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A majority of emerging infectious diseases are of zoonotic origin. Metagenomic Next-Generation Sequencing (mNGS) has been employed to identify uncommon and novel infectious etiologies and characterize virus diversity in human, animal, and environmental samples. Here, we systematically reviewed studies that performed viral mNGS in common livestock (cattle, small ruminants, poultry, and pigs). We identified 2481 records and 120 records were ultimately included after a first and second screening. Pigs were the most frequently studied livestock and the virus diversity found in samples from poultry was the highest. Known animal viruses, zoonotic viruses, and novel viruses were reported in available literature, demonstrating the capacity of mNGS to identify both known and novel viruses. However, the coverage of metagenomic studies was patchy, with few data on the virome of small ruminants and respiratory virome of studied livestock. Essential metadata such as age of livestock and farm types were rarely mentioned in available literature, and only 10.8% of the datasets were publicly available. Developing a deeper understanding of livestock virome is crucial for detection of potential zoonotic and animal pathogens and One Health preparedness. Metagenomic studies can provide this background but only when combined with essential metadata and following the “FAIR” (Findable, Accessible, Interoperable, and Reusable) data principles.

We compared viral load of emerging recombinant norovirus GII.P16-GII.2 with those for pandemic GII.Pe-GII.4 and epidemic GII.P17-GII.17 genotypes among inpatients in Hong Kong. Viral load of GII.P16-GII.2 was higher than those for other genotypes in different age groups. GII.P16-GII.2 is as replication competent as the pandemic genotype, explaining its high transmissibility and widespread circulation.

A new recombinant norovirus GII.P16-GII.2 outnumbered pandemic GII.4 as the predominant GII genotype in the winter of 2016–2017 in Hong Kong, China. Half of hospitalized case-patients were older children and adults, including 13 young adults. This emergent norovirus targets a wider age population compared with circulating pandemic GII.4 strains.

Hepatitis E virus (HEV) causes substantial morbidity and mortality in developing countries and is considered an emerging foodborne pathogen in developed countries in which it was previously not endemic. To investigate genetic association between human HEV infection and HEV-contaminated high-risk food in Hong Kong, we compared local virus strains obtained from hepatitis E patient sera with those surveyed from high-risk food items during 2014 to 2016. Twenty-four cases of laboratory-confirmed human HEV infections were identified from January 2014 to March 2016 in our hospitals. Five types of food items at risk of HEV contamination were purchased on a biweekly basis from April 2014 to March 2016 in two local market settings: supermarkets (lamb, oyster, and pig liver) and wet markets (oyster, pig blood curd, pig large intestine, and pig liver). HEV RNA detection was performed by a real-time reverse transcription-PCR assay. HEV RNA was detected in pig liver, pig intestine, and oyster samples with prevalences of 1.5%, 0.4%, and 0.2%, respectively. Neighbor-joining phylogenetic inference showed that all human and swine HEV strains belonged to genotype 4. HEV subtype distributions in humans and swine were highly comparable: subtype 4b predominated, while subtype 4d was the minority. Local human and swine HEV genotype 4 strains shared over 95% nucleotide identity and were genetically very similar, implicating swine as an important foodborne source of autochthonous human HEV infections in Hong Kong. Action should be taken to raise the awareness among public and health care professionals of hepatitis E as an emerging foodborne disease.

Summary IFITM3 and TLR3 SNPs are associated with fatal clinical outcome of Chinese patients with avian (H7N9) or pandemic (H1N1pdm09) influenza virus infections, and the risks are cumulative. Our findings pose important public health and clinical implications in the at-risk populations., Background. We examined associations between single-nucleotide polymorphisms (SNPs) of IFITM3, TLR3, and CD55 genes and influenza clinical outcomes in Chinese. Methods. A multicenter study was conducted on 275 adult cases of avian (H7N9) and pandemic (H1N1pdm09) influenza. Host DNA was extracted from diagnostic respiratory samples; IFITM3 rs12252, TLR3 rs5743313, CD55 rs2564978, and TLR4 rs4986790/4986791 were targeted for genotyping (Sanger sequencing). The primary outcome analyzed was death. Results. IFITM3 and TLR3 SNPs were in Hardy–Weinberg equilibrium; their allele frequencies (IFITM3/C-allele 0.56, TLR3/C-allele 0.88) were comparable to 1000 Genomes Han Chinese data. We found over-representation of homozygous IFITM3 CC (54.5% vs 33.2%; P = .02) and TLR3 CC (93.3% vs 76.9%; P = .04) genotypes among fatal cases. Recessive genetic models showed their significant independent associations with higher death risks (adjusted hazard ratio [aHR] 2.78, 95% confidence interval [CI] 1.29–6.02, and aHR 4.85, 95% CI 1.11−21.06, respectively). Cumulative effects were found (aHR 3.53, 95% CI 1.64−7.59 per risk genotype; aHR 9.99, 95% CI 1.27−78.59 with both). Results were consistent for each influenza subtype and other severity indicators. The CD55 TT genotype was linked to severity. TLR4 was nonpolymorphic. Conclusions. Host genetic factors may influence clinical outcomes of avian and pandemic influenza infections. Such findings have important implications on disease burden and patient care in at-risk populations.

We report emerging subtropical bimodal seasonality and alternating predominance of norovirus GII.4 and non-GII.4 genotypes in Hong Kong. GII.4 predominated in summer and autumn months and affected young children, whereas emergent non-GII.4 genotypes predominated in winter months and affected all age groups. This highly dynamic epidemiology should inform vaccination strategies.

