-CoV-2 under different situations. Conclusions: This is, to the best of our knowledge, the first work systematically investigating inter- and intra-individual variations of SARS-CoV-2 using amplicon- and capture-based whole-genome sequencing, as well as the first comparative study among multiple approaches. Our work offers practical solutions for genome sequencing and analyses of SARS-CoV-2 and other emerging viruses.

Background: Evidence with regard to antibiotic prophylaxis for patients with open fractures of the extremities is limited. We therefore conducted a systematic survey addressing current practice and recommendations.Methods: We included publications from January 2007 to June 2017. We searched Embase, MEDLINE, CINAHL, the Cochrane Central Registry of Controlled Trials (CENTRAL), and the Cochrane Database of Systematic Reviews for clinical studies and surveys of surgeons; WorldCat for textbooks; and web sites for guidelines and institutional protocols.Results: We identified 223 eligible publications that reported 100 clinical practice patterns and 276 recommendations with regard to systemic antibiotic administration, and 3 recommendations regarding local antibiotic administration alone. Most publications of clinical practice patterns used regimens with both gram-positive and gram-negative coverage and continued the administration for 2 to 3 days. Most publications recommended prophylactic systemic antibiotics. Most recommendations suggested gram-positive coverage for less severe injuries and administration duration of 3 days or less. For more severe injuries, most recommendations suggested broad antimicrobial coverage continued for 2 to 3 days. Most publications reported intravenous administration of antibiotics immediately.Conclusions: Current practice and recommendations strongly support early systemic antibiotic prophylaxis for patients with open fractures of the extremities. Differences in antibiotic regimens, doses, and durations of administration remain in both practice and recommendations. Consensus with regard to optimal practice will likely require well-designed randomized controlled trials.Clinical Relevance: The current survey of literature systematically provides surgeons’ practice and the available expert recommendations from 2007 to 2017 on the use of prophylactic antibiotics in the management of open fractures of extremities.

Sexually Transmitted Infections (STIs) are a global challenge. China, once said to have eradicated STIs, is now facing a rapid rise in the prevalence of HIV/STIs. This review of reviews aims to map HIV/STI risk factors among the Chinese population, with the objective of identifying risk factors to inform the formulation of effective prevention strategies. A systematic search using key terms related to HIV/STIs, risk factors and the Chinese population in both English and Chinese databases (PubMed, PsycINFO, the Cochrane Library; Wanfang data, CNKI, VIP and SINOMED) was conducted, and peer-reviewed systematic reviews on the topic from 1991 to 2014 were selected. Identified risk factors were grouped into different level determinants based on the HIV Social Epidemiology Model, and then evaluated and reported based on the PRISMA checklist. Of the twenty-eight reviews included, the majority were focused on well-established, individual level risk factors within key populations, with some highlighting the complexity of interacting factors (e.g., alcohol use and higher income in male migrants). While twenty-two reviews covered individual factors, only ten mentioned social factors and five had contents on structural factors. There are gaps in the evidence on social and structural level impacts of HIV/STIs, such as on stigma, discrimination, health policy, access to care, and illicit drug control policies. Migration and social expectation appear to pose a significant threat in aggravating the HIV/STI situation in China; for example, incarceration patterns indicated a significant risk of HIV/STIs for female sex workers. Since international guidelines recommend an integrated and multi-level approach to HIV/STI prevention, a comprehensive approach targeting interventions at all levels along the continuum of care is needed to effectively curtail HIV/STI transmission in China. More research is needed to better understand the impact of socio-political interventions within a Chinese context.

Chlamydia causes infertility and increases risk of HIV infection, and population-based studies provide essential information for effective infection control and prevention. This study examined Chlamydia trachomatis prevalence and risk factors among a representative sample of 18-49-year-old residents in Hong Kong. Census boundary map of 412 constituency areas was used as primary sampling units to construct the sampling frame and, residential buildings and units were randomly selected using geospatial modelling. A questionnaire on sexual practice and health was conducted, and polymerase chain reaction was used to test the urine for genital chlamydial infection. Invitation letters were sent to the selected households and a team of interviewers were sent to recruit one subject per household. Prevalence data was weighted according to the 2011 census and risk factors identified through logistic regression. Among 881 participants (response rate of 24.5%), the overall Chlamydia trachomatis prevalence was low at 1.4% (95%CI 0.8–2.5%) but sexually active young (18–26 years) women had relatively high prevalence (5.8%, 95%CI 1.7–18.2%) in Hong Kong. A unique U-shape disease burden was observed with peaks in younger and older (40–49 years) women. Amongst the sexually active women, the risk factors of Chlamydia trachomatis infection were: younger age (aOR = 25.4, 95% CI 2.81–230); living alone (aOR = 8.99, 95% CI 1.46–55.40); and, among all the sexually active participants, males (including the male partners of the female participants) who had travelled out of Hong Kong in the previous 12 months had higher risks of infection (aOR = 5.35; 95% CI 1.25–22.8). A core-peripheral geographical distribution of Chlamydia trachomatis prevalence was also observed. Young and older sexually active women in Hong Kong have high prevalence of chlamydia. Routine screening for sexually active women and young men should be considered. Further research on testing feasibility and linkage-to-care are urgently needed to control the infection.

Genitourinary tuberculosis (GUTB) accounts for up to 40% of extrapulmonary tuberculosis cases. Rapid tests for GUTB are urgently needed because it is often associated with delayed health-care seeking, leading to serious consequences. This study evaluated the performance of the Xpert MTB/RIF assay in the rapid diagnosis of urinary tract tuberculosis (UTB) and rifampicin-resistant tuberculosis with urine specimens. In all, 302 patients were included from four hospitals in China. Suspected UTB patients were tested with Xpert, smear, and MGIT 960 culture. Drug susceptibility testing (DST) was conducted for culture-positive cases. The performance of the assays was evaluated against MGIT 960 culture and a composite reference standard (CRS). Among all participants, 150 (49.7%) had CRS-positive UTB, of whom 36 (24.0%) were culture-confirmed. Against culture, Xpert and smear achieved a sensitivity of 94.4% (95% CI: 81.3–99.3%) and 22.2% (95% CI: 10.1–39.2%), respectively. Against CRS, the sensitivity of Xpert, smear and culture was 41.3% (95% CI: 33.4–49.7%), 7.3% (95% CI: 3.7–12.7%), and 24.0% (95% CI: 17.4–31.6%). Xpert had better performance than smear and culture in detecting UTB from urine samples and could be considered for the diagnosis of UTB. Moreover, Xpert showed better performance than MGIT 960-based DST using urine culture.