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1.
Emerg Microbes Infect ; 11(1): 1550-1553, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-1860765

ABSTRACT

In order to overcome the pandemic of COVID-19, messenger RNA (mRNA)-based vaccine has been extensively researched as a rapid and versatile strategy. Herein, we described the immunogenicity of mRNA-based vaccines for Beta and the most recent Omicron variants. The homologous mRNA-Beta and mRNA-Omicron and heterologous Ad5-nCoV plus mRNA vaccine exhibited high-level cross-reactive neutralization for Beta, original, Delta, and Omicron variants. It indicated that the COVID-19 mRNA vaccines have great potential in the clinical use against different SARS-CoV-2 variants.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Neutralizing , Antibodies, Viral , BNT162 Vaccine , COVID-19/prevention & control , Humans , RNA, Messenger/genetics , SARS-CoV-2/genetics , Vaccines, Synthetic , mRNA Vaccines
2.
Lancet ; 399(10321): 237-248, 2022 01 15.
Article in English | MEDLINE | ID: covidwho-1815307

ABSTRACT

BACKGROUND: The Ad5-nCoV vaccine is a single-dose adenovirus type 5 (Ad5) vectored vaccine expressing the SARS-CoV-2 spike protein that was well-tolerated and immunogenic in phase 1 and 2 studies. In this study, we report results on the final efficacy and interim safety analyses of the phase 3 trial. METHODS: This double-blind, randomised, international, placebo-controlled, endpoint-case driven, phase 3, clinical trial enrolled adults aged 18 years older at study centres in Argentina, Chile, Mexico, Pakistan, and Russia. Participants were eligible for the study if they had no unstable or severe underlying medical or psychiatric conditions; had no history of a laboratory-confirmed SARS-CoV-2 infection; were not pregnant or breastfeeding; and had no previous receipt of an adenovirus-vectored, coronavirus, or SARS-CoV-2 vaccine. After informed consent was obtained, 25 mL of whole blood was withdrawn from all eligible participants who were randomised in a 1:1 ratio to receive a single intramuscular dose of 0·5 mL placebo or a 0·5 mL dose of 5 × 1010 viral particle (vp)/mL Ad5-nCoV vaccine; study staff and participants were blinded to treatment allocation. All participants were contacted weekly by email, telephone, or text message to self-report any symptoms of COVID-19 illness, and laboratory testing for SARS-CoV-2 was done for all participants with any symptoms. The primary efficacy objective evaluated Ad5-nCoV in preventing symptomatic, PCR-confirmed COVID-19 infection occurring at least 28 days after vaccination in all participants who were at least 28 days postvaccination on Jan 15, 2021. The primary safety objective evaluated the incidence of any serious adverse events or medically attended adverse events postvaccination in all participants who received a study injection. This trial is closed for enrolment and is registered with ClinicalTrials.gov (NCT04526990). FINDINGS: Study enrolment began on Sept 22, 2020, in Pakistan, Nov 6, 2020, in Mexico, Dec 2, 2020, in Russia and Chile, and Dec 17, 2020, in Argentina; 150 endpoint cases were reached on Jan 15, 2021, triggering the final primary efficacy analysis. One dose of Ad5-nCoV showed a 57·5% (95% CI 39·7-70·0, p=0·0026) efficacy against symptomatic, PCR-confirmed, COVID-19 infection at 28 days or more postvaccination (21 250 participants; 45 days median duration of follow-up [IQR 36-58]). In the primary safety analysis undertaken at the time of the efficacy analysis (36 717 participants), there was no significant difference in the incidence of serious adverse events (14 [0·1%] of 18 363 Ad5-nCoV recipients and 10 [0·1%] of 18 354 placebo recipients, p=0·54) or medically attended adverse events (442 [2·4%] of 18 363 Ad5-nCoV recipients and 411 [2·2%] of 18 354 placebo recipients, p=0·30) between the Ad5-nCoV or placebo groups, or any serious adverse events considered related to the study product (none in both Ad5-nCoV and placebo recipients). In the extended safety cohort, 1004 (63·5%) of 1582 of Ad5-nCoV recipients and 729 (46·4%) of 1572 placebo recipients reported a solicited systemic adverse event (p<0·0001), of which headache was the most common (699 [44%] of Ad5-nCoV recipients and 481 [30·6%] of placebo recipients; p<0·0001). 971 (61·3%) of 1584 Ad5-nCoV recipients and 314 (20·0%) of 1573 placebo recipients reported an injection-site adverse event (p<0·0001), of which pain at the injection site was the most frequent; reported by 939 (59%) Ad5-nCoV recipients and 303 (19%) placebo recipients. INTERPRETATION: One dose of Ad5-nCoV is efficacious and safe in healthy adults aged 18 years and older. FUNDING: CanSino Biologics and the Beijing Institute of Biotechnology.


