microneedle covid
222136108
Reducing False Negatives in COVID 19 Testing by Using Microneedle Based Oropharyngeal Swabs
Coronavirus disease 2019 (COVID 19) has become a severe threat to human health worldwide. Early etiological diagnosis plays a critical role in controlling COVID 19 pandemic. However, etiological diagnosis has been largely compromised by high "false negative" rates of viral nucleic acid testing, resulting from limited sampling efficiency using conventional oropharyngeal swabs. Herein, we engineer regular swabs by using a microneedle (MN) patch to significantly improve the quality and quantity of virus collection. The combination of MNs with different crosslinking levels endows the patches with dual capability of mucus penetration and virus extraction. Moreover, the antibody (Ab) against viral spike protein was integrated into the patch, conferring MNs with an active virus capture potential. By taking advantage of the biological and engineered species, it is believed the designed MN/Ab swabs could serve as a promising tool to improve current sampling efficiency with less "false negatives" contributing to the containment of COVID 19 pandemic.
Matter
Wei Chen Bo Cai Zhi Geng Fenghua Chen Zaoxia Wang Lemin Wang Xiaoyu Chen
225512026
Evaluation of Microneedle Drug Delivery System and Nanoparticles Use in COVID 19 Patients
Ahmed Ma
228942240
Microneedle: Teknologi Baru Penghantar Vaksin COVID 19
Wabah COVID 19 telah menyebar lebih dari 200 negara dan menjadi perhatian kesehatan di seluruh dunia. SARS CoV 2 adalah virus penyebab COVID 19 berasal dari keluarga coronaviridae. Virus tersebut memiliki kesamaan genom dengan SARS CoV dan MERS CoV. Vaksinasi merupakan cara yang paling efektif untuk mencegah pernyebaran virus COVID 19. Sebagian besar pemberian vaksin menggunakan jarum konvensional, jarum hipodermik, yang tidak bisa digunakan dengan mudah oleh pasien. Selain itu, penggunaan jarum hipodermik dapat menimbulkan rasa sakit. Maka, jarum dibentuk dengan ukuran mikron, sehingga penetrasinya tidak mencapai ujung saraf yang peka terhadap nyeri. Microneedle dapat digunakan sendiri tanpa rasa sakit dan melalui mekanisme stress mekanikal dari microneedle dapat digunakan sebagai adjuvant dalam meningkatkan respon imun. Microneedle merupakan teknologi vaksinasi baru yang aman dan memberikan kekebalan protektif terhadap serangan virus COVID 19. Termostabil yang diberikan oleh microneedle dapat mengurangi penggunaan pendingin, sehingga mengurangi biaya produksi dan meningkatkan kemudahan dalam pendistribusiannya. Berdasarkan fitur fitur tersebut, microneedle memiliki potensi untuk digunakan sebagai penghantar vaksin yang efektif dalam mencegah penyebaran virus COVID 19.
Amilia Shafa Sriwidodo Sriwidodo
214757099
Microneedle array delivered recombinant coronavirus vaccines: Immunogenicity and rapid translational development
Abstract Background Coronaviruses pose a serious threat to global health as evidenced by Severe Acute Respiratory Syndrome (SARS) Middle East Respiratory Syndrome (MERS) and COVID 19. SARS Coronavirus (SARS CoV) MERS Coronavirus (MERS CoV) and the novel coronavirus, previously dubbed 2019 nCoV, and now officially named SARS CoV 2, are the causative agents of the SARS, MERS, and COVID 19 disease outbreaks, respectively. Safe vaccines that rapidly induce potent and long lasting virus specific immune responses against these infectious agents are urgently needed. The coronavirus spike (S) protein, a characteristic structural component of the viral envelope, is considered a key target for vaccines for the prevention of coronavirus infection. Methods We first generated codon optimized MERS S1 subunit vaccines fused with a foldon trimerization domain to mimic the native viral structure. In variant constructs, we engineered immune stimulants (RS09 or flagellin, as TLR4 or TLR5 agonists, respectively) into this trimeric design. We comprehensively tested the pre clinical immunogenicity of MERS CoV vaccines in mice when delivered subcutaneously by traditional needle injection, or intracutaneously by dissolving microneedle arrays (MNAs) by evaluating virus specific IgG antibodies in the serum of vaccinated mice by ELISA and using virus neutralization assays. Driven by the urgent need for COVID 19 vaccines, we utilized this strategy to rapidly develop MNA SARS CoV 2 subunit vaccines and tested their pre clinical immunogenicity in vivo by exploiting our substantial experience with MNA MERS CoV vaccines. Findings Here we describe the development of MNA delivered MERS CoV vaccines and their pre clinical immunogenicity. Specifically, MNA delivered MERS S1 subunit vaccines elicited strong and long lasting antigen specific antibody responses. Building on our ongoing efforts to develop MERS CoV vaccines, promising immunogenicity of MNA delivered MERS CoV vaccines, and our experience with MNA fabrication and delivery, including clinical trials, we rapidly designed and produced clinically translatable MNA SARS CoV 2 subunit