Microbiology & Immunology - Research Publications
Now showing items 1-12 of 3028
Water-Borne Nanocoating for Rapid Inactivation of SARS-CoV-2 and Other Viruses
(AMER CHEMICAL SOC, 2021-09-28)
The rise in coronavirus variants has resulted in surges of the disease across the globe. The mutations in the spike protein on the surface of the virion membrane not only allow for greater transmission but also raise concerns about vaccine effectiveness. Preventing the spread of SARS-CoV-2, its variants, and other viruses from person to person via airborne or surface transmission requires effective inactivation of the virus. Here, we report a water-borne spray-on coating for the complete inactivation of viral particles and degradation of their RNA. Our nanoworms efficiently bind and, through subsequent large nanoscale conformational changes, rupture the viral membrane and subsequently bind and degrade its RNA. Our coating completely inactivated SARS-CoV-2 (VIC01) and an evolved SARS-CoV-2 variant of concern (B.1.1.7 (alpha)), influenza A, and a surrogate capsid pseudovirus expressing the influenza A virus attachment glycoprotein, hemagglutinin. The polygalactose functionality on the nanoworms targets the conserved S2 subunit on the SARS-CoV-2 virion surface spike glycoprotein for stronger binding, and the additional attachment of guanidine groups catalyze the degradation of its RNA genome. Coating surgical masks with our nanoworms resulted in complete inactivation of VIC01 and B.1.1.7, providing a powerful control measure for SARS-CoV-2 and its variants. Inactivation was further observed for the influenza A and an AAV-HA capsid pseudovirus, providing broad viral inactivation when using the nanoworm system. The technology described here represents an environmentally friendly coating with a proposed nanomechanical mechanism for inactivation of both enveloped and capsid viruses. The functional nanoworms can be easily modified to target viruses in future pandemics, and is compatible with large scale manufacturing processes.
Accessible Platform for High-Throughput COVID-19 Molecular Diagnostics and Genome Sequencing Using a Repurposed 3D Printer for RNA Extraction
(AMER CHEMICAL SOC, 2021-09-13)
The COVID-19 pandemic has exposed the dependence of diagnostic laboratories on a handful of large corporations with market monopolies on the worldwide supply of reagents, consumables, and hardware for molecular diagnostics. Global shortages of key consumables for RT-qPCR detection of SARS-CoV-2 RNA have impaired the ability to run essential, routine diagnostic services. Here, we describe a workflow for rapid detection of SARS-CoV-2 RNA in upper respiratory samples including nasal swabs and saliva, utilizing low-cost equipment and readily accessible reagents. Using repurposed Creality3D Ender-3 three-dimensional (3D) printers, we built a semiautomated paramagnetic bead RNA extraction platform. The hardware for the system was built for $300 USD, and the material cost per reaction was $1 USD. Named the Ender VX500, instrument performance when paired with RT-qPCR for SARS-CoV-2 detection in nasal and saliva specimens was two virus copies per microliter. There was a high-performance agreement (assessed using 458 COVID-19 nasal swab specimens) with the Aptima SARS-CoV-2 assay run on the Hologic Panther, a commercial automated RNA extraction and detection platform. Inter- and intrainstrument precision was excellent (coefficients of variation (CoV) of 1.10 and 0.66-1.32%, respectively) across four instruments. The platform is scalable with throughput ranging from 23 specimens on a single instrument run by one user in 50 min to 364 specimens on four instruments run by four users in 190 min. Step-by-step instructions and protocols for building and running the Ender VX500 have been made available without restriction.
The origins of SARS-CoV-2: A critical review.
(Elsevier BV, 2021-09-16)
Since the first reports of a novel severe acute respiratory syndrome (SARS)-like coronavirus in December 2019 in Wuhan, China, there has been intense interest in understanding how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in the human population. Recent debate has coalesced around two competing ideas: a "laboratory escape" scenario and zoonotic emergence. Here, we critically review the current scientific evidence that may help clarify the origin of SARS-CoV-2.
Use of emerging testing technologies and approaches for SARS-CoV-2: review of literature and global experience in an Australian context
Emerging testing technologies for detection of SARS-CoV-2 include those that are rapid and can be used at point-of-care (POC), and those facilitating high throughput laboratory-based testing. Tests designed to be performed at POC (such as antigen tests and molecular assays) have the potential to expedite isolation of infectious patients and their contacts, but most are less sensitive than standard-of-care reverse transcription polymerase chain reaction (RT-PCR). Data on clinical performance of the majority of emerging assays are limited with most evaluations performed on contrived or stored laboratory samples. Further evaluations of these assays are required, particularly when performed at POC on symptomatic and asymptomatic patients and at various time-points after symptom onset. A few studies have so far shown several of these assays have high specificity. However, large prospective evaluations are needed to confirm specificity, particularly before the assays are implemented in low prevalence settings or asymptomatic populations. High throughput laboratory-based testing includes the use of new sample types (e.g., saliva to increase acceptability) or innovative uses of existing technology (e.g., sample pooling). Information detailing population-wide testing strategies for SARS-COV-2 is largely missing from peer-reviewed literature. Logistics and supply chains are key considerations in any plan to 'scale up' testing in the Australian context. The strategic use of novel assays will help strike the balance between achieving adequate test numbers without overwhelming laboratory capacity. To protect testing of high-risk populations, the aims of testing with respect to the phase of the pandemic must be considered.