Subject(s)
COVID-19 Vaccines/administration & dosage , COVID-19/prevention & control , Adolescent , Adult , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19/diagnosis , COVID-19/immunology , COVID-19/virology , COVID-19 Nucleic Acid Testing/statistics & numerical data , COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/immunology , Double-Blind Method , Female , Follow-Up Studies , Humans , Immunogenicity, Vaccine , Male , Middle Aged , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Vaccination/methods , Young Adult
3.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-330389

ABSTRACT

The SARS-CoV-2 Omicron variant has become the dominant SARS-CoV-2 variant around the world and exhibits immune escape to current COVID-19 vaccines to some extent due to its numerous spike mutations. Here, we evaluated the immune responses to booster vaccination with intramuscular adenovirus-vectored vaccine (Ad5-nCoV), aerosolized Ad5-nCoV, a recombinant protein subunit vaccine (ZF2001) or homologous inactivated vaccine (CoronaVac) in those who received two doses of inactivated COVID-19 vaccines 6 months prior. We found that the Ad5-nCoV booster induced potent neutralizing activity against the wild-type virus and Omicron variant, while aerosolized Ad5-nCoV generated the greatest neutralizing antibody responses against the Omicron variant at day 28 after booster vaccination, at 14.1-fold that of CoronaVac, 5.6-fold that of ZF2001 and 2.0-fold that of intramuscular Ad5-nCoV. Similarly, the aerosolized Ad5-nCoV booster produced the greatest IFNγ T-cell response at day 14 after booster vaccination. The IFNγ T-cell response to aerosolized Ad5-nCoV was 12.8-fold for CoronaVac, 16.5-fold for ZF2001, and 5.0-fold for intramuscular Ad5-nCoV. Aerosolized Ad5-nCoV booster also produced the greatest spike-specific B cell response. Our findings suggest that inactivated vaccine recipients should consider adenovirus-vectored vaccine boosters in China and that aerosolized Ad5-nCoV may provide a more efficient alternative in response to the spread of the Omicron variant.

4.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-330226

ABSTRACT

Background To determine the immunogenicity, efficacy, reactogenicity, and safety of a single dose of recombinant adenovirus type-5 vectored COVID-19 vaccine (Ad5-nCoV, 5 × 10 10 viral particles per 0.5 mL dose), we conducted a single-dose, randomised, double-blind, placebo-controlled, parallel group (3:1 Ad5-nCoV:placebo), phase 3 trial (Prometheus). Methods From 11-September-2020 to 05-May-2021, across six sites in the Russian Federation, 496 participants were injected with either placebo or Ad5-nCoV expressing the full-length spike (S) protein from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Results Seroconversion (the primary endpoint) rates of 78.5% (95% CI: 73.9;82.6) against receptor binding domain (RBD), 90.6% (95% CI: 87.2;93.4) against S protein and 59% (95% CI: 53.3;64.6) against neutralising SARS-CoV2 antibodies 28 days post-vaccination. Geometric mean titres (GMTs) were also elevated for antibodies against the RBD (405.32 [95% CI: 361.58;454.46]) and S protein (678.86 [95% CI: 607.44;754.40]) compared to the GMT of neutralising antibodies against SARS-CoV-2 (16.73 [95% CI: 15.36;18.22]). Using an IFN-γ ELISpot assay after stimulating the cells with full-length S protein we showed that the Ad5-nCoV vaccine induced the most robust cellular immune response on Days 14 and 28. Up to Day 28, the primary and all secondary endpoints of the Ad5-nCoV vaccine were statistically superior to the placebo (р <0.001). Systemic reactions were reported in 113 of 496 (22.8%) participants (Ad5-nCoV, 26.9%;Placebo, 10.5%), and local reactions were reported in 108 (21.8%) participants (Ad5-nCoV, 28.5%;Placebo, 1.6%). These were generally mild and resolved within 7 days after vaccination. Of the six serious adverse events reported, none of the events were vaccine related. There were no deaths or premature withdrawals. Conclusion A single-dose of Ad5-nCoV vaccine induced a marked specific humoral and cellular immune response with a favourable safety profile. Trial Registration ClinicalTrials.gov: NCT04540419