vaccines within 4 weeks of the identification of the SARS CoV 2 S1 sequence. Most importantly, these MNA delivered SARS CoV 2 S1 subunit vaccines elicited potent antigen specific antibody responses that were evident beginning 2 weeks after immunization. Interpretation MNA delivery of coronaviruses S1 subunit vaccines is a promising immunization strategy against coronavirus infection. Progressive scientific and technological efforts enable quicker responses to emerging pandemics. Our ongoing efforts to develop MNA MERS S1 subunit vaccines enabled us to rapidly design and produce MNA SARS CoV 2 subunit vaccines capable of inducing potent virus specific antibody responses. Collectively, our results support the clinical development of MNA delivered recombinant protein subunit vaccines against SARS, MERS, COVID 19, and other emerging infectious diseases.
EBioMedicine
Eun Kim Geza Erdos Shaohua Huang Thomas W Kenniston Stephen C Balmert Cara Donahue Carey V Stalin Raj Michael Epperly William B Klimstra Bart L Haagmans Emrullah Korkmaz Louis D Falo Andrea A Gambotto
221140547
Mass vaccination against COVID 19 may require replays of the polio vaccination drives
The Global Polio Eradication Initiative (GPEI) was built on the wisdom gained from smallpox eradication programs [1] In 1980s, polio used to cause paralysis of >1000 children daily but since then GPEI has achieved >99% reduction in polio. Surges in SARS CoV 2 infections have catalysed numerous vaccine development projects. However, deployment of an efficacious COVID 19 vaccine will need resolution of several notable issues on which preparatory analysis must be initiated now. Risk groups including the elderly, those with co morbidities and healthcare workers may be prioritized. Widening the vaccine target groups will increase supply chain burden. As COVID 19 vaccination window may be short, there will be added pressure on supply chains. Dosages (single versus multiple) and routes of administration will have direct consequences for costs and logistics. Route(s) of administration including injectable, intranasal, microneedle array patches, next generation jet injectors, oral tablets or sublingual oral gels would necessitate additional training of healthcare workers [2] Robust epidemiological estimates of herd immunity will be required to optimize population coverage, though individual protection for target groups will remain pivotal. Indeed, high vaccine coverage may be targeted to ablate reservoirs of infection. Since 2000, the Expanded Programmes on Immunizations have grown their antigen spectrum from six to a dozen for vaccine delivery [3] This formidable portfolio will need to cater to COVID 19 vaccine too. The additional challenges will include maintenance of cold chains, risks of imbalanced stocking, stocking of PPEs, back ups for logistical burnouts, optimization of transport capacities, and the urgent need to establish electronic surveillance [4] Despite prioritization for high risk groups, there would be additional costs of price per dose, vaccine devices, storage, transport and labour. Given the requirements for large demographic coverage, each country can expect egregious financial burden with the potential to adversely
EClinicalMedicine
Manju Rahi Amit Sharma
231714504
Low adenovirus vaccine doses administered to skin using microneedle patches induce better functional antibody immunogenicity as compared to systemic injection
Adenovirus based vaccines are demonstrating promising clinical potential for multiple infectious diseases including COVID 19. However the immunogenicity of the vector itself decreases its effectiveness as a boosting vaccine due to the induction of strong anti vector neutralising immunity. Here we determined how dissolvable microneedle patches (DMN) for skin immunization can overcome this issue, using a clinically relevant adenovirus based Plasmodium falciparum malaria vaccine, AdHu5 PfRH5, in mice. Incorporation of vaccine into patches significantly enhanced its thermostability compared to the liquid form. Conventional high dose repeated immunization by the intramuscular (IM) route induced low antigen specific IgG titres and high anti vector immunity. A low priming dose of vaccine, by the IM route but more so using DMN patches, induced the most efficacious immune responses, assessed by parasite growth inhibitory activity (GIA) assays. Administration of low dose AdHu5 PfRH5 using patches to the skin, boosted by high dose IM, induced the highest antigen specific serum IgG response after boosting, the greatest skewing of the antibody response towards the antigen and away from the vector and the highest efficacy. This study therefore demonstrates that repeated use of the same adenovirus vaccine can be highly immunogenic towards the transgene if a low dose is used to prime the response. It also provides a method of stabilising adenovirus vaccine, in easy to administer dissolvable microneedle patches, permitting storage and distribution out of cold chain.
