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1.
Front Digit Health ; 3: 799067, 2021.
Article in English | MEDLINE | ID: covidwho-1630985

ABSTRACT

Since the COronaVIrus Disease 2019 (COVID-19) outbreak, developing a digital diagnostic tool to detect COVID-19 from respiratory sounds with computer audition has become an essential topic due to its advantages of being swift, low-cost, and eco-friendly. However, prior studies mainly focused on small-scale COVID-19 datasets. To build a robust model, the large-scale multi-sound FluSense dataset is utilised to help detect COVID-19 from cough sounds in this study. Due to the gap between FluSense and the COVID-19-related datasets consisting of cough only, the transfer learning framework (namely CovNet) is proposed and applied rather than simply augmenting the training data with FluSense. The CovNet contains (i) a parameter transferring strategy and (ii) an embedding incorporation strategy. Specifically, to validate the CovNet's effectiveness, it is used to transfer knowledge from FluSense to COUGHVID, a large-scale cough sound database of COVID-19 negative and COVID-19 positive individuals. The trained model on FluSense and COUGHVID is further applied under the CovNet to another two small-scale cough datasets for COVID-19 detection, the COVID-19 cough sub-challenge (CCS) database in the INTERSPEECH Computational Paralinguistics challengE (ComParE) challenge and the DiCOVA Track-1 database. By training four simple convolutional neural networks (CNNs) in the transfer learning framework, our approach achieves an absolute improvement of 3.57% over the baseline of DiCOVA Track-1 validation of the area under the receiver operating characteristic curve (ROC AUC) and an absolute improvement of 1.73% over the baseline of ComParE CCS test unweighted average recall (UAR).

2.
Lancet ; 2021 Nov 11.
Article in English | MEDLINE | ID: covidwho-1586226
3.
Chin Med J (Engl) ; 134(17): 2037-2044, 2021 Aug 02.
Article in English | MEDLINE | ID: covidwho-1480004

ABSTRACT

ABSTRACT: With the outbreak of the coronavirus disease 2019 (COVID-19) pandemic, the importance of vaccines in epidemic prevention and public health has become even more obvious than ever. However, the emergence of multiple severe acute respiratory syndrome coronavirus 2 variants worldwide has raised concerns about the effectiveness of current COVID-19 vaccines. Here, we review the characteristics of COVID-19 vaccine candidates in five platforms and the latest clinical trial results of them. In addition, we further discuss future directions for the research and development of the next generation of COVID-19 vaccines. We also summarize the serious adverse events reported recently after the large-scale vaccination with the current COVID-19 vaccines, including the thromboembolism caused by the AstraZeneca and Johnson & Johnson vaccines.


Subject(s)
COVID-19 , Vaccines , COVID-19 Vaccines , Humans , SARS-CoV-2
4.
Syst Rev ; 10(1): 232, 2021 08 14.
Article in English | MEDLINE | ID: covidwho-1456005

ABSTRACT

BACKGROUND: Suicide is a leading cause of death in children and youth, with suicidal thoughts and suicide attempts (referred to as non-fatal suicidal behaviors (NFSB)) being among its strongest predictors. Positive parenting (e.g., warmth, responsiveness), negative parenting (e.g., control, hostility), and parent-child relationship quality (e.g., trust, communication) have been reported to be associated with differences in NFSB in this population. To date, no comprehensive systematic review has considered together the wide range of parenting factors studied in relation to NFSB, and no meta-analysis of existing findings has been conducted. The present study will critically appraise and synthesize the existing evidence from observational studies that examine the relationships between parenting factors and (i) suicidal ideation and (ii) suicide attempt in children and youth. METHODS: Studies will be retrieved from APA PsycInfo, MEDLINE, CINAHL, Embase, Scopus, and the Cochrane Library databases. Retrospective, cross-sectional, and longitudinal studies, conducted in clinical and population settings, among youth aged less than 25 years and published as articles and dissertations in English or French will be eligible. Two reviewers will select articles using the Covidence Software after title and abstract screening and full-text assessment, will extract information using double data entry, and will appraise studies' quality using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Any disagreements will be discussed with a third reviewer. Publication bias will be evaluated using funnel plots and Egger's test. In addition to a narrative summary of results, meta-analyses will be conducted using results from at least three studies. Three-level random effect models will allow to derive pooled estimates from dependent effect sizes (from the same sample or study). In case of significant heterogeneity, moderation analyses will be performed considering participants' characteristics and methodological aspects of studies. The results will be reported according to the PRISMA guidelines, and the certainty of evidence will be assessed using the GRADE approach. DISCUSSION: In highlighting parenting factors associated with NFSB and in estimating the overall strength of these associations in children and youth, our results will inform further intervention and prevention strategies designed for young people experiencing NFSB and their families. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020165345.