5.
Nat Prod Res ; : 1-5, 2021 Nov 30.
Article in English | MEDLINE | ID: covidwho-1730494

ABSTRACT

Artemisia argyi is a widely distributed and inexpensive plant resource, and study on its chemical compositions and biological activities will provide an important basis for its food applications and pharmaceutical developments. In this study, fourteen known guaiane-type sesquiterpenes (1-14), four known eudesmane-type sesquiterpenes (15-18), two known germacranolide-type sesquiterpenes (19, 20), and eight other types of terpenoids (20-28) were isolated from the leaves of A. argyi by polyamide and ODS CC and HPLC. The structures of all compounds are determined by 1 D NMR (1H-NMR、13C-NMR) and literature comparison. Among them, compounds 1 and 8 were isolated from Chinese folk medicine A. argyi for the first time. Besides, the LPS-induced RAW264.7 cell model has been evaluated the anti-inflammatory activities in vitro by the Griess reagent. The results indicated that the guaianolide sesquiterpenoids obtained from A. argyi have an excellent ability to inhibit NO production, especially Argyin A, a guaianolide sesquiterpenoid with isovaleryloxy substitution.

6.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-325437

ABSTRACT

Background: Coronavirus disease 2019 (COVID-19) outbreak has spread around the world, the high mortality rate and strong infectious cause surging global patients diagnosed patients and death while in response to the outbreak, a myriad of scientific research workers and researchers have made unremitting efforts, but effective treatments are still limited, even may say that there is no specific treatment. So a large number of patients with severe patients need treatment for respiratory support, in particular, based on various realistic factors, different way of ventilation is widely used in clinical, which kind of ventilation way is the best one of the most effective ventilation strategy is not clear, so we planned a network meta-analysis to evaluate different ventilation methods on new crown the efficacy and safety of patients, expect to find an optimal ventilation strategy. Methods: and analysis: Two authors will independently search the electronic databases, preprints databases, Clinical Study Registration website and COVID-19 research related project database from December 1, 2019 to November 5, 2020. The primary outcomes are 1) All-cause mortality;2) Transmission of COVID-19 to health care workers and other people;3) Length of hospital stay;4) Length of ICU stay. A systemic review and a network meta-analysis based on Bayesian framework will be performed to assess the effect of different ventilation modes on the outcomes of patients infected with COVID-19. The Grading of Recommendations Assessment, Development and Evaluation System (GRADE) will be used to evaluate the quality of evidence. Discussion: COVID-19 has spread around the world and become a global public health security problem. With limited treatment available, a large number of critically ill patients need ventilator support treatment, and the demand for ventilators has increased sharply. To our knowledge, this study will be the first systematic review and NMA to analyze the efficacy and safety of different ventilation modes in patients with COVID-19. This study expected to obtain the best choice of ventilation mode for COVID-19 patients based on high quality evidence. Ethics and dissemination: Ethical approval is not required owning to it is a literature-based study. The final conclusion will be disseminated through peer-reviewed publication. PROSPERO registration number: CRD42020219581

7.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-324319

ABSTRACT

Background: Due to the increased risk of viral infection and the severe shortage of medical resources during the pandemic of COVID-19, most hospitals in the epidemic areas significantly reduced non-emergency admissions and services, if not closed. As a result, it has been difficult to treat cancer patients on time, which adversely affects their prognosis. To address this problem, cancer centers must develop a strategic plan to manage both inpatients and outpatients during the pandemic, provide them with the necessary treatment, and at the same time prevent the spread of the virus among patients, visitors and medical staff. Methods: : Based upon the epidemic situation in Zhejiang Province, China, the number of running non-emergency medical wards in the Zhejiang Cancer Hospital was gradually increased in a controlled manner. All staff of the hospital received COVID-19 preventive training and was provided with three different levels of protection according to the risks of their services. Only patients without a known history of SARS-CoV-2 contact were eligible to schedule an appointment. Body temperature was measured on all patients upon their arrival at the hospital. Chest CT image, blood cell counting and travel/contact history were investigated in patients with fever. Respiratory tract samples, such as sputum and throat swabs, from all patients, including those clinically suspected of SARS-CoV-2 infection, were collected for nucleic acid detection of SARS-CoV-2 before treatment. Results: : A total of 3697 inpatients and 416 outpatients seeking cancer treatment were enrolled from February 1 to April 3, 2020, in compliance with the hospital’s infection-control interventions. The clinicopathological parameters of the patients were summarized herein. 4237 samples from 4101 patients produced negative RNA testing results. Four clinically suspected patients all presented negative RNA test results and were excluded from the SARS-CoV-2 infection through follow-up retesting and monitoring. Seven patients with only N-gene positive results were retested, followed by CT scan and SARS-CoV-2 contact history investigation. All of them were finally diagnosed as non-infected patients. There was one outpatient who was confirmed positive by virus RNA test and then followed up. She might be an asymptomatic laboratory-confirmed case. During the study period, there was no SARS-CoV-2 infection among staff, patients and escorts of patients in the Zhejiang Cancer Hospital. Conclusion: This study suggested our infection-control interventions, including viral nucleic acid test, could be used as a reliable method to screen cancer patients in the area with moderate COVID-19 prevalence. Cancer may not be a high-risk factor of SARS-CoV-2 infection.