Olivia Flynn Kate Dillane Juliane Sousa Lanza Jennifer M Marshall Jing Jin Sarah E Silk Simon J Draper Anne C Moore
225568890
The diagnostic potential of microneedles in infectious diseases
The coronavirus disease 2019 (COVID 19) pandemic has taught us much about our weaknesses in the management of infectious disease outbreaks. A key lesson has been the need for more effective point of care diagnostic tools that not only produce rapid and reliable results, but also facilitate decentralised testing to avoid overwhelming central test facilities when demand peaks in an outbreak. Microneedle devices can be inserted painlessly into the skin to detect biomolecules in the epidermal and dermal layers. They have been used to detect biomarkers both in the interstitial fluid and the capillary blood. Importantly, they are amenable to self administration. In this article, we provide an overview of existing microneedle based diagnostic technologies and discuss how they may be built upon to provide effective diagnostic tools for infectious diseases in general.
Rachael V Dixon Wing Man Lau Seyed Moein Moghimi Keng Wooi Ng
212656559
Clinical course and risk factors for mortality of adult inpatients with COVID 19 in Wuhan, China: a retrospective cohort study
Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID 19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS CoV 2) Epidemiological and clinical characteristics of patients with COVID 19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients =18 years old) with laboratory confirmed COVID 19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48% patients had a comorbidity, with hypertension being the most common (58 [30% patients) followed by diabetes (36 [19% patients) and coronary heart disease (15 [8% patients) Multivariable regression showed increasing odds of in hospital death associated with older age (odds ratio 1*10, 95% CI 1*03 1*17, per year increase; p=0*0043) higher Sequential Organ Failure Assessment (SOFA) score (5*65, 2*61 12*23; p<0*0001) and d dimer greater than 1 mg/mL (18*42, 2*64 128*55; p=0*0033) on admission. Median duration of viral shedding was 20*0 days (IQR 17*0 24*0) in survivors, but SARS CoV 2 was detectable until death in non survivors. The longest observed duration of viral shedding in survivors was 37 days. Interpretation The potential risk factors of older age, high SOFA score, and d dimer greater than 1 mg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.
The Lancet
Fei Zhou Ting Yu Ronghui Du Guohui Fan Ying Liu Zhibo Liu Jie Xiang Ye-ming Wang Bin Song Xiaoying Gu Lulu Guan Yuan Wei Hui Li Xudong Wu Jiuyang Xu Shengjin Tu Yi Zhang Hua Chen Bin Cao
211262395
Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID 19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention.
Background: Hospitalised COVID 19 patients are frequently elderly subjects with co morbidities receiving polypharmacy, all of which are known risk factors for d
JAMA
Zunyou Wu Jennifer M McGoogan
211245138
Pathological findings of COVID 19 associated with acute respiratory distress syndrome
bPortuguese Abstract:O surto do novo coronavArus (COVID 19) em Wuhan, China, iniciado em dezembro de 2019, evoluiu para se tornar uma pandemia global A
The Lancet Respiratory Medicine
Zhe Xu Lei Shi Yijin Wang Jiyuan Zhang Lei Huang Chao Zhang Shuhong Liu Peng Zhao Hongxia Liu Li Zhu Yanhong Tai Changqing Bai Tingting Gao Jinwen Song Peng Xia Jinghui Dong Jingmin Zhao Fu-Sheng Wang