Subject(s)
Parenting , Suicidal Ideation , Adolescent , Cross-Sectional Studies , Humans , Meta-Analysis as Topic , Observational Studies as Topic , Retrospective Studies , Systematic Reviews as Topic
5.
Natl Sci Rev ; 8(8): nwab053, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1358471

ABSTRACT

Mutations and transient conformational movements of the receptor binding domain (RBD) that make neutralizing epitopes momentarily unavailable present immune escape routes for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To mitigate viral escape, we developed a cocktail of neutralizing antibodies (NAbs) targeting epitopes located on different domains of spike (S) protein. Screening of a library of monoclonal antibodies generated from peripheral blood mononuclear cells of COVID-19 convalescent patients yielded potent NAbs, targeting the N-terminal domain (NTD) and RBD domain of S, effective at nM concentrations. Remarkably, a combination of RBD-targeting NAbs and NTD-binding NAbs, FC05, enhanced the neutralization potency in cell-based assays and an animal model. Results of competitive surface plasmon resonance assays and cryo-electron microscopy (cryo-EM) structures of antigen-binding fragments bound to S unveil determinants of immunogenicity. Combinations of immunogens, identified in the NTD and RBD of S, when immunized in rabbits and macaques, elicited potent protective immune responses against SARS-CoV-2. More importantly, two immunizations of this combination of NTD and RBD immunogens provided complete protection in macaques against a SARS-CoV-2 challenge, without observable antibody-dependent enhancement of infection. These results provide a proof of concept for neutralization-based immunogen design targeting SARS-CoV-2 NTD and RBD.

6.
Drug Evaluation Research ; 43(4):606-612, 2020.
Article in Chinese | CAB Abstracts | ID: covidwho-1352919

ABSTRACT

Since the initial cases of the Coronavirus Disease in 2019 (COVID-19) occurred in Wuhan in December 2019, more and more cases have been found and confirmed, not only in central China but also in other countries. Given there are still no effective drugs many approved "old drugs" are in clinical test for treating COVID-19 at present. Artemisinin, a first-line antimalarial drug recommended by WHO, has been validated to possess a variety of pharmacological effects, including, without limitation, antiinflammatory, immune regulation, anti-pulmonary fibrosis, antibacterial, antiviral and cardiovascular effects, and the like. In this paper, various pharmacological effects of Artemisinin and its derivatives have been summarized, with the emphasis on the mechanism of action, so as to explore its potential medicinal value, especially for treating COVID-19.

