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1.
Front Immunol ; 14: 1129118, 2023.
Article in English | MEDLINE | ID: covidwho-2298964

ABSTRACT

Chikungunya fever (CHIKF) has spread to more than 100 countries worldwide, with frequent outbreaks in Europe and the Americas in recent years. Despite the relatively low lethality of infection, patients can suffer from long-term sequelae. Until now, no available vaccines have been approved for use; however, increasing attention is being paid to the development of vaccines against chikungunya virus (CHIKV), and the World Health Organization has included vaccine development in the initial blueprint deliverables. Here, we developed an mRNA vaccine using the nucleotide sequence encoding structural proteins of CHIKV. And immunogenicity was evaluated by neutralization assay, Enzyme-linked immunospot assay and Intracellular cytokine staining. The results showed that the encoded proteins elicited high levels of neutralizing antibody titers and T cell-mediated cellular immune responses in mice. Moreover, compared with the wild-type vaccine, the codon-optimized vaccine elicited robust CD8+ T-cell responses and mild neutralizing antibody titers. In addition, higher levels of neutralizing antibody titers and T-cell immune responses were obtained using a homologous booster mRNA vaccine regimen of three different homologous or heterologous booster immunization strategies. Thus, this study provides assessment data to develop vaccine candidates and explore the effectiveness of the prime-boost approach.


Subject(s)
Chikungunya Fever , Chikungunya virus , Viral Vaccines , Animals , Mice , Chikungunya virus/genetics , Viral Vaccines/genetics , Antibodies, Viral , Antibodies, Neutralizing
2.
Front Immunol ; 14: 1142394, 2023.
Article in English | MEDLINE | ID: covidwho-2268865

ABSTRACT

The ongoing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or 2019-nCoV) variants has been associated with the transmission and pathogenicity of COVID-19. Therefore, exploring the optimal immunisation strategy to improve the broad-spectrum cross-protection ability of COVID-19 vaccines is of great significance. Herein, we assessed different heterologous prime-boost strategies with chimpanzee adenovirus vector-based COVID-19 vaccines plus Wuhan-Hu-1 (WH-1) strain (AdW) and Beta variant (AdB) and mRNA-based COVID-19 vaccines plus WH-1 strain (ARW) and Omicron (B.1.1.529) variant (ARO) in 6-week-old female BALB/c mice. AdW and AdB were administered intramuscularly or intranasally, while ARW and ARO were administered intramuscularly. Intranasal or intramuscular vaccination with AdB followed by ARO booster exhibited the highest levels of cross-reactive IgG, pseudovirus-neutralising antibody (PNAb) responses, and angiotensin-converting enzyme-2 (ACE2)-binding inhibition rates against different 2019-nCoV variants among all vaccination groups. Moreover, intranasal AdB vaccination followed by ARO induced higher levels of IgA and neutralising antibody responses against live 2019-nCoV than intramuscular AdB vaccination followed by ARO. A single dose of AdB administered intranasally or intramuscularly induced broader cross-NAb responses than AdW. Th1-biased cellular immune response was induced in all vaccination groups. Intramuscular vaccination-only groups exhibited higher levels of Th1 cytokines than intranasal vaccination-only and intranasal vaccination-containing groups. However, no obvious differences were found in the levels of Th2 cytokines between the control and all vaccination groups. Our findings provide a basis for exploring vaccination strategies against different 2019-nCoV variants to achieve high broad-spectrum immune efficacy.


