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1.
Nature ; 2020 Jul 29.
Article in English | MEDLINE | ID: covidwho-691301

ABSTRACT

The novel Coronavirus SARS-CoV-2 causes a respiratory illness called COVID-19 leading to a pandemic. An effective preventive vaccine against this virus is urgently needed. As the most critical step during infection, SARS-CoV-2 uses its Spike protein receptor-binding domain (S-RBD) to engage with the host cell receptor angiotensin-converting enzyme 2 (ACE2)1,2. Here we showed that a recombinant vaccine comprising residues 319-545 of the S-RBD could induce a potent functional antibody response in the immunized mice, rabbits and non-human primates (Macaca mulatta) as early as 7 or 14 days after a single dose injection. The sera from the immunized animals blocked RBD binding to ACE2 expressed on the cell surface and neutralized the infection by SARS-CoV-2 pseudovirus and live SARS-CoV-2 in vitro. Importantly, the vaccination also provided protection in non-human primates from SARS-CoV-2 challenge in vivo. The elevated RBD-specific antibodies were also found in the sera from patients with COVID-19. Several immune pathways and CD4 T lymphocytes were implicated in the induction of the vaccine antibody response. Our finding highlights the importance of the RBD domain in the SARS-CoV-2 vaccine design and provides the rationale for the development of a protective vaccine through the induction of antibody against the RBD domain.

2.
Frontiers in medicine ; 7:373-373, 2020.
Article | WHO COVID | ID: covidwho-689146

ABSTRACT

Background: With the adoption of powerful preventive and therapeutic measures, a large number of patients with COVID-19 have recovered and been discharged from hospitals in Wuhan, China Prevention of epidemic rebound is a top priority of current works However, information regarding post-discharge quarantine and surveillance of recovered patients with COVID-19 is scarce Methods: This study followed up 337 patients with COVID-19 in a Wuhan East-West Lake Fangcang shelter hospital during the post-discharge quarantine Demographic, clinical characteristics, comorbidities, and chest computed tomography (CT) image, mental state, medication status, and nucleic acid test data were summarized and analyzed Results: 21/337 (6 2%) patients were SARS-CoV-2 nucleic acid re-positive, and 4 /337(1 2%) patients were suspected positive The median day interval between the discharge to nucleic acid re-positivity was 7 5 days (IQR, 6-13), ranging from 6 to 13 days Cough/expectoration are the most common symptoms, followed by chest congestion/dyspnea during the 2 weeks post-discharge quarantine Risk factors of nucleic acid re-positivity including the number of lobes infiltration (odds ratio[OR], 1 14;95% CI, 1 09-1 19), distribution (OR, 0 16;95% CI, 0 13-0 19), CT imaging feature of patchy shadowing accompanying with consolidation (OR, 9 36;95% CI, 7 84-11 17), respiratory symptoms of cough accompanying with expectoration (OR, 1 39;95% CI, 1 28-1 52), and chest congestion accompanying by dyspnea (OR, 1 42;95% CI, 1 28-1 57) Conclusion: The 2 weeks post-discharge quarantine may be an effective measure to prevent the outbreak from rebounding from the recovered patients The second week is a critical period during post-discharge quarantine Special attention should be paid to cough, expectoration, chest congestion, and dyspnea in recovered COVID-19 patients A few recovered patients may prolong the quarantine based on clinical symptoms and signs and nucleic acid results in the 2 weeks of medical observation

3.
Thrombosis Research ; 2020.
Article | WHO COVID | ID: covidwho-680809

ABSTRACT

Introduction Abnormal coagulation function has been demonstrated to be involved in the disease progression of COVID-19 However, the association between D-dimer levels and the severity of COVID-19 is not clear The study was aimed to investigate the association between D-dimer levels and the severity of COVID-19 based on a cohort study and meta-analysis Materials and methods Demographic and clinical data of all confirmed cases with COVID-19 on admission to Tongji Hospital from January 27 to March 5, 2020, were collected and analyzed, and coagulation function parameters were described and compared between patients with severe infection and those with non-severe infection Cohort studies reporting risk estimates for the D-dimer and severity of COVID-19 association were searched and included to perform a meta-analysis Results In our cohort study, patients with severe disease were more likely to exhibit dysregulated coagulation function, and a significantly higher D-dimer level (median 1 8 μg/ml [interquartile range 0 9–4 6] vs 0 5 [0 3–1 1], p < 0 001) was found in severe cases than the mild ones, on admission In the meta-analysis of 13 cohort studies (including the current study), patients with severe disease had an increase in mean D-dimer value by 0 91 (95% confidence interval, 0 51–1 31, p < 0 001) μg/ml compared to those with non-severe disease, and odds of severe infection was associated with D-dimer greater than 0 5 μg/ml (odds ratio = 5 78, 95% confidence interval, 2 16–15 44, p < 0 001) on admission Conclusions Patients with severe COVID-19 have a higher level of D-dimer than those with non-severe disease, and D-dimer greater than 0 5 μg/ml is associated with severe infection in patients with COVID-19