7.
Chin Med J (Engl) ; 134(11): 1289-1298, 2021 Apr 28.
Article in English | MEDLINE | ID: covidwho-1343718

ABSTRACT

BACKGROUND: The significant morbidity and mortality resulted from the infection of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) call for urgent development of effective and safe vaccines. We report the immunogenicity and safety of an inactivated SARS-CoV-2 vaccine, KCONVAC, in healthy adults. METHODS: Phase 1 and phase 2 randomized, double-blind, and placebo-controlled trials of KCONVAC were conducted in healthy Chinese adults aged 18 to 59 years. The participants in the phase 1 trial were randomized to receive two doses, one each on Days 0 and 14, of either KCONVAC (5 or 10 µg/dose) or placebo. The participants in the phase 2 trial were randomized to receive either KCONVAC (at 5 or 10 µg/dose) or placebo on Days 0 and 14 (0/14 regimen) or Days 0 and 28 (0/28 regimen). In the phase 1 trial, the primary safety endpoint was the proportion of participants experiencing adverse reactions/events within 28 days following the administration of each dose. In the phase 2 trial, the primary immunogenicity endpoints were neutralization antibody seroconversion and titer and anti-receptor-binding domain immunoglobulin G seroconversion at 28 days after the second dose. RESULTS: In the phase 1 trial, 60 participants were enrolled and received at least one dose of 5-µg vaccine (n = 24), 10-µg vaccine (n = 24), or placebo (n = 12). In the phase 2 trial, 500 participants were enrolled and received at least one dose of 5-µg vaccine (n = 100 for 0/14 or 0/28 regimens), 10-µg vaccine (n = 100 for each regimen), or placebo (n = 50 for each regimen). In the phase 1 trial, 13 (54%), 11 (46%), and seven (7/12) participants reported at least one adverse event (AE) after receiving 5-, 10-µg vaccine, or placebo, respectively. In the phase 2 trial, 16 (16%), 19 (19%), and nine (18%) 0/14-regimen participants reported at least one AE after receiving 5-, 10-µg vaccine, or placebo, respectively. Similar AE incidences were observed in the three 0/28-regimen treatment groups. No AEs with an intensity of grade 3+ were reported, expect for one vaccine-unrelated serious AE (foot fracture) reported in the phase 1 trial. KCONVAC induced significant antibody responses; 0/28 regimen showed a higher immune responses than that did 0/14 regimen after receiving two vaccine doses. CONCLUSIONS: Both doses of KCONVAC are well tolerated and able to induce robust immune responses in healthy adults. These results support testing 5-µg vaccine in the 0/28 regimen in an upcoming phase 3 efficacy trial. TRIAL REGISTRATION: http://www.chictr.org.cn/index.aspx (No. ChiCTR2000038804, http://www.chictr.org.cn/showproj.aspx?proj=62350; No. ChiCTR2000039462, http://www.chictr.org.cn/showproj.aspx?proj=63353).


Subject(s)
COVID-19 , SARS-CoV-2 , Adult , COVID-19 Vaccines , Double-Blind Method , Humans , Vaccines, Inactivated/adverse effects
8.
Signal Transduct Target Ther ; 6(1): 271, 2021 07 15.
Article in English | MEDLINE | ID: covidwho-1315588

ABSTRACT

COVID-19 vaccines from multiple manufacturers are needed to cope with the problem of insufficient supply. We did two single-center, randomised, double-blind, placebo-controlled phase 1 and phase 2 trials to assess the safety, tolerability and immunogenicity of a recombinant COVID-19 vaccine (Sf9 cells) in healthy population aged 18 years or older in China. Eligible participants were enrolled, the ratio of candidate vaccine and placebo within each dose group was 3:1 (phase 1) or 5:1 (phase 2). From August 28, 2020, 168 participants were sequentially enrolled and randomly assigned to receive the low dose vaccine, high dose vaccine or placebo with the schedule of 0, 28 days or 0, 14, 28 days in phase 1 trial. From November 18, 2020, 960 participants were randomly assigned to receive the low dose vaccine, high dose vaccine or placebo with the schedule of 0, 21 days or 0, 14, 28 days in phase 2 trial. The most common solicited injection site adverse reaction within 7 days in both trials was pain. The most common solicited systematic adverse reactions within 7 days were fatigue, cough, sore throat, fever and headache. ELISA antibodies and neutralising antibodies increased at 14 days, and peaked at 28 days (phase 1) or 30 days (phase 2) after the last dose vaccination. The GMTs of neutralising antibody against live SARS-CoV-2 at 28 days or 30 days after the last dose vaccination were highest in the adult high dose group (0, 14, 28 days), with 102.9 (95% CI 61.9-171.2) and 102.6 (95% CI 75.2-140.1) in phase 1 and phase 2 trials, respectively. Specific T-cell response peaked at 14 days after the last dose vaccination in phase 1 trial. This vaccine is safe, and induced significant immune responses after three doses of vaccination.


Subject(s)
COVID-19 Vaccines , COVID-19 , Immunogenicity, Vaccine , SARS-CoV-2/immunology , Adolescent , Adult , COVID-19/blood , COVID-19/immunology , COVID-19/prevention & control , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/immunology , Female , Humans , Male , Middle Aged
9.
Lancet Infect Dis ; 21(7): 891-893, 2021 07.
Article in English | MEDLINE | ID: covidwho-1290968
10.
Engineering (Beijing) ; 7(7): 903-907, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1233416
11.
Preprint in English | medRxiv | ID: ppmedrxiv-21253850