Subject(s)
COVID-19 , Viral Vaccines , Female , Humans , Animals , Mice , COVID-19 Vaccines , SARS-CoV-2 , COVID-19/prevention & control , RNA, Messenger , Immunization , Vaccination , Antibodies, Neutralizing , Immunity, Cellular
3.
Biogerontology ; 2023 Feb 04.
Article in English | MEDLINE | ID: covidwho-2237549

ABSTRACT

SARS-Cov-2 infection, which has caused the COVID-19 global pandemic, triggers cellular senescence. In this study, we investigate the role of the SARS-COV-2 spike protein (S-protein) in regulating the senescence of RPE cells. The results showed that administration or overexpression of S-protein in ARPE-19 decreased cell proliferation with cell cycle arrest at the G1 phase. S-protein increased SA-ß-Gal positive ARPE-19 cells with high expression of P53 and P21, senescence-associated inflammatory factors (e.g., IL-1ß, IL-6, IL-8, ICAM, and VEGF), and ROS. Elimination of ROS by N-acetyl cysteine (NAC) or knocking down p21 by siRNA diminished S-protein-induced ARPE cell senescence. Both administrated and overexpressed S-protein colocalize with the ER and upregulate ER-stress-associated BIP, CHOP, ATF3, and ATF6 expression. S-protein induced P65 protein nuclear translocation. Inhibition of NF-κB by bay-11-7082 reduced S-protein-mediated expression of senescence-associated factors. Moreover, the intravitreal injection of S-protein upregulates senescence-associated inflammatory factors in the zebrafish retina. In conclusions, the S-protein of SARS-Cov-2 induces cellular senescence of ARPE-19 cells in vitro and the expression of senescence-associated cytokines in zebrafish retina in vivo likely by activating ER stress, ROS, and NF-κb. These results may uncover a potential association between SARS-cov-2 infection and development of AMD.

4.
Electrochimica Acta ; : 141055, 2022.
Article in English | ScienceDirect | ID: covidwho-1982968

ABSTRACT

In this study, TiO2 nanotube arrays (TiO2-NTA) were used as an intermediate layer to provide effective electrocatalytic activity and stability for Ti/TiO2-NTA/Ti4O7 anode. Compared with Ti/Ti4O7 anode, Ti/TiO2-NTA/Ti4O7 anode exhibited higher oxygen evolution potential (2.40 V), larger active specific surface areas (1.81 m2 g−1), stronger radical generation capacity (64.42 μM), longer accelerated service life (56.0 h), and superior favipiravir removal ratio. The flow-through electrochemical reaction system was constructed by using the porous Ti/TiO2-NTA/Ti4O7 anode. The removal ratio, TOC removal ratio and mineralization current efficiency of favipiravir in the flow-by electrochemical system were significantly improved and the energy consumption was reduced compared with the conventional flow-by electrochemical system, verifying the superiority of the porous flow-through Ti/TiO2-NTA/Ti4O7 anode. The effects of operating parameters on the removal of favipiravir in the flow-through electrochemical reaction system were investigated. The degradation mechanisms of favipiravir are the synergetic effects of the free radical (•OH and SO4−•) and the direct electron transfer. Ti/TiO2-NTA/Ti4O7 anode displayed excellent stability in five consecutive cycles, exhibited significant removal ratio (87.7%) of favipiravir from actual wastewater, and remained efficient and versatile for a wide range of typical PPCPs pollutants. Therefore, Ti/TiO2-NTA/Ti4O7 is a promising porous anode material in the engineering application.

5.
Emerg Microbes Infect ; 11(1): 1890-1899, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-1915484

ABSTRACT

The efficacy of many coronavirus disease 2019 (COVID-19) vaccines has been shown to decrease to varying extents against new severe acute respiratory syndrome coronavirus 2 variants, which are responsible for the continuing COVID-19 pandemic. Combining intramuscular and intranasal vaccination routes is a promising approach for achieving more potent immune responses. We evaluated the immunogenicity of prime-boost protocols with a chimpanzee adenovirus serotype 68 vector-based vaccine, ChAdTS-S, administered via both intranasal and intramuscular routes in BALB/c mice. Intramuscular priming followed by an intranasal booster elicited the highest levels of IgG, IgA, and pseudovirus neutralizing antibody titres among all the protocols tested at day 42 after prime immunization compared with the intranasal priming/intramuscular booster and prime-boost protocols using only one route. In addition, intramuscular priming followed by an intranasal booster induced high T-cell responses, measured using the IFN-γ ELISpot assay, that were similar to those observed upon intramuscular vaccination. All ChAdTS-S vaccination groups induced Th1-skewing of the T-cell response according to intracellular cytokine staining and Meso Scale Discovery cytokine profiling assays on day 56 after priming. This study provides reference data for assessing vaccination schemes of adenovirus-based COVID-19 vaccines with high immune efficacy.


