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1.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-334972

ABSTRACT

Omicron, a highly transmissible SARS-CoV-2, emerged in November 2021. The high mutation rates within spike protein of Omicron raised concerns about increased breakthrough infections among the vaccinated. We tested cross-reactivity of antibodies induced by UB-612 against Omicron and other variants. After 2 doses, UB-612 elicited low levels of neutralization antibodies against ancestral virus and Omicron. A booster dose delivered 7-9 months after primary vaccination dramatically increased antibody levels, with only a 1.4-fold loss in neutralization titer against Omicron compared to the ancestral strain. Using a model bridging vaccine efficacy with ancestral virus RBD binding antibody responses, predicted efficacy against symptomatic COVID-19 after UB-612 booster is estimated at 95%. UB-612 is anticipated to be a potent booster against current and emerging SARS-CoV-2 variants. One-Sentence Summary UB-612 booster induced broadly neutralizing antibodies against Omicron and is presumed to be protective against COVID-19.

2.
Preprint in English | bioRxiv | ID: ppbiorxiv-484436

ABSTRACT

The highly transmissible Omicron variant has caused high rates of breakthrough infections among vaccinated and convalescent individuals. Here, we demonstrate that a booster dose of UB-612 vaccine candidate delivered 7-9 months after primary vaccination increases neutralizing antibody levels by 131-, 61- and 49-fold against ancestral SARS-CoV-2, Omicron BA.1 and BA.2 variants, respectively. Based on the RBD protein binding antibody responses, we estimated a [~]95% efficacy against symptomatic COVID-19 caused by the ancestral strain after a UB-612 booster. Our results support UB-612 vaccine as a potent booster against current and emerging SARS-CoV-2 variants.

3.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-328391

ABSTRACT

This article was migrated. The article was marked as recommended. Background: Healthcare professionals are playing an important role in the recent COVID-19 outbreak. It is crucial that the health systems maintain their ability to train students and residents during this time. However, there is a paucity of literature on the measures taken by higher education institutions to ensure academic continuity. The aim of this article is to share the systematic measures that were taken during the COVID-19 pandemic by Yong Loo Lin School of Medicine, National University of Singapore. Methods: We discussed our multi-faceted approach to protect students, staff and patients/ standardized patients during the COVID-19 outbreak that occurred during a pivotal time in the school's academic calendar. Results: Our approach to ensuring academic continuity and quality were based on best practices in the following areas: 1) A coordinated leadership and management process 2) Prioritising safety for all stakeholders 3) Dissemination of information amongst the stakeholders in a transparent and efficient way, and 4) Maintaining the rigour and quality of training. Conclusion: The initiatives were implemented as we leveraged on the available infrastructure and the collective team efforts of all involved. Further research will be done to evaluate the usefulness of these measures. We hope that this article would be a useful reference for other schools as they evaluate their pandemic preparedness in the event that the COVID-19 outbreak affects their country or similar crisis event in the future.

4.
Postgrad Med ; 134(2): 224-229, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1612255

ABSTRACT

AIM: The COVID-19 pandemic has disrupted the delivery of healthcare to vulnerable older adults, prompting the expansion of telemedicine usage. This study surveyed the acceptance of virtual medical consultations among older adults and caregivers within geriatric outpatient services in a tertiary hospital during the pandemic. METHODS: A cross-sectional survey was conducted among caregivers and patients attending geriatric outpatient services in Kuala Lumpur, Malaysia. The survey measured the availability of equipment for virtual consultations, prior knowledge and experience of telemedicine, and willingness to consult geriatricians through virtual technology, using the Unified Theory of Acceptance and Use of Technology (UTAUT) scale. RESULTS: A total of 197 caregivers and 42 older patients with a mean age of 54.28 (±13.22) and 75.62 (±7.32) years, respectively, completed the survey. One hundred and fifty-six (79.2%) of the caregivers were adult children accompanying patients. The mean UTAUT score was 65.97 (±13.71) out of 90, with 66.64 (±13.25) for caregivers and 62.79 (±15.44) for older adults, suggesting a high acceptance of adopting virtual consultations in lieu of face-to-face care. The independent predictors of acceptance of virtual consultation were : possession of an electronic device capable of video-communication, living with someone, living in a care home, weekly online banking usage, and perceived familiarity with virtual platforms. CONCLUSION: Caregivers and patients indicated a high level of acceptance of virtual medical consultations, which is likely facilitated by caregivers such as adult children or spouses at home or staff in care homes. To minimize the transmission of COVID-19 in a highly vulnerable group, virtual consultations are an acceptable alternative to face-to-face consultations for older people and their caregivers in our setting.


