Vaccine development for emerging infectious diseases.
TL;DR: The authors examined the vaccine strategies and technical platforms used for the COVID-19 pandemic in the context of those used for previous emerging and reemerging infectious diseases and pandemics may offer some mutually beneficial lessons.
Abstract: Examination of the vaccine strategies and technical platforms used for the COVID-19 pandemic in the context of those used for previous emerging and reemerging infectious diseases and pandemics may offer some mutually beneficial lessons. The unprecedented scale and rapidity of dissemination of recent emerging infectious diseases pose new challenges for vaccine developers, regulators, health authorities and political constituencies. Vaccine manufacturing and distribution are complex and challenging. While speed is essential, clinical development to emergency use authorization and licensure, pharmacovigilance of vaccine safety and surveillance of virus variants are also critical. Access to vaccines and vaccination needs to be prioritized in low- and middle-income countries. The combination of these factors will weigh heavily on the ultimate success of efforts to bring the current and any future emerging infectious disease pandemics to a close.
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TL;DR: In this paper, the authors present a comprehensive synthesis of evidence regarding the value and impact of nudges to address vaccine hesitancy (VH) and the global decline of vaccine coverage are a major global health threat and novel approaches for increasing vaccine confidence and uptake are urgently needed.
Abstract: Background Vaccine hesitancy (VH) and the global decline of vaccine coverage are a major global health threat, and novel approaches for increasing vaccine confidence and uptake are urgently needed. ‘Nudging’, defined as altering the environmental context in which a decision is made or a certain behaviour is enacted, has shown promising results in several health promotion strategies. We present a comprehensive synthesis of evidence regarding the value and impact of nudges to address VH. Methods We conducted a systematic review to determine if nudging can mitigate VH and improve vaccine uptake. Our search strategy used Medical Subject Headings (MeSH) and non-MeSH terms to identify articles related to nudging and vaccination in nine research databases. 15 177 titles were extracted and assessed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The final list of included articles was evaluated using the Mixed Methods Appraisal Tool and the Grading of Recommendations, Assessment, Development and Evaluations framework. Findings Identified interventions are presented according to a framework for behaviour change, MINDSPACE. Articles (n=48) from 10 primarily high-income countries were included in the review. Nudging-based interventions identified include using reminders and recall, changing the way information is framed and delivered to an intended audience, changing the messenger delivering information, invoking social norms and emotional affect (eg, through storytelling, dramatic narratives and graphical presentations), and offering incentives or changing defaults. The most promising evidence exists for nudges that offer incentives to parents and healthcare workers, that make information more salient or that use trusted messengers to deliver information. The effectiveness of nudging interventions and the direction of the effect varies substantially by context. Evidence for some approaches is mixed, highlighting a need for further research, including how successful interventions can be adapted across settings. Conclusion Nudging-based interventions show potential to increase vaccine confidence and uptake, but further evidence is needed for the development of clear recommendations. The ongoing COVID-19 pandemic increases the urgency of undertaking nudging-focused research. PROSPERO registration number CRD42020185817.
52 citations
TL;DR: In this article, the authors outline the hypotheses on the mechanisms behind the very rare thrombotic thromboembolic reactions reported after the COVID-19 vaccination, along with currently existing evidence and future research prospects.
50 citations
01 Feb 2022
TL;DR: A phase I first-in-human dose-ranging trial of a saRNA COVID-19 vaccine candidate LNP-nCoVsaRNA, was conducted at Imperial Clinical Research Facility, and participating centres in London, UK, between 19th June to 28th October 2020 as mentioned in this paper .
Abstract: Lipid nanoparticle (LNP) encapsulated self-amplifying RNA (saRNA) is a novel technology formulated as a low dose vaccine against COVID-19.A phase I first-in-human dose-ranging trial of a saRNA COVID-19 vaccine candidate LNP-nCoVsaRNA, was conducted at Imperial Clinical Research Facility, and participating centres in London, UK, between 19th June to 28th October 2020. Participants received two intramuscular (IM) injections of LNP-nCoVsaRNA at six different dose levels, 0.1-10.0μg, given four weeks apart. An open-label dose escalation was followed by a dose evaluation. Solicited adverse events (AEs) were collected for one week from enrolment, with follow-up at regular intervals (1-8 weeks). The binding and neutralisation capacity of anti-SARS-CoV-2 antibody raised in participant sera was measured by means of an anti-Spike (S) IgG ELISA, immunoblot, SARS-CoV-2 pseudoneutralisation and wild type neutralisation assays. (The trial is registered: ISRCTN17072692, EudraCT 2020-001646-20).192 healthy individuals with no history or serological evidence of COVID-19, aged 18-45 years were enrolled. The vaccine was well tolerated with no serious adverse events related to vaccination. Seroconversion at week six whether measured by ELISA or immunoblot was related to dose (both p<0.001), ranging from 8% (3/39; 0.1μg) to 61% (14/23; 10.0μg) in ELISA and 46% (18/39; 0.3μg) to 87% (20/23; 5.0μg and 10.0μg) in a post-hoc immunoblot assay. Geometric mean (GM) anti-S IgG concentrations ranged from 74 (95% CI, 45-119) at 0.1μg to 1023 (468-2236) ng/mL at 5.0μg (p<0.001) and was not higher at 10.0μg. Neutralisation of SARS-CoV-2 by participant sera was measurable in 15% (6/39; 0.1μg) to 48% (11/23; 5.0μg) depending on dose level received.Encapsulated saRNA is safe for clinical development, is immunogenic at low dose levels but failed to induce 100% seroconversion. Modifications to optimise humoral responses are required to realise its potential as an effective vaccine against SARS-CoV-2.This study was co-funded by grants and gifts from the Medical Research Council UKRI (MC_PC_19076), and the National Institute Health Research/Vaccine Task Force, Partners of Citadel and Citadel Securities, Sir Joseph Hotung Charitable Settlement, Jon Moulton Charity Trust, Pierre Andurand, Restore the Earth.
