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1.
Sci Rep ; 10(1): 17492, 2020 Oct 15.
Article in English | MEDLINE | ID: covidwho-872738

ABSTRACT

The novel SARS-CoV-2 outbreak has swiftly spread worldwide. The rapid genome sequencing of SARS-CoV-2 strains has become a helpful tool for better understanding the genomic characteristics and origin of the virus. To obtain virus whole-genome sequences directly from clinical specimens, we performed nanopore sequencing using a modified ARTIC protocol in a portable nanopore sequencer and validated a routine 8-h workflow and a 5-h rapid pipeline. We conducted some optimization to improve the genome sequencing workflow. The sensitivity of the workflow was also tested by serially diluting RNA from clinical samples. The optimized pipeline was finally applied to obtain the whole genomes of 29 clinical specimens collected in Hangzhou from January to March 2020. In the 29 obtained complete genomes of SARS-CoV-2, 33 variations were identified and analyzed. The genomic variations and phylogenetic analysis hinted at multiple sources and different transmission patterns during the COVID-19 epidemic in Hangzhou, China. In conclusion, the genomic characteristics and origin of the virus can be quickly determined by nanopore sequencing following our workflows.

3.
Preprint | SSRN | ID: ppcovidwho-717

ABSTRACT

Background: The purpose of this study was to investigate the psychological status of the general population in mainland China during the outbreak of coronavirus

5.
Biomed Res Int ; 2020: 1594726, 2020.
Article in English | MEDLINE | ID: covidwho-633800

ABSTRACT

Acute kidney injury (AKI) is a common complication of sepsis and has also been observed in some patients suffering from the new coronavirus pneumonia COVID-19, which is currently a major global concern. Thymoquinone (TQ) is one of the most active ingredients in Nigella sativa seeds. It has a variety of beneficial properties including anti-inflammatory and antioxidative activities. Here, we investigated the possible protective effects of TQ against kidney damage in septic BALB/c mice. Eight-week-old male BALB/c mice were divided into four groups: control, TQ, cecal ligation and puncture (CLP), and TQ+CLP. CLP was performed after 2 weeks of TQ gavage. After 48 h, we measured the histopathological alterations in the kidney tissue and the serum levels of creatinine (CRE) and blood urea nitrogen (BUN). We also evaluated pyroptosis (NLRP3, caspase-1), apoptosis (caspase-3, caspase-8), proinflammatory (TNF-α, IL-1ß, and IL-6)-related protein and gene expression levels. Our results demonstrated that TQ inhibited CLP-induced increased serum CRE and BUN levels. It also significantly inhibited the high levels of NLRP3, caspase-1, caspase-3, caspase-8, TNF-α, IL-1ß, and IL-6 induced by CLP. Furthermore, NF-κB protein level was significantly decreased in the TQ+CLP group than in the CLP group. Together, our results indicate that TQ may be a potential therapeutic agent for sepsis-induced AKI.


Subject(s)
Acute Kidney Injury/drug therapy , Acute Kidney Injury/etiology , Benzoquinones/therapeutic use , Sepsis/complications , Sepsis/drug therapy , Acute Kidney Injury/pathology , Animals , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Antioxidants/therapeutic use , Apoptosis/drug effects , Betacoronavirus , Blood Urea Nitrogen , Coronavirus Infections/complications , Coronavirus Infections/drug therapy , Creatinine/blood , Cytokines/metabolism , Disease Models, Animal , Humans , Inflammation Mediators/metabolism , Kidney/drug effects , Kidney/metabolism , Kidney/pathology , Male , Mice , Mice, Inbred BALB C , NF-kappa B/metabolism , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/drug therapy
6.
BMC Psychiatry ; 20(1): 426, 2020 08 27.
Article in English | MEDLINE | ID: covidwho-733045

