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Background Growing numbers of people have been potentially exposed to avian influenza (AI), as the United Kingdom has managed the largest and most sustained series outbreaks in recent years. Antiviral medication is recommended for exposed individuals for chemoprophylaxis to reduce the severity of illness and the likelihood of secondary transmission. However, some individuals have been hesitant or declined antivirals. In this study, we aimed to identify the factors affecting the uptake of and adherence to antiviral medication. Methods We interviewed 14 individuals occupationally exposed to avian influenza and conducted focus groups with 15 public health professionals involved in advising and arranging antivirals. The data were analysed thematically based on COM-B factors (capability, opportunity, motivation). Results Although participants saw avian influenza as a severe disease, most did not consider themselves susceptible to it because they felt safe in personal protective equipment and knew that bird-to-human transmission was rare. The biggest barrier to uptake and adherence was experiencing side effects, especially if these disrupted day-to-day life or work. Participants who took antivirals followed medical advice in a novel situation, had health conditions or vulnerable family members they wanted to protect. As responding to an outbreak was exhausting, easy access to antivirals for those at most risk was considered important for improving uptake. Conclusions The factors affecting antiviral uptake were multifaceted. Public health interventions should prioritise those at most risk and address multiple components of behaviour, such as advising how to manage side effects, addressing concerns about long-term usage and providing convenient access to antivirals for those at most risk.

In 2024, an unprecedented outbreak of H5N1 high pathogenicity avian influenza was detected in dairy cattle in the USA resulting in spillbacks into poultry, wild birds and other mammals including humans. Here, we present molecular and virological evidence that the cattle B3.13 genotype H5N1 viruses rapidly accumulated adaptations in polymerase genes that enabled better replication in bovine cells and tissues, as well as cells of other mammals including humans. We find evidence of several mammalian adaptations in cattle including PB2 M631L, which is found in all cattle sequences, and PA K497R, which is found in the majority. Structurally, PB2 M631L maps to the polymerase-ANP32 interface, an essential host factor for viral genome replication. We show that this mutation adapts the polymerase to better interact with bovine ANP32 proteins, particularly ANP32A, and thereby enhances virus replication in bovine mammary systems and primary human airway cultures. We show that ongoing evolution in the PB2 gene, including E627K and a convergently arising D740N substitution, further increase polymerase activity and virus replication in a range of mammalian cells. Thus, circulation of H5N1 in dairy cattle allows virus adaption improving replicative ability in cattle and poses a continued risk of zoonotic spillover. Avian influenza jumped from wild birds into dairy cattle. Here, the authors report that two mutations in the viral polymerase helped the virus to quickly adapt to cattle. Mutations increased the polymerase activity and made the virus better at replicating in human cells.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant (B.1.1.529) rapidly replaced Delta (B.1.617.2) to become dominant in England. Our study assessed differences in transmission between Omicron and Delta using two independent data sources and methods. Omicron and Delta cases were identified through genomic sequencing, genotyping and S-gene target failure in England from 5–11 December 2021. Secondary attack rates for named contacts were calculated in household and non-household settings using contact tracing data, while household clustering was identified using national surveillance data. Logistic regression models were applied to control for factors associated with transmission for both methods. For contact tracing data, higher secondary attack rates for Omicron vs. Delta were identified in households (15.0% vs. 10.8%) and non-households (8.2% vs. 3.7%). For both variants, in household settings, onward transmission was reduced from cases and named contacts who had three doses of vaccine compared to two, but this effect was less pronounced for Omicron (adjusted risk ratio, aRR 0.78 and 0.88) than Delta (aRR 0.62 and 0.68). In non-household settings, a similar reduction was observed only in contacts who had three doses vs. two doses for both Delta (aRR 0.51) and Omicron (aRR 0.76). For national surveillance data, the risk of household clustering, was increased 3.5-fold for Omicron compared to Delta (aRR 3.54 (3.29–3.81)). Our study identified increased risk of onward transmission of Omicron, consistent with its successful global displacement of Delta. We identified a reduced effectiveness of vaccination in lowering risk of transmission, a likely contributor for the rapid propagation of Omicron.

A programme of asymptomatic swabbing was piloted in 2021/2022 in England to further understand the risk of human infection with avian influenza in exposed individuals and to evaluate this surveillance approach as a public health measure. There were challenges in deploying this pilot that will need to be addressed for future seasons. However, there was one detection of avian influenza A(H5N1) in a human despite low uptake in eligible exposed persons. Future use of asymptomatic swabbing could help provide an evidence base to quantify asymptomatic infection, quickly identify signals of increased animal to human transmission and improve public health preparedness.