ABSTRACT

BackgroundThe significant morbidity and mortality resulted from the infection of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) call for urgent development of effective and safe vaccines. We report the immunogenicity and safety of a SARS-CoV-2 inactivated vaccine, KCONVAC, in healthy adults. MethodsTwo phase 1 and phase 2 randomized, double-blind, and placebo-controlled trials of KCONVAC were conducted in Chinese healthy adults aged 18 through 59 years. The phase 1 trial was conducted in a manner of dosage escalation. The first 30 participants were randomized in a ratio of 4:1 to receive two doses of either KCONVAC at 5 g per dose or placebo on Day 0 and Day 14, and the second 30 participants were randomized to receive either KCONVAC at 10 g per dose or placebo following the same procedures. The participants in the phase 2 trial were randomized in a ratio of 2:2:1 to receive either KCONVAC at 5 g or 10 g per dose, or placebo on Day 0 and Day 14, or Day 0 and Day 28. In the phase 1 trial, the primary safety endpoint was the proportion of participants experiencing adverse reactions/events within 28 days following each vaccination. Antibody response and cellular response were assayed in the phase 1 trial. In the phase 2 trial, the primary immunogenicity endpoint was the seroconversion and titre of neutralization antibody, and the seroconversion of receptor binding domain (RBD)-IgG 28 days after the second dose. FindingsIn the phase 1 trial, 60 participants were enrolled and received at least one dose of 5-g vaccine (N=24), 10-g vaccine (N=24), or placebo (N=12). In the phase 2 trial, 500 participants were enrolled and received at least one dose of 5-g vaccine (N=100 for 0/14 or 0/28 regimens), 10-g vaccine (N=100 for each regimen), or placebo (N=50 for each regimen). In the phase 1 trial, 13 (54%), 11(46%), and 7 (58%) participants reported at least one adverse event (AE), of whom 10 (42%), 6 (25%), and 6 (50%) participants reported at least one vaccination-related AE after receiving 5-g vaccine, 10-g vaccine, or placebo, respectively. In the phase 2 trial, 16 (16%), 19 (19%), and 9 (18%) participants reported at least one AE, of whom 13 (13%), 17 (17%), and 6 (12%) participants reported at least one vaccination-related AE after receiving 5-g vaccine, 10-g vaccine, or placebo at the regimen of Day 0/14, respectively. Similar results were observed in the three treatment groups of Day 0/28 regimen. All the AEs were grade 1 or 2 in intensity. No AE of grade 3 or more was reported. One SAE (foot fracture) was reported in the phase 1 trial. KCONVAC induced significant antibody response. 87{middle dot}5% (21/24) to 100% (24/24) of participants in the phase 1 trial and 83{middle dot}0% (83/100) to 100% (99/99) of participants in the phase 2 trial seroconverted for neutralising antibody to live virus, neutralising antibody to pseudovirus, and RBD-IgG after receiving two doses. Across the treatment groups in the two trials, the geometric mean titres (GMTs) of neutralising antibody to live virus ranged from 29{middle dot}3 to 49{middle dot}1 at Day 0/14 regimen and from 100{middle dot}2 to 131{middle dot}7 at Day 0/28 regimen, neutralising antibody to pseudovirus ranged from 69{middle dot}4 to 118{middle dot}7 at Day 0/14 regimen and from 153{middle dot}6 to 276{middle dot}6 at Day 0/28 regimen, and RBD-IgG ranged from 605{middle dot}3 to 1169{middle dot}8 at Day 0/14 regimen and from 1496{middle dot}8 to 2485{middle dot}5 at Day 0/28 regimen. RBD-IgG subtyping assay showed that a significant part of RBD-IgG was IgG1. The vaccine induced obvious T-cell response with 56{middle dot}5% (13/23) and 62{middle dot}5% (15/24) of participants in 5-g and 10-g vaccine groups showed positive interferon-{gamma} enzyme-linked immunospot responses 14 days after the second dose in the phase 1 trial, respectively. InterpretationKCONVAC is well tolerated and able to induce robust antibody response and cellular response in adults aged 18 to 59 years, which warrants further evaluation with this vaccine in the upcoming phase 3 efficacy trial. FundingGuandong Emergency Program for Prevention and Control of COVID-19 (2020A1111340002) and Shenzhen Key Research Project for Prevention and Control of COVID-19.

