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1.
J Infect Dis ; 2022 Apr 22.
Article in English | MEDLINE | ID: covidwho-1886443

ABSTRACT

SARS-CoV-2 Variants of Concern (VoCs) negatively impact the effectiveness of vaccines. In this study, we challenge hamsters with the Delta variant after two- or three-dose inoculations with SARS-CoV-2 vaccines constructed from stabilized prefusion spike proteins (S-2P) of Wuhan (W) and Beta (B) variants. Compared to three doses of W S-2P, two doses of W S-2P followed by a third dose of B S-2P induced the highest neutralizing antibody titer against live SARS-CoV-2 virus and enhanced neutralization of Omicron variant pseudovirus. Reduced lung live virus titer and pathology suggested that all vaccination regimens protect hamsters from SARS-CoV-2 Delta variant challenge.

2.
Angewandte Chemie International Edition ; : 1, 2022.
Article in English | Academic Search Complete | ID: covidwho-1825859

ABSTRACT

The dynamic interactions between RNAs and proteins play crucial roles in regulating diverse cellular processes. Proteome‐wide characterization of these interactions in their native cellular context remains desirable but challenging. Herein, we developed a photocatalytic crosslinking (PhotoCAX) strategy coupled with mass spectrometry (PhotoCAX‐MS) and RNA sequencing (PhotoCAX‐seq) for the study of the composition and dynamics of protein‐RNA interactions. By integrating the blue light‐triggered photocatalyst with a dual‐functional RNA–protein crosslinker (RP‐linker) and the phase separation‐based enrichment strategy, PhotoCAX‐MS revealed a total of 2044 RBPs in human HEK293 cells. We further employed PhotoCAX to investigate the dynamic change of RBPome in macrophage cells upon LPS‐stimulation, as well as the identification of RBPs interacting directly with the 5′ untranslated regions of SARS‐CoV‐2 RNA. [ FROM AUTHOR] Copyright of Angewandte Chemie International Edition is the property of John Wiley & Sons, Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

3.
Journal of Translational Critical Care Medicine ; 3(1):1-4, 2021.
Article in English | EuropePMC | ID: covidwho-1824143

ABSTRACT

Background and Objectives: To explore the superiority of flipping-classroom lended learning in which the stay-home e-learning and traditional internship complements each other in resident training of endcorinology during coronavirus disease 2019 restriction period. Materials and Methods: A total of 44 residents were randomized as the study population. In the endocrine-rotation training, we reformed the clinical learning by unified online-teaching led by teachers' combination with individual guidance by residents. Moreover, the final implementation assessment was conducted by standard double-blind examinations. Results: After 4–8 weeks training, the 44 residents were assessed for clinical skills from six dimensions, including medical history collection, physical examination, history report and inpatient record writing, case analysis, and overviewing capability. Compared with the mean scores of 68 residents rotated in internal medicine in 2019, the mean scores on physical examination, inpatient record writing, and overviewing capability in 2020 group were higher with significance ([85.72 ± 8.33] vs.[79.22 ± 10.12], P = 0.0006), ([90.28 ± 10.70] vs. [81.82 ± 8.03], P < 0.0001), ([80.31 ± 8.70] vs. [73.04 ± 12.74], P = 0.0012), whereas scores on skills of medical history collection and history report were slightly lower ([82.11 ± 9.02] vs. [85.06 ± 7.23], P = 0.0586), ([79.30 ± 8.17] vs. [83.21 ± 5.01], P = 0.0022), while scores on case analysis did not show huge gap but with polarized performance in 2020 group ([74.38 ± 10.29] vs. [78.13 ± 8.53], P = 0.0386). Conclusions: Providing the novel pattern of unified online-teaching combined with individual-guidance at the bedside to the front-line residents can reduce the risk of cluster epidemics and effectively ensure the training effect on them but still with shortcomings. The future online teaching reform is better for focus more on how to make up for or reduce the actual problem of disconnection between theory and practice in the process of online clinical skills training for residents and teachers.