ABSTRACT

BACKGROUND: The purpose of this study was to investigate the psychological status of the general population in mainland China during the outbreak of coronavirus disease 2019 (COVID-19), and to explore the factors influencing psychological distress, in order to provide the basis for further psychological intervention programs. METHODS: We administered three questionnaires on-line to a convenience sample of the general population from different regions of mainland China from February 1 to February 4, 2020. We used the Mandarin versions of the six-item Kessler psychological distress scale (K6), the Simplified Coping Style Questionnaire (SCSQ), and the Social Support Rating Scale (SSRS). We also collected demographic data and other information related to the COVID-19 outbreak. Multivariate binary logistic regression analysis was used to identify factors influencing psychological distress. RESULTS: Of 1607 respondents, 1588 returned valid questionnaires and were included in the analysis. Nearly one quarter (22.8%) had high levels of psychological distress (K6 score ≥ 13). Individuals with higher psychological distress were more likely to be unmarried, spend more than 6 h per day searching for information about COVID-19, more frequently adopt a passive coping style, and report less social support than those with lower psychological distress. CONCLUSIONS: The COVID-19 outbreak in China has a great impact on the mental health status of the general population. Active coping strategies and increased social support are significantly correlated with decreased psychological distress, and may serve as the basis for psychological interventions.


Subject(s)
Adaptation, Psychological , Coronavirus Infections , Pandemics , Pneumonia, Viral , Psychological Distress , Social Support , Adult , Betacoronavirus , China/epidemiology , Coronavirus Infections/epidemiology , Coronavirus Infections/psychology , Female , Humans , Male , Pneumonia, Viral/epidemiology , Pneumonia, Viral/psychology , Public Health/methods , Surveys and Questionnaires
8.
Front. Med. ; (7)20200710.
Article in English | ELSEVIER | ID: covidwho-689650

ABSTRACT

Objective: The aim of the study was to analyze the characteristics of renal function in patients diagnosed with COVID-19. Methods: In this retrospective, single-center study, we included all confirmed cases of COVID-19 in a tertiary hospital in Guangdong, China from January 20, 2020 to March 20, 2020. Blood and urine laboratory findings related to renal function were summarized, and the estimated glomerular filtration rate (eGFR) and endogenous creatinine clearance (Ccr) were also calculated to assess the renal function. Results: A total of 12 admitted hospital patients were diagnosed with COVID-19, included 3 severe cases, and 9 common cases. Serum creatinine (Scr) was not abnormally elevated in all of the patients, and blood urea nitrogen (BUN) was abnormally elevated in only 25.0% of the patients. However, compared with the recovery period, the patient's Scr and BUN increased significantly in peak of disease (p-scr = 0.002 & p-bun < 0.001). By observing the fluctuations in Scr and BUN from admission to recovery, it was found that the peak of Scr and BUN appeared within the first 14 day of the course of the disease. Urinary microprotein detection indicated that the abnormally elevated rates of urine microalbumin (UMA), α1-microglobulin (A1M), urine immunoglobulin-G (IGU), and urine transferring (TRU) standardized by urinary creatinine in peak of disease were 41.7, 41.7, 50.0, and 16.7%, respectively. The abnormal rates of the calculated eGFR and Ccr were 66.7 and 41.7%. Conclusion: Scr and BUN were generally increased during the course of COVID-19. Detection of urinary microproteins and application of multiple indicators assessment could be helpful for discovering abnormal renal function in patients with COVID-19. However, the evidence is limited due to the small sample size and observational nature. Additional studies, especially large prospective cohort studies, are required to confirm these findings.