49 citations
TL;DR: Determinant factors found in this study are critical and should be considered as essential elements in developing COVID-19 vaccination campaigns to boost vaccination uptake in the populations.
Abstract: Background Mass vaccination campaigns have significantly reduced the COVID-19 burden. However, vaccine hesitancy has posed significant global concerns. The purpose of this study was to determine the characteristics that influence perceptions of COVID-19 vaccine efficacy, acceptability, hesitancy and decision making to take vaccine among general adult populations in a variety of socioeconomic and cultural contexts. Methods Using a snowball sampling approach, we conducted an online cross-sectional study in 20 countries across four continents from February to May 2021. Results A total of 10,477 participants were included in the analyses with a mean age of 36±14.3 years. The findings revealed the prevalence of perceptions towards COVID-19 vaccine’s effectiveness (78.8%), acceptance (81.8%), hesitancy (47.2%), and drivers of vaccination decision-making (convenience [73.3%], health providers’ advice [81.8%], and costs [57.0%]). The county-wise distribution included effectiveness (67.8–95.9%; 67.8% in Egypt to 95.9% in Malaysia), acceptance (64.7–96.0%; 64.7% in Australia to 96.0% in Malaysia), hesitancy (31.5–86.0%; 31.5% in Egypt to 86.0% in Vietnam), convenience (49.7–95.7%; 49.7% in Austria to 95.7% in Malaysia), advice (66.1–97.3%; 66.1% in Austria to 97.3% in Malaysia), and costs (16.0–91.3%; 16.0% in Vietnam to 91.3% in Malaysia). In multivariable regression analysis, several socio-demographic characteristics were identified as associated factors of outcome variables including, i) vaccine effectiveness: younger age, male, urban residence, higher education, and higher income; ii) acceptance: younger age, male, urban residence, higher education, married, and higher income; and iii) hesitancy: male, higher education, employed, unmarried, and lower income. Likewise, the factors associated with vaccination decision-making including i) convenience: younger age, urban residence, higher education, married, and lower income; ii) advice: younger age, urban residence, higher education, unemployed/student, married, and medium income; and iii) costs: younger age, higher education, unemployed/student, and lower income. Conclusions Most participants believed that vaccination would effectively control and prevent COVID-19, and they would take vaccinations upon availability. Determinant factors found in this study are critical and should be considered as essential elements in developing COVID-19 vaccination campaigns to boost vaccination uptake in the populations.
40 citations
TL;DR: In this article, the authors assessed the psychological antecedents associated with COVID-19 vaccination in the Arab population and found that around 26.7% of the participants were found to be confident about the vaccination, 10.5% indicated no constraints, 48.8% had a preference for calculation and 40.4% indicated collective responsibility.
Abstract: Background Following the emergency approval of the coronavirus disease 2019 (COVID-19) vaccines, research into its vaccination hesitancy saw a substantial increase. However, the psychological behaviors associated with this hesitancy are still not completely understood. This study assessed the psychological antecedents associated with COVID-19 vaccination in the Arab population. Methodology The validated Arabic version of the 5C questionnaire was distributed online across various social media platforms in Arabic-speaking countries. The questionnaire had three sections, namely, socio-demographics, COVID-19 related infection and vaccination, and the 5C scale of vaccine psychological antecedents of confidence, complacency, constraints, calculation, and collective responsibility. Results In total, 4,474 participants with a mean age of 32.48 ± 10.76 from 13 Arab countries made up the final sample, 40.8% of whom were male. Around 26.7% of the participants were found to be confident about the COVID-19 vaccination, 10.7% indicated complacency, 96.5% indicated they had no constraints, 48.8% had a preference for calculation and 40.4% indicated they had collective responsibility. The 5C antecedents varied across the studied countries with the confidence and collective responsibility being the highest in the United Arab Emirates (59.0% and 58.0%, respectively), complacency and constraints in Morocco (21.0% and 7.0%, respectively) and calculation in Sudan (60.0%). The regression analyses revealed that sex, age, educational degrees, being a health care professional, history of COVID-19 infection and having a relative infected or died from COVID-19 significantly predicted the 5C psychological antecedents by different degrees. Conclusion There are wide psychological antecedent variations between Arab countries, and different determinants can have a profound effect on the COVID-19 vaccine's psychological antecedents.