4.
Biosci Trends ; 16(1): 4-6, 2022 Mar 11.
Article in English | MEDLINE | ID: covidwho-1705129

ABSTRACT

As the number of people with COVID-19 increases daily around the world, point-of-care testing (POCT) is gaining attention as a tool that can provide immediate test results and greatly help to deter infection and determine what to do next. POCT has several drawbacks such as a low sensitivity and specificity, but according to studies POCT has increased sensitivity on par with that of polymerase chain reaction testing. The advantage of POCT is that the results can be obtained quickly, regardless of the location. To further enhance its benefits, POCT is being developed and researched in conjunction with the Internet of medical things (IoMT), which allows POCT results to be collected, recorded, and managed over a network. IoMT will be beneficial not only for the use of POCT simply as a testing tool but also for its integration into diagnostic and health management systems. IoMT will enable people to regularly receive their test results in their daily lives and to provide personalized diagnosis and treatment of individual conditions, which will be beneficial in terms of disease prevention and maintenance of health.


Subject(s)
COVID-19 , COVID-19/diagnosis , Humans , Internet , Point-of-Care Testing , SARS-CoV-2 , Sensitivity and Specificity
5.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-313412

ABSTRACT

Coronavirus Disease 2019 (COVID-19) has become a serious global epidemic in the past few months and caused huge loss to human society worldwide. For such a large-scale epidemic, early detection and isolation of potential virus carriers is essential to curb the spread of the epidemic. Recent studies have shown that one important feature of COVID-19 is the abnormal respiratory status caused by viral infections. During the epidemic, many people tend to wear masks to reduce the risk of getting sick. Therefore, in this paper, we propose a portable non-contact method to screen the health condition of people wearing masks through analysis of the respiratory characteristics. The device mainly consists of a FLIR one thermal camera and an Android phone. This may help identify those potential patients of COVID-19 under practical scenarios such as pre-inspection in schools and hospitals. In this work, we perform the health screening through the combination of the RGB and thermal videos obtained from the dual-mode camera and deep learning architecture.We first accomplish a respiratory data capture technique for people wearing masks by using face recognition. Then, a bidirectional GRU neural network with attention mechanism is applied to the respiratory data to obtain the health screening result. The results of validation experiments show that our model can identify the health status on respiratory with the accuracy of 83.7\% on the real-world dataset. The abnormal respiratory data and part of normal respiratory data are collected from Ruijin Hospital Affiliated to The Shanghai Jiao Tong University Medical School. Other normal respiratory data are obtained from healthy people around our researchers. This work demonstrates that the proposed portable and intelligent health screening device can be used as a pre-scan method for respiratory infections, which may help fight the current COVID-19 epidemic.

6.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-325065

ABSTRACT

Background: Many Pre-exposure prophylaxis (PrEP) users have difficulty attending the quarterly facility-based HIV testing, which leads to the potential risk of drug resistance in the context of breakthrough infection with low drug compliance. We explored the acceptance of HIV self-testing (HIVST) service among PrEP recipients. Methods: : MSM were recruited for the PrEP demonstration in four major cities in China from December 2018 to September 2019, provided with regimens of both daily and on-demand PrEP. Facility-based HIV testing was provided quarterly at clinic visits. Previous HIV testing history and acceptance of free HIVST kits to use between each quarterly clinic visit was collected. Correlates of levels of acceptance were analysed using multivariable ordinal logistic regression. Results: : We recruited 1,222 MSM. among which 48.5% preferred daily PrEP and 51.5% preferred on-demand PrEP. There was 26.8% (321/1222) had never been to any facility-based HIV testing previously, and the self-reported major reason was that they had already routinely used HIVST. A quarter of the participants (74.5%, 910/1222) had used HIVST previously. There were 1184 MSM (96.9%) accepted to use HIVST between each quarterly clinic visits during PrEP usage, composing 947 ( 77.5%) very willing to, 237(19.4%)willing to, 29 (2.4%) unwilling to, and 9 (0.7%) very unwilling to. Participants preferred daily PrEP (vs. on-demand PrEP, aOR=1.8, 95% CI:1.3-2.4) and had less than 2 times of facility-based HIV testing in the past year (vs. ³2, aOR=1.4,95% CI:1.1-1.9) were more likely to have higher level of acceptance of HIVST. Conclusions: : MSM had high acceptance of HIVST, especially among those preferred daily PrEP and with less facility-based HIV testing in the previous year. Offering HIVST services PrEP recipients is feasible and necessary. Above result is of great significance for promoting HIVST among PrEP users during COVID-19, improving awareness of their HIV infection status and ensuring compliance with medication. Future study should exam the impact of HIVST on HIV testing frequency among PrEP users. Trial registration: ChiCTR1800020374 on 27 th Dec 2018. http://www.chictr.org.cn/searchproj.aspx