Subject(s)
COVID-19 , Telemedicine , Aged , COVID-19/epidemiology , Caregivers , Child , Cross-Sectional Studies , Humans , Malaysia/epidemiology , Middle Aged , Pandemics , Pilot Projects , Referral and Consultation , SARS-CoV-2
5.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-291772

ABSTRACT

SARS-CoV-2 breakthrough infection occurs due to waning immunity time-to-vaccine, to which the globally-dominant, highly-contagious Delta variant is behind the scene. In the primary 2-dose and booster series of clinical Phase-1 trial, UB-612 vaccine, which contains S1-RBD and synthetic Th/CTL peptide pool for activation of humoral and T-cell immunity, induces substantial, prolonged viral-neutralizing antibodies that goes parallel with a long-lasting T-cell immunity;and a booster (3rd ) dose can prompt recall of memory immunity to induce profound, striking antibodies with the highest level of 50% viral-neutralizing GMT titers against live Delta variant reported for any vaccine. The unique design of S1-RBD only plus multitope T-cell peptides may have underpinned UB-612’s potent anti-Delta effect, while the other full S protein-based vaccines are affected additionally by mutations in the N-terminal domain sequence which contains additional neutralizing epitopes. UB-612, safe and well-tolerated, could be effective for boosting other vaccine platforms that have shown modest homologous boosting. [Funded by United Biomedical Inc., Asia;ClinicalTrials.gov ID: NCT04967742 and NCT04545749]

6.
Health Econ Rev ; 11(1): 25, 2021 Jul 06.
Article in English | MEDLINE | ID: covidwho-1344122

ABSTRACT

BACKGROUND AND OBJECTIVE: The COVID-19 pandemic started in Wuhan, China, in December 2019. Although there are some doubts about the reporting of cases and deaths in China, it seems that this country was able to control the epidemic more effectively than many other countries. In this paper, we would like to analyze the measures taken in China and compare them with other countries in order to find out what they can learn from China. METHODS: We develop a system dynamics model of the COVID-19 pandemic in Wuhan. Based on a number of simulations we analyze the impact of changing parameters, such as contact rates, on the development of a second wave. RESULTS: Although China's health care system seems to be poorly financed and inefficient, the epidemic was brought under control in a comparably short period of time and no second wave was experienced in Wuhan until today. The measures to contain the epidemic do not differ from what was implemented in other countries, but China applied them very early and rigorously. For instance, the consequent implementation of health codes and contact-tracking technology contributed to contain the disease and effectively prevented the second and third waves. CONCLUSIONS: China's success in fighting COVID-19 is based on a very strict implementation of a set of measures, including digital management. While other countries discuss relaxing the lock-down at a rate of 50 per 100,000 inhabitants, China started local lock-downs at a rate of 3 per 100,000. We call for a public debate whether this policy would be feasible for more liberal countries as well.

7.
Nat Metab ; 3(7): 909-922, 2021 07.
Article in English | MEDLINE | ID: covidwho-1279905

ABSTRACT

Exosomes represent a subtype of extracellular vesicle that is released through retrograde transport and fusion of multivesicular bodies with the plasma membrane1. Although no perfect methodologies currently exist for the high-throughput, unbiased isolation of pure plasma exosomes2,3, investigation of exosome-enriched plasma fractions of extracellular vesicles can confer a glimpse into the endocytic pathway on a systems level. Here we conduct high-coverage lipidomics with an emphasis on sterols and oxysterols, and proteomic analyses of exosome-enriched extracellular vesicles (EVs hereafter) from patients at different temporal stages of COVID-19, including the presymptomatic, hyperinflammatory, resolution and convalescent phases. Our study highlights dysregulated raft lipid metabolism that underlies changes in EV lipid membrane anisotropy that alter the exosomal localization of presenilin-1 (PS-1) in the hyperinflammatory phase. We also show in vitro that EVs from different temporal phases trigger distinct metabolic and transcriptional responses in recipient cells, including in alveolar epithelial cells, which denote the primary site of infection, and liver hepatocytes, which represent a distal secondary site. In comparison to the hyperinflammatory phase, EVs from the resolution phase induce opposing effects on eukaryotic translation and Notch signalling. Our results provide insights into cellular lipid metabolism and inter-tissue crosstalk at different stages of COVID-19 and are a resource to increase our understanding of metabolic dysregulation in COVID-19.


