Dominic E Dwyer

Dominic E Dwyer
  • MD, FRACP, FRCPA
  • The University of Sydney

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629
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Publications

Publications (629)
Preprint
Simultaneous genomic sequencing of multiple respiratory pathogens from clinical samples can provide real-time data on viral evolution, co-circulation and co-infection during seasonal epidemics. Influenza is a major global respiratory pathogen, with a mature genomic epidemiology framework, that has yet to be integrated with genomic surveillance of o...
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Background Continued phenotyping and ongoing molecular epidemiology are important in current and future monitoring of emerging SARS-CoV-2 lineages. Herein we developed pragmatic strategies to track the emergence, spread and phenotype of SARS-CoV-2 variants in Australia in an era of decreasing diagnostic PCR testing and focused cohort-based studies....
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HIV drug resistant strains and adherence to ART
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Background Pilgrimages and travel to religious Mass Gatherings (MGs) are part of all major religions. This narrative review aims to describe some characteristics, including health risks, of the more well known and frequently undertaken ones. Methods A literature search was conducted using keywords related to the characteristics (frequency of occur...
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Introduction New South Wales (NSW) has one of the world's highest uptake rates of HIV pre‐exposure prophylaxis (PrEP). This uptake has been credited with sharp declines in HIV transmission, particularly among Australian‐born gay and bisexual men. Concerns have been raised around the potential for the emergence of tenofovir (TFV) and XTC (lamivudine...
Preprint
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Background: Continued phenotyping and ongoing surveillance are important in current and future monitoring of emerging SARS-CoV-2 lineages. Herein we developed pragmatic strategies to track the emergence, spread and phenotype of SARS-CoV-2 variants in Australia in an era of decreasing diagnostic PCR testing and focused cohort-based studies. This was...
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Introduction Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus that causes encephalitis and other morbidity in Southeast Asia. Since February 2022, geographically dispersed JEV human, animal and vector detections occurred on the Australian mainland for the first time. This study will determine the prevalence of JEV-specific antibodie...
Article
In response to the emergence of the monkeypox virus (MPXV) in Australia in May 2022, we developed and evaluated indirect immunofluorescence assays (IFA) for MPXV and Vaccinia virus (VACV) IgG and IgM antibodies using serum samples from patients with nucleic acid amplification test (NAAT)‐confirmed mpox and uninfected unvaccinated controls. Addition...
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Background COVID-HEROES is a multicentre study of Australian healthcare workers (HCW) assessing 1) incidence of and risk factors for SARS-CoV-2 infection and 2) serological response to SARS-CoV-2 vaccination and infection.Figure 1:Cases of SARS-CoV-2 over time by diagnostic method Methods We conducted a multi-centre, prospective observational coho...
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Constantly evolving viral populations affect the specificity of primers and the quality of genomic surveillance. This study presents a framework for the continuous optimization of sequencing efficiency for public health surveillance based on the ongoing evolution of the COVID-19 pandemic. SARS-CoV-2 genomic clustering capacity based on three amplif...
Preprint
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Aims To explore viral evolution during in vitro neutralisation using next generation sequencing, and to determine whether sera from individuals immunised with two doses of the Pfizer-BioNTech vaccine (BNT162b2) are as effective at neutralising the SARS-CoV-2 variant of concern (VOC) Delta (B 1.617.2) compared to the earlier lineages Beta (B.1.351)...
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Intense public interest in scientific claims about COVID-19, concerning its origins, modes of spread, evolution, and preventive and therapeutic strategies, has focused attention on the values to which scientists are assumed to be committed and the relationship between science and other public discourses. A much discussed claim, which has stimulated...
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Objective Circulation patterns of influenza and other respiratory viruses have been globally disrupted since the emergence of coronavirus disease (COVID-19) and the introduction of public health and social measures (PHSMs) aimed at reducing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission. Methods We reviewed respiratory v...
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Objective: Circulation patterns of influenza and other respiratory viruses have been globally disrupted since the emergence of coronavirus disease (COVID-19) and the introduction of public health and social measures (PHSMs) aimed at reducing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission. Methods: We reviewed respiratory...
