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1.
Int J Biol Sci ; 17(6): 1486-1496, 2021.
Article in English | MEDLINE | ID: covidwho-1206432

ABSTRACT

The pandemic of Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome 2 coronavirus (SARS-CoV-2) continues to be a global health crisis. Fundamental studies at genome, transcriptome, proteome, and interactome levels have revealed many viral and host targets for therapeutic interventions. Hundreds of antibodies for treating COVID-19 have been developed at preclinical and clinical stages in the format of polyclonal antibodies, monoclonal antibodies, and cocktail antibodies. Four products, i.e., convalescent plasma, bamlanivimab, REGN-Cov2, and the cocktail of bamlanivimab and etesevimab have been authorized by the U.S. Food and Drug Administration (FDA) for emergency use. Hundreds of relevant clinical trials are ongoing worldwide. Therapeutic antibody therapies have been a very active and crucial part of COVID-19 treatment. In this review, we focus on the progress of therapeutic COVID-19 antibody development and application, discuss corresponding problems and challenges, suggesting new strategies and solutions.

2.
Emerg Microbes Infect ; 10(1): 874-884, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1199439

ABSTRACT

The Coronavirus Disease 2019 (COVID-19) pandemic is unlikely to abate until sufficient herd immunity is built up by either natural infection or vaccination. We previously identified ten linear immunodominant sites on the SARS-CoV-2 spike protein of which four are located within the RBD. Therefore, we designed two linkerimmunodominant site (LIS) vaccine candidates which are composed of four immunodominant sites within the RBD (RBD-ID) or all the 10 immunodominant sites within the whole spike (S-ID). They were administered by subcutaneous injection and were tested for immunogenicity and in vivo protective efficacy in a hamster model for COVID-19. We showed that the S-ID vaccine induced significantly better neutralizing antibody response than RBD-ID and alum control. As expected, hamsters vaccinated by S-ID had significantly less body weight loss, lung viral load, and histopathological changes of pneumonia. The S-ID has the potential to be an effective vaccine for protection against COVID-19.

3.
Chin J Nat Med ; 19(4): 305-320, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1193536

ABSTRACT

Qing-Fei-Pai-Du decoction (QFPDD) is a Chinese medicine compound formula recommended for combating corona virus disease 2019 (COVID-19) by National Health Commission of the People's Republic of China. The latest clinical study showed that early treatment with QFPDD was associated with favorable outcomes for patient recovery, viral shedding, hospital stay, and course of the disease. However, the effective constituents of QFPDD remain unclear. In this study, an UHPLC-Q-Orbitrap HRMS based method was developed to identify the chemical constituents in QFPDD and the absorbed prototypes as well as the metabolites in mice serum and tissues following oral administration of QFPDD. A total of 405 chemicals, including 40 kinds of alkaloids, 162 kinds of flavonoids, 44 kinds of organic acids, 71 kinds of triterpene saponins and 88 kinds of other compounds in the water extract of QFPDD were tentatively identified via comparison with the retention times and MS/MS spectra of the standards or refereed by literature. With the help of the standards and in vitro metabolites, 195 chemical components (including 104 prototypes and 91 metabolites) were identified in mice serum after oral administration of QFPDD. In addition, 165, 177, 112, 120, 44, 53 constituents were identified in the lung, liver, heart, kidney, brain, and spleen of QFPDD-treated mice, respectively. These findings provided key information and guidance for further investigation on the pharmacologically active substances and clinical applications of QFPDD.


Subject(s)
Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacokinetics , Administration, Oral , Alkaloids/analysis , Animals , Chromatography, High Pressure Liquid , Flavonoids/analysis , Mice , Saponins/analysis , Triterpenes/analysis
4.
Mil Med Res ; 8(1): 21, 2021 03 17.
Article in English | MEDLINE | ID: covidwho-1140518