4.
Journal of the Formosan Medical Association ; 2020.
Article | WHO COVID | ID: covidwho-680413
5.
Diabetes Res Clin Pract ; : 108338, 2020 Jul 23.
Article in English | MEDLINE | ID: covidwho-664497

ABSTRACT

AIMS: The objective of this study is to explore the association between documented diabetes, fasting plasma glucose (FPG), and the clinical outcomes of Coronavirus disease 2019 (COVID-19) . METHODS: This retrospective study included 255 patients with COVID-19. Of these, 214 were admitted to isolation wards and 41were admitted to intensive care units (ICUs).Demographic, clinical, treatment, and laboratory data were collected and compared between ICU and non-ICU patients. Multivariable logistic regression models were used to explore the risk factors associated with poor clinical outcomes (ICU admission or death). RESULTS: There were significant changes in several clinical parameters in ICU patients (leukopenia, lymphopenia, elevated D-dimer, as well as higher levels of FPG, cardiac troponin, serum ferritin,IL-6, and high-sensitivity C-reactive protein)compared with non-ICU patients. The prevalence of known diabetes was substantially higher in ICU than non-ICU patients (31.7% vs. 17.8%, P=0.0408).Multivariable regression analysis showed that a history of diabetes [odds ratio (OR), 0.099; 95% confidence interval (CI), 0.016-0.627; P=0.014], high FPG at admission (OR, 1.587; 95% CI, 1.299-1.939, P<0.001), high IL-6 (OR, 1.01; 95% CI, 1.002-1.018, P=0.013), and D-dimer higher than 1 mg/L at admission (OR, 4.341; 95% CI, 1.139-16.547, P=0.032) were independent predictors of poor outcomes. Cox proportional hazards analysis showed that compared with FPG <7mmol/L, FPG levels of 7.0-11.1 mmol/L and ≥11.1mmol/L were associated with an increased hazard ratio (HR) for poor outcome (HR, 5.538 [95% CI, 2.269-13.51] and HR, 11.55 [95% CI, 4.45-29.99], respectively). CONCLUSION: Hyperglycemia and a history of diabetes on admission predicted poor clinical outcomes in COVID-19.

9.
J Allergy Clin Immunol ; 146(1): 137-146.e3, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-637807

ABSTRACT

BACKGROUND: Accumulating evidence proposed Janus-associated kinase (JAK) inhibitors as therapeutic targets warranting rapid investigation. OBJECTIVE: This study evaluated the efficacy and safety of ruxolitinib, a JAK1/2 inhibitor, for coronavirus disease 2019. METHODS: We conducted a prospective, multicenter, single-blind, randomized controlled phase II trial involving patients with severe coronavirus disease 2019. RESULTS: Forty-three patients were randomly assigned (1:1) to receive ruxolitinib plus standard-of-care treatment (22 patients) or placebo based on standard-of-care treatment (21 patients). After exclusion of 2 patients (1 ineligible, 1 consent withdrawn) from the ruxolitinib group, 20 patients in the intervention group and 21 patients in the control group were included in the study. Treatment with ruxolitinib plus standard-of-care was not associated with significantly accelerated clinical improvement in severe patients with coronavirus disease 2019, although ruxolitinib recipients had a numerically faster clinical improvement. Eighteen (90%) patients from the ruxolitinib group showed computed tomography improvement at day 14 compared with 13 (61.9%) patients from the control group (P = .0495). Three patients in the control group died of respiratory failure, with 14.3% overall mortality at day 28; no patients died in the ruxolitinib group. Ruxolitinib was well tolerated with low toxicities and no new safety signals. Levels of 7 cytokines were significantly decreased in the ruxolitinib group in comparison to the control group. CONCLUSIONS: Although no statistical difference was observed, ruxolitinib recipients had a numerically faster clinical improvement. Significant chest computed tomography improvement, a faster recovery from lymphopenia, and favorable side-effect profile in the ruxolitinib group were encouraging and informative to future trials to test efficacy of ruxolitinib in a larger population.