13.
Eur J Clin Invest ; 51(1): e13443, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-901035

ABSTRACT

BACKGROUND: To reveal detailed histopathological changes, virus distributions, immunologic properties and multi-omic features caused by SARS-CoV-2 in the explanted lungs from the world's first successful lung transplantation of a COVID-19 patient. MATERIALS AND METHODS: A total of 36 samples were collected from the lungs. Histopathological features and virus distribution were observed by optical microscope and transmission electron microscope (TEM). Immune cells were detected by flow cytometry and immunohistochemistry. Transcriptome and proteome approaches were used to investigate main biological processes involved in COVID-19-associated pulmonary fibrosis. RESULTS: The histopathological changes of the lung tissues were characterized by extensive pulmonary interstitial fibrosis and haemorrhage. Viral particles were observed in the cytoplasm of macrophages. CD3+ CD4- T cells, neutrophils, NK cells, γ/δ T cells and monocytes, but not B cells, were abundant in the lungs. Higher levels of proinflammatory cytokines iNOS, IL-1ß and IL-6 were in the area of mild fibrosis. Multi-omics analyses revealed a total of 126 out of 20,356 significant different transcription and 114 out of 8,493 protein expression in lung samples with mild and severe fibrosis, most of which were related to fibrosis and inflammation. CONCLUSIONS: Our results provide novel insight that the significant neutrophil/ CD3+ CD4- T cell/ macrophage activation leads to cytokine storm and severe fibrosis in the lungs of COVID-19 patient and may contribute to a better understanding of COVID-19 pathogenesis.


Subject(s)
COVID-19/pathology , Hemorrhage/pathology , Lung Transplantation , Lung/pathology , Lymph Nodes/pathology , Pulmonary Fibrosis/pathology , B-Lymphocytes/pathology , B-Lymphocytes/ultrastructure , B-Lymphocytes/virology , COVID-19/genetics , COVID-19/metabolism , COVID-19/surgery , Chromatography, Liquid , Flow Cytometry , Gene Expression Profiling , Humans , Interleukin-1beta/metabolism , Interleukin-6/metabolism , Killer Cells, Natural/pathology , Killer Cells, Natural/ultrastructure , Killer Cells, Natural/virology , Lung/metabolism , Lung/ultrastructure , Lung/virology , Lymph Nodes/metabolism , Lymph Nodes/ultrastructure , Lymph Nodes/virology , Macrophages, Alveolar/pathology , Macrophages, Alveolar/ultrastructure , Macrophages, Alveolar/virology , Male , Middle Aged , Monocytes/pathology , Monocytes/ultrastructure , Monocytes/virology , Neutrophils/pathology , Neutrophils/ultrastructure , Neutrophils/virology , Nitric Oxide Synthase Type II/metabolism , Proteomics , Pulmonary Fibrosis/genetics , Pulmonary Fibrosis/metabolism , Pulmonary Fibrosis/surgery , RNA-Seq , SARS-CoV-2 , Severity of Illness Index , T-Lymphocytes/pathology , T-Lymphocytes/ultrastructure , T-Lymphocytes/virology , Tandem Mass Spectrometry
14.
J Stroke Cerebrovasc Dis ; 29(10): 105079, 2020 10.
Article in English | MEDLINE | ID: covidwho-806543
15.
Preprint in English | bioRxiv | ID: ppbiorxiv-309294

ABSTRACT

Mutations and transient conformational movements of receptor binding domain (RBD) that make neutralizing epitopes momentarily unavailable, present immune escape routes to SARS-CoV-2. To mitigate viral escape, we developed a cocktail of neutralizing antibodies (NAbs) targeting epitopes located on different domains of spike (S) protein. Screening of a library of monoclonal antibodies generated from peripheral blood mononuclear cells of COVID-19 convalescent patients yielded potent NAbs, targeting N-terminal domain (NTD) and RBD domain of S, effective at nM concentrations. Remarkably, combination of RBD-targeting NAbs and NTD-binding NAb, FC05, dramatically enhanced the neutralization potency in cell-based assays and animal model. Results of competitive SPR assays and cryo-EM structures of Fabs bound to S unveil determinants of immunogenicity. Combinations of immunogens, identified in NTD and RBD of S, when immunized in rabbits elicited potent protective immune responses against SARS-CoV-2. These results provide a proof-of-concept for neutralization-based immunogen design targeting SARS-CoV-2 NTD and RBD. One sentence summaryImmunogens identified in the NTD and RBD of the SARS-CoV-2 spike protein using a cocktail of non-competing NAbs when injected in rabbits elicited a potent protective immune response against SARS-CoV-2.