ABSTRACT

BACKGROUND: To develop an effective model of predicting fatal outcomes in the severe coronavirus disease 2019 (COVID-19) patients. METHODS: Between February 20, 2020 and April 4, 2020, consecutive confirmed 2541 COVID-19 patients from three designated hospitals were enrolled in this study. All patients received chest computed tomography (CT) and serological examinations at admission. Laboratory tests included routine blood tests, liver function, renal function, coagulation profile, C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6), and arterial blood gas. The SaO2 was measured using pulse oxygen saturation in room air at resting status. Independent high-risk factors associated with death were analyzed using Cox proportional hazard model. A prognostic nomogram was constructed to predict the survival of severe COVID-19 patients. RESULTS: There were 124 severe patients in the training cohort, and there were 71 and 76 severe patients in the two independent validation cohorts, respectively. Multivariate Cox analysis indicated that age ≥ 70 years (HR = 1.184, 95% CI 1.061-1.321), panting (breathing rate ≥ 30/min) (HR = 3.300, 95% CI 2.509-6.286), lymphocyte count < 1.0 × 109/L (HR = 2.283, 95% CI 1.779-3.267), and interleukin-6 (IL-6) >  10 pg/ml (HR = 3.029, 95% CI 1.567-7.116) were independent high-risk factors associated with fatal outcome. We developed the nomogram for identifying survival of severe COVID-19 patients in the training cohort (AUC = 0.900, 95% CI 0.841-0.960, sensitivity 95.5%, specificity 77.5%); in validation cohort 1 (AUC = 0.811, 95% CI 0.763-0.961, sensitivity 77.3%, specificity 73.5%); in validation cohort 2 (AUC = 0.862, 95% CI 0.698-0.924, sensitivity 92.9%, specificity 64.5%). The calibration curve for probability of death indicated a good consistence between prediction by the nomogram and the actual observation. The prognosis of severe COVID-19 patients with high levels of IL-6 receiving tocilizumab were better than that of those patients without tocilizumab both in the training and validation cohorts, but without difference (P = 0.105 for training cohort, P = 0.133 for validation cohort 1, and P = 0.210 for validation cohort 2). CONCLUSIONS: This nomogram could help clinicians to identify severe patients who have high risk of death, and to develop more appropriate treatment strategies to reduce the mortality of severe patients. Tocilizumab may improve the prognosis of severe COVID-19 patients with high levels of IL-6.


Subject(s)
/mortality , Clinical Decision Rules , Nomograms , Acute Disease , Adult , Age Factors , Aged , Aged, 80 and over , China/epidemiology , Female , Humans , Male , Middle Aged , Proportional Hazards Models , Retrospective Studies , Risk Factors , Sex Factors , Survival Analysis , Young Adult
5.
Food Chem Toxicol ; 149: 111998, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1139497

ABSTRACT

Corona Virus Disease 2019 (COVID-19) has spread all over the world and brings significantly negative effects on human health. To fight against COVID-19 in a more efficient way, drug-drug or drug-herb combinations are frequently used in clinical settings. The concomitant use of multiple medications may trigger clinically relevant drug/herb-drug interactions. This study aims to assay the inhibitory potentials of Qingfei Paidu decoction (QPD, a Chinese medicine compound formula recommended for combating COVID-19 in China) against human drug-metabolizing enzymes and to assess the pharmacokinetic interactions in vivo. The results demonstrated that QPD dose-dependently inhibited CYPs1A, 2A6, 2C8, 2C9, 2C19, 2D6 and 2E1 but inhibited CYP3A in a time- and NADPH-dependent manner. In vivo test showed that QPD prolonged the half-life of lopinavir (a CYP3A substrate-drug) by 1.40-fold and increased the AUC of lopinavir by 2.04-fold, when QPD (6 g/kg) was co-administrated with lopinavir (160 mg/kg) to rats. Further investigation revealed that Fructus Aurantii Immaturus (Zhishi) in QPD caused significant loss of CYP3A activity in NADPH-generating system. Collectively, our findings revealed that QPD potently inactivated CYP3A and significantly modulated the pharmacokinetics of CYP3A substrate-drugs, which would be very helpful for the patients and clinicians to avoid potential drug-interaction risks in COVID-19 treatment.


