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BACKGROUND AND AIMS: Hepatitis E virus (HEV) variants causing human infection predominantly belong to HEV species A (HEV-A). HEV species C genotype 1 (HEV-C1) circulates in rats and is highly divergent from HEV-A. It was previously considered unable to infect humans, but the first case of human HEV-C1 infection was recently discovered in Hong Kong. The aim of this study is to further describe the features of this zoonosis in Hong Kong. APPROACH AND RESULTS: We conducted a territory-wide prospective screening study for HEV-C1 infection over a 31-month period. Blood samples from 2,860 patients with abnormal liver function (n = 2,201) or immunosuppressive conditions (n = 659) were screened for HEV-C1 RNA. In addition, 186 captured commensal rats were screened for HEV-C1 RNA. Sequences of human-derived and rat-derived HEV-C1 isolates were compared. Epidemiological and clinical features of HEV-C1 infection were analyzed. HEV-C1 RNA was detected in 6/2,201 (0.27%) patients with hepatitis and 1/659 (0.15%) immunocompromised persons. Including the previously reported case, eight HEV-C1 infections were identified, including five in patients who were immunosuppressed. Three patients had acute hepatitis, four had persistent hepatitis, and one had subclinical infection without hepatitis. One patient died of meningoencephalitis, and HEV-C1 was detected in cerebrospinal fluid. HEV-C1 hepatitis was generally milder than HEV-A hepatitis. HEV-C1 RNA was detected in 7/186 (3.76%) rats. One HEV-C1 isolate obtained from a rat captured near the residences of patients was closely related to the major outbreak strain. CONCLUSIONS: HEV-C1 is a cause of hepatitis E in humans in Hong Kong. Immunosuppressed individuals are susceptible to persistent HEV-C1 infection and extrahepatic manifestations. Subclinical HEV-C1 infection threatens blood safety. Tests for HEV-C1 are required in clinical laboratories.
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Reservatórios de Doenças/veterinária , Vírus da Hepatite E/genética , Hepatite E/epidemiologia , Hepatite E/transmissão , Idoso , Idoso de 80 Anos ou mais , Animais , Reservatórios de Doenças/virologia , Feminino , Vírus da Hepatite E/classificação , Hepatite Viral Animal/transmissão , Hong Kong/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Filogenia , Estudos Prospectivos , RNA Viral/genética , Ratos , Zoonoses/transmissão , Zoonoses/virologiaRESUMO
Coronavirus disease 2019 (COVID-19) pandemic has been a catastrophic burden to global healthcare systems. The fast spread of the etiologic agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), highlights the need to identify unknown coronaviruses rapidly for prompt clinical and public health decision making. Moreover, owing to the high mutation rate of RNA viruses, periodic surveillance on emerging variants of key virus components is essential for evaluating the efficacy of antiviral drugs, diagnostic assays and vaccines. These 2 knowledge gaps formed the basis of this study. In the first place, we evaluated the feasibility of characterizing coronaviruses directly from respiratory specimens. We amplified partial RdRP gene, a stable genetic marker of coronaviruses, from a collection of 57 clinical specimens positive for SARS-CoV-2 or other human coronaviruses, and sequenced the amplicons with Nanopore Flongle and MinION, the fastest and the most scalable massively-parallel sequencing platforms to-date. Partial RdRP sequences were successfully amplified and sequenced from 82.46% (47/57) of specimens, ranging from 75 to 100% by virus type, with consensus accuracy of 100% compared with Sanger sequences available (n = 40). In the second part, we further compared 19 SARS-CoV-2 RdRP sequences collected from the first to third waves of COVID-19 outbreak in Hong Kong with 22,173 genomes from GISAID EpiCoV™ database. No single nucleotide variants (SNVs) were found in our sequences, and 125 SNVs were observed from global data, with 56.8% being low-frequency (n = 1-47) missense mutations affecting the rear part of RNA polymerase. Among the 9 SNVs found on 4 conserved domains, the frequency of 15438G > T was highest (n = 34) and was predominantly found in Europe. Our data provided a glimpse into the sequence diversity of a primary antiviral drug and diagnostic target. Further studies are warranted to investigate the significance of these mutations.