8.
Emerg Microbes Infect ; 11(1): 438-441, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-1662090

ABSTRACT

Mucosal immunity provides a potential for preventing initial infection and stopping subsequent transmission of SARS-CoV-2. Here, we examined the safety and immunogenicity of a replication-defective adenovirus type-5 vectored vaccine (Ad5-nCov) encoding SARS-CoV-2 spike protein delivered by nebulization inhalation in rhesus macaques. The vaccine-associated clinical pathology and toxicity were not observed in the NHP model. The extensive safety study indicated that Ad5-nCoV was mainly confined to the organs related to respiratory system and was rapidly cleared away from the system. Our results showed that Ad5-nCoV delivered by inhalation robustly elicited both systematic and mucosal immune responses against SARS-nCoV-2 and variants. Thus, Ad5-nCoV inhalation may provide an effective, safe and non-invasive vaccination strategy for the control of SARS-CoV-2.


Subject(s)
Adenoviridae/immunology , COVID-19 Vaccines/immunology , COVID-19/immunology , Genetic Vectors/immunology , Immunity, Mucosal , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Adenoviridae/genetics , Administration, Inhalation , Animals , COVID-19/prevention & control , COVID-19/virology , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/genetics , Disease Models, Animal , Genetic Vectors/genetics , Humans , Immunogenicity, Vaccine , Macaca mulatta , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/administration & dosage , Spike Glycoprotein, Coronavirus/genetics
9.
Nat Med ; 28(2): 401-409, 2022 02.
Article in English | MEDLINE | ID: covidwho-1655605

ABSTRACT

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and the waning of vaccine-elicited neutralizing antibodies suggests that additional coronavirus disease 2019 (COVID-19) vaccine doses may be needed for individuals who initially received CoronaVac. We evaluated the safety and immunogenicity of the recombinant adenovirus type 5 (AD5)-vectored COVID-19 vaccine Convidecia as a heterologous booster versus those of CoronaVac as homologous booster in adults previously vaccinated with CoronaVac in an ongoing, randomized, observer-blinded, parallel-controlled phase 4 trial ( NCT04892459 ). Adults who had received two doses of CoronaVac in the past 3-6 months were vaccinated with Convidecia (n = 96) or CoronaVac (n = 102). Adults who had received one dose of CoronaVac in the past 1-3 months were also vaccinated with Convidecia (n = 51) or CoronaVac (n = 50). The co-primary endpoints were the occurrence of adverse reactions within 28 d after vaccination and geometric mean titers (GMTs) of neutralizing antibodies against live wild-type SARS-CoV-2 virus at 14 d after booster vaccination. Adverse reactions after vaccination were significantly more frequent in Convidecia recipients but were generally mild to moderate in all treatment groups. Heterologous boosting with Convidecia elicited significantly increased GMTs of neutralizing antibody against SARS-CoV-2 than homologous boosting with CoronaVac in participants who had previously received one or two doses of CoronaVac. These data suggest that heterologous boosting with Convidecia following initial vaccination with CoronaVac is safe and more immunogenic than homologous boosting.


Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/immunology , Immunogenicity, Vaccine/immunology , SARS-CoV-2/immunology , Adenoviridae/immunology , Adolescent , Adult , COVID-19/immunology , COVID-19/prevention & control , China , Female , Humans , Immunization, Secondary , Immunoglobulin G/blood , Injection Site Reaction/pathology , Male , Middle Aged , T-Lymphocytes/immunology , Vaccination , Vaccines, Inactivated/immunology , Young Adult
10.
Lancet Infect Dis ; 21(12): 1654-1664, 2021 12.
Article in English | MEDLINE | ID: covidwho-1531911