7.
Cell Discov ; 8(1): 9, 2022 Feb 01.
Article in English | MEDLINE | ID: covidwho-1661959

ABSTRACT

Safe, effective, and economical vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are needed to achieve adequate herd immunity and end the pandemic. We constructed a novel SARS-CoV-2 vaccine, CoVac501, which is a self-adjuvanting peptide vaccine conjugated with Toll-like receptor 7 (TLR7) agonists. The vaccine contains immunodominant peptides screened from the receptor-binding domain (RBD) and is fully chemically synthesized. It has been formulated in an optimized nanoemulsion formulation and is stable at 40 °C for 1 month. In non-human primates (NHPs), CoVac501 elicited high and persistent titers of protective neutralizing antibodies against multiple RBD mutations, SARS-CoV-2 original strain, and variants (B.1.1.7 and B.1.617.2). Specific peptides booster immunization against the B.1.351 variant has also been shown to be effective in improving protection against B.1.351. Meanwhile, CoVac501 elicited the increase of memory T cells, antigen-specific CD8+ T-cell responses, and Th1-biased CD4+ T-cell immune responses in NHPs. Notably, at an extremely high SARS-CoV-2 challenge dose of 1 × 107 TCID50, CoVac501 provided near-complete protection for the upper and lower respiratory tracts of cynomolgus macaques.

8.
Expert Rev Mol Med ; 24: e4, 2022 01 21.
Article in English | MEDLINE | ID: covidwho-1641781

ABSTRACT

Viruses completely rely on the energy and metabolic systems of host cells for life activities. Viral infections usually lead to cytopathic effects and host diseases. To date, there are still no specific clinical vaccines or drugs against most viral infections. Therefore, understanding the molecular and cellular mechanisms of viral infections is of great significance to prevent and treat viral diseases. A variety of viral infections are related to the p38 MAPK signalling pathway, and p38 is an important host factor in virus-infected cells. Here, we introduce the different signalling pathways of p38 activation and then summarise how different viruses induce p38 phosphorylation. Finally, we provide a general summary of the effect of p38 activation on virus replication. Our review provides integrated data on p38 activation and viral infections and describes the potential application of targeting p38 as an antiviral strategy.


Subject(s)
Virus Diseases , p38 Mitogen-Activated Protein Kinases , Humans , MAP Kinase Signaling System , Phosphorylation , Virus Replication , p38 Mitogen-Activated Protein Kinases/genetics , p38 Mitogen-Activated Protein Kinases/metabolism
9.
Front Med (Lausanne) ; 8: 654754, 2021.
Article in English | MEDLINE | ID: covidwho-1638235

ABSTRACT

Purpose: To summarize the imaging results of COVID-19 pneumonia and develop a computerized tomography (CT) screening procedure for patients at our institution with malignant tumors. Methods: Following epidemiological investigation, 1,429 patients preparing to undergo anti-tumor-treatment underwent CT scans between February 17 and April 16, 2020. When CT findings showed suspected COVID-19 pneumonia after the supervisor radiologist and the thoracic experience radiologist had double-read the initial CT images, radiologists would report the result to our hospital infection control staff. Further necessary examinations, including the RT-PCR test, in the assigned hospital was strongly recommended for patients with positive CT results. The CT examination room would perform sterilization for 30 min to 1 h. If the negative results of any suspected COVID-19 pneumonia CT findings were identified, the radiologists would upload the results to our Hospital Information Systems and inform clinicians within 2 h. Results: Fifty (0.35%, 50/1,429) suspected pneumonia cases, including 29 males and 21 females (median age: 59.5 years old; age range 27-79 years), were identified. A total of 34.0% (17/50) of the patients had a history of lung cancer and 54.0 (27/50) underwent chemotherapy or targeted therapy. Forty-six patients (92.0%) had prior CT scans, and 35 patients (76.1%) with suspected pneumonia were newly seen (median interval time: 62 days). Sub-pleura small patchy or strip-like lesions most likely due to fibrosis or hypostatic pneumonia and cluster of nodular lesions were the two main signs of suspected cases on CT images (34, 68.0%). Twenty-seven patients (54.0%) had, at least once, follow-up CT scan (median interval time: 18.0 days). Only one patient had an increase in size (interval time: 8 days), the immediately RT-PCR test result was negative. Conclusion: CT may be useful as a screening tool for COVID-19 based on imaging features. But the differential diagnosis between COVID-19 and other pulmonary infection and/or non-infectious disease is very difficult due to its overlapping imaging features.The confirmed diagnosis of the COVID-19 infection should be based on the etiologic eventually. The cancer patients at a low-incidence area would continue treatment by screening carefully before admission.