Persons experiencing homelessness (PEH) or rough sleeping are a vulnerable population, likely to be disproportionately affected by the coronavirus disease 2019 (COVID-19) pandemic. The impact of COVID-19 infection on this population is yet to be fully described in England. We present a novel method to identify COVID-19 cases in this population and describe its findings. A phenotype was developed and validated to identify PEH or rough sleeping in a national surveillance system. Confirmed COVID-19 cases in England from March 2020 to March 2022 were address-matched to known homelessness accommodations and shelters. Further cases were identified using address-based indicators, such as NHS pseudo postcodes. In total, 1835 cases were identified by the phenotype. Most were <39 years of age (66.8%) and male (62.8%). The proportion of cases was highest in London (29.8%). The proportion of cases of a minority ethnic background and deaths were disproportionality greater in this population, compared to all COVID-19 cases in England. This methodology provides an approach to track the impact of COVID-19 on a subset of this population and will be relevant to policy making. Future surveillance systems and studies may benefit from this approach to further investigate the impact of COVID-19 and other diseases on select populations.

Avian influenza viruses (AIVs) are a global public health risk; human infection is typically associated with high mortality. While the relationship between several mammalian adaptive mutations and host factors have been described, it is unknown whether additional uncharacterised mutations lead to adaptation. Here, we combine phylogenetic analysis and complementary experimental methods to quantify the impact of novel mutations that emerge at the avian-mammal interface. We constructed phylogenetic trees of mammalian and avian influenza sequences for the polymerase (PA, PB1, PB2) and nucleoprotein (NP) segments and identified potential avian to mammal spillover events. We found >6500 mutations across the polymerase and NP, including known signatures of mammalian adaptation such as PB2 E627K and D701N which occurred independently in mammals 143 and 56 times respectively. We selected 95 mutations which were mostly undescribed and emerged independently multiple times in a range of species and subtypes. Using a minigenome assay in an avian H5N1 backbone to measure the effect of these mutations in human cells we identified PA P28S, NP I425V and G485R as novel mutations leading to polymerase adaptation. In addition, to determine the mechanism of adaptive mutations, we measured polymerase activity in cells lacking a key host factor, ANP32, and cells overexpressing host restriction factors MxA and BTN3A3. Our combined approach revealed novel mammalian adaptive mutations and demonstrated the benefit of combining phylogenetic and molecular approaches in validating novel adaptive mutations.

In early 2024, an unprecedented outbreak of H5N1 high pathogenicity avian influenza was detected in dairy cattle in the USA. The epidemic remains uncontrolled, with spillbacks into poultry, wild birds and other mammals including humans. Here, we present molecular and virological evidence that the cattle B3.13 genotype H5N1 viruses rapidly accumulated adaptations in polymerase genes that enabled better replication in bovine cells, as well as cells of other mammalian species including humans and pigs. We find evidence of several mammalian adaptations gained early in the evolution of these viruses in cattle including PB2 M631L, which is found in all cattle sequences, and PA K497R, which is found in the majority. Structurally, PB2 M631L maps to the polymerase-ANP32 interface, an essential host factor for viral genome replication. We show this mutation adapts the virus to co-opt bovine ANP32 proteins and thereby enhances virus replication in bovine and primary human airway cells. Importantly, we show that ongoing evolution during 2024 in the PB2 gene, including a convergently arising D740N substitution, further increases polymerase activity in a range of mammalian cells. Thus, the continued circulation of H5N1 in dairy cattle allows virus adaption improving replicative ability in cattle and increasing zoonotic spillover risk.Competing Interest StatementThe authors have declared no competing interest.Footnotes* Figure 2 and Figure 3 were transposed on the original submission and this has now been corrected.

Purpose To identify risk factors present at admission in adult patients hospitalised due to influenza virus infection during the 2009/10 and 2010/11 seasons—including whether infection was from pandemic or seasonal influenza A infections—that were associated with the likelihood of developing severe pneumonia with multilobar involvement and shock. Methods Prospective cohort study. Patients hospitalised due to influenza virus infection were recruited. We collected information on sociodemographic characteristics, pre-existing medical conditions, vaccinations, toxic habits, previous medications, exposure to social environments, and EuroQoL-5D (EQ-5D). Severe pneumonia with multilobar involvement and/or shock (SPAS) was the primary outcome of interest. We constructed two multivariate logistic regression models to explain the likelihood of developing SPAS and to create a clinical prediction rule for developing SPAS that includes clinically relevant variables. Results Laboratory-confirmed A(H1N1)pdm09, EQ-5D utility score 7 days before admission, more than one comorbidity, altered mental status, dyspnoea on arrival, days from onset of symptoms, and influenza season were associated with SPAS. In addition, not being vaccinated against seasonal influenza in the previous year, anaemia, altered mental status, fever and dyspnoea on arrival at hospital, difficulties in performing activities of daily living in the previous 7 days, and days from onset of symptoms to arrival at hospital were related to the likelihood of SPAS (area under the curve value of 0.75; Hosmer–Lemeshow p value of 0.84). Conclusions These variables should be taken into account by physicians evaluating a patient affected by influenza as additional information to that provided by the usual risk scores.