Subject(s)
/drug therapy , Cytochrome P-450 CYP3A/metabolism , Drugs, Chinese Herbal/pharmacology , Herb-Drug Interactions , Animals , Area Under Curve , China , Drugs, Chinese Herbal/therapeutic use , Lopinavir/pharmacokinetics , Male , Microsomes, Liver , NADP/metabolism , Phytotherapy , Rats, Sprague-Dawley
6.
J Aerosol Med Pulm Drug Deliv ; 34(2): 108-114, 2021 04.
Article in English | MEDLINE | ID: covidwho-1127303

ABSTRACT

Background: Severe acute respiratory syndrome coronavirus 2 infection is associated with strong infectiousness and has no effective therapy. We aimed to explore the efficacy and safety of Mycobacterium vaccae nebulization in the treatment of Coronavirus Disease 2019 (COVID-19). Methods: In this randomized, double-blind, placebo-controlled clinical trial, we included 31 adult patients with moderate COVID-19 who were admitted to the Fourth People's Hospital of Nanning (Nanning, China) between January 22, 2020 and February 17, 2020. Patients were randomly divided into two groups: group A (standard care group) and group B (M. vaccae in combination with standard care group). The primary outcome was the time interval from admission to viral RNA negative conversion (oropharyngeal swabs were used in this study). Secondary outcomes included chest computed tomography (CT), mortality, length of hospital stay, complications during treatment, and so on. Patients were followed up to 4 weeks after discharge (reexamination of viral RNA, chest CT, etc.). Results: Nucleic acid test negative conversion time in group B was shorter than that in group A (2.9 days [2.7-8.7] vs. 6.8 days [3.3-13.8]; p = 0.045). No death and no conversion to severe or critical cases were observed in both groups. Two weeks after discharge, neither "relapse" nor "return to positive" cases were found. Four weeks after discharge, it was found that there was no case of " relapse " or "return to positive" in group B, and 1 patient in group A showed "return to positive", but there was no clinical manifestation and imaging progression. No adverse reactions related to M. vaccae were found during observation period. Conclusion: M. vaccae treatment might shorten the time interval from admission to viral RNA negative conversion, which might be beneficial to the prevention and treatment of COVID-19. Clinical Trial Registration: ChiCTR2000030016.


Subject(s)
/therapy , Length of Stay , Mycobacteriaceae/immunology , Tomography, X-Ray Computed , Administration, Inhalation , Adolescent , Adult , Aged , /mortality , Double-Blind Method , Female , Humans , Male , Middle Aged , Time Factors , Treatment Outcome , Young Adult
7.
J Med Internet Res ; 23(3): e26997, 2021 03 02.
Article in English | MEDLINE | ID: covidwho-1121849

ABSTRACT

BACKGROUND: Artificial intelligence (AI) methods can potentially be used to relieve the pressure that the COVID-19 pandemic has exerted on public health. In cases of medical resource shortages caused by the pandemic, changes in people's preferences for AI clinicians and traditional clinicians are worth exploring. OBJECTIVE: We aimed to quantify and compare people's preferences for AI clinicians and traditional clinicians before and during the COVID-19 pandemic, and to assess whether people's preferences were affected by the pressure of pandemic. METHODS: We used the propensity score matching method to match two different groups of respondents with similar demographic characteristics. Respondents were recruited in 2017 and 2020. A total of 2048 respondents (2017: n=1520; 2020: n=528) completed the questionnaire and were included in the analysis. Multinomial logit models and latent class models were used to assess people's preferences for different diagnosis methods. RESULTS: In total, 84.7% (1115/1317) of respondents in the 2017 group and 91.3% (482/528) of respondents in the 2020 group were confident that AI diagnosis methods would outperform human clinician diagnosis methods in the future. Both groups of matched respondents believed that the most important attribute of diagnosis was accuracy, and they preferred to receive combined diagnoses from both AI and human clinicians (2017: odds ratio [OR] 1.645, 95% CI 1.535-1.763; P<.001; 2020: OR 1.513, 95% CI 1.413-1.621; P<.001; reference: clinician diagnoses). The latent class model identified three classes with different attribute priorities. In class 1, preferences for combined diagnoses and accuracy remained constant in 2017 and 2020, and high accuracy (eg, 100% accuracy in 2017: OR 1.357, 95% CI 1.164-1.581) was preferred. In class 2, the matched data from 2017 were similar to those from 2020; combined diagnoses from both AI and human clinicians (2017: OR 1.204, 95% CI 1.039-1.394; P=.011; 2020: OR 2.009, 95% CI 1.826-2.211; P<.001; reference: clinician diagnoses) and an outpatient waiting time of 20 minutes (2017: OR 1.349, 95% CI 1.065-1.708; P<.001; 2020: OR 1.488, 95% CI 1.287-1.721; P<.001; reference: 0 minutes) were consistently preferred. In class 3, the respondents in the 2017 and 2020 groups preferred different diagnosis methods; respondents in the 2017 group preferred clinician diagnoses, whereas respondents in the 2020 group preferred AI diagnoses. In the latent class, which was stratified according to sex, all male and female respondents in the 2017 and 2020 groups believed that accuracy was the most important attribute of diagnosis. CONCLUSIONS: Individuals' preferences for receiving clinical diagnoses from AI and human clinicians were generally unaffected by the pandemic. Respondents believed that accuracy and expense were the most important attributes of diagnosis. These findings can be used to guide policies that are relevant to the development of AI-based health care.