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COVID-19/virologia , RNA-Polimerase RNA-Dependente de Coronavírus/genética , SARS-CoV-2/genética , COVID-19/diagnóstico , COVID-19/epidemiologia , Teste de Ácido Nucleico para COVID-19 , Coronavirus/genética , Monitoramento Epidemiológico , Estudos de Viabilidade , Genoma Viral/genética , Hong Kong/epidemiologia , Humanos , Mutação de Sentido Incorreto , Sequenciamento por Nanoporos , SARS-CoV-2/isolamento & purificaçãoRESUMO
The BIOFIRE SPOTFIRE Respiratory (R) Panel is a novel, in vitro diagnostic PCR assay with 15 pathogen targets. The runtime is about 15 min which is the shortest among similar panels in the market. We evaluated the performance of the SPOTFIRE R Panel with 151 specimens, including 133 collected from the upper respiratory tract (URT), 13 from the lower respiratory tract (LRT) and 5 external quality assessment program (EQAP) samples. The respiratory specimens were enrolled throughout the first two post-COVID-19 influenza seasons in Hong Kong (March to December 2023). For URT specimens, full concordance was observed between the SPOTFIRE R Panel and the standard-of-care FilmArray Respiratory 2.1 plus Panel (RP2.1plus) for 109 specimens (109/133, 81.95%). After discrepant analysis, the SPOTFIRE R Panel identified more pathogens than the RP2.1plus in 15 specimens and vice versa in 3 specimens. The per-target negative and positive percentage agreement (NPA and PPA) were 92.86-100% except the PPA of adenovirus (88.24%). For LRT and EQAP samples, all results were fully concordant. To conclude, the performance of the SPOTFIRE R Panel was comparable to the RP2.1plus.
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COVID-19 , Infecções Respiratórias , SARS-CoV-2 , Humanos , COVID-19/diagnóstico , COVID-19/virologia , Infecções Respiratórias/virologia , Infecções Respiratórias/diagnóstico , Hong Kong , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Sensibilidade e Especificidade , Técnicas de Diagnóstico Molecular/métodos , Teste de Ácido Nucleico para COVID-19/métodosRESUMO
COVID-19 has swept across the globe since 2019 and repeated waves of infection have been caused by different variants of the original SARS-CoV-2 (wild type), with the Omicron and Delta variants having dominated recently. Vaccination is among the most important measures in the absence of widespread use of antivirals for prevention of morbidity and mortality. Inactivated virus vaccine has been abundantly used in many countries as the primary two-dose regimen. We aim to study the safety and immunogenicity of CoronaVac (three-dose inactivated virus vaccine) and the BNT162b2 (two-dose inactivated virus vaccine followed by an mRNA vaccine) booster. Both CoronaVac and BNT162b2 boosters are generally safe and have good immunogenicity against the wild type SARS-CoV-2 and the Delta variant with the majority having neutralizing antibodies (NAb) on day 30 and day 90. However, the BNT162b2 booster is associated with a much higher proportion of positive NAb against the Omicron variant. Only 8% of day 30 and day 90 samples post CoronaVac booster have NAb against the Omicron variant. In addition, more BNT162b2 booster recipients are having positive T-cell responses using interferon gamma release assay. In places using inactivated virus vaccine as the primary two-dose scheme, the heterologous mRNA vaccine booster is safe and more immunogenic against the Omicron variant and should be considered as a preferred option during the current outbreak.
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As the COVID-19 pandemic progresses, there is an increasing need for rapid, accessible assays for SARS-CoV-2 detection. We present a clinical evaluation and real-world implementation of the INDICAID COVID-19 rapid antigen test (INDICAID rapid test). A multisite clinical evaluation of the INDICAID rapid test using prospectively collected nasal (bilateral anterior) swab samples from symptomatic subjects was performed. The INDICAID rapid test demonstrated a positive percent agreement (PPA) and negative percent agreement (NPA) of 85.3% (95% confidence interval [95% CI], 75.6% to 91.6%) and 94.9% (95% CI, 91.6% to 96.9%), respectively, compared to laboratory-based reverse transcriptase PCR (RT-PCR) using nasal specimens. The INDICAID rapid test was then implemented at COVID-19 outbreak screening centers in Hong Kong as part of a testing algorithm (termed "dual-track") to screen asymptomatic individuals for prioritization for confirmatory RT-PCR testing. In one approach, preliminary positive INDICAID rapid test results triggered expedited processing for laboratory-based RT-PCR, reducing the average time to confirmatory result from 10.85 h to 7.0 h. In a second approach, preliminary positive results triggered subsequent testing with an onsite rapid RT-PCR, reducing the average time to confirmatory result to 0.84 h. In 22,994 asymptomatic patients, the INDICAID rapid test demonstrated a PPA of 84.2% (95% CI, 69.6% to 92.6%) and an NPA of 99.9% (95% CI, 99.9% to 100%) compared to laboratory-based RT-PCR using combined nasal/oropharyngeal specimens. The INDICAID rapid test has excellent performance compared to laboratory-based RT-PCR testing and, when used in tandem with RT-PCR, reduces the time to confirmatory positive result. IMPORTANCE Laboratory-based RT-PCR, the current gold standard for COVID-19 testing, can require a turnaround time of 24 to 48 h from sample collection to result. The delayed time to result limits the effectiveness of centralized RT-PCR testing to reduce transmission and stem potential outbreaks. To address this, we conducted a thorough evaluation of the INDICAID COVID-19 rapid antigen test, a 20-minute rapid antigen test, in both symptomatic and asymptomatic populations. The INDICAID rapid test demonstrated high sensitivity and specificity with RT-PCR as the comparator method. A dual-track testing algorithm was also evaluated utilizing the INDICAID rapid test to screen for preliminary positive patients, whose samples were then prioritized for RT-PCR testing. The dual-track method demonstrated significant improvements in expediting the reporting of positive RT-PCR test results compared to standard RT-PCR testing without prioritization, offering an improved strategy for community testing and controlling SARS-CoV-2 outbreaks.