ABSTRACT

BACKGROUND: SARS-CoV-2 has caused millions of deaths, and, since Aug 11, 2020, 20 intramuscular COVID-19 vaccines have been approved for use. We aimed to evaluate the safety and immunogenicity of an aerosolised adenovirus type-5 vector-based COVID-19 vaccine (Ad5-nCoV) in adults without COVID-19 from China. METHOD: This was a randomised, single-centre, open-label, phase 1 trial done in Zhongnan Hospital (Wuhan, China), to evaluate the safety and immunogenicity of the Ad5-nCoV vaccine by aerosol inhalation in adults (≥18 years) seronegative for SARS-CoV-2. Breastfeeding or pregnant women and people with major chronic illnesses or history of allergies were excluded. Participants were enrolled and randomly assigned (1:1:1:1:1) into five groups to be vaccinated via intramuscular injection, aerosol inhalation, or both. Randomisation was stratified by sex and age (18-55 years or ≥56 years) using computer-generated randomisation sequences (block sizes of five). Only laboratory staff were masked to group assignment. The participants in the two aerosol groups received an initial high dose (2 × 1010 viral particles; HDmu group) or low dose (1 × 1010 viral particles; LDmu group) of Ad5-nCoV vaccine on day 0, followed by a booster on day 28. The mixed vaccination group received an initial intramuscular (5 × 1010 viral particles) vaccine on day 0, followed by an aerosolised booster (2 × 1010 viral particles) vaccine on day 28 (MIX group). The intramuscular groups received one dose (5 × 1010 viral particles; 1Dim group) or two doses (10 × 1010 viral particles; 2Dim group) of Ad5-nCoV on day 0. The primary safety outcome was adverse events 7 days after each vaccination, and the primary immunogenicity outcome was anti-SARS-CoV-2 spike receptor IgG antibody and SARS-CoV-2 neutralising antibody geometric mean titres at day 28 after last vaccination. This trial is registered with ClinicalTrials.gov, number NCT04552366. FINDINGS: Between Sept 28, 2020, and Sept 30, 2020, 230 individuals were screened for inclusion, of whom 130 (56%) participants were enrolled into the trial and randomly assigned into one of the five groups (26 participants per group). Within 7 days after vaccination, adverse events occurred in 18 (69%) in the HDmu group, 19 (73%) in the LDmu group, 19 (73%) in the MIX group, 19 (73%) in the 1Dim group, and 15 (58%) in the 2Dim group. The most common adverse events reported 7 days after the first or booster vaccine were fever (62 [48%] of 130 participants), fatigue (40 [31%] participants), and headache (46 [35%] participants). More adverse events were reported in participants who received intramuscular vaccination, including participants in the MIX group (49 [63%] of 78 participants), than those who received aerosol vaccine (13 [25%] of 52 participants) after the first vaccine vaccination. No serious adverse events were noted within 56 days after the first vaccine. At days 28 after last vaccination, geometric mean titres of SARS-CoV-2 neutralising antibody was 107 (95% CI 47-245) in the HDmu group, 105 (47-232) in the LDmu group, 396 (207-758) in the MIX group, 95 (61-147) in the 1Dim group, and 180 (113-288) in the 2Dim group. The geometric mean concentrations of receptor binding domain-binding IgG was 261 EU/mL (95% CI 121-563) in the HDmu group, 289 EU/mL (138-606) in the LDmu group, 2013 EU/mL (1180-3435) in the MIX group, 915 EU/mL (588-1423) in the 1Dim group, and 1190 EU/mL (776-1824) in the 2Dim group. INTERPRETATION: Aerosolised Ad5-nCoV is well tolerated, and two doses of aerosolised Ad5-nCoV elicited neutralising antibody responses, similar to one dose of intramuscular injection. An aerosolised booster vaccination at 28 days after first intramuscular injection induced strong IgG and neutralising antibody responses. The efficacy and cost-effectiveness of aerosol vaccination should be evaluated in future studies. FUNDING: National Key Research and Development Programme of China and National Science and Technology Major Project. TRANSLATION: For the Chinese translation of the Summary see Supplementary Material.


Subject(s)
COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/immunology , COVID-19/prevention & control , SARS-CoV-2/immunology , Administration, Inhalation , Adolescent , Adult , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19/immunology , COVID-19 Vaccines/adverse effects , China , Double-Blind Method , Female , Humans , Immunity, Cellular/immunology , Immunization Schedule , Immunization, Secondary , Immunogenicity, Vaccine , Immunoglobulin G/blood , Injections, Intramuscular , Male , Middle Aged , Spike Glycoprotein, Coronavirus/immunology , Vaccination , Young Adult
11.
Eur J Med Chem ; 227: 113910, 2022 Jan 05.
Article in English | MEDLINE | ID: covidwho-1458683