Preprint
Constantly evolving viral populations affect the specificity of primers and quality of genomic surveillance. This study presents a framework for continuous optimisation of sequencing efficiency for public health surveillance based on the ongoing evolution of the COVID-19 pandemic. SARS-CoV-2 genomic clustering capacity based on three amplification...
Article
Background: Epstein-Barr virus (EBV) is implicated in MS risk; evidence for other herpesviruses is inconsistent. Here we test blood markers of infection with Human herpesvirus 6 (HHV-6), varicella-zoster virus (VZV) and cytomegalovirus (CMV), as risk factors for a first clinical diagnosis of CNS demyelination (FCD) in the context of markers of EBV...
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Background: Antibody-based therapies for respiratory viruses are of increasing importance. The INSIGHT006 trial administered anti-influenza hyperimmune intravenous immunoglobulin (Flu-IVIG) to patients hospitalised with influenza. Flu-IVIG treatment improved outcomes in patients with influenza B but showed no benefit for influenza A. Methods: To...
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The emergence of resistance to antiviral drugs increasingly used to treat SARS-CoV-2 infections has been recognised as a significant threat to COVID-19 control. In addition, some SARS-CoV-2 variants of concern appear to be intrinsically resistant to several classes of these antiviral agents. Therefore, there is a critical need for rapid recognition...
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Full-text available
Emerging infectious disease threats require rapid response tools to inform diagnostics, treatment, and outbreak control. RNA-based metagenomics offers this; however, most approaches are time-consuming and laborious. Here, we present a simple and fast protocol, the RAPIDprep assay, with the aim of providing a cause-agnostic laboratory diagnosis of i...
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Chronic obstructive pulmonary disease (COPD) is among the leading causes of death worldwide and HIV is an independent risk factor for the development of COPD. However, the etiology of this increased risk and means to identify persons with HIV (PWH) at highest risk for COPD have remained elusive. Biomarkers may reveal etiologic pathways and allow be...
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In the context of an emerging Japanese encephalitis outbreak within Australia, we describe a novel locally acquired case in New South Wales. A man in his 70s had rapidly progressive, fatal meningoencephalitis, diagnosed as caused by Japanese encephalitis virus by RNA-based metagenomic next-generation sequencing performed on postmortem brain tissue.
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Flaviviruses are a diverse group of enveloped RNA viruses that cause significant clinical manifestations in the pregnancy and postpartum periods. This review highlights the epidemiology, pathophysiology, clinical features, diagnosis, and prevention of the key arthropod-borne flaviviruses of concern in pregnancy and the neonatal period—Zika, Dengue,...
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Objectives: To describe the epidemiology and impact of Omicron BR.2.1, an emergent SARS-CoV-2 Omicron BA.2.75 sublineage displaying high fitness compared to other co-circulating subvariants in New South Wales (NSW), Australia. Methods: From 1 September to 26 November 2022, 4,971 SARS-CoV-2 consensus genomes from unique patients were generated, a...
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Objective: To describe the effectiveness of the public health response to COVID-19 in our local region by documenting detection of SARS-CoV-2 infection by nucleic acid testing (NAT) positivity and seroprevalence. Methods: In this prospective study (ACTRN12620000487910), symptomatic adult international travellers returning to regional Australia i...
Article
An outbreak of severe pneumonia of unknown cause was identified in Wuhan, China in December 2019: the causative agent was a novel betacoronavirus, severe acute respiratory syndrome-cotonavirus-2 (SARS-CoV-2), a virus that joins a list of coronaviruses causing severe (e.g., SARS and Middle East respiratory syndrome) or milder (e.g., 229E, OC43, NL63...
Preprint
Full-text available
Emerging infectious disease threats require rapid response tools to inform diagnostics, treatment, and outbreak control. RNA-based metagenomics offers this; however, most approaches are time-consuming and laborious. Here, we present a simple and fast protocol – the RAPIDprep assay – with the aim to provide cause agnostic laboratory diagnosis of inf...