Subject(s)
COVID-19 Vaccines , COVID-19 , Adenoviridae/genetics , Animals , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines/immunology , Cytokines , Immunity, Cellular , Immunity, Humoral , Immunization, Secondary , Mice , Mice, Inbred BALB C , Pan troglodytes , SARS-CoV-2 , Vaccination
6.
BMJ Open ; 12(1), 2022.
Article in English | ProQuest Central | ID: covidwho-1849454

ABSTRACT

ObjectivesThis study aimed to examine the prevalence of peritraumatic stress symptoms (PTSSs), perceived threat, social support and factors contributing to clinically significant PTSS among frontline COVID-19 healthcare workers (HCWs) in China.Design and settingAn online survey through self-administered questionnaires was conducted from 18 February to 4 March 2020, during the outbreak of COVID-19.Outcomes measuresPTSS was assessed using the post-traumatic stress disorder (PTSD) self-rating scale. Demographic and socioeconomic characteristics, self-reported health, physical/psychological symptoms, perceived threat from frontline work and perceived social support were investigated. Multivariable line regression analysis distinguished factors associated with HCWs’ PTSS scores.ResultsA total of 676 (58.1%) HCWs have shown clinically significant high levels of PTSS. Only 441 (37.9%) self-reported good health. Most had physical symptom(s) (915 (78.7%)), psychological symptom(s) (906 (77.9%)), inability to vent emotions (284 (24.4%)), emotional exhaustion (666 (57.3%)) and 1037 (89.2%) needed professional respect. Moreover, social support received was less than expected, and the receipt of psychological services/help scored the lowest (3.11±1.73). Combined psychological and physical symptoms, difficulty in releasing tension and venting emotions timely, fear of infection, emotional exhaustion and depersonalisation are significantly associated with PTSS scores among frontline HCWs. Working ≥8 hours, having the senior professional title, self-reported health, enjoying perfect protection and control measures, economic subsidy and control policy on reducing discriminatory practices are negatively correlated with PTSS scores.ConclusionsDuring the outbreak of COVID-19, frontline HCWs experienced clinically significant high levels of PTSS and heavy workload, and the emergency resulted in their inadequate psychosocial support. If this is left unchecked, HCWs have a higher risk of developing PTSD. Early detection, identification and person-directed, targeted multidisciplinary interventions should be undertaken to address various influencing factors. Comprehensive measures, including setting up emotional release channels, as well as providing psychological and social support intervention for HCWs globally, are highly recommended.

7.
Signal Transduct Target Ther ; 7(1): 94, 2022 03 23.
Article in English | MEDLINE | ID: covidwho-1758181

ABSTRACT

To date, the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has determined 399,600,607 cases and 5,757,562 deaths worldwide. COVID-19 is a serious threat to human health globally. The World Health Organization (WHO) has declared COVID-19 pandemic a major public health emergency. Vaccination is the most effective and economical intervention for controlling the spread of epidemics, and consequently saving lives and protecting the health of the population. Various techniques have been employed in the development of COVID-19 vaccines. Among these, the COVID-19 messenger RNA (mRNA) vaccine has been drawing increasing attention owing to its great application prospects and advantages, which include short development cycle, easy industrialization, simple production process, flexibility to respond to new variants, and the capacity to induce better immune response. This review summarizes current knowledge on the structural characteristics, antigen design strategies, delivery systems, industrialization potential, quality control, latest clinical trials and real-world data of COVID-19 mRNA vaccines as well as mRNA technology. Current challenges and future directions in the development of preventive mRNA vaccines for major infectious diseases are also discussed.