Subject(s)
Artificial Intelligence , /epidemiology , Adult , Female , Humans , Male , Pandemics , Propensity Score , Research Design , /isolation & purification
8.
Eur J Radiol ; 137: 109602, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1084604

ABSTRACT

PURPOSE: Differentiating COVID-19 from other acute infectious pneumonias rapidly is challenging at present. This study aims to improve the diagnosis of COVID-19 using computed tomography (CT). METHOD: COVID-19 was confirmed mainly by virus nucleic acid testing and epidemiological history according to WHO interim guidance, while other infectious pneumonias were diagnosed by antigen testing. The texture features were extracted from CT images by two radiologists with 5 years of work experience using modified wavelet transform and matrix computation analyses. The random forest (RF) classifier was applied to identify COVID-19 patients and images. RESULTS: We retrospectively analysed the data of 95 individuals (291 images) with COVID-19 and 96 individuals (279 images) with other acute infectious pneumonias, including 50 individuals (160 images) with influenza A/B. In total, 6 texture features showed a positive association with COVID-19, while 4 features were negatively associated. The mean AUROC, accuracy, sensitivity, and specificity values of the 5-fold test sets were 0.800, 0.722, 0.770, and 0.680 for image classification and 0.858, 0.826, 0.809, and 0.842 for individual classification, respectively. The feature 'Correlation' contributed most both at the image level and individual level, even compared with the clinical factors. In addition, the texture features could discriminate COVID-19 from influenza A/B, with an AUROC of 0.883 for images and 0.957 for individuals. CONCLUSIONS: The developed texture feature-based RF classifier could assist in the diagnosis of COVID-19, which could be a rapid screening tool in the era of pandemic.


Subject(s)
Humans , Machine Learning , Retrospective Studies , Tomography, X-Ray Computed
9.
Chin Med J (Engl) ; 133(12): 1390-1396, 2020 Jun 20.
Article in English | MEDLINE | ID: covidwho-1050186

ABSTRACT

BACKGROUND: Critical patients with the coronavirus disease 2019 (COVID-19), even those whose nucleic acid test results had turned negative and those receiving maximal medical support, have been noted to progress to irreversible fatal respiratory failure. Lung transplantation (LT) as the sole therapy for end-stage pulmonary fibrosis related to acute respiratory distress syndrome has been considered as the ultimate rescue therapy for these patients. METHODS: From February 10 to March 10, 2020, three male patients were urgently assessed and listed for transplantation. After conducting a full ethical review and after obtaining assent from the family of the patients, we performed three LT procedures for COVID-19 patients with illness durations of more than one month and extremely high sequential organ failure assessment scores. RESULTS: Two of the three recipients survived post-LT and started participating in a rehabilitation program. Pearls of the LT team collaboration and perioperative logistics were summarized and continually improved. The pathological results of the explanted lungs were concordant with the critical clinical manifestation, and provided insight towards better understanding of the disease. Government health affair systems, virology detection tools, and modern communication technology all play key roles towards the survival of the patients and their rehabilitation. CONCLUSIONS: LT can be performed in end-stage patients with respiratory failure due to COVID-19-related pulmonary fibrosis. If confirmed positive-turned-negative virology status without organ dysfunction that could contraindicate LT, LT provided the final option for these patients to avoid certain death, with proper protection of transplant surgeons and medical staffs. By ensuring instant seamless care for both patients and medical teams, the goal of reducing the mortality rate and salvaging the lives of patients with COVID-19 can be attained.


