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.

Quantifying multi-virion aerosols in respiratory infection transmission.

Infectious aerosols are expired in various sizes, and the number of contained virions is expected to significantly vary among expired aerosols. To evaluate the effect of the number of contained virions on infection risk, multi-virion aerosols in expired air should be first quantified. In this study, we categorised expired aerosols into traditional aerosol size bins and aerosols containing different number of virions.

High throughput profiling identified PA-L106R amino acid substitution in A(H1N1)pdm09 influenza virus that confers reduced susceptibility to baloxavir in vitro.

Baloxavir acid (BXA) is a pan-influenza antiviral that targets the cap-dependent endonuclease of the polymerase acidic (PA) protein required for viral mRNA synthesis. To gain a comprehensive understanding on the molecular changes associated with reduced susceptibility to BXA and their fitness profile, we performed a deep mutational scanning at the PA endonuclease domain of an A (H1N1)pdm09 virus. The recombinant virus libraries were serially passaged in vitro under increasing concentrations of BXA followed by next-generation sequencing to monitor PA amino acid substitutions with increased detection frequencies.

Cross-Reactive Antibody Responses to Coronaviruses Elicited by SARS-CoV-2 Infection or Vaccination.

Background: The newly emerged SARS-CoV-2 possesses shared antigenic epitopes with other human coronaviruses. We investigated if COVID-19 vaccination or SARS-CoV-2 infection may boost cross-reactive antibodies to other human coronaviruses.

Methods: Prevaccination and postvaccination sera from SARS-CoV-2 naïve healthy subjects who received three doses of the mRNA vaccine (BioNTech, BNT) or the inactivated vaccine (CoronaVac, CV) were used to monitor the level of cross-reactive antibodies raised against other human coronaviruses by enzyme-linked immunosorbent assay.

A longitudinal environmental surveillance study for SARS-CoV-2 from the emergency department of a teaching hospital in Hong Kong.

Background: Understanding factors associated with SARS-CoV-2 exposure risk in the hospital setting may help improve infection control measures for prevention.

Aim: To monitor SARS-CoV-2 exposure risk among healthcare workers and to identify risk factors associated with SARS-CoV-2 detection.

Methods: Surface and air samples were collected longitudinally over 14 months spanning 2020-2022 at the Emergency Department (ED) of a teaching hospital in Hong Kong.

Risk of air and surface contamination during application of different noninvasive respiratory support for patients with COVID-19.

Objectives: We compared the risk of environmental contamination among patients with COVID-19 who received high-flow nasal cannula (HFNC), noninvasive ventilation (NIV), and conventional oxygen therapy (COT) via nasal cannula for respiratory failure.

Methods: Air was sampled from the hospital isolation rooms with 12 air changes/hr where 26 patients with COVID-19 received HFNC (up to 60 l/min, n = 6), NIV (n = 6), or COT (up to 5 l/min of oxygen, n = 14). Surface samples were collected from 16 patients during air sampling.

Imprinted Anti-Hemagglutinin and Anti-Neuraminidase Antibody Responses after Childhood Infections of A(H1N1) and A(H1N1)pdm09 Influenza Viruses.

Immune imprinting is a driver known to shape the anti-hemagglutinin (HA) antibody landscape of individuals born within the same birth cohort. With the HA and neuraminidase (NA) proteins evolving at different rates under immune selection pressures, anti-HA and anti-NA antibody responses since childhood influenza virus infections have not been evaluated in parallel at the individual level. This is partly due to the limited knowledge of changes in NA antigenicity, as seasonal influenza vaccines have focused on generating neutralizing anti-HA antibodies against HA antigenic variants.

Influenza antivirals and their role in pandemic preparedness.

Effective antivirals provide crucial benefits during the early phase of an influenza pandemic, when vaccines are still being developed and manufactured. Currently, two classes of viral protein-targeting drugs, neuraminidase inhibitors and polymerase inhibitors, are approved for influenza treatment and post-exposure prophylaxis. Resistance to both classes has been documented, highlighting the need to develop novel antiviral options that may include both viral and host-targeted inhibitors.

Robustness of the Ferret Model for Influenza Risk Assessment Studies: a Cross-Laboratory Exercise.

Past pandemic influenza viruses with sustained human-to-human transmissibility have emerged from animal influenza viruses. Employment of experimental models to assess the pandemic risk of emerging zoonotic influenza viruses provides critical information supporting public health efforts. Ferret transmission experiments have been utilized to predict the human-to-human transmission potential of novel influenza viruses.

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.

Determining Existing Human Population Immunity as Part of Assessing Influenza Pandemic Risk.

Zoonotic influenza infections continue to threaten human health. Ongoing surveillance and risk assessment of animal viruses are needed for pandemic preparedness, and population immunity is an important component of risk assessment. We determined age-stratified hemagglutinin inhibition seroprevalence against 5 swine influenza viruses circulating in Hong Kong and Guangzhou in China.

Global update on the susceptibilities of human influenza viruses to neuraminidase inhibitors and the cap-dependent endonuclease inhibitor baloxavir, 2018-2020.

Global analysis of the susceptibility of influenza viruses to neuraminidase (NA) inhibitors (NAIs) and the polymerase acidic (PA) inhibitor (PAI) baloxavir was conducted by five World Health Organization Collaborating Centres for Reference and Research on Influenza during two periods (May 2018-May 2019 and May 2019-May 2020). Combined phenotypic and NA sequence-based analysis revealed that the global frequency of viruses displaying reduced or highly reduced inhibition (RI or HRI) or potential to show RI/HRI by NAIs remained low, 0.5% (165/35045) and 0.

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.

