Optimizing Global Genomic Surveillance for Early Detection of Emerging SARS-CoV-2 Variants.

Background: Global viral threats underscore the need for effective genomic surveillance, but high costs and uneven resource distribution hamper its implementation. Targeting surveillance to international travelers in major travel hubs may offer a more efficient strategy for the early detection of SARS-CoV-2 variants.

Methods: We developed and calibrated a multiple-strain metapopulation model of global SARS-CoV-2 transmission using extensive epidemiological, phylogenetic, and high-resolution air travel data.

Detection and characterisation of high pathogenicity avian influenza virus (H5N1/H5N8) clade 2.3.4.4b, Hong Kong SAR, China, 2021 to 2024.

We isolated three genotypes of highly pathogenic avian influenza virus (HPAIV) clade 2.3.4.

An interferon-stimulated long non-coding RNA USP30-AS1 as an immune modulator in influenza A virus infection.

Long non-coding RNAs (lncRNAs) are essential components of innate immunity, maintaining the functionality of immune systems that control virus infection. However, how lncRNAs engage immune responses during influenza A virus (IAV) infection remains unclear. Here, we show that lncRNA USP30-AS1 is up-regulated by infection of multiple different IAV subtypes and is required for tuning inflammatory and antiviral response in IAV infection.

The effect of residential greenness on cardiovascular mortality from a large cohort in South China: An in-depth analysis of effect modification by multiple demographic and lifestyle characteristics.

Background: The potential for residential greenness to improve cardiovascular health through both physical and psychological mechanisms is well recognized. However, evidence from rapidly urbanizing developing countries and cohort-based causal inference approaches, remains limited. We aim to examine the effect of residential greenness and time to cardiovascular mortality in South China.

Cross-neutralizing antibody against emerging Omicron subvariants of SARS-CoV-2 in infection-naïve individuals with homologous BNT162b2 or BNT162b2(WT + BA.4/5) bivalent booster vaccination.

Since the emergence of SARS-CoV-2, different variants and subvariants successively emerged to dominate global virus circulation as a result of immune evasion, replication fitness or both. COVID-19 vaccines continue to be updated in response to the emergence of antigenically divergent viruses, the first being the bivalent RNA vaccines that encodes for both the Wuhan-like and Omicron BA.5 subvariant spike proteins.

Single-cycle influenza virus vaccine generates lung CD8 Trm that cross-react against viral variants and subvert virus escape mutants.

Influenza virus-specific tissue-resident memory (Trm) CD8 T cells located along the respiratory tract provide cross-strain protection against a breadth of influenza viruses. We show that immunization with a single-cycle influenza virus vaccine candidate (S-FLU) results in the deposition of influenza virus nucleoprotein (NP)-specific CD8 Trm along the respiratory tract that were more cross-reactive against viral variants and less likely to drive the development of cytotoxic T lymphocyte (CTL) escape mutants, as compared to the lung memory NP-specific CD8 T cell pool established following influenza infection. This immune profile was linked to the limited inflammatory response evoked by S-FLU vaccination, which increased TCR repertoire diversity within the memory CD8 T cell compartment.

Refining detection methods for emerging SARS-CoV-2 mutants in wastewater: A case study on the Omicron variants.

COVID-19 is an ongoing public health threat worldwide driven by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Wastewater surveillance has emerged as a complementary tool to clinical surveillance to control the COVID-19 pandemic. With the emergence of new variants of SARS-CoV-2, accumulated mutations that occurred in the SARS-CoV-2 genome raise new challenges for RT-qPCR diagnosis used in wastewater surveillance.

Wastewater genomic sequencing for SARS-CoV-2 variants surveillance in wastewater-based epidemiology applications.

Wastewater-based epidemiology (WBE) has been widely used as a complementary approach to SARS-CoV-2 clinical surveillance. Wastewater genomic sequencing could provide valuable information on the genomic diversity of SARS-CoV-2 in the surveyed population. However, reliable detection and quantification of variants or mutations remain challenging.

Resurgence of Omicron BA.2 in SARS-CoV-2 infection-naive Hong Kong.

Hong Kong experienced a surge of Omicron BA.2 infections in early 2022, resulting in one of the highest per-capita death rates of COVID-19. The outbreak occurred in a dense population with low immunity towards natural SARS-CoV-2 infection, high vaccine hesitancy in vulnerable populations, comprehensive disease surveillance and the capacity for stringent public health and social measures (PHSMs).

Within-host genetic diversity of SARS-CoV-2 lineages in unvaccinated and vaccinated individuals.

Viral and host factors can shape SARS-CoV-2 evolution. However, little is known about lineage-specific and vaccination-specific mutations that occur within individuals. Here, we analysed deep sequencing data from 2,820 SARS-CoV-2 respiratory samples with different viral lineages to describe the patterns of within-host diversity under different conditions, including vaccine-breakthrough infections.

Risk of within-hotel transmission of SARS-CoV-2 during on-arrival quarantine in Hong Kong: an epidemiological and phylogenomic investigation.