Absence of SARS-CoV-2 antibodies in pre-pandemic plasma from children and adults in Vietnam.
(Elsevier BV, 2021-07-31)
We tested pre-pandemic (2015--2019) plasma samples from 148 Vietnamese children and 100 Vietnamese adults at high risk of zoonotic infections for antibodies against SARS-CoV-2 nucleocapsid and spike proteins. None was positive. The data thus demonstrated no evidence of prior serological cross-reactivity with SARS-CoV-2 that might explain the low numbers of COVID-19 in Vietnam. No pre-existing cross-reactivity might explain Vietnam success of COVID-19 control.
Staff to staff transmission as a driver of healthcare worker infections with COVID-19.
(Elsevier BV, 2021-07-17)
BACKGROUND: High rates of healthcare worker (HCW) infections due to COVID-19 have been attributed to several factors, including inadequate personal protective equipment (PPE), exposure to a high density of patients with COVID-19, and poor building ventilation. We investigated an increase in the number of staff COVID-19 infections at our hospital to determine the factors contributing to infection and to implement the interventions required to prevent subsequent infections. METHODS: We conducted a single-centre retrospective cohort study of staff working at a tertiary referral hospital who tested positive for SARS-CoV-2 between 25 January 2020 and 25 November 2020. The primary outcome was the source of COVID-19 infection. RESULTS: Of 45 staff who returned a positive test result for SARS-CoV-2, 19 were determined to be acquired at our hospital. Fifteen (15/19; 79% [95% CI: 54-94%]) of these were identified through contact tracing and testing following exposures to other infected staff and were presumed to be staff-to-staff transmission, including an outbreak in 10 healthcare workers (HCWs) linked to a single ward that cared for COVID-19 patients. The staff tearoom was identified as the likely location for transmission, with subsequent reduction in HCW infections and resolution of the outbreak following implementation of enhanced control measures in tearoom facilities. No HCW contacts (0/204; 0% [95% CI: 0-2%]) developed COVID-19 infection following exposure to unrecognised patients with COVID-19. CONCLUSION: Unrecognised infections among staff may be a significant driver of HCW infections in healthcare settings. Control measures should be implemented to prevent acquisition from other staff as well as patient-staff transmission.
Safety and efficacy of COVID-19 vaccines in multiple sclerosis patients.
(Elsevier BV, 2021-07-15)
COVID-19 vaccination is recommended for multiple sclerosis patients. Disease-modifying therapies can influence the safety and efficacy of COVID-19 vaccines. RNA, DNA, protein, and inactivated vaccines are likely safe for multiple sclerosis patients. A few incidences of central demyelination were reported with viral vector vaccines, but their benefits likely outweigh their risks if alternatives are unavailable. Live-attenuated vaccines should be avoided whenever possible in treated patients. Interferon-beta, glatiramer acetate, teriflunomide, fumarates, and natalizumab are not expected to impact vaccine efficacy, while cell-depleting agents (ocrelizumab, rituximab, ofatumumab, alemtuzumab, and cladribine) and sphingosine-1-phosphate modulators will likely attenuate vaccine responses. Coordinating vaccine timing with dosing regimens for some therapies may optimize vaccine efficacy.