10.
Curr Rheumatol Rep ; 23(11): 79, 2021 11 12.
Article in English | MEDLINE | ID: covidwho-1638234

ABSTRACT

PURPOSE OF REVIEW: Three COVID-19 vaccines obtained emergency authorization from the Food and Drug Administration (FDA) and are widely used in the USA. Unfortunately, there is a paucity of evidence on the safety and efficacy of these vaccines in patients with autoimmune inflammatory rheumatic diseases (AIIRD), as these patients were excluded from all phases of vaccine development. Here we reviewed current data on COVID-19 vaccination in patients with AIIRD, with emphasis on systemic lupus erythematosus (SLE), and provided a comprehensive update on the benefits and risks of vaccination. RECENT FINDINGS: Patients with SLE have worse immune responses following SARS-CoV-2 vaccination than healthy controls. The efficacy of the COVID-19 vaccines seems to be further reduced by immunosuppressive medications, such as glucocorticoids (GC), methotrexate (MTX), mycophenolate/mycophenolic acid (MMF), and rituximab (RTX). However, these data do not substantiate that AIIRD patients are at greater risk of disease flares or have a higher incidence of side effects following vaccination. There is no significant safety concern for the use of COVID-19 vaccines in patients with AIIRD. The benefits of vaccination far outweigh the risks in patients with AIIRD, including SLE. More data are needed to determine the necessity of a booster vaccine dose and appropriate adjustment of immunosuppressants around the administration of vaccine.


Subject(s)
Autoimmune Diseases , COVID-19 , Lupus Erythematosus, Systemic , Rheumatic Diseases , Vaccines , COVID-19 Vaccines , Humans , SARS-CoV-2 , United States
11.
Methods Mol Biol ; 2410: 209-228, 2022.
Article in English | MEDLINE | ID: covidwho-1576030

ABSTRACT

The COVID-19 pandemic brought to the fore the urgent need for vaccine design and delivery platforms that can be rapidly deployed for manufacture and distribution. Though the mRNA and adenoviral vector platforms have been enormously successful to control SARS-CoV-2 viral infections, it is unclear if this could be replicated against more complex pathogens or the emerging variants. Recently, we described a "universal" platform that can incorporate multiple vaccine targets into the same nanoparticle scaffold by CRISPR engineering of bacteriophage T4. A T4-COVID vaccine designed with this technology elicited broad immunogenicity and complete protection against virus challenge in a mouse model. Here, we describe the detailed methodology to generate recombinant bacteriophage T4 backbones using CRISPR that can also be broadly applicable to other bacteriophages that abundantly pervade the Earth.


Subject(s)
Bacteriophage T4 , COVID-19 Vaccines , COVID-19 , Clustered Regularly Interspaced Short Palindromic Repeats , Animals , Bacteriophage T4/genetics , COVID-19/prevention & control , Humans , Mice , Pandemics , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
12.
Lupus Science & Medicine ; 8(Suppl 2):A32-A33, 2021.
Article in English | ProQuest Central | ID: covidwho-1504871