9.
Zool Res ; 41(5): 517-526, 2020 Sep 18.
Article in English | MEDLINE | ID: covidwho-671953

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic continues to pose a global threat to the human population. Identifying animal species susceptible to infection with the SARS-CoV-2/ HCoV-19 pathogen is essential for controlling the outbreak and for testing valid prophylactics or therapeutics based on animal model studies. Here, different aged Chinese tree shrews (adult group, 1 year old; old group, 5-6 years old), which are close relatives to primates, were infected with SARS-CoV-2. X-ray, viral shedding, laboratory, and histological analyses were performed on different days post-inoculation (dpi). Results showed that Chinese tree shrews could be infected by SARS-CoV-2. Lung infiltrates were visible in X-ray radiographs in most infected animals. Viral RNA was consistently detected in lung tissues from infected animals at 3, 5, and 7 dpi, along with alterations in related parameters from routine blood tests and serum biochemistry, including increased levels of aspartate aminotransferase (AST) and blood urea nitrogen (BUN). Histological analysis of lung tissues from animals at 3 dpi (adult group) and 7 dpi (old group) showed thickened alveolar septa and interstitial hemorrhage. Several differences were found between the two different aged groups in regard to viral shedding peak. Our results indicate that Chinese tree shrews have the potential to be used as animal models for SARS-CoV-2 infection.


Subject(s)
Betacoronavirus/growth & development , Coronavirus Infections/diagnosis , Disease Models, Animal , Lung/pathology , Pneumonia, Viral/diagnosis , Tupaiidae/physiology , Age Factors , Animals , Betacoronavirus/physiology , Coronavirus Infections/transmission , Coronavirus Infections/virology , Female , Humans , Lung/virology , Male , Pandemics , Pneumonia, Viral/transmission , Pneumonia, Viral/virology , Tupaiidae/virology , Virus Shedding/physiology
10.
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
15.
Hu Li Za Zhi ; 67(3): 4-5, 2020 Jun.
Article in Chinese | MEDLINE | ID: covidwho-559630

ABSTRACT

The global spread of coronavirus disease 2019 (COVID-19) is rapidly increasing the number of patients who are critically ill with this disease, with the related rate of mortality expected to peak in 2020 (Alhazzani et al., 2020). As severe acute respiratory syndrome is the major cause of mortality after COVID-19 infection, patients with COVID-19 who are prone to severe acute respiratory problems may require mechanical ventilation or extracorporeal membrane oxygenation (ECMO; Alhazzani et al., 2020). Ongoing advances in intensive care medicine are continuing to improve survival in critically ill patients (Kaukonen, Bailey, Suzuki, Pilcher, & Bellomo, 2014). However, intensive care unit (ICU) survivors may experience complications and problems related to their disease and treatment such as critical illness polyneuropathy, critical illness myopathy, and post intensive care syndrome (PICS; Alhazzani et al., 2020). Harvey (2012) reported that 85%-95% of ICU patients have ICU-acquired weakness after ICU discharge and 74% of ICU patients with acute respiratory distress syndrome have cognitive impairment after ICU discharge. Physical disabilities, cognitive impairment, and mental or psychological distress (e.g., anxiety, depression, and post-traumatic stress disorder) after ICU discharge may be symptoms of PICS, and may continue to affect surviving patients for several years after ICU discharge (Elliott et al., 2014; Held & Moss, 2019; Jackson et al., 2014; Jubran et al., 2010). Efforts to prevent and treat COVID-19 in Taiwan have proven more effective compared to most other places in the world. In addition to the low number of diagnosed cases, the mortality rate (seven of 440 confirmed cases) in Taiwan has been significantly lower than in most other countries (Taiwan Centers for Disease Control, ROC, 2020, May 14). However, post-discharge care for ICU survivors, especially those hospitalized after a sudden onset of severe disease symptoms and then discharged after a long ICU stay or after receiving mechanical ventilation, require specialized care to minimize PICS. Nurses are responsible not only for treating patients with the disease but also for preventing the further spread of disease. Therefore, providing continued care to patients discharged from the ICU is essential. Specifically, interventions to avoid PICS must be implemented rapidly by multidisciplinary medical teams during and immediately after ICU discharge.