16.
Preprint in English | medRxiv | ID: ppmedrxiv-20161216

ABSTRACT

BACKGROUNDThe top priority for the control of COVID-19 pandemic currently is the development of a vaccine. A phase 2 trial conducted to further evaluate the immunogenicity and safety of a SARS-CoV-2 inactivated vaccine (CoronaVac). METHODSWe conducted a randomized, double-blind, placebo-controlled trial to evaluate the optimal dose, immunogenicity and safety of the CoronaVac. A total of 600 healthy adults aged 18-59 years were randomly assigned to receive 2 injections of the trial vaccine at a dose of 3 g/0.5 mL or 6 g /0.5mL, or placebo on Day 0,14 schedule or Day 0,28 schedule. For safety evaluation, solicited and unsolicited adverse events were collected after each vaccination within 7 days and 28 days, respectively. Blood samples were taken for antibody assay. RESULTSCoronaVac was well tolerated, and no dose-related safety concerns were observed. Most of the adverse reactions fell in the solicited category and were mild in severity. Pain at injection site was the most frequently reported symptoms. No Grade 3 adverse reaction or vaccine related SAEs were reported. CoronaVac showed good immunogenicity with the lower 3 g dose eliciting 92.4% seroconversion under Day 0,14 schedule and 97.4% under Day 0,28 schedule. 28 days after two-dose vaccination, the Nab levels of individual schedules range from 23.8 to 65.4 among different dosage and vaccination schedules. CONCLUSIONSFavorable safety and immunogenicity of CoronaVac was demonstrated on both schedules and both dosages, which support the conduction of phase 3 trial with optimum schedule/dosage per different scenarios.

17.
Lancet ; 396(10249): 479-488, 2020 08 15.
Article in English | MEDLINE | ID: covidwho-666142

ABSTRACT

BACKGROUND: This is the first randomised controlled trial for assessment of the immunogenicity and safety of a candidate non-replicating adenovirus type-5 (Ad5)-vectored COVID-19 vaccine, aiming to determine an appropriate dose of the candidate vaccine for an efficacy study. METHODS: This randomised, double-blind, placebo-controlled, phase 2 trial of the Ad5-vectored COVID-19 vaccine was done in a single centre in Wuhan, China. Healthy adults aged 18 years or older, who were HIV-negative and previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-free, were eligible to participate and were randomly assigned to receive the vaccine at a dose of 1 × 1011 viral particles per mL or 5 × 1010 viral particles per mL, or placebo. Investigators allocated participants at a ratio of 2:1:1 to receive a single injection intramuscularly in the arm. The randomisation list (block size 4) was generated by an independent statistician. Participants, investigators, and staff undertaking laboratory analyses were masked to group allocation. The primary endpoints for immunogenicity were the geometric mean titres (GMTs) of specific ELISA antibody responses to the receptor binding domain (RBD) and neutralising antibody responses at day 28. The primary endpoint for safety evaluation was the incidence of adverse reactions within 14 days. All recruited participants who received at least one dose were included in the primary and safety analyses. This study is registered with ClinicalTrials.gov, NCT04341389. FINDINGS: 603 volunteers were recruited and screened for eligibility between April 11 and 16, 2020. 508 eligible participants (50% male; mean age 39·7 years, SD 12·5) consented to participate in the trial and were randomly assigned to receive the vaccine (1 × 1011 viral particles n=253; 5 × 1010 viral particles n=129) or placebo (n=126). In the 1 × 1011 and 5 × 1010 viral particles dose groups, the RBD-specific ELISA antibodies peaked at 656·5 (95% CI 575·2-749·2) and 571·0 (467·6-697·3), with seroconversion rates at 96% (95% CI 93-98) and 97% (92-99), respectively, at day 28. Both doses of the vaccine induced significant neutralising antibody responses to live SARS-CoV-2, with GMTs of 19·5 (95% CI 16·8-22·7) and 18·3 (14·4-23·3) in participants receiving 1 × 1011 and 5 × 1010 viral particles, respectively. Specific interferon γ enzyme-linked immunospot assay responses post vaccination were observed in 227 (90%, 95% CI 85-93) of 253 and 113 (88%, 81-92) of 129 participants in the 1 × 1011 and 5 × 1010 viral particles dose groups, respectively. Solicited adverse reactions were reported by 183 (72%) of 253 and 96 (74%) of 129 participants in the 1 × 1011 and 5 × 1010 viral particles dose groups, respectively. Severe adverse reactions were reported by 24 (9%) participants in the 1 × 1011 viral particles dose group and one (1%) participant in the 5 × 1010 viral particles dose group. No serious adverse reactions were documented. INTERPRETATION: The Ad5-vectored COVID-19 vaccine at 5 × 1010 viral particles is safe, and induced significant immune responses in the majority of recipients after a single immunisation. FUNDING: National Key R&D Programme of China, National Science and Technology Major Project, and CanSino Biologics.