Subject(s)
Betacoronavirus , Coronavirus Infections/complications , Lung Transplantation/methods , Pneumonia, Viral/complications , Pulmonary Fibrosis/surgery , /surgery , Aged , Coronavirus Infections/mortality , Extracorporeal Membrane Oxygenation , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/mortality , Pulmonary Fibrosis/mortality , /mortality
10.
Bioeng Transl Med ; : e10202, 2020 Dec 12.
Article in English | MEDLINE | ID: covidwho-985967

ABSTRACT

The S1 subunit of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein contains an immunogenic receptor-binding domain (RBD), which is a promising candidate for the development of a potential vaccine. This study demonstrated that intradermal delivery of an S-RBD vaccine using a dissolvable microneedle skin patch can induce both significant B-cell and significant T-cell responses against S-RBD. Importantly, the outcomes were comparable to that of conventional bolus injection.

11.
EBioMedicine ; 62: 103125, 2020 Nov 21.
Article in English | MEDLINE | ID: covidwho-938894

ABSTRACT

BACKGROUND: The pharmacokinetics and appropriate dose regimens of favipiravir are unknown in hospitalized influenza patients; such data are also needed to determine dosage selection for favipiravir trials in COVID-19. METHODS: In this dose-escalating study, favipiravir pharmacokinetics and tolerability were assessed in critically ill influenza patients. Participants received one of two dosing regimens; Japan licensed dose (1600 mg BID on day 1 and 600 mg BID on the following days) and the higher dose (1800 mg/800 mg BID) trialed in uncomplicated influenza. The primary pharmacokinetic endpoint was the proportion of patients with a minimum observed plasma trough concentration (Ctrough) ≥20 mg/L at all measured time points after the second dose. RESULTS: Sixteen patients were enrolled into the low dose group and 19 patients into the high dose group of the study. Favipiravir Ctrough decreased significantly over time in both groups (p <0.01). Relative to day 2 (48 hrs), concentrations were 91.7% and 90.3% lower in the 1600/600 mg group and 79.3% and 89.5% lower in the 1800/800 mg group at day 7 and 10, respectively. In contrast, oseltamivir concentrations did not change significantly over time. A 2-compartment disposition model with first-order absorption and elimination described the observed favipiravir concentration-time data well. Modeling demonstrated that less than 50% of patients achieved Ctrough ≥20 mg/L for >80% of the duration of treatment of the two dose regimens evaluated (18.8% and 42.1% of patients for low and high dose regimen, respectively). Increasing the favipravir dosage predicted a higher proportion of patients reaching this threshold of 20 mg/L, suggesting that dosing regimens of ≥3600/2600 mg might be required for adequate concentrations. The two dosing regimens were well-tolerated in critical ill patients with influenza. CONCLUSION: The two dosing regimens proposed for uncomplicated influenza did not achieve our pre-defined treatment threshold.

