Corpus overview


MeSH Disease

Human Phenotype


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    Does Respiratory Co-Infection MESHD Facilitate Dispersal of SARS-CoV-2? Investigation of a Super-Spreading Event in an Open-Space Office

    Authors: Dana Weissberg; Jürg Böni; Silvana Rampini; Verena Kufner; Maryam Zaheri; Peter W. Schreiber; Irene A. Abela; Michael Huber; Hugo Sax; Aline Wolfensberger

    doi:10.21203/ Date: 2020-09-06 Source: ResearchSquare

    Background: Super-spreaders are individuals infecting disproportionately large numbers of contacts. They probably play a crucial role in the transmission TRANS of severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2). We describe a super-spreading event within a team working in an open-space office and investigate factors potentially having facilitated SARS-CoV-2 transmission TRANS.Methods: In this retrospective cohort study, semi-structured telephone interviews with all team members were carried out to identify symptoms, contacts, and adherence to basic hygiene measures. During site visits, we gathered information about workplace and seating arrangements. The secondary attack rate TRANS in office and households was calculated. Potential respiratory viral co-infections MESHD were assessed by multiplex PCR. SARS-CoV-2 whole-genome sequencing was performed using a tiled-amplicon sequencing approach.Results: Of 13 team members, 11 fell HP ill with Coronavirus disease MESHD 2019 (COVID-19). Due to the sequence of events and full genome sequence data, one person was considered the index case for this outbreak, directly infecting 67% to 83% of the teammates. All team members reported repetitive close contacts TRANS among themselves during joint computer work, team meetings and a “Happy Birthday” serenade. Two individuals shared nuts and dates. The arrangement of the office and meeting rooms precluded sufficient adherence to physical distancing. The index case and a further individual were diagnosed with an adenovirus serotype 4 co-infection MESHD, but secondary household attack rate TRANS was not higher for co-infected MESHD individuals. Conclusion: We identified several environmental and behavioral factors that probably have facilitated the transmission TRANS of SARS-CoV-2. The relevance of the adenovirus co-infection MESHD remains unclear and merits further investigation.

    Engineered interferon alpha effectively improves clinical outcomes of COVID-19 patients

    Authors: Chuan Li; Fengming Luo; Chengwu Liu; Nian Xiong; Zhihua Xu; Wei Zhang; Ming Yang; Ye Wang; Dan Liu; Chao Yu; Jia Zeng; Li Zhang; Duo Li; Yanbin Liu; Mei Feng; Ruoyang Liu; Jiandong Mei; Senyi Deng; Zhen Zeng; Yuanhong He; Haiyan Liu; Zhengyu Shi; Meng Duan; Deying Kang; Jiayu Liao; Weimin Li; Lunxu Liu

    doi:10.21203/ Date: 2020-08-25 Source: ResearchSquare

    Interferons are key to the antiviral host defense, yet the therapeutic value of interferon for coronavirus disease MESHD 2019 (COVID-19) is unknown. Recombinant super-compound interferon ( rSIFN-co MESHD) is a new genetically engineered interferon, thus we conducted a multicenter, randomized controlled trial (ChiCTR2000029638) to evaluate the efficacy and safety of recombinant super-compound interferon versus traditional interferon alpha added to baseline antiviral agents (lopinavir–ritonavir or umifenovir) for the treatment of moderate-to-severe COVID-19. Participants received rSIFN-co MESHD (12 million international units [IU], twice daily) or interferon alpha (5 million IU, twice daily) nebulization added to baseline antiviral agents for no more than 28 days. The primary outcome was the time to clinical improvement. Secondary outcomes included the overall rate of clinical improvement assessed on day 28,the time to radiological improvement and virus nucleic acid negative conversion, and adverse events. 94 patients hospitalized with moderate-to-severe COVID-19 were included in the safety set (46 patients assigned to rSIFN-co group, 48 to interferon alpha group). Individuals in the rSIFN-co group showed shorter time to clinical improvement (11.5 days vs 14.0 days; P = 0.019) as compared to those in the interferon alpha group. The overall rate of clinical improvement on day 28 was much higher in the rSIFN-co MESHD group than that in the interferon alpha group (93.5% vs 77.1%; difference, 16.4%; 95% confidence interval 3% to 30%). The time to radiological improvement and the time to virus nucleic acid negative conversion were also much shorter in the rSIFN-co group (8.0 days vs 10.0 days, P = 0.002; 7.0 days vs 10.0 days, P = 0.018, respectively). Adverse events were reported in 13 (28.3%) patients in the rSIFN-co group and 18 (37.5%) patients in the interferon alpha group. No patients died during the study. Our study showed that rSIFN-co added to antiviral agents was safe and more efficient than interferon alpha plus antiviral agents in the treatment of moderate-to-severe COVID-19. Future clinical study of rSIFN-co therapy alone or combined with other antiviral therapy is warranted.