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Full-text available
The long‐term health consequences of SARS‐CoV‐2 infection are still being understood. The molecular and phenotypic properties of SARS‐CoV‐2 antigen‐specific T cells suggest a dysfunctional profile that persists in convalescence in those who were severely ill. By contrast, the antigen‐specific memory B cell (MBC) population has not yet been analysed...
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Genomic surveillance of SARS-CoV-2 has been essential to inform public health response to outbreaks. The high incidence of infection has resulted in a smaller proportion of cases undergoing whole genome sequencing due to finite resources. We present a framework for estimating the impact of reduced depths of genomic surveillance on the resolution of...
Article
Objective: Western Sydney Local Health District (WSLHD) measured the utility and validity of rapid molecular point-of-care testing (POCT) in aged care facilities (ACFs) experiencing influenza-like illness (ILI) outbreaks against routine laboratory testing. Methods: A descriptive epidemiological study into 82 respiratory outbreaks reported across...
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In late November 2021, the World Health Organization declared the SARS-CoV-2 lineage B.1.1.529 the fifth variant of concern, Omicron. This variant has acquired over 30 mutations in the spike protein (with 15 in the receptor-binding domain), raising concerns that Omicron could evade naturally acquired and vaccine-derived immunity. We utilized an aut...
Article
Phagocytic responses by effector cells to opsonized viruses have been recognized to play a key role in antiviral immunity. Limited data on coronavirus disease 2019 suggest that the role of Ab-dependent and -independent phagocytosis may contribute to the observed immunological and inflammatory responses; however, their development, duration, and rol...
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The detection of a new and unexpected Japanese encephalitis virus (JEV) outbreak in March 2022 in Australia, where JEV is not endemic, demanded the rapid development of a robust diagnostic framework to facilitate the testing of suspected patients across the state of New South Wales (NSW). This nascent but comprehensive JEV diagnostic service encomp...
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Background: Human metapneumovirus (hMPV), first described in 2001, is a cause of acute respiratory tract infection in the elderly, with symptoms ranging from mild to severe, including pneumonia, but outbreaks are rarely described. Methods: Between 1 July and 31 December 2018, there were three outbreaks of Influenza-like Illness (ILI) where hMPV...
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In order to rapidly differentiate sublineages BA.1 and BA.2 of the SARS-CoV-2 variant of concern Omicron, we developed a real-time reverse-transcriptase polymerase chain reaction to target the discriminatory spike protein deletion at amino acid position 69–70 (S:del69–70). Compared to the gold standard of whole genome sequencing, the candidate assa...
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The unprecedented emergence of Japanese encephalitis (JE) in mainland Australia represents an outbreak of high clinical and public health significance. JE is a zoonosis spread by mosquitoes and is one of the most important causes of endemic viral encephalitis in South-East Asia and the Indian subcontinent. While occasional cases of human Japanese e...
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Full-text available
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 durin...
Preprint
Full-text available
The emergence of resistance to antiviral drugs increasingly used to treat SARS-CoV-2 infections has been recognised as a significant threat to COVID-19 control. In addition, some SARS-CoV-2 variants of concern appear to be intrinsically resistant to several classes of these antiviral agents. Therefore, there is a critical need for rapid recognition...
Article
Background: Since November 2021, a new variant of concern (VOC), the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineage B.1.1.529 (Omicron) has emerged as the dominant coronavirus disease 2019 (COVID-19) infection worldwide. We describe the clinical presentation, risk factors, and outcomes in a cohort of kidney and kidney pancrea...
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Co-infections with different variants of SARS-CoV-2 are a key precursor to recombination events that are likely to drive SARS-CoV-2 evolution. Rapid identification of such co-infections is required to determine their frequency in the community, particularly in populations at-risk of severe COVID-19, which have already been identified as incubators...
Article
Influenza is a common cause of acute respiratory infection, and is a major cause of morbidity and mortality. This report summarises the epidemiology of hospitalisations with laboratory-confirmed influenza during the 2019 influenza season. The Influenza Complications Alert Network (FluCAN) is a sentinel hospital-based surveillance program that opera...