ABSTRACT

1105 Table 1Telemedicine Seven-item QuestionnaireQuestionnaire Item Response N (%) How satisfied were you with your previous telemedicine visit? Highly satisfied 50 (50%) Satisfied 34 (34%) Neither satisfied nor unsatisfied 11 (11%) Not satisfied 5 (5%) Highly unsatisfied 0 (0%) Reasons for satisfaction? Avoid coming into the office 73 (73%) Call went smoothly 77 (77%) Decrease their concerns over condition, medications and risk of COVID-19 75 (75%) Reasons for unsatisfaction? Technical difficulties 4 (4%) Visit was too short 2 (2%) Visit was too basic for their needs 4 (4%) How comfortable were you with your previous telemedicine visits? Very comfortable 62 (62%) Comfortable 24 (24%) Neither comfortable nor uncomfortable 11 (11%) Uncomfortable 3 (3%) Highly uncomfortable 0 (0%) The physician was able to address what was bothering me through the telemedicine visit? Strongly agree 54 (54%) Agree 37 (37%) Don’t know 5 (5%) Disagree 4 (4%) Strongly disagree 0 (0%) Overall, compared to an in-person visit, the telemedicine visit was? Much better 10 (10%) Better 6 (6%) Same 57 (57%) Worse 25 (25%) Much worse 2 (2%) I would have a telemedicine appointment in the future, if given the option. Yes 77 (77%) Unsure 14 (14%) No 9 (9%) Abstract 1105 Table 2Demographic characteristics of study subjectsCharacteristics Categories N (%) Gender Male 9 (9%) Female 91 (91%) Age (years) 20-30 18 (18%) 30-40 22 (22%) 40-50 22 (22%) 50-60 21 (21%) 60-70 13 (13%) 70-80 4 (4%) Race White 41 (41%) Black or African American 25 (25%) Asian 7 (7%) Hispanic 26 (26%) Health insurance Insured 100 (100%) Uninsured 0 (0%) Diagnoses Systemic Lupus Erythematosus (SLE) 60 (60%) Rheumatoid Arthritis (RA) 7 (7%) Undifferentiated Connective Tissue Diseases (UCTD) 7 (7%) Psoriatic Arthritis (PsA) 5 (5%) Sjogren’s Syndrome (SS) 4 (4%) Spondylitis 3 (3%) Other (Sarcoidosis, Myositis, Osteoarthritis, Fibromyalgia, Uveitis, Vasculitis) 14 (14%) ConclusionsOur cohort showed high rate of patient satisfaction with telemedicine healthcare. However, the relatively low healthcare provider satisfaction rate raises concern as to whether elemedicine constitutes a satisfactory alternative to conventional in-person care. Additional researches are required to investigate the feasibility of telemedicine in long-term disease activity evaluation and patient outcome measurement.

13.
BMJ ; 369: m1849, 2020 05 14.
Article in English | MEDLINE | ID: covidwho-1495142

ABSTRACT

OBJECTIVE: To assess the efficacy and safety of hydroxychloroquine plus standard of care compared with standard of care alone in adults with coronavirus disease 2019 (covid-19). DESIGN: Multicentre, open label, randomised controlled trial. SETTING: 16 government designated covid-19 treatment centres in China, 11 to 29 February 2020. PARTICIPANTS: 150 patients admitted to hospital with laboratory confirmed covid-19 were included in the intention to treat analysis (75 patients assigned to hydroxychloroquine plus standard of care, 75 to standard of care alone). INTERVENTIONS: Hydroxychloroquine administrated at a loading dose of 1200 mg daily for three days followed by a maintenance dose of 800 mg daily (total treatment duration: two or three weeks for patients with mild to moderate or severe disease, respectively). MAIN OUTCOME MEASURE: Negative conversion of severe acute respiratory syndrome coronavirus 2 by 28 days, analysed according to the intention to treat principle. Adverse events were analysed in the safety population in which hydroxychloroquine recipients were participants who received at least one dose of hydroxychloroquine and hydroxychloroquine non-recipients were those managed with standard of care alone. RESULTS: Of 150 patients, 148 had mild to moderate disease and two had severe disease. The mean duration from symptom onset to randomisation was 16.6 (SD 10.5; range 3-41) days. A total of 109 (73%) patients (56 standard of care; 53 standard of care plus hydroxychloroquine) had negative conversion well before 28 days, and the remaining 41 (27%) patients (19 standard of care; 22 standard of care plus hydroxychloroquine) were censored as they did not reach negative conversion of virus. The probability of negative conversion by 28 days in the standard of care plus hydroxychloroquine group was 85.4% (95% confidence interval 73.8% to 93.8%), similar to that in the standard of care group (81.3%, 71.2% to 89.6%). The difference between groups was 4.1% (95% confidence interval -10.3% to 18.5%). In the safety population, adverse events were recorded in 7/80 (9%) hydroxychloroquine non-recipients and in 21/70 (30%) hydroxychloroquine recipients. The most common adverse event in the hydroxychloroquine recipients was diarrhoea, reported in 7/70 (10%) patients. Two hydroxychloroquine recipients reported serious adverse events. CONCLUSIONS: Administration of hydroxychloroquine did not result in a significantly higher probability of negative conversion than standard of care alone in patients admitted to hospital with mainly persistent mild to moderate covid-19. Adverse events were higher in hydroxychloroquine recipients than in non-recipients. TRIAL REGISTRATION: ChiCTR2000029868.