Background: On-arrival quarantine has been one of the primary measures to prevent the introduction of SARS-CoV-2 into Hong Kong since the start of the pandemic. Most on-arrival quarantines have been done in hotels, with the duration of quarantine and testing frequency during quarantine modified over time along with other pandemic control measures. However, hotels are not designed with infection control in mind.

Development of multiplex RT-ddPCR assays for detection of SARS-CoV-2 and other common respiratory virus infections.

Background: Measures for mitigation of Coronavirus Disease 2019 (COVID-19) were set to reduce the spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). SARS-CoV-2 and other respiratory viruses share similar transmission routes and some common clinical manifestations. Co-circulation of SARS-CoV-2 and other common respiratory viruses is imminent.

Heterosubtypic immune pressure accelerates emergence of influenza A virus escape phenotypes in mice.

Rapid antigenic evolution of the influenza A virus surface antigen hemagglutinin undermines protection conferred by seasonal vaccines. Protective correlates targeted by universal vaccines such as cytotoxic T cells or HA stem directed broadly neutralizing antibodies have been shown to select for immune escape mutants during infection. We developed an in vivo serial passage mouse model for viral adaptation and used next generation sequencing to evaluate full genome viral evolution in the context of broadly protective immunity.

Priming conditions shape breadth of neutralizing antibody responses to sarbecoviruses.

Vaccines that are broadly cross-protective against current and future SARS-CoV-2 variants of concern (VoC) or across the sarbecoviruses subgenus remain a priority for public health. Virus neutralization is the best available correlate of protection. To define the magnitude and breadth of cross-neutralization in individuals with different exposure to SARS-CoV-2 infection and vaccination, we here use a multiplex surrogate neutralization assay based on virus spike receptor binding domains of multiple SARS-CoV-2 VoC, as well as related bat and pangolin viruses.

Replication of SARS-CoV-2 Omicron BA.2 variant in ex vivo cultures of the human upper and lower respiratory tract.

Background: The Omicron BA.2 sublineage has replaced BA.1 worldwide and has comparable levels of immune evasion to BA.

Within-host diversity of SARS-CoV-2 lineages and effect of vaccination.

Viral and host factors can shape SARS-CoV-2 within-host viral diversity and virus evolution. However, little is known about lineage-specific and vaccination-specific mutations that occur within individuals. Here we analysed deep sequencing data from 2,146 SARS-CoV-2 samples with different viral lineages to describe the patterns of within-host diversity in different conditions, including vaccine-breakthrough infections.

Reduced Pathogenicity and Transmission Potential of Omicron BA.1 and BA.2 Sublineages Compared with the Early Severe Acute Respiratory Syndrome Coronavirus 2 D614G Variant in Syrian Hamsters.

Background: The epidemiological advantage of Omicron variant is evidenced by its rapid spread and the ability to outcompete prior variants. Among Omicron sublineages, early outbreaks were dominated by BA.1, while BA.

SARS-CoV-2 accessory proteins reveal distinct serological signatures in children.

The antibody response magnitude and kinetics may impact clinical severity, serological diagnosis and long-term protection of COVID-19, which may play a role in why children experience lower morbidity. We therefore tested samples from 122 children in Hong Kong with symptomatic (n = 78) and asymptomatic (n = 44) SARS-CoV-2 infections up to 200 days post infection, relative to 71 infected adults (symptomatic n = 61, and asymptomatic n = 10), and negative controls (n = 48). We assessed serum IgG antibodies to a 14-wide antigen panel of structural and accessory proteins by Luciferase Immuno-Precipitation System (LIPS) assay and circulating cytokines.

Recombinant BA.1/BA.2 SARS-CoV-2 Virus in Arriving Travelers, Hong Kong, February 2022.

We studied SARS-CoV-2 genomes from travelers arriving in Hong Kong during November 2021-February 2022. In addition to Omicron and Delta variants, we detected a BA.1/BA.

Next-generation T cell-activating vaccination increases influenza virus mutation prevalence.

To determine the potential for viral adaptation to T cell responses, we probed the full influenza virus genome by next-generation sequencing directly ex vivo from infected mice, in the context of an experimental T cell-based vaccine, an H5N1-based viral vectored vaccinia vaccine Wyeth/IL-15/5Flu, versus the current standard-of-care, seasonal inactivated influenza vaccine (IIV) and unvaccinated conditions. Wyeth/IL-15/5Flu vaccination was coincident with increased mutation incidence and frequency across the influenza genome; however, mutations were not enriched within T cell epitope regions, but high allele frequency mutations within conserved hemagglutinin stem regions and PB2 mammalian adaptive mutations arose. Depletion of CD4 and CD8 T cell subsets led to reduced frequency of mutants in vaccinated mice; therefore, vaccine-mediated T cell responses were important drivers of virus diversification.

Transmission of SARS-CoV-2 delta variant (AY.127) from pet hamsters to humans, leading to onward human-to-human transmission: a case study.

Background: Transmission of SARS-CoV-2 from humans to other mammals, including pet animals, has been reported. However, with the exception of farmed mink, there is no previous evidence that these infected animals can infect humans, resulting in sustained human-to-human transmission. Following a confirmed SARS-CoV-2 infection of a pet shop worker, animals in the shop and the warehouse supplying it were tested for evidence of SARS-CoV-2 infection.