33 citations
References
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TL;DR: The epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of patients with laboratory-confirmed 2019-nCoV infection in Wuhan, China, were reported.
36,578 citations
TL;DR: Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily, which is the seventh member of the family of coronaviruses that infect humans.
Abstract: In December 2019, a cluster of patients with pneumonia of unknown cause was linked to a seafood wholesale market in Wuhan, China. A previously unknown betacoronavirus was discovered through the use of unbiased sequencing in samples from patients with pneumonia. Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily. Different from both MERS-CoV and SARS-CoV, 2019-nCoV is the seventh member of the family of coronaviruses that infect humans. Enhanced surveillance and further investigation are ongoing. (Funded by the National Key Research and Development Program of China and the National Major Project for Control and Prevention of Infectious Disease in China.).
21,455 citations
TL;DR: The epidemiological and clinical characteristics of novel coronavirus (2019-nCoV)-infected pneumonia in Wuhan, China, and hospital-associated transmission as the presumed mechanism of infection for affected health professionals and hospitalized patients are described.
Abstract: Importance In December 2019, novel coronavirus (2019-nCoV)–infected pneumonia (NCIP) occurred in Wuhan, China. The number of cases has increased rapidly but information on the clinical characteristics of affected patients is limited. Objective To describe the epidemiological and clinical characteristics of NCIP. Design, Setting, and Participants Retrospective, single-center case series of the 138 consecutive hospitalized patients with confirmed NCIP at Zhongnan Hospital of Wuhan University in Wuhan, China, from January 1 to January 28, 2020; final date of follow-up was February 3, 2020. Exposures Documented NCIP. Main Outcomes and Measures Epidemiological, demographic, clinical, laboratory, radiological, and treatment data were collected and analyzed. Outcomes of critically ill patients and noncritically ill patients were compared. Presumed hospital-related transmission was suspected if a cluster of health professionals or hospitalized patients in the same wards became infected and a possible source of infection could be tracked. Results Of 138 hospitalized patients with NCIP, the median age was 56 years (interquartile range, 42-68; range, 22-92 years) and 75 (54.3%) were men. Hospital-associated transmission was suspected as the presumed mechanism of infection for affected health professionals (40 [29%]) and hospitalized patients (17 [12.3%]). Common symptoms included fever (136 [98.6%]), fatigue (96 [69.6%]), and dry cough (82 [59.4%]). Lymphopenia (lymphocyte count, 0.8 × 109/L [interquartile range {IQR}, 0.6-1.1]) occurred in 97 patients (70.3%), prolonged prothrombin time (13.0 seconds [IQR, 12.3-13.7]) in 80 patients (58%), and elevated lactate dehydrogenase (261 U/L [IQR, 182-403]) in 55 patients (39.9%). Chest computed tomographic scans showed bilateral patchy shadows or ground glass opacity in the lungs of all patients. Most patients received antiviral therapy (oseltamivir, 124 [89.9%]), and many received antibacterial therapy (moxifloxacin, 89 [64.4%]; ceftriaxone, 34 [24.6%]; azithromycin, 25 [18.1%]) and glucocorticoid therapy (62 [44.9%]). Thirty-six patients (26.1%) were transferred to the intensive care unit (ICU) because of complications, including acute respiratory distress syndrome (22 [61.1%]), arrhythmia (16 [44.4%]), and shock (11 [30.6%]). The median time from first symptom to dyspnea was 5.0 days, to hospital admission was 7.0 days, and to ARDS was 8.0 days. Patients treated in the ICU (n = 36), compared with patients not treated in the ICU (n = 102), were older (median age, 66 years vs 51 years), were more likely to have underlying comorbidities (26 [72.2%] vs 38 [37.3%]), and were more likely to have dyspnea (23 [63.9%] vs 20 [19.6%]), and anorexia (24 [66.7%] vs 31 [30.4%]). Of the 36 cases in the ICU, 4 (11.1%) received high-flow oxygen therapy, 15 (41.7%) received noninvasive ventilation, and 17 (47.2%) received invasive ventilation (4 were switched to extracorporeal membrane oxygenation). As of February 3, 47 patients (34.1%) were discharged and 6 died (overall mortality, 4.3%), but the remaining patients are still hospitalized. Among those discharged alive (n = 47), the median hospital stay was 10 days (IQR, 7.0-14.0). Conclusions and Relevance In this single-center case series of 138 hospitalized patients with confirmed NCIP in Wuhan, China, presumed hospital-related transmission of 2019-nCoV was suspected in 41% of patients, 26% of patients received ICU care, and mortality was 4.3%.
16,635 citations
TL;DR: A two-dose regimen of BNT162b2 conferred 95% protection against Covid-19 in persons 16 years of age or older and safety over a median of 2 months was similar to that of other viral vaccines.
Abstract: Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (Covid-19) have afflicted tens of millions of people in a world...
10,274 citations
TL;DR: A SARS-CoV-2 variant carrying the Spike protein amino acid change D614G has become the most prevalent form in the global pandemic, and it is found that the G614 variant grows to higher titer as pseudotyped virions.
3,302 citations