Subject(s)
Antiviral Agents/therapeutic use , Coronavirus Infections/drug therapy , Hydroxychloroquine/therapeutic use , Pneumonia, Viral/drug therapy , Adult , COVID-19 , China , Female , Humans , Male , Middle Aged , Pandemics , Treatment Outcome
14.
Front Public Health ; 9: 720512, 2021.
Article in English | MEDLINE | ID: covidwho-1456303

ABSTRACT

Ensuring the well-being of persons with disabilities (PWDs) is a priority in the public sector during the coronavirus disease 2019 (COVID-19) pandemic. To contain this unprecedented public crisis in China, a set of nationwide anti-epidemic discourse systems centered on war metaphors has guided the epidemic's prevention and control. While the public is immersed in the joy brought by the stage victory, most ignore the situation of the disadvantaged PWDs. Accordingly, this study adopts and presents a qualitative research method to explore the impact of war metaphors on PWDs. The results showed that while there was some formal and informal support for PWDs during this period, they were increasingly marginalized. Owing to the lack of a disability lens and institutional exclusion, PWDs were placed on the margins of the epidemic prevention and control system like outsiders. Affected by pragmatism under war metaphors, PWDs are regarded as non-contributory or inefficient persons; therefore, they are not prioritized and are thus placed into a state of being voiceless and invisible. This research can provide inspiration for improving public services for PWDs in the context of COVID-19.


Subject(s)
COVID-19 , Disabled Persons , China/epidemiology , Humans , Metaphor , Pandemics/prevention & control , SARS-CoV-2
15.
Biosci Trends ; 15(4): 201-204, 2021 Sep 22.
Article in English | MEDLINE | ID: covidwho-1436244

ABSTRACT

Traditional Chinese medicine (TCM) is a valuable form of medicine with a long history in China. It has played a significant role in the control and prevention of infectious diseases including SARS and H7N9 flu. After the outbreak of COVID-19, China's National Health Commission included TCM in the Diagnosis and Treatment Protocol for COVID-19. During the COVID-19 pandemic, three traditional Chinese medicines (Jinhua Qinggan granules, Lianhua Qingwen medicine, and a Xuebijing Injection) and three TCM preparations (a Qingfei Paidu decoction, a Huashi Baidu decoction, and a Xuanfei Baidu decoction) have been screened for their efficacy against COVID-19. More than 150 trials involving TCMs are registered in the Chinese Clinical Trial Registry (ChiCTR), and those trials cover prevention, treatment, recovery, and illnesses diagnosed in accordance with TCM principles. TCM can effectively alleviate the symptoms of patients with COVID-19, delay the disease's progression from mild to severe or critical, and reduce severe and critical all-cause mortality. The underlying mechanisms of TCM mainly involve action against SARS-CoV-2, anti-inflammatory and immunomodulatory action, and organ protection. The current work provides a brief description of the current status of and issues with TCM to treat this novel infectious disease. The hope is that TCM can help considerably to control this global epidemic.


Subject(s)
COVID-19/drug therapy , Drugs, Chinese Herbal/therapeutic use , Anti-Inflammatory Agents/adverse effects , Anti-Inflammatory Agents/therapeutic use , Antiviral Agents/adverse effects , Antiviral Agents/therapeutic use , China , Clinical Trials as Topic , Drugs, Chinese Herbal/adverse effects , Humans , Medicine, Chinese Traditional
16.
Sci Adv ; 7(37): eabh1547, 2021 Sep 10.
Article in English | MEDLINE | ID: covidwho-1405213

ABSTRACT

A "universal" platform that can rapidly generate multiplex vaccine candidates is critically needed to control pandemics. Using the severe acute respiratory syndrome coronavirus 2 as a model, we have developed such a platform by CRISPR engineering of bacteriophage T4. A pipeline of vaccine candidates was engineered by incorporating various viral components into appropriate compartments of phage nanoparticle structure. These include expressible spike genes in genome, spike and envelope epitopes as surface decorations, and nucleocapsid proteins in packaged core. Phage decorated with spike trimers was found to be the most potent vaccine candidate in animal models. Without any adjuvant, this vaccine stimulated robust immune responses, both T helper cell 1 (TH1) and TH2 immunoglobulin G subclasses, blocked virus-receptor interactions, neutralized viral infection, and conferred complete protection against viral challenge. This new nanovaccine design framework might allow the rapid deployment of effective adjuvant-free phage-based vaccines against any emerging pathogen in the future.