Article
Objective: To assess the prevalence of CMV viremia in HIV-positive patients starting antiretroviral therapy (ART) and to evaluate its impact on clinical outcomes. Design: Retrospective analysis of four clinical trials (INSIGHT FIRST, SMART, START, and ANRS REFLATE TB). Methods: Stored plasma samples from participants were used to measure CMV v...
Article
Introduction: Influenza is a common cause of acute respiratory infection, and is a major cause of morbidity and mortality. Coronavirus disease 2019 (COVID-19) is an acute respiratory infection that emerged as a pandemic worldwide before the start of the 2020 Australian influenza season. This report summarises the epidemiology of hospitalisations w...
Research
Research Title: “The HIV strains infecting the Fijian population including the resistant variants after the introduction of ART”. Authors: Filimone Raikanikoda, Dominic E. Dwyer, Choo B. Chew; 2008. Abstract Since the introduction of highly active antiretroviral therapy (HAART) in the treatment of HIV/AIDS in the late nineteen-nineties, there has...
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Timely and accurate diagnostic testing is a critical component of the public health response to COVID-19. Antigen tests are used widely in many countries to provide rapid, economical and accessible point-of-care testing (1). The vast majority of antigen tests detect nucleocapsid (N) protein, a structural protein that displays less variation than th...
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We identified the co-infection of the SARS-CoV-2 Omicron and Delta variants in two epidemiologically unrelated patients with chronic kidney disease requiring haemodialysis. Both SARS-CoV-2 variants were co-circulating locally at the time of detection. Amplicon- and probe-based sequencing using short- and long-read technologies identified and quanti...
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Responses to the early (February–July 2020) COVID-19 pandemic varied widely, globally. Reasons for this are multiple but likely relate to the healthcare and financial resources then available, and the degree of trust in, and economic support provided by, national governments. Cultural factors also affected how different populations reacted to the v...
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Background As of mid-2021, Australia’s only nation-wide COVID-19 epidemic occurred in the first six months of the pandemic. Subsequently there has been limited transmission in most states and territories. Understanding community spread during the first wave was hampered by initial limitations on testing and surveillance. To characterize the prevale...
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Understanding the long-term maintenance of SARS-CoV-2 immunity is critical for predicting protection against reinfection. In an age and gender matched cohort of 24 participants, the association of disease severity and early immune responses on the maintenance of humoral immunity 12 months post-infection is examined. All severely affected participan...
Preprint
Full-text available
Phagocytic responses by effector cells to antibody or complement-opsonised viruses have been recognized to play a key role in anti-viral immunity. These include antibody dependent cellular phagocytosis mediated via Fc-receptors, phagocytosis mediated by classically activated complement-fixing IgM or IgG1 antibodies and antibody independent phagocyt...
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Several Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) neutralising monoclonal antibodies (mAbs) have received emergency use authorisation by regulatory agencies for treatment and prevention of Coronavirus Disease 2019 (COVID-19), including in patients at risk for progression to severe disease. Here we report the persistence of viable...
Preprint
Full-text available
In late November 2021, the World Health Organization declared the SARS-CoV-2 lineage B.1.1.529 the fifth variant of concern, Omicron. This variant has acquired 15 mutations in the receptor binding domain of the spike protein, raising concerns that Omicron could evade naturally acquired and vaccine-derived immunity. We utilized an authentic virus, m...
Article
Full-text available
Objective To adapt ‘fishplots’ to describe real-time evolution of SARS-CoV-2 genomic clusters. Results This novel analysis adapted the fishplot to depict the size and duration of circulating genomic clusters over time in New South Wales, Australia. It illuminated the effectiveness of interventions on the emergence, spread and eventual elimination...
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Introduction: In May 2020, The Communicable Diseases Network of Australia (CDNA) case definition introduced serological criteria to support the diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We present findings that support the utility of SARS-CoV-2-specific serology for public health investigations. Methods: From 24 Jan...
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SARS-CoV-2 genomic surveillance has been vital in understanding the spread of COVID-19, the emergence of viral escape mutants and variants of concern. However, low viral loads in clinical specimens affect variant calling for phylogenetic analyses and detection of low frequency variants, important in uncovering infection transmission chains. We syst...
