Detection of influenza in managed quarantine in Australia and the estimated risk of importation.

BACKGROUND: Influenza circulated at historically-low levels during 2020 and 2021 due to COVID-19 pandemic travel restrictions. In Australia, international arrivals to Australia were required to undertake 14 days hotel quarantine to limit new introduction of SARS-CoV-2 virus. METHODS: We used routine testing data for travellers arriving on repatriation flights to Darwin, Australia from 3 January to 11 October 2021 to identify importations of influenza virus into Australia and used this information to estimate the risk of a case exiting quarantine while still infectious. Influenza-positive samples were sequenced and cases were followed-up to identify transmission clusters. Data on the number of cases and total passengers was used to infer the risk of influenza cases existing quarantine while infectious. RESULTS: Despite very low circulation of influenza globally, 42 cases were identified among 15,026 returned travellers, of which 30 were A(H3N2), two were A(H1N1)pdm09 and 10 were B/Victoria. Virus sequencing data identified potential in-flight transmission, as well as independent infections prior to travel. Under the quarantine strategy in place at the time, the probability that these cases could initiate influenza outbreaks in Australia neared 0. However, this probability rose as quarantine requirements relaxed. CONCLUSIONS: Detection of influenza virus infections in repatriated travellers provided a source of influenza viruses otherwise unavailable and enabled development of the A(H3N2) vaccine seed viruses included in the 2022 Southern Hemisphere influenza vaccine. Failing to test quarantined returned travellers for influenza, represents a missed opportunity for enhanced surveillance to better inform public health preparedness.

A Prospective Study Investigating the Impact of Obesity on the Immune Response to the Quadrivalent Influenza Vaccine in Children and Adolescents.

Obesity can increase the severity of influenza infection. Data are limited regarding immune responses to influenza vaccination in obese children. We aimed to investigate the impact of obesity on quadrivalent influenza vaccine responses in children. Children with obesity (body mass index (BMI) ≥ 95th percentile for age and gender) and children without obesity (BMI < 95th percentile) were enrolled in the study. Blood samples were collected before, 1, and 6 months after influenza vaccination, to measure antibody responses by haemagglutination inhibition (HI) assay. Vaccine immunogenicity outcomes were compared between children with and without obesity. Forty-four children (mean age 13.3 ± 2.1 years, 18 males and 14 with obesity) completed the 6-month study. More than 90% of the participants with and without obesity had seroprotective antibody titres (HI ≥ 40) at both 1 and 6 months following vaccination for each of the four influenza strains (A/H3N2, A/H1N1, B/(Victoria) and B/(Yamagata)). Influenza-specific geometric mean titres at baseline, 1, and 6 months post-vaccination were similar between children with and without obesity for all influenza vaccine strains. Children with and without obesity have robust, sustained antibody responses over 6 months to the quadrivalent influenza vaccine.

Off-season RSV epidemics in Australia after easing of COVID-19 restrictions.

Human respiratory syncytial virus (RSV) is an important cause of acute respiratory infection with the most severe disease in the young and elderly. Non-pharmaceutical interventions and travel restrictions for controlling COVID-19 have impacted the circulation of most respiratory viruses including RSV globally, particularly in Australia, where during 2020 the normal winter epidemics were notably absent. However, in late 2020, unprecedented widespread RSV outbreaks occurred, beginning in spring, and extending into summer across two widely separated regions of the Australian continent, New South Wales (NSW) and Australian Capital Territory (ACT) in the east, and Western Australia. Through genomic sequencing we reveal a major reduction in RSV genetic diversity following COVID-19 emergence with two genetically distinct RSV-A clades circulating cryptically, likely localised for several months prior to an epidemic surge in cases upon relaxation of COVID-19 control measures. The NSW/ACT clade subsequently spread to the neighbouring state of Victoria and to cause extensive outbreaks and hospitalisations in early 2021. These findings highlight the need for continued surveillance and sequencing of RSV and other respiratory viruses during and after the COVID-19 pandemic, as mitigation measures may disrupt seasonal patterns, causing larger or more severe outbreaks.

Global Pandemic Preparedness: Optimizing Our Capabilities and the Influenza Experience.