Subject(s)
Coronavirus Infections/drug therapy , Janus Kinase Inhibitors/therapeutic use , Pneumonia, Viral/drug therapy , Pyrazoles/therapeutic use , Aged , Betacoronavirus , Coronavirus Infections/mortality , Female , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/mortality , Single-Blind Method , Treatment Outcome
11.
Eur Respir J ; 55(6)2020 06.
Article in English | MEDLINE | ID: covidwho-622479

ABSTRACT

BACKGROUND: During the outbreak of coronavirus disease 2019 (COVID-19), consistent and considerable differences in disease severity and mortality rate of patients treated in Hubei province compared to those in other parts of China have been observed. We sought to compare the clinical characteristics and outcomes of patients being treated inside and outside Hubei province, and explore the factors underlying these differences. METHODS: Collaborating with the National Health Commission, we established a retrospective cohort to study hospitalised COVID-19 cases in China. Clinical characteristics, the rate of severe events and deaths, and the time to critical illness (invasive ventilation or intensive care unit admission or death) were compared between patients within and outside Hubei. The impact of Wuhan-related exposure (a presumed key factor that drove the severe situation in Hubei, as Wuhan is the epicentre as well the administrative centre of Hubei province) and the duration between symptom onset and admission on prognosis were also determined. RESULTS: At the data cut-off (31 January 2020), 1590 cases from 575 hospitals in 31 provincial administrative regions were collected (core cohort). The overall rate of severe cases and mortality was 16.0% and 3.2%, respectively. Patients in Hubei (predominantly with Wuhan-related exposure, 597 (92.3%) out of 647) were older (mean age 49.7 versus 44.9 years), had more cases with comorbidity (32.9% versus 19.7%), higher symptomatic burden, abnormal radiologic manifestations and, especially, a longer waiting time between symptom onset and admission (5.7 versus 4.5 days) compared with patients outside Hubei. Patients in Hubei (severe event rate 23.0% versus 11.1%, death rate 7.3% versus 0.3%, HR (95% CI) for critical illness 1.59 (1.05-2.41)) have a poorer prognosis compared with patients outside Hubei after adjusting for age and comorbidity. However, among patients outside Hubei, the duration from symptom onset to hospitalisation (mean 4.4 versus 4.7 days) and prognosis (HR (95%) 0.84 (0.40-1.80)) were similar between patients with or without Wuhan-related exposure. In the overall population, the waiting time, but neither treated in Hubei nor Wuhan-related exposure, remained an independent prognostic factor (HR (95%) 1.05 (1.01-1.08)). CONCLUSION: There were more severe cases and poorer outcomes for COVID-19 patients treated in Hubei, which might be attributed to the prolonged duration of symptom onset to hospitalisation in the epicentre. Future studies to determine the reason for delaying hospitalisation are warranted.


Subject(s)
Coronavirus Infections/mortality , Hospitalization , Pneumonia, Viral/mortality , Adult , Aged , Betacoronavirus , Cardiovascular Diseases/epidemiology , China , Cohort Studies , Comorbidity , Coronavirus Infections/complications , Coronavirus Infections/diagnostic imaging , Cough/etiology , Diabetes Mellitus/epidemiology , Disease Outbreaks , Dyspnea/etiology , Fatigue/etiology , Female , Fever/etiology , Geography , Humans , Hypertension/epidemiology , Intensive Care Units/statistics & numerical data , Lung/diagnostic imaging , Male , Middle Aged , Pandemics , Pharyngitis/etiology , Pneumonia, Viral/complications , Pneumonia, Viral/diagnostic imaging , Prognosis , Proportional Hazards Models , Respiration, Artificial/statistics & numerical data , Retrospective Studies , Severity of Illness Index , Time Factors , Time-to-Treatment/statistics & numerical data , Tomography, X-Ray Computed
13.
EClinicalMedicine ; 2020.
Article in English | ELSEVIER | ID: covidwho-613224