Genomics-informed responses in the elimination of COVID-19 in Victoria, Australia: an observational, genomic epidemiological study
(ELSEVIER SCI LTD, 2021-08-01)
BACKGROUND: A cornerstone of Australia's ability to control COVID-19 has been effective border control with an extensive supervised quarantine programme. However, a rapid recrudescence of COVID-19 was observed in the state of Victoria in June, 2020. We aim to describe the genomic findings that located the source of this second wave and show the role of genomic epidemiology in the successful elimination of COVID-19 for a second time in Australia. METHODS: In this observational, genomic epidemiological study, we did genomic sequencing of all laboratory-confirmed cases of COVID-19 diagnosed in Victoria, Australia between Jan 25, 2020, and Jan 31, 2021. We did phylogenetic analyses, genomic cluster discovery, and integrated results with epidemiological data (detailed information on demographics, risk factors, and exposure) collected via interview by the Victorian Government Department of Health. Genomic transmission networks were used to group multiple genomic clusters when epidemiological and genomic data suggested they arose from a single importation event and diversified within Victoria. To identify transmission of emergent lineages between Victoria and other states or territories in Australia, all publicly available SARS-CoV-2 sequences uploaded before Feb 11, 2021, were obtained from the national sequence sharing programme AusTrakka, and epidemiological data were obtained from the submitting laboratories. We did phylodynamic analyses to estimate the growth rate, doubling time, and number of days from the first local infection to the collection of the first sequenced genome for the dominant local cluster, and compared our growth estimates to previously published estimates from a similar growth phase of lineage B.1.1.7 (also known as the Alpha variant) in the UK. FINDINGS: Between Jan 25, 2020, and Jan 31, 2021, there were 20 451 laboratory-confirmed cases of COVID-19 in Victoria, Australia, of which 15 431 were submitted for sequencing, and 11 711 met all quality control metrics and were included in our analysis. We identified 595 genomic clusters, with a median of five cases per cluster (IQR 2-11). Overall, samples from 11 503 (98·2%) of 11 711 cases clustered with another sample in Victoria, either within a genomic cluster or transmission network. Genomic analysis revealed that 10 426 cases, including 10 416 (98·4%) of 10 584 locally acquired cases, diagnosed during the second wave (between June and October, 2020) were derived from a single incursion from hotel quarantine, with the outbreak lineage (transmission network G, lineage D.2) rapidly detected in other Australian states and territories. Phylodynamic analyses indicated that the epidemic growth rate of the outbreak lineage in Victoria during the initial growth phase (samples collected between June 4 and July 9, 2020; 47·4 putative transmission events, per branch, per year [1/years; 95% credible interval 26·0-85·0]), was similar to that of other reported variants, such as B.1.1.7 in the UK (mean approximately 71·5 1/years). Strict interventions were implemented, and the outbreak lineage has not been detected in Australia since Oct 29, 2020. Subsequent cases represented independent international or interstate introductions, with limited local spread. INTERPRETATION: Our study highlights how rapid escalation of clonal outbreaks can occur from a single incursion. However, strict quarantine measures and decisive public health responses to emergent cases are effective, even with high epidemic growth rates. Real-time genomic surveillance can alter the way in which public health agencies view and respond to COVID-19 outbreaks. FUNDING: The Victorian Government, the National Health and Medical Research Council Australia, and the Medical Research Future Fund.
Ethnically Disparate Disease Progression and Outcomes among Acute Rheumatic Fever Patients in New Zealand, 1989-2015
(CENTERS DISEASE CONTROL & PREVENTION, 2021-07-01)
We investigated outcomes for patients born after 1983 and hospitalized with initial acute rheumatic fever (ARF) in New Zealand during 1989-2012. We linked ARF progression outcome data (recurrent hospitalization for ARF, hospitalization for rheumatic heart disease [RHD], and death from circulatory causes) for 1989-2015. Retrospective analysis identified initial RHD patients <40 years of age who were hospitalized during 2010-2015 and previously hospitalized for ARF. Most (86.4%) of the 2,182 initial ARF patients did not experience disease progression by the end of 2015. Progression probability after 26.8 years of theoretical follow-up was 24.0%; probability of death, 1.0%. Progression was more rapid and ≈2 times more likely for indigenous Māori or Pacific Islander patients. Of 435 initial RHD patients, 82.2% had not been previously hospitalized for ARF. This young cohort demonstrated low mortality rates but considerable illness, especially among underserved populations. A national patient register could help monitor, prevent, and reduce ARF progression.
From influenza to COVID-19: Lipid nanoparticle mRNA vaccines at the frontiers of infectious diseases
(ELSEVIER SCI LTD, 2021-09-01)
Vaccination represents the best line of defense against infectious diseases and is crucial in curtailing pandemic spread of emerging pathogens to which a population has limited immunity. In recent years, mRNA vaccines have been proposed as the new frontier in vaccination, owing to their facile and rapid development while providing a safer alternative to traditional vaccine technologies such as live or attenuated viruses. Recent breakthroughs in mRNA vaccination have been through formulation with lipid nanoparticles (LNPs), which provide both protection and enhanced delivery of mRNA vaccines in vivo. In this review, current paradigms and state-of-the-art in mRNA-LNP vaccine development are explored through first highlighting advantages posed by mRNA vaccines, establishing LNPs as a biocompatible delivery system, and finally exploring the use of mRNA-LNP vaccines in vivo against infectious disease towards translation to the clinic. Furthermore, we highlight the progress of mRNA-LNP vaccine candidates against COVID-19 currently in clinical trials, with the current status and approval timelines, before discussing their future outlook and challenges that need to be overcome towards establishing mRNA-LNPs as next-generation vaccines. STATEMENT OF SIGNIFICANCE: With the recent success of mRNA vaccines developed by Moderna and BioNTech/Pfizer against COVID-19, mRNA technology and lipid nanoparticles (LNP) have never received more attention. This manuscript timely reviews the most advanced mRNA-LNP vaccines that have just been approved for emergency use and are in clinical trials, with a focus on the remarkable development of several COVID-19 vaccines, faster than any other vaccine in history. We aim to give a comprehensive introduction of mRNA and LNP technology to the field of biomaterials science and increase accessibility to readers with a new interest in mRNA-LNP vaccines. We also highlight current limitations and future outlook of the mRNA vaccine technology that need further efforts of biomaterials scientists to address.