ABSTRACT

The current COVID-19 epidemic has greatly accelerated the application of mRNA technology to our real world, and during this battle mRNA has proven it's unique advantages compared to traditional biopharmaceutical and vaccine technology. In order to overcome mRNA instability in human physiological environments, mRNA chemical modifications and nano delivery systems are two key factors for their in vivo applications. In this review, we would like to summarize the challenges for clinical translation of mRNA-based therapeutics, with an emphasis on recent advances in innovative materials and delivery strategies. The nano delivery systems include lipid delivery systems (lipid nanoparticles and liposomes), polymer complexes, micelles, cationic peptides and so on. The similarities and differences of lipid nanoparticles and liposomes are also discussed. In addition, this review also present the applications of mRNA to other areas than COVID-19 vaccine, such as infectious diseases, tumors, and cardiovascular disease, for which a variety of candidate vaccines or drugs have entered clinical trials. Furthermore, mRNA was found that it might be used to treat some genetic disease, overcome the immaturity of the immune system due to the small fetal size in utero, treat some neurological diseases that are difficult to be treated surgically, even be used in advancing the translation of iPSC technology et al. In short, mRNA has a wide range of applications, and its era has just begun.


Subject(s)
/chemistry , RNA, Messenger/chemistry , COVID-19/prevention & control , COVID-19/virology , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/chemistry , Humans , Liposomes/chemistry , Micelles , Nanoparticles/chemistry , Peptides/chemistry , RNA, Messenger/metabolism , SARS-CoV-2/isolation & purification
12.
Signal Transduct Target Ther ; 6(1): 346, 2021 09 24.
Article in English | MEDLINE | ID: covidwho-1437668

ABSTRACT

Antibody-dependent cellular cytotoxicity (ADCC) responses to viral infection are a form of antibody regulated immune responses mediated through the Fc fragment. Whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) triggered ADCC responses contributes to COVID-19 disease development is currently not well understood. To understand the potential correlation between ADCC responses and COVID-19 disease development, we analyzed the ADCC activity and neutralizing antibody response in 255 individuals ranging from asymptomatic to fatal infections over 1 year post disease. ADCC was elicited by 10 days post-infection, peaked by 11-20 days, and remained detectable until 400 days post-infection. In general, patients with severe disease had higher ADCC activities. Notably, patients who had severe disease and recovered had higher ADCC activities than patients who had severe disease and deceased. Importantly, ADCC activities were mediated by a diversity of epitopes in SARS-COV-2-infected mice and induced to comparable levels against SARS-CoV-2 variants of concern (VOCs) (B.1.1.7, B.1.351, and P.1) as that against the D614G mutant in human patients and vaccinated mice. Our study indicates anti-SARS-CoV-2 ADCC as a major trait of COVID-19 patients with various conditions, which can be applied to estimate the extra-neutralization level against COVID-19, especially lethal COVID-19.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Antibody-Dependent Cell Cytotoxicity , COVID-19/immunology , SARS-CoV-2/immunology , Adult , Aged , Animals , Cell Line, Tumor , Female , Humans , Male , Mice , Middle Aged
13.
Clin Infect Dis ; 2021 Sep 22.
Article in English | MEDLINE | ID: covidwho-1434382

ABSTRACT

BACKGROUND: We assessed the safety and immunogenicity of a recombinant adenovirus type-5 (Ad5)-vectored COVID-19 vaccine with homologous prime-boost regimens in healthy participants aged 6 years and above. METHODS: In this randomised, double-blind, placebo-controlled trial, participants received low-dose vaccine, middle-dose vaccine or placebo. Prime-booster regimens were given intramuscularly 56 days apart. ELISA antibodies to the receptor binding domain (RBD) and pseudovirus neutralising antibodies were detected. Adverse events were monitored for 28 days following each vaccination. RESULTS: A total of 430 participants were enrolled in the study, with 30 participants aged 18-55 years (MID cohort), 250 participants aged 56 years and older (OLD cohort), and 150 participants aged 6-17 years (MIN cohort). Ad5-vectored COVID-19 vaccine induced significant RBD-specific ELISA antibodies which decreased with increasing age, with geometric mean titres (GMTs) of 1037.5 in MIN cohort, 647.2 in MID cohort, and 338.0 in OLD cohort receiving 5×10 10 viral particles on day 28 following boost vaccination. Pseudovirus neutralising antibodies showed a similar pattern, with GMTs of 168.0 in MIN cohort, 76.8 in MID cohort, and 79.7 in OLD cohort. A single dose in children and adolescents induced higher antibody responses than that elicited by two doses in adults, with GMTs of 1091.6 and 96.6 in ELISA antibody and neutralising antibody, respectively. Homologous prime-boost vaccination was safety and tolerable. CONCLUSIONS: Ad5-vectored COVID-19 vaccine with a single dose was safe and induced robust immune responses in children and adolescents aged 6-17 years. A prime-boost regimen needs further exploration for Ad5-vectored COVID-19 vaccine.