ABSTRACT

Background: The outbreak of COVID-19 has laid unprecedented threats and challenges to health workers (HWs) in Wuhan, China. We aimed to assess the sociodemographic characteristics and hospital support measures associated with the immediate psychological impact on HWs at Tongji Hospital in Wuhan during COVID-19 outbreak. Methods: We conducted a single-center, cross-sectional survey of HWs via online questionnaires between February 8th and 10th, 2020. We evaluated stress, depression and anxiety by IES-R, PHQ-9, and GAD-7, respectively. We also designed a questionnaire to assess the perceptions of threat of COVID-19, and the satisfactions of the hospital's support measures. Multivariate logistic regressions were used to identify associated variables of acute stress, depression, and anxiety. Findings: We received 5062 completed questionnaires (response rate, 77.1%). 29.8%, 13.5% and 24.1% HWs reported stress, depression and anxiety symptoms. Women (odds ratio [OR], 1.31; 95% CI, 0.47–0.97; p = 0.032), years of working >10 years (OR, 2.02; 95% CI, 1.47–2.79; p<0.001), concomitant chronic diseases (OR, 1.51; 95% CI, 1.27–1.80; p<0.001), history of mental disorders (OR, 3.27; 95% CI, 1.77–6.05; p<0.001), family members or relatives confirmed or suspected (OR, 1.23; 95% CI, 1.02–1.48; p = 0.03), hospital-based and department-based care (OR, 0.76; 95% CI, 0.60–0.97; p = 0.024) and full coverage of all departments for avoiding nosocomial infection (OR, 0.69; 95% CI, 0.53–0.89; p = 0.004) were associated with stress. Interpretation: Women and those who have more than 10 years of working, concomitant chronic diseases, history of mental disorders, and family members or relatives confirmed or suspected are susceptible to stress, depression and anxiety among HWs during the pandemic. In addition, since HWs often have a greater stigma against mental problems than the general public, it is worthwhile to address the needs of the HWs during this pandemic and to provide appropriate psychological supports for those people at high risk of mental problems.

14.
15.
Medicine (Baltimore) ; 99(25): e20706, 2020 Jun 19.
Article in English | MEDLINE | ID: covidwho-607007

ABSTRACT

BACKGROUND: Corona Virus Disease 2019 (COVID-19) has caused a worldwide epidemic since its discovery. The outbreak of virus infection has aroused great concern of the World Health Organization (WHO). COVID-19 is highly infectious and has a high infection rate. So far, no specific drug has been found to cure it. China as one of the first countries attacked by epidemic has shown outstanding in fighting against the COVID-19. The contribution of traditional Chinese medicine can not be ignored. As a kind of representative of traditional Chinese medicine, the Chinese patent medicine injection has significant effect in reducing the clinical symptoms of patients and preventing the deterioration of the disease. However, there is no systematic review of its efficacy and safety. The purpose of this study is to evaluate the efficacy and safety of Chinese patent medicine injection in the treatment of COVID-19. METHODS: All randomized controlled trials of Chinese patent medicine injection for COVID-19 will be included. The following electronic databases will be searched: PubMed, Web of Science, the Cochrane Library, EMBASE, China National Knowledge Infrastructure, Wanfang Database, Chinese Scientific Journal Database, Chinese Biomedical Literature database and some clinical trial registration websites. Two researchers will independently screen titles, abstracts, full texts, and extract data, then assess the bias risk of each study. We will conduct meta-analyses to assess all the available evidence of the efficacy and safety. RESULTS: Systematic review of current evidence will be provided from the indexes of efficacy and safety. CONCLUSION: Evidence regarding the efficacy and safety of Chinese patent medicine injection in the treatment of COVID-19 will be provided to clinicians.PROSPERO registration number: CRD42020182725.


Subject(s)
Coronavirus Infections/drug therapy , Drugs, Chinese Herbal/administration & dosage , Drugs, Chinese Herbal/adverse effects , Meta-Analysis as Topic , Pneumonia, Viral/drug therapy , Systematic Reviews as Topic , Betacoronavirus , Humans , Injections , Pandemics
16.
Plast. Reconstr. Surg., Glob. Open ; 2020.
Article in English | ELSEVIER | ID: covidwho-604672

ABSTRACT

Background: The novel Coronavirus Disease 2019 (COVID-19) has rapidly become a health threat worldwide and has been declared global pandemic by the World Health Organization. Possible transmission routes, including respiratory droplets, close contact, and aerosol propagation, have put plastic and reconstructive healthcare professionals at high risk, especially during surgical procedures. The aim of this study was to summarize and share our experience of infection control measures and corresponding outcomes during the COVID-19 pandemic. Methods: Infection control measures, including workflow optimization, useful epidemiologic survey methods, and personal full protective clothing, were discussed. Characteristics and outcomes of emergency cases and elective cases under local and general anesthesia during the COVID-19 pandemic were summarized. Results: A hierarchy of interventions were applied mainly from 4 aspects. First, administration control and online consultation significantly decreased patient attendance. Second, a triage workflow was established to identify high-/low-risk patients, with clinical manifestations (fever, fatigue, cough, nasal discharge, etc), epidemiologic survey, blood test, chest computed tomographic scan, and coronavirus test if necessary. Third, strict environmental control was adopted using increasing ventilation, isolated room for inpatients, etc. Fourth, proper rotation of healthcare staff was ensured to reduce workload and minimize possible contact. A total of 904 emergency interventions, 2561 local anesthesia, and 570 general anesthesia were performed during this period, and none of the cases/healthcare professionals were found to be infected. Conclusions: Our experience could help global plastic and reconstructive healthcare professionals to get better preparation and continue to give qualified medical services during the COVID-19 pandemic. Proper adjustments should be taken according to their own clinical settings.