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Pandemic dynamics and health care responses are markedly different during the COVID-19 pandemic than in earlier outbreaks. Compared with established infectious disease such as influenza, we currently know relatively little about the origin, reservoir, cross-species transmission and evolution of SARS-CoV-2. Health care services, drug availability, l...
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Authors of the March WHO report into how COVID-19 emerged warn that further delay makes crucial inquiry biologically difficult
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Respiratory syncytial virus (RSV) is an important human respiratory pathogen. In temperate regions, a distinct seasonality is observed, where peaks of infections typically occur in early winter, often preceding the annual influenza season. Infections are associated with high rates of morbidity and mortality and in some populations exceed that of in...
Preprint
Full-text available
Human respiratory syncytial virus (RSV) is an important cause of acute respiratory infection (ARI) with the most severe disease in the young and elderly. Non-pharmaceutical interventions (NPIs) and travel restrictions for controlling COVID-19 have impacted the circulation of most respiratory viruses including RSV globally, particularly in Australia...
Article
Full-text available
The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) antibody neutralization response and its evasion by emerging viral variants and variant of concern (VOC) are unknown, but critical to understand reinfection risk and breakthrough infection following vaccination. Antibody immunoreactivity against SARS-CoV-2 antigens and Spike variants,...
Preprint
Full-text available
Objective: To adapt ‘fishplots’ to describe SARS-CoV-2 genomic cluster evolution. Results: This novel analysis adapted the fishplot to depict the size and duration of circulating genomic clusters over time in New South Wales, Australia. It illuminated the effectiveness of interventions on the emergence, spread and eventual elimination of clusters a...
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Full-text available
Objectives: Rhinoviruses (RV) represent the most common aetiological agent of all acute respiratory tract infections across all age groups and a significant burden of disease among children. Recent studies have shown that RV-A and RV-C species are associated with increased disease severity. In order to better understand potential associations betw...
Preprint
Full-text available
SARS-CoV-2 genomic surveillance has been vital in understanding the spread of COVID-19, the emergence of viral escape mutants and variants of concern. However, low viral loads in clinical specimens affect variant calling for phylogenetic analyses and detection of low frequency variants, important in uncovering infection transmission chains. We syst...
Article
Full-text available
Many viruses cause seasonal respiratory infections in temperate climates that peak in the winter months. They cause varying degrees of respiratory illness across all age groups, and include respiratory syncytial virus (RSV), parainfluenza viruses (types 1‐4), human metapneumovirus, rhinoviruses, seasonal coronaviruses (OC43, 229E, NL63, HKU1), ente...
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Full-text available
Human metapneumovirus (HMPV) is an important cause of upper and lower respiratory tract disease in individuals of all ages. It is estimated that most individuals will be infected by HMPV by the age of five years old. Despite this burden of disease, there remain caveats in our knowledge of global genetic diversity due to a lack of HMPV sequencing, p...
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Considerable concerns relating to the duration of protective immunity against SARS-CoV-2 exist, with evidence of antibody titres declining rapidly after infection and reports of reinfection. Here we monitor the antibody responses against SARS-CoV-2 receptor binding domain (RBD) for up to six months after infection. While antibody titres are maintai...
Article
Objectives: To estimate SARS-CoV-2-specific antibody seroprevalence after the first epidemic wave of coronavirus disease 2019 (COVID-19) in Sydney. Setting, participants: People of any age who had provided blood for testing at selected diagnostic pathology services (general pathology); pregnant women aged 20-39 years who had received routine ant...
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Introduction The human immunodeficiency virus 1 (HIV‐1) pandemic is characterized by numerous distinct sub‐epidemics (clusters) that continually fuel local transmission. The aims of this study were to identify active growing clusters, to understand which factors most influence the transmission dynamics, how these vary between different subtypes and...
Preprint
Full-text available
The SARS-CoV-2 antibody neutralization response and its evasion by emerging viral variants are unknown. Antibody immunoreactivity against SARS-CoV-2 antigens and Spike variants, inhibition of Spike-driven virus-cell fusion, and infectious SARS-CoV-2 neutralization were characterized in 807 serial samples from 233 RT-PCR-confirmed COVID-19 individua...