Two commonly used norovirus enzyme immunoassays have reduced diagnostic performance, with clinical sensitivities ranging from 11% to 35% for the detection of the recently emerging genogroup II genotype 17 (GII.17) Kawasaki 2014 variant that caused the majority of infections in Asia during the winter of 2014 to 2015. False-negative results can compromise infection control and patient management.

Norovirus genogroup II genotype 4 (GII.4) has been the predominant cause of viral gastroenteritis since 1996. Here we show that during the winter of 2014–2015, an emergent variant of a previously rare norovirus GII.17 genotype, Kawasaki 2014, predominated in Hong Kong and outcompeted contemporary GII.4 Sydney 2012 in hospitalized cases. GII.17 cases were significantly older than GII.4 cases. Root-to-tip and Bayesian BEAST analyses estimate GII.17 viral protein 1 (VP1) evolves one order of magnitude faster than GII.4 VP1. Residue substitutions and insertion occur in four of five inferred antigenic epitopes, suggesting immune evasion. Sequential GII.4-GII.17 infections are noted, implicating a lack of cross-protection. Virus bound to saliva of secretor histo-blood groups A, B and O, indicating broad susceptibility. This fast-evolving, broadly recognizing and probably immune-escaped emergent GII.17 variant causes severe gastroenteritis and hospitalization across all age groups, including populations who were previously less vulnerable to GII.4 variants; therefore, the global spread of GII.17 Kawasaki 2014 needs to be monitored., Norovirus GII.4 has been predominating in viral gastroenteritis for 20 years. Here the authors report the emergence and predominance of a novel fast-evolving GII.17 lineage norovirus causing viral gastroenteritis in Hong Kong, with a shift in age distribution of affected individuals towards an older age as compared to GII.4.

The complete genome sequence of a novel recombinant GII.Pe_GII.17 norovirus strain, tentatively named GII.17 Hong Kong 2015, was determined. RNA-dependent RNA polymerase has 95.6% and 98.4% and viral protein 1 has 90.6% and 95.9% identity at the nucleotide and amino acid levels, respectively, to the closest sequences in GenBank.

Background Whether host genetic factors determine clinical severity of influenza virus infections is unclear. This study examined the effects of single nucleotide polymorphisms (SNPs) of IFITM3, TLR3, CD55 , and TLR4 genes on outcomes of avian influenza A (H7N9) and pandemic influenza A (H1N1) pdm09 in Chinese patients. Methods This multicentre cohort study took place in four centres in Hong Kong, Beijing, Guangdong, and Shanghai and included adults prospectively diagnosed with H7N9 and H1N1 pdm09 infections during three respective seasonal outbreaks (H7N9, 2013–15; H1N1 pdm09 , 2011–14). The inclusion criteria were PCR-confirmed H7N9 or H1N1 pdm09 virus infection, age 18 years or older, and Chinese ethnicity. Host DNA was extracted from diagnostic respiratory samples, and IFITM3 (rs12252), TLR3 (rs5743313), CD55 (rs2564978), and TLR4 (rs4986790/4986791) were genotyped by Sanger sequencing. The data were tested to see whether they deviated from the Hardy-Weinberg equilibrium, and were compared with the 1000 Genomes data. The primary outcome for analysis was mortality. The effects of the SNPs were examined under different genetic models (recessive, additive, and dominant). The joint effect of significant loci was tested by computing the genetic risk score. All identifying patient information was removed from the dataset, and only anonymous data were used for analysis; individual consent was not required. Ethics approvals were obtained from the institutional review boards of all participating institutes. Findings Our cohort consisted of 275 adults with H7N9 and H1N1 pdm09 infections, of whom 33 died. In patients who died, we found over-representation of the homozygous IFITM3 CC genotype (18 [54%] of 33 patients with available data who died vs 70 [33%] of 211 with available data who survived; p=0·017) and the TLR3 CC genotype (28 [93%] of 30 vs 160 [77%] of 208; p=0·039). Recessive genetic models, adjusted for age, comorbidity, and antiviral treatment, showed that these genotypes had a significant association with increased risk of death ( IFITM3 CC genotype, adjusted hazard ratio [HR] 2·78 [95% CI 1·29–6·02]; and TLR3 CC genotype, adjusted HR 4·85 [1·11–21·06]). Cumulative effects were found (adjusted HR 3·53 [95% CI 1·64–7·59] per risk genotype; adjusted HR 9·99 [1·27–78·59] with both genotypes). The case-fatality rate in patients with a genetic risk score of 2, 1, and 0 was 23%, 11%, and 3%, respectively. Results were similar for each influenza subtype and other severity indicators such as development of acute respiratory failure. The population-attributable risk for mortality was 35·5% (95% CI 9·9–69·8) for IFITM3 CC and 74·6% (21·7–100) for TLR3 CC (combined effect, 83·6% [52·3–100]), owing to their high prevalence among Chinese people. A SNP of CD55 (genotype TT) was linked to severity of influenza as indicated by an increased risk for hospital admission (adjusted odds ratio [OR] 2·77, 95% CI 1·21–6·36; p=0·02); TLR4 was shown to be non-polymorphic in this cohort. Interpretation Host genetic factors might influence clinical outcomes of avian and pandemic influenza. Our findings could have important implications on public health and health-care planning, patient care, and design of clinical trials. Funding Health and Medical Research Fund (RRG-09) of the Hong Kong Special Administrative Region, China.

Analysis of complete capsid sequences of the emerging norovirus GII. 17 Kawasaki 308 from 13 countries demonstrated that they originated from a single haplotype since the initial emergence in China in late 2014. Global spread of a sublineage SL2 was identified. A new sublineage SL3 emerged in China in 2016.