Predominant airborne transmission and insignificant fomite transmission of SARS-CoV-2 in a two-bus COVID-19 outbreak originating from the same pre-symptomatic index case.

The number of people infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to increase worldwide, but despite extensive research, there remains significant uncertainty about the predominant routes of SARS-CoV-2 transmission. We conducted a mechanistic modeling and calculated the exposure dose and infection risk of each passenger in a two-bus COVID-19 outbreak in Hunan province, China. This outbreak originated from a single pre-symptomatic index case.

Ancestral sequence reconstruction pinpoints adaptations that enable avian influenza virus transmission in pigs.

Understanding the evolutionary adaptations that enable avian influenza viruses to transmit in mammalian hosts could allow better detection of zoonotic viruses with pandemic potential. We applied ancestral sequence reconstruction to gain viruses representing different adaptive stages of the European avian-like (EA) H1N1 swine influenza virus as it transitioned from avian to swine hosts since 1979. Ancestral viruses representing the avian-like precursor virus and EA swine influenza viruses from 1979-1983, 1984-1987 and 1988-1992 were reconstructed and characterized.

Limited onward transmission potential of reassortment genotypes from chickens co-infected with H9N2 and H7N9 avian influenza viruses.

The segmented genome of influenza A virus has conferred significant evolutionary advantages to this virus through genetic reassortment, a mechanism that facilitates the rapid expansion of viral genetic diversity upon influenza co-infections. Therefore, co-infection of genetically diverse avian influenza viruses in poultry may pose a significant public health risk in generating novel reassortants with increased zoonotic potential. This study investigated the reassortment patterns of a Pearl River Delta-lineage avian influenza A(H7N9) virus and four genetically divergent avian influenza A(H9N2) viruses upon co-infection in embryonated chicken eggs and chickens.

Neutralizing Monoclonal Antibodies That Target the Spike Receptor Binding Domain Confer Fc Receptor-Independent Protection against SARS-CoV-2 Infection in Syrian Hamsters.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein is the main target for neutralizing antibodies. These antibodies can be elicited through immunization or passively transferred as therapeutics in the form of convalescent-phase sera or monoclonal antibodies (MAbs). Potently neutralizing antibodies are expected to confer protection; however, it is unclear whether weakly neutralizing antibodies contribute to protection.

Cellular tropism of SARS-CoV-2 in the respiratory tract of Syrian hamsters and B6.Cg-Tg(K18-ACE2)2Prlmn/J transgenic mice.

Several animal models have been developed to study the pathophysiology of SARS-CoV-2 infection and to evaluate vaccines and therapeutic agents for this emerging disease. Similar to infection with SARS-CoV-1, infection of Syrian hamsters with SARS-CoV-2 results in moderate respiratory disease involving the airways and lung parenchyma but does not lead to increased mortality. Using a combination of immunohistochemistry and transmission electron microscopy, we showed that the epithelium of the conducting airways of hamsters was the primary target for viral infection within the first 5 days of infection, with little evidence of productive infection of pneumocytes.

Reducing Influenza Virus Transmission: The Potential Value of Antiviral Treatment.

Prompt antiviral treatment has the potential to reduce influenza virus transmission to close contacts, but rigorous data on the magnitude of treatment effects on transmission are limited. Animal model data indicate that rapid reductions in viral replication after antiviral treatment reduce the risk of transmission. Observational and clinical trial data with oseltamivir and other neuraminidase inhibitors indicate that prompt treatment of household index patients seems to reduce the risk of illness in contacts, although the magnitude of the reported effects has varied widely across studies.

A(H1N1)pdm09 Influenza Viruses Replicating in Ferret Upper or Lower Respiratory Tract Differed in Onward Transmission Potential by Air.

Background: A(H1N1)pdm09 influenza viruses replicate efficiently in respiratory epithelia and are transmitted via respiratory droplets and aerosols expelled by infected hosts. The relative onward transmission potential of influenza viruses replicating in the upper and lower respiratory epithelial cells has not been fully defined.

Methods: Wild-type and barcoded A(H1N1)pdm09 viruses that differed by 2 synonymous mutations per gene segment were inoculated into ferrets via intranasal and intratracheal routes.

Lack of cross-transmission of SARS-CoV-2 between passenger's cabins on the cruise ship.

An outbreak of COVID-19 occurred on the cruise ship in January and February 2020 in Japan. We analysed information on the cases of infection to infer whether airborne transmission of SARS-CoV-2, the causative agent of COVID-19, had occurred between cabins. We infer from our analysis that most infections in passengers started on 28 January and were completed by 6 February, except in those who shared a cabin with another infected passenger.

Phenotypic and Functional Characteristics of a Novel Influenza Virus Hemagglutinin-Specific Memory NK Cell.

Immune memory represents the most efficient defense against invasion and transmission of infectious pathogens. In contrast to memory T and B cells, the roles of innate immunity in recall responses remain inconclusive. In this study, we identified a novel mouse spleen NK cell subset expressing NKp46 and NKG2A induced by intranasal influenza virus infection.

Deficits in Processing of Lexical Tones in Mandarin-Speaking Children With Developmental Language Disorder: Electrophysiological Evidence.

Purpose This study explored the neural marker indexing deficits in discriminating lexical tone changes in Mandarin-speaking children with developmental language disorders (DLDs) using mismatch negativity, an event-related potential component for auditory change detection. Mandarin has four lexical tones characterized by a high-level tone (T1), high-rising tone (T2), low-dipping tone (T3), and high-falling tone (T4), in which the T2/T3 contrast is acoustically less discriminable in developmental groups. Therefore, this study further examined how deficits in children with DLD would vary with tonal contrasts' acoustic saliency.