14.
Hepatobiliary Surg Nutr ; 10(4): 486-497, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1372186

ABSTRACT

BACKGROUND: Increased risks have been found for patients undergoing liver transplantation due to the blood supply shortage following the ongoing coronavirus disease 2019 (COVID-19) pandemic. Hence, exploring a method to alleviate this dilemma is urgent. This phase I, nonrandomized, prospective trial aimed to evaluate the safety and feasibility of using donor-specific red blood cell transfusion (DRBCT) as an urgent measurement to alleviate the blood supply shortage in deceased donor liver transplantation (DDLT). METHODS: The outcomes of 26 patients who received DRBCT and 37 patients in the control group who only received 3rd party packed red blood cells (pRBCs) transfusion between May 2020 and January 2021 were compared. RESULTS: Patients receiving DRBCT did not develop transfusion-related complications, and the incidence of postoperative infection was similar to that in the control group (23.1% vs. 18.9%, P=0.688). Because the patients received the red blood cells from organ donors, the median volume of intraoperative allogeneic red blood cell transfusion from blood bank was 4.0 U (IQR 1.1-8.0 U) in the DRBCT group, which is significantly lower than that (7.5 U, IQR 4.0-10.0 U) in the control group (P=0.018). The peak aspartate aminotransferase (AST) level was significantly lower in the DRBCT group than in the control group (P=0.008) and so were the AST levels in the first two days after the operation (P=0.006 and P=0.033). CONCLUSIONS: DRBCT is a safe and effective procedure to lower the need for blood supply and is associated with a reduction in AST levels after transplantation. DRBCT is beneficial to patients receiving life-saving transplantation without sufficient blood supply during the COVID-19 pandemic.

15.
BMC Cancer ; 20(1): 1194, 2020 Dec 07.
Article in English | MEDLINE | ID: covidwho-962804

ABSTRACT

BACKGROUND: Due to the increased risk of viral infection and the severe shortage of medical resources during the pandemic of COVID-19, most hospitals in the epidemic areas significantly reduced non-emergency admissions and services, if not closed. As a result, it has been difficult to treat cancer patients on time, which adversely affects their prognosis. To address this problem, cancer centers must develop a strategic plan to manage both inpatients and outpatients during the pandemic, provide them with the necessary treatment, and at the same time prevent the spread of the virus among patients, visitors and medical staff. METHODS: Based upon the epidemic situation in Zhejiang Province, China, the number of running non-emergency medical wards in the Zhejiang Cancer Hospital was gradually increased in a controlled manner. All staff of the hospital received COVID-19 preventive training and was provided with three different levels of protection according to the risks of their services. Only patients without a known history of SARS-CoV-2 contact were eligible to schedule an appointment. Body temperature was measured on all patients upon their arrival at the hospital. Chest CT image, blood cell counting and travel/contact history were investigated in patients with fever. Respiratory tract samples, such as sputum and throat swabs, from all patients, including those clinically suspected of SARS-CoV-2 infection, were collected for nucleic acid detection of SARS-CoV-2 before treatment. RESULTS: A total of 3697 inpatients and 416 outpatients seeking cancer treatment were enrolled from February 1 to April 3, 2020, in compliance with the hospital's infection-control interventions. The clinicopathological parameters of the patients were summarized herein. 4237 samples from 4101 patients produced negative RNA testing results. Four clinically suspected patients all presented negative RNA test results and were excluded from the SARS-CoV-2 infection through follow-up retesting and monitoring. Seven patients with only N-gene positive results were retested, followed by CT scan and SARS-CoV-2 contact history investigation. All of them were finally diagnosed as non-infected patients. There was one outpatient who was confirmed positive by virus RNA test and then followed up. She might be an asymptomatic laboratory-confirmed case. During the study period, there was no SARS-CoV-2 infection among staff, patients and escorts of patients in the Zhejiang Cancer Hospital. CONCLUSION: This study suggested our infection-control interventions, including viral nucleic acid test, could be used as a reliable method to screen cancer patients in the area with moderate COVID-19 prevalence. Cancer may not be a high-risk factor of SARS-CoV-2 infection.