Subject(s)
Betacoronavirus , Coronavirus Infections , Intensive Care Units , Pandemics , Pneumonia, Viral , Critical Care , Humans , Taiwan
16.
Lancet ; 395(10240): 1845-1854, 2020 06 13.
Article in English | MEDLINE | ID: covidwho-342974

ABSTRACT

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


Subject(s)
Coronavirus Infections/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Viral Vaccines/administration & dosage , Adenoviridae , Adolescent , Adult , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Betacoronavirus , China , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immunity, Cellular , Immunity, Humoral , Injections, Intramuscular , Male , Middle Aged , T-Lymphocytes/immunology , Vaccines, Synthetic/administration & dosage , Vaccines, Synthetic/adverse effects , Vaccines, Synthetic/therapeutic use , Viral Vaccines/adverse effects , Viral Vaccines/therapeutic use , Young Adult
18.
Preprint | medRxiv | ID: ppmedrxiv-20032599

ABSTRACT

Objectives The aim of the study was to analyze the incidence of COVID-19 with early renal injury, and to explore the value of multi-index combined detection in diagnosis of early renal injury in COVID-19. Design The study was an observational, descriptive study. Setting This study was carried out in a tertiary hospital in Guangdong, China. Participants 12 patients diagnosed with COVID-19 from January 20, 2020 to February 20, 2020. Primary and secondary outcome measures The primary outcome was to evaluate the incidence of early renal injury in COVID-19. In this study, the estimated glomerular filtration rate (eGFR), endogenous creatinine clearance (Ccr) and urine microalbumin / urinary creatinine ratio (UACR) were calculated to assess the incidence of early renal injury. Secondary outcomes were the diagnostic value of urine microalbumin (UMA), 1-microglobulin (A1M), urine immunoglobulin-G (IGU), urine transferring (TRU) alone and in combination in diagnosis of COVID-19 with early renal injury. Results While all patients had no significant abnormalities in serum creatinine (Scr) and blood urea nitrogen (BUN), the abnormal rates of eGFR, Ccr, and UACR were 66.7%, 41.7%, and 41.7%, respectively. Urinary microprotein detection indicated that the area under curve (AUC) of multi-index combined to diagnose early renal injury in COVID-19 was 0.875, which was higher than UMA (0,813), A1M (0.813), IGU (0.750) and TRU (0.750) alone. Spearman analysis showed that the degree of early renal injury was significantly related to C-reactive protein (CRP) and neutrophil ratio (NER), suggesting that the more severe the infection, the more obvious the early renal injury. Hypokalemia and hyponatremia were common in patients with COVID-19, and there was a correlation with the degree of renal injury. Conclusions Early renal injury was common in patients with COVID-19. Combined detection of UMA, A1M, IGU, and TRU was helpful for the diagnosis of early renal injury in COVID-19.

19.
Int J Infect Dis ; 93: 264-267, 2020 Apr.
Article in English | MEDLINE | ID: covidwho-2506

ABSTRACT

An ongoing outbreak of severe respiratory pneumonia associated with the 2019 novel coronavirus has recently emerged in China. Here we report the epidemiological, clinical, laboratory and radiological characteristics of 19 suspect cases. We compared the positive ratio of 2019-nCoV nucleic acid amplification test results from different samples including oropharyngeal swab, blood, urine and stool with 3 different fluorescent RT-PCR kits. Nine out of the 19 patients had 2019-nCoV infection detected using oropharyngeal swab samples, and the virus nucleic acid was also detected in eight of these nine patients using stool samples. None of positive results was identified in the blood and urine samples. These three different kits got the same result for each sample and the positive ratio of nucleic acid detection for 2019-nCoV was only 47.4% in the suspect patients. Therefore, it is possible that infected patients have been missed by using nucleic acid detection only. It might be better to make a diagnosis combining the computed tomography scans and nucleic acid detection.


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/diagnosis , Nucleic Acid Amplification Techniques , Pneumonia, Viral/diagnosis , Blood/virology , China/epidemiology , Coronavirus Infections/virology , Feces/virology , Female , Humans , Nucleic Acid Amplification Techniques/standards , Pandemics , Pharynx/virology , Pneumonia, Viral/virology , Urine/virology , Young Adult
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