Subject(s)
COVID-19/metabolism , COVID-19/virology , Extracellular Vesicles/metabolism , Lipidomics , Metabolomics , SARS-CoV-2 , Biological Transport , COVID-19/epidemiology , Cell Fractionation , Cell Membrane/metabolism , Chemical Fractionation , Cluster Analysis , Computational Biology/methods , Exosomes/metabolism , Host-Pathogen Interactions , Humans , Lipidomics/methods , Metabolome , Metabolomics/methods , Retrospective Studies , SARS-CoV-2/genetics , SARS-CoV-2/immunology
8.
Preprint in English | bioRxiv | ID: ppbiorxiv-399154

ABSTRACT

A novel multitope protein-peptide vaccine against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and disease is described in this report. The initial development and characterization experiments are presented along with proof-of-concept studies for the vaccine candidate UB-612. UB-612 consists of eight components rationally designed for induction of potently neutralizing antibodies and broad T cell responses against SARS-CoV-2: the S1-RBD-sFc fusion protein, six synthetic peptides (one universal peptide and five SARS-CoV-2-derived peptides), a proprietary CpG TLR-9 agonist at low concentration as an excipient, and aluminum phosphate adjuvant. Through immunogenicity studies in Guinea pigs and rats, we optimized the design of protein/peptide immunogens and selected an adjuvant system, yielding a vaccine that provides excellent S1-RBD binding and high neutralizing antibody responses, robust cellular responses, and a Th1-oriented response at low doses. In challenge studies, UB- 612 vaccination reduced viral load and prevented development of disease in mouse and non-human primate challenge models. With a Phase 1 trial completed, a Phase 2 trial ongoing in Taiwan, and additional trials planned to support global authorizations, UB-612 is a highly promising and differentiated vaccine candidate for prevention of SARS-CoV-2 infection and COVID-19 disease. Author SummarySARS-CoV-2 virus, the causative agent of Coronavirus Disease 2019 (COVID-19), has spread globally since its origin in 2019, causing an unprecedented public health crisis that has resulted in greater than 4.7 million deaths worldwide. Many vaccines are under development to limit disease spread and reduce the number of cases, but additional candidates that promote a robust immune response are needed. Here, we describe a multitope protein-peptide vaccine platform that is unique among COVID-19 vaccines. The advantages of our approach are induction of both high levels of neutralizing antibodies as well as a Th/CTL response in the vaccinated host, which mimics the immune response that occurs after natural infection with SARS-CoV-2. We demonstrate that our vaccine is immunogenic and effective in preventing disease in several animal models, including AAV- hACE-2 transduced mice, and both rhesus and cynomolgus macaques. Importantly, no immunopathology was observed in the lungs of immunized animals, therefore showing that antibody-dependent enhancement (ADE) does not occur. Our study provides an additional, novel vaccine candidate for advancement in clinical trials to treat and prevent SARS-CoV-2 infection and COVID-19 disease.

10.
Preprint in English | medRxiv | ID: ppmedrxiv-20072611

ABSTRACT

BackgroundPatients with pre-existing cirrhosis are considered at increased risk of severe coronavirus disease 2019 (COVID-19) but the clinical course in these patients has not yet been reported. This study aimed to provide a detailed report of the clinical characteristics and outcomes among COVID-19 patients with pre-existing cirrhosis. MethodsIn this retrospective, multicenter cohort study, we consecutively included all adult inpatients with laboratory-confirmed COVID-19 and pre-existing cirrhosis that had been discharged or had died by 24 March 2020 from 16 designated hospitals in China. Demographic, clinical, laboratory and radiographic findings on admission, treatment, complications during hospitalization and clinical outcomes were collected and compared between survivors and non-survivors. FindingsTwenty-one patients were included consecutively in this study, of whom 16 were cured and 5 died in hospital. Seventeen patients had compensated cirrhosis and hepatitis B virus infection was the most common etiology. Lymphocyte and platelet counts were lower, and direct bilirubin levels were higher in patients who died than those who survived (p= 0{middle dot}040, 0{middle dot}032, and 0{middle dot}006, respectively). Acute respiratory distress syndrome and secondary infection were both the most frequently observed complications. Only one patient developed acute on chronic liver failure. Of the 5 non-survivors, all patients developed acute respiratory distress syndrome and 2 patients progressed to multiple organ dysfunction syndrome. InterpretationLower lymphocyte and platelet counts, and higher direct bilirubin level might represent poor prognostic indicators in SARS-CoV-2-infected patients with pre-existing cirrhosis.

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