The coronavirus disease 2019 (COVID-19) pandemic has prompted rapid investigation and deployment of vaccine platforms never before used to combat human disease. The severe impact on the health system and the high economic cost of non-pharmaceutical interventions, such as lockdowns and international border closures employed to mitigate the spread of COVID-19 prior to the arrival of effective vaccines, have led to calls for development and deployment of novel vaccine technologies as part of a "100-day response ambition" for the next pandemic. Prior to COVID-19, all of the pandemics (excluding HIV) in the past century have been due to influenza viruses, and influenza remains one of the most likely future pandemic threats along with new coronaviruses. New and emerging vaccine platforms are likely to play an important role in combatting the next pandemic. However, the existing well-established, proven platforms for seasonal and pandemic influenza manufacturing will also continue to be utilized to rapidly address the next influenza threat. The field of influenza vaccine manufacturing has a long history of successes, including approval of vaccines within approximately 100 days after WHO declaration of the A(H1N1) 2009 influenza pandemic. Moreover, many advances in vaccine science and manufacturing capabilities have been made in the past decade to optimize a rapid and timely response should a new influenza pandemic threat emerge.

Human seasonal influenza under COVID-19 and the potential consequences of influenza lineage elimination.

Annual epidemics of seasonal influenza cause hundreds of thousands of deaths, high levels of morbidity, and substantial economic loss. Yet, global influenza circulation has been heavily suppressed by public health measures and travel restrictions since the onset of the COVID-19 pandemic. Notably, the influenza B/Yamagata lineage has not been conclusively detected since April 2020, and A(H3N2), A(H1N1), and B/Victoria viruses have since circulated with considerably less genetic diversity. Travel restrictions have largely confined regional outbreaks of A(H3N2) to South and Southeast Asia, B/Victoria to China, and A(H1N1) to West Africa. Seasonal influenza transmission lineages continue to perish globally, except in these select hotspots, which will likely seed future epidemics. Waning population immunity and sporadic case detection will further challenge influenza vaccine strain selection and epidemic control. We offer a perspective on the potential short- and long-term evolutionary dynamics of seasonal influenza and discuss potential consequences and mitigation strategies as global travel gradually returns to pre-pandemic levels.

The importance of influenza vaccination during the COVID-19 pandemic.

The COVID-19 pandemic and the measures taken to mitigate its spread have had a dramatic effect on the circulation patterns of other respiratory viruses, most especially influenza viruses. Since April 2020, the global circulation of influenza has been markedly reduced; however, it is still present in a number of different countries and could pose a renewed threat in the upcoming Northern Hemisphere winter. Influenza vaccination remains the most effective preventive measure that we have at our disposal against influenza infections and should not be ignored for the 2021-2022 season.

Genetic and Antigenic Characterization of an Influenza A(H3N2) Outbreak in Cambodia and the Greater Mekong Subregion during the COVID-19 Pandemic, 2020.

Introduction of non-pharmaceutical interventions to control COVID-19 in early 2020 coincided with a global decrease in active influenza circulation. However, between July and November 2020, an influenza A(H3N2) epidemic occurred in Cambodia and in other neighboring countries in the Greater Mekong Subregion in Southeast Asia. We characterized the genetic and antigenic evolution of A(H3N2) in Cambodia and found that the 2020 epidemic comprised genetically and antigenically similar viruses of Clade3C2a1b/131K/94N, but they were distinct from the WHO recommended influenza A(H3N2) vaccine virus components for 2020-2021 Northern Hemisphere season. Phylogenetic analysis revealed multiple virus migration events between Cambodia and bordering countries, with Laos PDR and Vietnam also reporting similar A(H3N2) epidemics immediately following the Cambodia outbreak: however, there was limited circulation of these viruses elsewhere globally. In February 2021, a virus from the Cambodian outbreak was recommended by WHO as the prototype virus for inclusion in the 2021-2022 Northern Hemisphere influenza vaccine. IMPORTANCE The 2019 coronavirus disease (COVID-19) pandemic has significantly altered the circulation patterns of respiratory diseases worldwide and disrupted continued surveillance in many countries. Introduction of control measures in early 2020 against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection has resulted in a remarkable reduction in the circulation of many respiratory diseases. Influenza activity has remained at historically low levels globally since March 2020, even when increased influenza testing was performed in some countries. Maintenance of the influenza surveillance system in Cambodia in 2020 allowed for the detection and response to an influenza A(H3N2) outbreak in late 2020, resulting in the inclusion of this virus in the 2021-2022 Northern Hemisphere influenza vaccine.