Subject(s)
COVID-19 Vaccines , COVID-19 , COVID-19/prevention & control , COVID-19 Vaccines/genetics , Humans , Pandemics/prevention & control , RNA, Messenger/genetics , SARS-CoV-2/genetics , Vaccines, Synthetic , mRNA Vaccines
9.
Foods ; 10(11)2021 Oct 26.
Article in English | MEDLINE | ID: covidwho-1533878

ABSTRACT

The main goal of this online survey was to investigate the attitudes of Brazilians towards "cell-based meat", which has become the subject of great scientific and media enthusiasm. The answers of 4471 respondents concluded that 46.6% of them thought "cell-based meat" was promising and acceptable. More than 66% would be willing to try this novel product compared to 23% who expressed reluctance to do so. Nearly 40% of the total respondents did not want to eat "cell-based meat" regularly at all, whereas 29%, 43.2%, and 39.9% were willing to eat it regularly in restaurants, at home, and/or in ready-made meals, respectively. However, the majority of respondents (71%) were keen to pay much less for "cell-based meat" than conventionally produced meat (or even nothing at all), compared to 24.3% who were willing to pay the same price as conventional meat, whereas only 4.8% were willing to pay more. Approximately 51% of them considered that "cell-based meat" should not be called "meat" for marketing purposes. Job, monthly income, age, and gender were major factors impacting consumer acceptance. Meat professionals and consumers with higher incomes were less willing to eat "cell-based meat" regularly. Women (especially younger women) were the most concerned about the ethical and environmental issues related to meat production and were the most convinced that reducing meat consumption could be a good solution to the meat industry's problems. Respondents who did not accept "cell-based meat" and did not eat meat substitutes had a negative attitude to this novel food (they considered it absurd and/or disgusting) and did not believe that "cell-based meat" should be called "meat" for marketing purposes. In contrast, the people who thought that "cell-based meat" could be called "meat" perceived it in a rather positive way. These results are important for consumers of meat and meat substitutes and for companies aiming to enter the potential future Brazilian market of "cell-based meat".

10.
Signal Transduct Target Ther ; 6(1): 213, 2021 05 31.
Article in English | MEDLINE | ID: covidwho-1249203

ABSTRACT

Although inoculation of COVID-19 vaccines has rolled out globally, there is still a critical need for safe and effective vaccines to ensure fair and equitable supply for all countries. Here, we report on the development of a highly efficacious mRNA vaccine, SW0123 that is composed of sequence-modified mRNA encoding the full-length SARS-CoV-2 Spike protein packaged in core-shell structured lipopolyplex (LPP) nanoparticles. SW0123 is easy to produce using a large-scale microfluidics-based apparatus. The unique core-shell structured nanoparticle facilitates vaccine uptake and demonstrates a high colloidal stability, and a desirable biodistribution pattern with low liver targeting effect upon intramuscular administration. Extensive evaluations in mice and nonhuman primates revealed strong immunogenicity of SW0123, represented by induction of Th1-polarized T cell responses and high levels of antibodies that were capable of neutralizing not only the wild-type SARS-CoV-2, but also a panel of variants including D614G and N501Y variants. In addition, SW0123 conferred effective protection in both mice and non-human primates upon SARS-CoV-2 challenge. Taken together, SW0123 is a promising vaccine candidate that holds prospects for further evaluation in humans.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/prevention & control , COVID-19/virology , COVID-19 Vaccines/therapeutic use , Female , Humans , Immunogenicity, Vaccine/immunology , Lymphocyte Activation/immunology , Mice , SARS-CoV-2/pathogenicity , Spike Glycoprotein, Coronavirus/antagonists & inhibitors , Th1 Cells/immunology , Th1 Cells/virology , Vaccines, Synthetic/immunology , Vaccines, Synthetic/therapeutic use , Viral Vaccines/immunology
12.
Int J Infect Dis ; 102: 319-326, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-1060136