12.
Front Oncol ; 10: 1272, 2020.
Article in English | MEDLINE | ID: covidwho-853981

ABSTRACT

Background: A recent outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), which began in Wuhan, China, with a high level of human-to-human transmission has been reported. There are limited data available on Coronavirus Disease 2019 (COVID-19) patients with hematological malignancies with more than 60 days of follow-up. This study describes the clinical characteristics, including multiple recurrences of COVID-19, in a patient with chronic lymphocytic leukemia (CLL) during 69 days of follow-up. Case Presentation: A 72-year-old female was admitted to hospital isolation after being infected with COVID-19 as part of a family cluster on January 30, 2020. Apart from SARS-Cov-2 virus infection, laboratory results revealed lymphocytosis of uncertain etiology and abnormal distribution of T lymphocytes. On blood smears, small blue lymphocytes with scant cytoplasm were observed, and the presence of high levels of circulating clonal B cells was also demonstrated by flow cytometry. The patient was diagnosed with COVID-19 and CLL. Among her family members, she had the highest viral loads and the fastest progression on lung injury and developed severe pneumonia. Serological results showed she had both 2019-nCoV-specific IgM and IgG antibodies; however, only IgG antibodies were detected in her husband's plasma. Results: A combination regimen of antiviral therapy and high-dose intravenous immunoglobulin (IVIG) in the early stage seemed to be effective for treating CLL and SARS-Cov-2 infection. Because of the low humoral immune response, the CLL patient could not effectively clear the SARS-Cov-2 infection and suffered from recurrence twice during the 69-day follow-up. Conclusion: In CLL, a neoplastic antigen-specific B-cell clone proliferates, and the progeny cells accumulate and outgrow other B cells, leading to immune deficiency. Considering the low humoral immune response and ineffective clearance of SARS-Cov-2 in CLL patients, the follow-up and home quarantine period should be extended. We need further studies to clarify suspending or continuing CLL therapy during COVID infection. For those patients who are prone to progression to severe disease, administering humoral immunity therapies can help to prevent disease progression and quickly meet the cure criteria.

13.
J Med Internet Res ; 22(9): e21685, 2020 09 17.
Article in English | MEDLINE | ID: covidwho-796020

ABSTRACT

A novel pneumonia-like coronavirus disease (COVID-19) caused by a novel coronavirus named SARS-CoV-2 has swept across China and the world. Public health measures that were effective in previous infection outbreaks (eg, wearing a face mask, quarantining) were implemented in this outbreak. Available multidimensional social network data that take advantage of the recent rapid development of information and communication technologies allow for an exploration of disease spread and control via a modernized epidemiological approach. By using spatiotemporal data and real-time information, we can provide more accurate estimates of disease spread patterns related to human activities and enable more efficient responses to the outbreak. Two real cases during the COVID-19 outbreak demonstrated the application of emerging technologies and digital data in monitoring human movements related to disease spread. Although the ethical issues related to using digital epidemiology are still under debate, the cases reported in this article may enable the identification of more effective public health measures, as well as future applications of such digitally directed epidemiological approaches in controlling infectious disease outbreaks, which offer an alternative and modern outlook on addressing the long-standing challenges in population health.


Subject(s)
Betacoronavirus , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Disease Outbreaks/statistics & numerical data , Epidemiologic Methods , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , China/epidemiology , Humans , Masks , Pandemics , Quarantine/statistics & numerical data
14.
Clin Infect Dis ; 2020 Aug 25.
Article in English | MEDLINE | ID: covidwho-729112

ABSTRACT

BACKGROUND: Waning immunity occurs in patients who have recovered from COVID-19. However, it remains unclear whether true re-infection occurs. METHODS: Whole genome sequencing was performed directly on respiratory specimens collected during two episodes of COVID-19 in a patient. Comparative genome analysis was conducted to differentiate re-infection from persistent viral shedding. Laboratory results, including RT-PCR Ct values and serum SARS-CoV-2 IgG, were analyzed. RESULTS: The second episode of asymptomatic infection occurred 142 days after the first symptomatic episode in an apparently immunocompetent patient. During the second episode, there was serological evidence of elevated C-reactive protein and SARS-CoV-2 IgG seroconversion. Viral genomes from first and second episodes belong to different clades/lineages. Compared to viral genomes in GISAID, the first virus genome has a stop codon at position 64 of orf8 leading to a truncation of 58 amino acids, and was phylogenetically closely related to strains collected in March/April 2020, while the second virus genome was closely related to strains collected in July/August 2020. Another 23 nucleotide and 13 amino acid differences located in 9 different proteins, including positions of B and T cell epitopes, were found between viruses from the first and second episodes. CONCLUSIONS: Epidemiological, clinical, serological and genomic analyses confirmed that the patient had re-infection instead of persistent viral shedding from first infection. Our results suggest SARS-CoV-2 may continue to circulate among the human populations despite herd immunity due to natural infection or vaccination. Further studies of patients with re-infection will shed light on protective correlates important for vaccine design.