18.
Nat Commun ; 12(1): 4887, 2021 08 09.
Article in English | MEDLINE | ID: covidwho-1349665

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus that is spreading rapidly, which seriously impacts global public health and economy. Thus, developing effective drugs remains urgent. We identify two potent antibodies, nCoVmab1 and nCoVmab2, targeting the SARS-CoV-2 spike protein receptor-binding domain (RBD) with high affinities from a naïve human phage-displayed Fab library. nCoVmab1 and nCoVmab2 neutralize authentic SARS-CoV-2 with picomolar and nanomolar IC50 values, respectively. No detectable defects of nCoVmab1 and nCoVmab2 are found during the preliminary druggability evaluation. nCoVmab1 could reduce viral titer and lung injury when administered prophylactically and therapeutically in human angiotensin-converting enzyme II (hACE2)-transgenic mice. Therefore, phage display platform could be efficiently used for rapid development of neutralizing monoclonal antibodies (nmabs) with clinical potential against emerging infectious diseases. In addition, we determinate epitopes in RBD of these antibodies to elucidate the neutralizing mechanism. We also convert nCoVmab1 and nCoVmab2 to their germline formats for further analysis, which reveals the contribution of somatic hypermutation (SHM) during nCoVmab1 and nCoVmab2 maturation. Our findings not only provide two highly potent nmabs against SARS-CoV-2 as prophylactic and therapeutic candidates, but also give some clues for development of anti-SARS-CoV-2 agents (e.g., drugs and vaccines) targeting the RBD.


Subject(s)
Antibodies, Neutralizing/therapeutic use , Antibodies, Viral/therapeutic use , COVID-19/drug therapy , SARS-CoV-2/drug effects , Angiotensin-Converting Enzyme 2/genetics , Animals , Antibodies, Monoclonal/therapeutic use , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Binding Sites , COVID-19/immunology , COVID-19/pathology , COVID-19/virology , Chlorocebus aethiops , Epitopes/immunology , Humans , Male , Mice , Mice, Transgenic , Protein Binding , Receptors, Virus/drug effects , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus , Vero Cells
20.
J Asthma Allergy ; 14: 829-838, 2021.
Article in English | MEDLINE | ID: covidwho-1314478

ABSTRACT

BACKGROUND: To tackle the COVID-19 pandemic and mitigate viral transmission, mainland China has implemented various disease prevention measures and arrangements. We hypothesize that these measures may be pose challenges to the management of pediatric asthma. Here, we studied the situation of pediatric asthma in Chengdu during the COVID-19 pandemic and compared the pediatric asthma situation before so as to provide a reference for designing effective management plan for pediatric asthma patients in the future facing the outbreak of epidemic. METHODS: An observational study was done to compare the pediatric asthma situation in Chengdu from 2017 to 2019 to the situation under COVID-19 pandemic. Asthma incidence, severe asthma attack, air quality, temperature, and patient follow-up were examined. RESULTS: The number of monthly asthma cases decreased significantly in February 2020. The number of asthma cases in 2017-2019 positively correlated with levels of particulate matter PM 2.5 (p = 0.006) and PM10 (p = 0.005), while it negatively correlated with temperature (p = 0.048). No correlation was identified in 2020. A higher rate of severe asthma attack cases (9.69%) was observed among asthma patients in 2020 (p = 0.014). Differences were identified between the monthly severe asthma attack during the period 2017-2020 (p<0.001). The rate of severe asthma attack cases peaked in June and September 2020. The percentage of patients who failed to undergo pulmonary function tests was 34.5% in 2020, remarkably higher than in the previous 3 years (p<0.001). CONCLUSION: The situation and management of pediatric asthma during the 2020 COVID-19 pandemic differed from those in previous years, with more emphasis placed on disease prevention practices and facilities. To design future pediatric asthma management practice, the environmental and psychological impact on asthma management should also be considered. Local areas should make good use of telemedicine to manage pediatric asthma effectively.

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