Subject(s)
COVID-19/epidemiology , Disease Management , Neoplasms/diagnosis , Pandemics , Adolescent , Adult , China/epidemiology , Female , Humans , Male , Middle Aged , Neoplasms/therapy , Patients , Young Adult
16.
Talanta ; 224: 121726, 2021 Mar 01.
Article in English | MEDLINE | ID: covidwho-894232

ABSTRACT

The outbreak of COVID-19 caused by a novel Coronavirus (termed SARS-CoV-2) has spread to over 210 countries around the world. Currently, reverse transcription quantitative qPCR (RT-qPCR) is used as the gold standard for diagnosis of SARS-CoV-2. However, the sensitivity of RT-qPCR assays of pharyngeal swab samples are reported to vary from 30% to 60%. More accurate and sensitive methods are urgently needed to support the quality assurance of the RT-qPCR or as an alternative diagnostic approach. A reverse transcription digital PCR (RT-dPCR) method was established and evaluated. To explore the feasibility of RT-dPCR in diagnostic of SARS-CoV-2, a total of 196 clinical pharyngeal swab samples from 103 suspected patients, 77 close contacts and 16 supposed convalescents were analyzed by RT-qPCR and then measured by the proposed RT-dPCR. For the 103 fever suspected patients, 19 (19/25) negative and 42 (42/49) equivocal tested by RT-qPCR were positive according to RT-dPCR. The sensitivity of SARS-CoV-2 detection was significantly improved from 28.2% by RT-qPCR to 87.4% by RT-dPCR. For 29 close contacts (confirmed by additional sample and clinical follow up), 16 (16/17) equivocal and 1 negative tested by RT-qPCR were positive according to RT-dPCR, which is implying that the RT-qPCR is missing a lot of asymptomatic patients. The overall sensitivity, specificity and diagnostic accuracy of RT-dPCR were 91%, 100% and 93%, respectively. RT-dPCR is highly accurate method and suitable for detection of pharyngeal swab samples from COVID-19 suspected patients and patients under isolation and observation who may not be exhibiting clinical symptoms.


Subject(s)
COVID-19 Nucleic Acid Testing/methods , COVID-19/diagnosis , RNA, Viral/analysis , Reverse Transcriptase Polymerase Chain Reaction/methods , SARS-CoV-2/genetics , Coronavirus Envelope Proteins/genetics , Coronavirus Nucleocapsid Proteins/genetics , Humans , Pharynx/virology , Phosphoproteins/genetics , Polyproteins/genetics , Viral Proteins/genetics
17.
Front Med (Lausanne) ; 7: 460, 2020.
Article in English | MEDLINE | ID: covidwho-707710

ABSTRACT

During the COVID-19 pandemic, ensuring the gradual recovery of anesthesia nursing unit and avoiding cross-infection between surgical patients and staff are difficult problems for hospital managers. We outlined the emergency response measures and the transition to normal operation of the anesthesia nursing unit in West China Hospital, which is a large teaching hospital. This mainly included hospital and operating room channel management, three-level screening management of patients and medical staff, classification management of patients undergoing anesthesia and recovery, training management of medical personnel, strict environmental management, and online teaching management.

18.
J Cardiothorac Vasc Anesth ; 34(7): 1727-1732, 2020 07.
Article in English | MEDLINE | ID: covidwho-45999

ABSTRACT

The COVID-19 pandemic is spreading globally. COVID-19 has an effect on the systemic state, cardiopulmonary function and primary disease of patients undergoing surgery. COVID-19's high contagiousness makes anesthesia and intraoperative management more difficult. This expert consensus aims to comprehensively introduce the application of perioperative ultrasound in COVID-19 patients, including pulmonary ultrasound and anesthesia management, ultrasound and airway management, ultrasound-guided regional anesthesia and echocardiography for COVID-19 patients.


Subject(s)
Anesthesia/methods , Betacoronavirus , Coronavirus Infections/diagnostic imaging , Perioperative Care/methods , Pneumonia, Viral/diagnostic imaging , Ultrasonography/methods , Airway Management/methods , Anesthesia, Conduction/methods , COVID-19 , Cardiovascular Diseases/complications , Cardiovascular Diseases/diagnostic imaging , Coronavirus Infections/complications , Coronavirus Infections/transmission , Echocardiography/methods , Hemodynamics , Humans , Lung/diagnostic imaging , Lung Diseases/diagnostic imaging , Lung Diseases/microbiology , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/transmission , SARS-CoV-2 , Tracheotomy/methods , Ultrasonography, Interventional/methods , Ventilator Weaning/methods
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