ABSTRACT

OBJECTIVES: There was an outbreak of pediatric multisystem inflammation syndrome (PMIS) was observed in multiple countries recently, and this syndrome was suspected to be associated with SARS-CoV-2 infection. At present, there is still no standardized diagnostic criteria and treatment regimen for PMIS, while the etiology and pathogenesis still remain unclear. METHODS: We performed a systematic review on PubMed and Embase from the time of inception to June 24th 2020 in order to find relevant cases. RESULTS: There are seven studies included, and 80% of patients suffered persistent fever and 90% appeared gastrointestinal symptoms. IgG antibody against SARS-CoV-2 was positive on 81% of patients, while 37% of the patients were nucleic acid positive. C-reactive protein, IL-6 and PCT were elevated and intravenous immunoglobulin was a routine treatment for PMIS. There were more than half of patients required inotropic supports and mechanical ventilation were applied to 33% of patients. The median length of hospital stay was 10.66 days and 74% had admitted to accept intensive care. CONCLUSIONS: Our study documented three common types of PMIS clinical presentation: persistent fever and gastrointestinal symptoms, shocked with heart dysfunction and Kawasaki disease-like syndrome. PMIS patients proved with a marked inflammatory state were possibly associated with SARS-CoV-2 infection.


Subject(s)
COVID-19 Drug Treatment , COVID-19/diagnosis , Systemic Inflammatory Response Syndrome/diagnosis , Systemic Inflammatory Response Syndrome/drug therapy , Adolescent , COVID-19/virology , Child , Child, Preschool , Critical Care , Female , Humans , Immunoglobulin G/administration & dosage , Length of Stay , Male , Respiration, Artificial , SARS-CoV-2/physiology , Systemic Inflammatory Response Syndrome/virology
13.
Academic Journal of Second Military Medical University ; 41(8):824-827, 2020.
Article in Chinese | GIM | ID: covidwho-1006269

ABSTRACT

Since the outbreak of the coronavirus disease 2019 (COVID-19), tens of thousands of medical staff and paramedical staff have been involved in the treatment of COVID-19 patients. Heavy personal protective equipment and continuous high-intensity work have brought great challenges to the staff. Fainting incidents occur frequently in the isolation ward. The emergency treatment after fainting is directly related to the safety and health of the injured. Based on the latest domestic and international literatures and guidelines, we proposed a first-aid procedure for staff who fainted in the isolation ward, aiming to provide reference for the treatment of staff fainting in the isolation ward.

14.
Biomed Pharmacother ; 133: 111072, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-987144

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a progressive pulmonary interstitial inflammatory disease of unknown etiology, and is also a sequela in severe patients with the Coronavirus Disease 2019 (COVID-19). Nintedanib and pirfenidone are the only two known drugs which are conditionally recommended for the treatment of IPF by the FDA. However, these drugs pose some adverse side effects such as nausea and diarrhoea during clinical applications. Therefore, it is of great value and significance to identify effective and safe therapeutic drugs to solve the clinical problems associated with intake of western medicine. As a unique medical treatment, Traditional Chinese Medicine (TCM) has gradually exerted its advantages in the treatment of IPF worldwide through a multi-level and multi-target approach. Further, to overcome the current clinical problems of oral and injectable intakes of TCM, pulmonary drug delivery system (PDDS) could be designed to reduce the systemic metabolism and adverse reactions of the drug and to improve the bioavailability of drugs. Through PubMed, Google Scholar, Web of Science, and CNKI, we retrieved articles published in related fields in recent years, and this paper has summarized twenty-seven Chinese compound prescriptions, ten single TCM, and ten active ingredients for effective prevention and treatment of IPF. We also introduce three kinds of inhaling PDDS, which supports further research of TCM combined with PDDS to treat IPF.