16.
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 , China , Coronavirus Infections/immunology , Double-Blind Method , Female , Genetic Vectors , Humans , Male , Middle Aged , Spike Glycoprotein, Coronavirus/immunology , T-Lymphocytes/immunology , Viral Vaccines/administration & dosage , Young Adult
19.
Ann Vasc Surg ; 68: 76-82, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-601188

ABSTRACT

BACKGROUND: The aim of this pilot study was to evaluate the effectiveness and patients satisfaction of using telemedicine virtual communications to provide remote health care to vascular patients during the coronavirus disease 2019 (COVID-19) period in China. METHODS: Video calls using WeChat software (Tencent, Shenzhen, China) between patients and vascular surgeons were conducted in a period when there were restrictions and limitations for people' travels in China. At the end of each video call, a short questionnaire was used to evaluate the patient satisfaction level. RESULTS: During the COVID-19 period from 19 February to March 16, 2020, a sample of 114 from 165 (69%) patients was reached after one phone call attempt. One hundred forty-two telemedicine remote communications were made between the two vascular surgeons and 114 patients. The mean age of this cohort of patients were 60 ± 15.2 (range 25 to 90) years old, and 74 (65%) were men. Twenty-five patients (22%) were outside of our province when they received the video call. The mean duration of the video call was 11.0 ± 8.9 minutes. All of the patients thought telemedicine was a good substitute for coming to hospital, and 95% (108/114) of them preferred to have remote telemedicine rather than postpone the appointment. All the patients agreed with the advantages of telemedicine including no infection risks, no need to travel, and no need to wait for long time. All the patients were "satisfied" or "highly satisfied" with the video call and they would like to use telemedicine for follow-up in the future. CONCLUSIONS: Telemedicine virtual communications was effective to provide remote health care with a high patient satisfaction during the COVID-19 period. Telemedicine offers support to vulnerable vascular patients without the need for travel and face-to-face hospital consultation, and so avoided transmission and infection.


Subject(s)
Betacoronavirus , Coronavirus Infections/epidemiology , Pandemics , Patient Satisfaction , Pneumonia, Viral/epidemiology , Referral and Consultation/organization & administration , Telemedicine/methods , Vascular Diseases/diagnosis , Video Recording/methods , China/epidemiology , Comorbidity , Coronavirus Infections/diagnosis , Female , Humans , Male , Middle Aged , Pilot Projects , Pneumonia, Viral/diagnosis , Surveys and Questionnaires , Vascular Diseases/epidemiology , Vascular Diseases/therapy
20.
J Infect Public Health ; 13(7): 932-934, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-548408

ABSTRACT

Since the outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, Hubei Province, China [1], a large number of confirmed cases met the discharge criteria (one of which is two consecutive negative nucleic acid tests with an interval of at least 24 h) [2]. Previous studies have paid more attention to the epidemic situation of COVID-19 and patient diagnosis and treatment. Close attention also should be paid to the discharged patients. Surprisingly, a previous follow-up reported that some patients' nucleic acid retest results were positive again after discharge [3]. Factors impacting these follow-up test results should be further investigated. Since the first confirmed case was diagnosed in our hospital (Chongqing Emergency Medical Center, the designated transfer hospital) on February 4th, we confirmed a total of 17 cases. All patients infected with the novel coronavirus were transferred to a designated hospital in Southwest China's Chongqing by ambulance with an inbuilt negative-pressure chamber [4]. In the follow-up examination of these patients, RT-PCR tests were conducted again 3 days after discharged from the designated hospital. Four patients showed recurrence of positive results after a few days of discharge. Thus, we examined these cases herein, aiming to provide information for policy formulation and modification of discharge plans.


Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , RNA, Viral/isolation & purification , Reverse Transcriptase Polymerase Chain Reaction , Adult , Child , China/epidemiology , Coronavirus Infections/virology , Female , Hospitals , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/virology
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