Transmission of paediatric respiratory syncytial virus and influenza in the wake of the COVID-19 pandemic.

The non-pharmaceutical interventions implemented to slow the spread of SARS-CoV-2 have had consequences on the transmission of other respiratory viruses, most notably paediatric respiratory syncytial virus (RSV) and influenza. At the beginning of 2020, lockdown measures in the southern hemisphere led to a winter season with a marked reduction in both infections. Intermittent lockdowns in the northern hemisphere also appeared to interrupt transmission during winter 2020/21. However, a number of southern and northern hemisphere countries have now seen delayed RSV peaks. We examine the implications of these unpredictable disease dynamics for health service delivery in Europe, such as paediatric hospital and intensive care bed space planning, or palivizumab prophylaxis. We discuss the challenges for RSV vaccine trials and influenza immunisation campaigns, and highlight the considerable research opportunities that have arisen with the SARS-CoV-2 pandemic. We argue that the rapid advances in viral whole genome sequencing, phylogenetic analysis, and open data sharing during the pandemic are applicable to the ongoing surveillance of RSV and influenza. Lastly, we outline actions to prepare for forthcoming influenza seasons and for future implementation of RSV vaccines.

Rapid detection of human respiratory syncytial virus A and B by duplex real-time RT-PCR.

Respiratory syncytial virus (RSV) is a common cause of acute respiratory disease worldwide, especially in young children. The World Health Organization (WHO) has initiated an RSV Surveillance Pilot program that aims to perform worldwide RSV surveillance, requiring the development of reliable and rapid molecular methods to detect and identify RSV. A duplex real-time RT-PCR assay developed for simultaneous detection of both A and B subtypes of RSV was included as part of this program. This duplex assay targeted a conserved region of the RSV polymerase gene and was validated for analytical sensitivity, specificity, reproducibility and clinical performance with a wide range of respiratory specimens. The assay was highly specific for RSV and did not react with non-RSV respiratory pathogens, including the SARS-CoV-2 virus.

Where has all the influenza gone? The impact of COVID-19 on the circulation of influenza and other respiratory viruses, Australia, March to September 2020.

The coronavirus disease pandemic was declared in March 2020, as the southern hemisphere's winter approached. Australia expected co-circulation of severe acute respiratory syndrome coronavirus 2, influenza and other seasonal respiratory viruses. However, influenza notifications were 7,029 (March-September) compared with an average 149,832 for the same period in 2015-2019 [corrected], despite substantial testing. Restrictions on movement within and into Australia may have temporarily eliminated influenza. Other respiratory pathogens also showed remarkably changed activity in 2020.

New Technologies for Influenza Vaccines.

Vaccine development has been hampered by the long lead times and the high cost required to reach the market. The 2020 pandemic, caused by a new coronavirus (SARS-CoV-2) that was first reported in late 2019, has seen unprecedented rapid activity to generate a vaccine, which belies the traditional vaccine development cycle. Critically, much of this progress has been leveraged off existing technologies, many of which had their beginnings in influenza vaccine development. This commentary outlines the most promising of the next generation of non-egg-based influenza vaccines including new manufacturing platforms, structure-based antigen design/computational biology, protein-based vaccines including recombinant technologies, nanoparticles, gene- and vector-based technologies, as well as an update on activities around a universal influenza vaccine.

SARS-CoV-2 does not replicate in embryonated hen's eggs or in MDCK cell lines.

The advent of COVID-19, has posed a risk that human respiratory samples containing human influenza viruses may also contain SARS-CoV-2. This potential risk may lead to SARS-CoV-2 contaminating conventional influenza vaccine production platforms as respiratory samples are used to directly inoculate embryonated hen's eggs and continuous cell lines that are used to isolate and produce influenza vaccines. We investigated the ability of these substrates to propagate SARS-CoV-2 and found that neither could support SARS-CoV-2 replication.