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Antígenos Virais/análise , Doenças Assintomáticas , Teste para COVID-19/métodos , COVID-19/diagnóstico , COVID-19/imunologia , SARS-CoV-2/isolamento & purificação , Adulto , Técnicas de Laboratório Clínico/métodos , Reações Falso-Negativas , Reações Falso-Positivas , Feminino , Hong Kong , Humanos , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Pandemias , Reação em Cadeia da Polimerase , SARS-CoV-2/genética , Sensibilidade e Especificidade , Manejo de Espécimes , Fatores de Tempo , Adulto JovemRESUMO
BACKGROUND AND AIMS: Chronic hepatitis C genotype 6 is common in Hong Kong, especially among i.v. drug abusers. Responses of these patients to combination of pegylated interferon and ribavirin treatment were inconsistent and the numbers of patients involved in previous studies were small. We performed a retrospective study to compare the therapeutic responses of this regimen in patients infected with genotype 6 and genotype 1. METHODS: Seventy patients with either genotype 6 or genotype 1 were recruited. Both groups received 800-1200 mg of ribavirin daily plus either 180 mg of pegylated alpha-interferon-2a or 1.5 mg/kg pegylated alpha-interferon-2b weekly for 48 weeks. Their responses to treatments were compared. RESULTS: The early virological response to combination therapy of patients with genotype 6 was significantly better than that of genotype 1 (88.6% vs 74.3%, P = 0.03). Significant difference was also identified in the end of treatment response of the two genotypes (60% vs 81.4% for genotype 1 and 6, respectively; P = 0.005). The sustained virological response (SVR) to treatment in patients with genotype 6 was also significantly superior to that of patients with genotype 1 (75.7% vs 57.1%, P = 0.02). Multiple logistic regression analysis demonstrated that age of 55 years or less, genotypes of hepatitis C virus, liver biopsy staging and baseline hepatitis C virus RNA of 200,000 IU/mL or less were independent predictors for better SVR in this cohort. CONCLUSION: Patients with chronic hepatitis C genotype 6 respond better to pegylated interferon and ribavirin combination treatment than patients with genotype 1.
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Antivirais/uso terapêutico , Vírus da Hepatite B/genética , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Ribavirina/uso terapêutico , Adolescente , Adulto , Fatores Etários , Idoso , Antivirais/efeitos adversos , Biópsia , Distribuição de Qui-Quadrado , Quimioterapia Combinada , Feminino , Genótipo , Hepatite C Crônica/diagnóstico , Hong Kong , Humanos , Interferon alfa-2 , Interferon-alfa/efeitos adversos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Fenótipo , Polietilenoglicóis/efeitos adversos , RNA Viral/sangue , Proteínas Recombinantes , Estudos Retrospectivos , Ribavirina/efeitos adversos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Carga Viral , Adulto JovemRESUMO
We sequenced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes from deep throat saliva samples of three imported cases in Hong Kong by Nanopore sequencing. Epidemiological and clinical features of these coronavirus disease 2019 (COVID-19) cases were presented for genomic epidemiology studies.
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Melioidosis, although endemic in many parts of Southeast Asia, has not been systematically studied in Hong Kong, which is a predominantly urban area located in the subtropics. This review describes the early outbreaks of melioidosis in captive animals in Hong Kong in the 1970s, as well as the early reports of human clinical cases in the 1980s. A review of all hospitalized human cases of culture-confirmed melioidosis in the last twenty years showed an increasing trend in the incidence of the disease, with significant mortality observed. The lack of awareness of this disease among local physicians, the delay in laboratory diagnosis and the lack of epidemiological surveillance are among the greatest challenges of managing melioidosis in the territory.