17.
J Med Virol ; 2020 Jun 15.
Article in English | MEDLINE | ID: covidwho-602538

ABSTRACT

A pandemic of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection broke out all over the world; however, epidemiological data and viral shedding in pediatric patients are limited. We conducted a retrospective, multicenter study, and followed-up with all children from the families with SARS-CoV-2 infected members in Zhejiang Province, China. All infections were confirmed by testing the SARS-CoV-2 RNA with real-time reverse transcription PCR method, and epidemiological data between children and adults in the same families were compared. Effect of antiviral therapy was evaluated observationally and fecal-viral excretion times among groups with different antiviral regiments were compared with Kaplan-Meier plot. By 29 February 2020, 1298 cases from 883 families were confirmed with SARS-CoV-2 infection and 314 of which were families with children. Incidence of infection in child close contacts was significantly lower than that in adult contacts (13.2% vs 21.2%). The mean age of 43 pediatric cases was 8.2 years and mean incubation period was 9.1 days. Forty (93.0%) were family clustering. Thirty-three children had coronavirus disease 2019 (20 pneumonia) with mild symptoms and 10 were asymptomatic. Fecal SARS-CoV-2 RNA detection was positive in 91.4% (32/35) cases and some children had viral excretion time over 70 days. Viral clearance time was not different among the groups treated with different antiviral regiments. No subsequent infection was observed in family contacts of fecal-viral-excreting children. Children have lower susceptibility of SARS-CoV-2 infection, longer incubation, and fecal-viral excretion time. Positive results of fecal SARS-CoV-2 RNA detection were not used as indication for hospitalization or quarantine.

18.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 36(4): 376-382, 2020 Apr.
Article in Chinese | MEDLINE | ID: covidwho-595772

ABSTRACT

During the pandemic of coronavirus disease 2019 (COVID-19), the Chinese Ministry of Education put forward the requirement of turning offline education into online teaching to universities. Our department positively responded and rapidly mobilized to establish an online teaching system of medical immunology based on the small private online course (SPOC) model, which has a main body of the SPOC model with "video course as the main part, supplemented by online Q&A". The system also has feedback improvement sections of online discussion and chapter tests and evaluates the quality and effect of teaching with students' group display, course examination, and questionnaires. At the same time, the COVID-19 hotspot is also organically combined with immunological knowledge throughout the online teaching. In this process, our department continuously summarizes experiences and discovers problems. Herein, we generalize and sort out the exploration and practice of constructing the online teaching system, to carry out offline teaching after the pandemic and to continue this teaching model in the future, for reference and guidance.


Subject(s)
Allergy and Immunology , Coronavirus Infections , Coronavirus , Education, Distance , Models, Educational , Pandemics , Pneumonia, Viral , Allergy and Immunology/education , Betacoronavirus , Coronavirus Infections/epidemiology , Humans , Internet , Pneumonia, Viral/epidemiology
20.
HLA ; 96(2): 194-196, 2020 08.
Article in English | MEDLINE | ID: covidwho-590717

ABSTRACT

COVID-19 is a respiratory disease caused by a novel coronavirus and is currently a global pandemic. HLA variation is associated with COVID-19 because HLA plays a pivotal role in the immune response to pathogens. Here, 82 individuals with COVID-19 were genotyped for HLA-A, -B, -C, -DRB1, -DRB3/4/5, -DQA1, -DQB1, -DPA1, and -DPB1 loci using next-generation sequencing (NGS). Frequencies of the HLA-C*07:29, C*08:01G, B*15:27, B*40:06, DRB1*04:06, and DPB1*36:01 alleles were higher, while the frequencies of the DRB1*12:02 and DPB1*04:01 alleles were lower in COVID-19 patients than in the control population, with uncorrected statistical significance. Only HLA-C*07:29 and B*15:27 were significant when the corrected P-value was considered. These data suggested that some HLA alleles may be associated with the occurrence of COVID-19.


Subject(s)
Coronavirus Infections/genetics , HLA Antigens/genetics , Pneumonia, Viral/genetics , Alleles , Asian Continental Ancestry Group/genetics , Betacoronavirus , China/epidemiology , Coronavirus Infections/immunology , Gene Frequency , Genotype , Haplotypes , High-Throughput Nucleotide Sequencing , Humans , Immune System , Models, Statistical , Pandemics , Pneumonia, Viral/immunology , Polymorphism, Genetic
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