Subject(s)
Betacoronavirus/immunology , Coronavirus Infections/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Viral Vaccines/adverse effects , Viral Vaccines/immunology , Adenoviridae , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19 , COVID-19 Vaccines , China , Coronavirus Infections/immunology , Double-Blind Method , Female , Genetic Vectors , Humans , Male , Middle Aged , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/immunology , T-Lymphocytes/immunology , Viral Vaccines/administration & dosage , Young Adult
18.
Lancet ; 395(10240): 1845-1854, 2020 06 13.
Article in English | MEDLINE | ID: covidwho-342974

ABSTRACT

BACKGROUND: A vaccine to protect against COVID-19 is urgently needed. We aimed to assess the safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 (Ad5) vectored COVID-19 vaccine expressing the spike glycoprotein of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain. METHODS: We did a dose-escalation, single-centre, open-label, non-randomised, phase 1 trial of an Ad5 vectored COVID-19 vaccine in Wuhan, China. Healthy adults aged between 18 and 60 years were sequentially enrolled and allocated to one of three dose groups (5 × 1010, 1 × 1011, and 1·5 × 1011 viral particles) to receive an intramuscular injection of vaccine. The primary outcome was adverse events in the 7 days post-vaccination. Safety was assessed over 28 days post-vaccination. Specific antibodies were measured with ELISA, and the neutralising antibody responses induced by vaccination were detected with SARS-CoV-2 virus neutralisation and pseudovirus neutralisation tests. T-cell responses were assessed by enzyme-linked immunospot and flow-cytometry assays. This study is registered with ClinicalTrials.gov, NCT04313127. FINDINGS: Between March 16 and March 27, 2020, we screened 195 individuals for eligibility. Of them, 108 participants (51% male, 49% female; mean age 36·3 years) were recruited and received the low dose (n=36), middle dose (n=36), or high dose (n=36) of the vaccine. All enrolled participants were included in the analysis. At least one adverse reaction within the first 7 days after the vaccination was reported in 30 (83%) participants in the low dose group, 30 (83%) participants in the middle dose group, and 27 (75%) participants in the high dose group. The most common injection site adverse reaction was pain, which was reported in 58 (54%) vaccine recipients, and the most commonly reported systematic adverse reactions were fever (50 [46%]), fatigue (47 [44%]), headache (42 [39%]), and muscle pain (18 [17%]. Most adverse reactions that were reported in all dose groups were mild or moderate in severity. No serious adverse event was noted within 28 days post-vaccination. ELISA antibodies and neutralising antibodies increased significantly at day 14, and peaked 28 days post-vaccination. Specific T-cell response peaked at day 14 post-vaccination. INTERPRETATION: The Ad5 vectored COVID-19 vaccine is tolerable and immunogenic at 28 days post-vaccination. Humoral responses against SARS-CoV-2 peaked at day 28 post-vaccination in healthy adults, and rapid specific T-cell responses were noted from day 14 post-vaccination. Our findings suggest that the Ad5 vectored COVID-19 vaccine warrants further investigation. FUNDING: National Key R&D Program of China, National Science and Technology Major Project, and CanSino Biologics.


Subject(s)
Coronavirus Infections/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Viral Vaccines/administration & dosage , Adenoviridae , Adolescent , Adult , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Betacoronavirus , COVID-19 , COVID-19 Vaccines , China , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immunity, Cellular , Immunity, Humoral , Injections, Intramuscular , Male , Middle Aged , SARS-CoV-2 , T-Lymphocytes/immunology , Vaccines, Synthetic/administration & dosage , Vaccines, Synthetic/adverse effects , Vaccines, Synthetic/therapeutic use , Viral Vaccines/adverse effects , Viral Vaccines/therapeutic use , Young Adult
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