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Changes over time in HIV-1 subtype diversity within a population reflect changes in factors influencing the development of local epidemics. Here we report on the genetic diversity of 2364 reverse transcriptase sequences from people living with HIV-1 in New South Wales (NSW) notified between 2004 and 2018. These data represent >70% of all new HIV-1...
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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 sa...
Preprint
Background Rhinoviruses (RV) represent the most common aetiological agent of all acute respiratory tract infections across all age groups and a significant burden of disease among children. Recent studies have shown that RV-A and RV-C species are associated with varying degrees of disease severity and clinical symptoms. Methods In this study, we un...
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Full-text available
A second cluster of COVID-19 cases imported from Europe occured in Vietnam from early March 2020. We describe 44 SARS-CoV-2 RT-PCR positive patients (cycle threshold value <30) admitted to the National Hospital for Tropical Diseases in Hanoi between March 6 and April 15 2020. Whole SARS-CoV-2 genomes from these patients were sequenced using Illumin...
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Background On 31 December 2019, the World Health Organization recognised clusters of pneumonia‐like cases due to a novel coronavirus disease (COVID‐19). COVID‐19 became a pandemic 71 days later. Aim To report the clinical and epidemiological features, laboratory data and outcomes of the first group of 11 returned travellers with COVID‐19 in Austra...
Preprint
Full-text available
Respiratory syncytial virus (RSV) is an important human respiratory pathogen. In temperate regions a distinct seasonality is observed, where peaks of infections typically occur in early winter, often preceding the annual influenza season. Infections are associated with high rates of morbidity and mortality, and in some populations exceeds that of i...
Article
Full-text available
Background The detection of SARS-CoV-2 RNA by real-time polymerase chain reaction (PCR) in respiratory samples collected from persons recovered from COVID-19 does not necessarily indicate shedding of infective virions. By contrast, the isolation of SARS-CoV-2 using cell-based culture likely indicates infectivity, but there are limited data on the c...
Preprint
Full-text available
Considerable concerns relating to the duration of protective immunity against SARS-CoV-2 have been raised, with evidence of antibody titres declining rapidly after infection and reports of reinfection. Here we monitored antibody responses against SARS-CoV-2 receptor binding domain (RBD) for up to six months after infection. While antibody titres we...
Article
Full-text available
Background In this large-scale cluster-randomized controlled trial (cRCT) we sought to assess the effectiveness of facemasks against viral respiratory infections. Methods and results Over three consecutive Hajj seasons (2013, 2014, 2015) pilgrims’ tents in Makkah were allocated to ‘facemask’ or ‘no facemask’ group. Fifty facemasks were offered to...
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In January 2020, a novel betacoronavirus (family Coronaviridae), named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified as the etiological agent of a cluster of pneumonia cases occurring in Wuhan City, Hubei Province, China1,2. The disease arising from SARS-CoV-2 infection, coronavirus disease 2019 (COVID-19), subsequent...
Article
The aim of this study was to assess the analytic and clinical performance of four rapid lateral flow point-of-care tests (POCTs) for identifying SARS-CoV-2-specific antibodies. A retrospective study was conducted between 22 January and 30 March 2020 on 132 serum samples for SARS-CoV-2-specific antibody detection referred to a tertiary referral hosp...
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Background Testing for SARS-CoV-2-specific antibodies has become an important tool, complementing nucleic acid tests (NATs) for diagnosis and for determining the prevalence of COVID-19 in population serosurveys. The magnitude and persistence of antibody responses are critical for assessing the duration of immunity. Methods A SARS-CoV-2-specific im...
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Objective To determine population-level immunity to mumps in Australia. Methods We tested randomly selected specimens from people aged 1–49 years using the Enzygnost anti-parotitis IgG enzyme immunoassay from an opportunistically collected serum bank in 2012–2013. Weighted estimates of the proportion seropositive and equivocal for mumps-specific Ig...
Article
Background School closures have occurred globally during the COVID-19 pandemic. However, empiric data on transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among children and in educational settings are scarce. In Australia, most schools have remained open during the first epidemic wave, albeit with reduced student physica...

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