Subject(s)
COVID-19/complications , Drugs, Chinese Herbal/therapeutic use , Idiopathic Pulmonary Fibrosis/drug therapy , Medicine, Chinese Traditional/methods , Phytotherapy , Drug Compounding , Drugs, Chinese Herbal/administration & dosage , Drugs, Chinese Herbal/chemistry , History, 15th Century , History, 16th Century , History, 17th Century , History, 18th Century , History, 19th Century , History, 20th Century , History, Ancient , History, Medieval , Humans , Idiopathic Pulmonary Fibrosis/etiology , Idiopathic Pulmonary Fibrosis/prevention & control , Medicine, Chinese Traditional/history , Nebulizers and Vaporizers , Respiratory Therapy
15.
Blood Purif ; 50(4-5): 513-519, 2021.
Article in English | MEDLINE | ID: covidwho-975762

ABSTRACT

BACKGROUND: In December 2019, pneumonia associated with COVID-19 has spread from Wuhan to other areas in China. In the present study, we aimed to further clarify the clinical features and outcomes of acute kidney injury (AKI) in patients infected with COVID-19 in Xiangyang, Hubei, China. METHODS: All confirmed cases of COVID-19 with AKI in Xiangyang Central Hospital from January 22 to May 31, 2020, were included in this retrospective study. Data of epidemiological, clinical, laboratory, radiological tests, treatment, complication, and outcomes were collected and analyzed. Patients were divided into intensive care unit (ICU) group and isolation ward (non-ICU) group. RESULTS: Of the total patients, 33.3% in the non-ICU group and 85.7% in the ICU group had chronic diseases. In addition, 85.7% of patients in the ICU group died. The most common symptoms were fever, cough, and fatigue. The lymphocyte count in the ICU group was significantly reduced compared with the non-ICU group. The chest computed tomography (CT) images appeared showed multiple mottles and ground-glass opacity. Strip shadow could be found in chest CT images of some recovered patients. All patients received antiviral treatment. Most patients in the ICU group were given methylprednisolone, immunoglobulin, antibiotics, and mechanical ventilation and 35.7% of patients in the ICU group received continuous renal replacement therapy. CONCLUSIONS: Elderly with chronic comorbidities were more susceptible to COVID-19, showing a higher mortality rate due to multiple organ damage, and 35.7% of patients with AKI in ICU received renal replacement therapy. Moreover, part of the cured patients might need additional time to recover for poor lung function.


Subject(s)
Acute Kidney Injury/epidemiology , COVID-19/complications , Hospital Mortality , SARS-CoV-2 , Acute Kidney Injury/etiology , Acute Kidney Injury/therapy , Adult , Aged , Antiviral Agents/therapeutic use , COVID-19/blood , COVID-19/diagnostic imaging , COVID-19/therapy , Cardiovascular Agents/therapeutic use , Cardiovascular Diseases/drug therapy , Cardiovascular Diseases/epidemiology , China/epidemiology , Chronic Disease/mortality , Comorbidity , Female , Hospitals, Urban/statistics & numerical data , Humans , Immunization, Passive , Intensive Care Units/statistics & numerical data , Lymphocyte Count , Male , Middle Aged , Multiple Organ Failure/etiology , Multiple Organ Failure/mortality , Plasma Exchange/methods , Plasma Exchange/statistics & numerical data , Renal Dialysis/methods , Renal Dialysis/statistics & numerical data , Renal Insufficiency, Chronic/complications , Respiration, Artificial/adverse effects , Respiration, Artificial/statistics & numerical data , Retrospective Studies , Symptom Assessment , Tomography, X-Ray Computed , COVID-19 Drug Treatment , COVID-19 Serotherapy
16.
Front Psychiatry ; 11: 575705, 2020.
Article in English | MEDLINE | ID: covidwho-940205

ABSTRACT

Background: The outbreak of coronavirus disease 2019 in Wuhan, Hubei Province, China has seriously affected people's mental health. We aimed to assess the psychological impact of the coronavirus disease 2019 on health care workers and non-health care workers in three different epidemic areas in China and to identify independent risk factors. Methods: We surveyed 1,020 non-health care workers and 480 health care workers in Wuhan, other cities in Hubei except Wuhan and other provinces in China except Hubei. Results: Health care workers in Hubei had higher levels of anxiety and depression than non-health care workers (p < 0.05), but there was no such difference in other provinces in China except Hubei (p > 0.05). Compared with other regions, health care workers in Wuhan was more anxious (p < 0.05), and this anxiety may be caused by concerns about occupational exposure and wearing protective clothing for a long time daily; health care workers in Hubei had more obvious depression (p < 0.05), which may be associated with long days participating in epidemic work and wearing protective clothing for a long time daily. Meanwhile, 62.5% of health care workers were proud of their work. The anxiety and depression of non-health care workers in Wuhan were also the most serious. Conclusions: In Wuhan, where the epidemic is most severe, levels of anxiety and depression seem to be higher, especially among health care workers. This information may help to better prepare for future events.

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.
Ann Transl Med ; 8(10): 642, 2020 May.
Article in English | MEDLINE | ID: covidwho-609917

ABSTRACT

BACKGROUND: Since early December 2019, the 2019 novel coronavirus (COVID-19) has emerged in Wuhan and spread rapidly in China. We aimed to describe the clinical characteristics of hospitalized patients with confirmed COVID-19 infection in Shaoxing, and provide an insight into the treatment of COVID-19 across China and elsewhere. METHODS: In this retrospective, single-center, study, we enrolled 16 patients with laboratory-confirmed COVID-19 admitted to the Affiliated Hospital of Shaoxing University between February 24 and January 25, 2020. Epidemiological, demographic, clinical, laboratory, radiological feature, and treatment data were all collected. Outcomes were followed up until March 16, 2020. RESULTS: Among the 16 patients with COVID-19 infection, 11 patients (68.8%) had traveled or lived in Wuhan or surrounding areas, and 2 (12.5%) patients had exposure to patients with confirmed COVID-19 infection. The average age of the patients was 44.1 (16.5) years, and there were 10 women (62.5%) and 6 men (37.5%). More than half had chronic diseases [9 (56.3%)]. The most common symptoms at onset of COVID-19 infection were fever [12 (75%)] and cough [8 (50%)]; 11 (68.8%) patients had lymphopenia, and 12 (75%) had elevated C-reactive protein. On admission, abnormalities in computed tomography (CT) or chest X-ray images were revealed among all patients, and 11 (68.8%) of 16 patients had bilateral involvement. All patients were given psychological counseling, 15 (93.8%) patients were administered with antiviral therapy, 8 (50%) received empirical antibiotic treatment, and 5 (31.3%) patients were given systematic corticosteroids. Complications included acute respiratory distress syndrome (ARDS) requiring non-invasive mechanical ventilation [1 (6.3%)], acute respiratory injury [4 (25%)], acute renal injury [1 (6.3%)], septic shock [1 (6.3%)], liver dysfunction [5 (31.3%)], electrolyte disturbance [8 (50.0%)], and hospital-acquired pneumonia [3 (18.8%)]. None of the 16 patients died of COVID-19 pneumonia. CONCLUSIONS: Compared with the symptoms of the initial patients with COVID-19 infection in Wuhan, the symptoms of the patients from Shaoxing city were relatively mild. Currently, there is no effective drug treatment or vaccine for COVID-19, and psychological counseling cannot be ignored. Drugs and vaccines against COVID-19 infection need to be developed as soon as possible.

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