    The Discovery of a Recombinant SARS2-like CoV Strain Provides Insight Into SARS and COVID-19 Pandemics

    Authors: Xin Li; Xiufeng Jin; Shunmei Chen; Liangge Wang; Tung On Yau; Jianyi Yang; Zhangyong Hong; Jishou Ruan; Guangyou Duan; Shan Gao

    doi:10.21203/ Date: 2020-08-16 Source: ResearchSquare

    Background: In December 2019, the world awoke to a new zoonotic strain of coronavirus named severe acute respiratory syndrome coronavirus-2 MESHD (SARS-CoV-2).Results: In the present study, we classified betacoronavirus subgroup B into the SARS-CoV-2, SARS-CoV MESHD and SARS-like CoV clusters, and the ORF8 genes of these three clusters into types 1, 2 and 3, respectively. One important result of our study is that we reported—for the first time—a recombination event of ORF8 at the whole-gene level in a bat, which had been co-infected MESHD by two betacoronavirus strains. This result provides substantial proof for long-existing hypotheses regarding the recombination and biological functions of ORF8. Based on the analysis of recombination events in the Spike gene, we propose that the Spike protein of SARS-CoV-2 may have more than one specific receptor for its function as gp120 of HIV has CD4 and CCR5. In the present study, we also found that the ancestor of betacoronavirus had a strong first Internal Ribosome Entry Site (IRES) and at least one furin cleavage site (FCS) in the junction region between S1 and S2 subunits.Conclusions: We concluded that the junction FCS in SARS-CoV-2 may increase the efficiency of its entry into cells, while the type 2 ORF8 acquired by SARS-CoV may increase its replication efficiency. These two most critical events provide the most likely explanation for SARS and COVID-19 pandemics.

    Analysis of COVID-19 and comorbidity co-infection MESHD Model with Optimal Control

    Authors: Dr. Andrew Omame; Nometa Ikenna

    doi:10.1101/2020.08.04.20168013 Date: 2020-08-04 Source: medRxiv

    The new coronavirus disease MESHD 2019 (COVID-19) infection MESHD is a double challenge for people infected MESHD with comorbidities such as cardiovascular and cerebrovascular diseases MESHD and diabetes MESHD. Comorbidities have been reported to be risk factors for the complications of COVID-19. In this work, we develop and analyze a mathematical model for the dynamics of COVID-19 infection MESHD in order to assess the impacts of prior comorbidity on COVID-19 complications and COVID-19 re-infection. The model is simulated using data relevant to the dynamics of the diseases in Lagos, Nigeria, making predictions for the attainment of peak periods in the presence or absence of comorbidity. The model is shown to undergo the phenomenon of backward bifurcation caused by the parameter accounting for increased susceptibility to COVID-19 infection MESHD by comorbid susceptibles as well as the rate of re-infection by those who have recovered from a previous COVID-19 infection MESHD. Sensitivity SERO analysis of the model when the population of individuals co-infected MESHD with COVID-19 and comorbidity is used as response function revealed that the top ranked parameters that drive the dynamics of the co-infection MESHD model are the effective contact rate for COVID-19 transmission TRANS, $\beta\sst{cv}$, the parameter accounting for increased susceptibility to COVID-19 by comorbid susceptibles, $\chi\sst{cm}$, the comorbidity development rate, $\theta\sst{cm}$, the detection rate for singly infected and co-infected MESHD individuals, $\eta_1$ and $\eta_2$, as well as the recovery rate from COVID-19 for co-infected MESHD individuals, $\varphi\sst{i2}$. Simulations of the model reveal that the cumulative confirmed cases TRANS (without comorbidity) may get up to 180,000 after 200 days, if the hyper susceptibility rate of comorbid susceptibles is as high as 1.2 per day. Also, the cumulative confirmed cases TRANS (including those co-infected MESHD with comorbidity) may be as high as 1000,000 cases by the end of November, 2020 if the re-infection rates for COVID-19 is 0.1 per day. It may be worse than this if the re-infection rates increase higher. Moreover, if policies are strictly put in place to step down the probability of COVID-19 infection MESHD by comorbid susceptibles to as low as 0.4 per day and step up the detection rate for singly infected MESHD individuals to 0.7 per day, then the reproduction number TRANS can be brought very low below one, and COVID-19 infection eliminated from the population. In addition, optimal control and cost-effectiveness analysis of the model reveal that the the strategy that prevents COVID-19 infection MESHD by comorbid susceptibles has the least ICER and is the most cost-effective of all the control strategies for the prevention of COVID-19.

    Clinical characteristics and outcome of influenza virus infection MESHD among adults TRANS hospitalized with severe COVID-19: A retrospective cohort study from Wuhan, China

    Authors: Xunliang Tong; Xiaomao Xu; Guoyue Lv; He Wang; Anqi Cheng; Dingyi Wang; Yue Zhang; Yanming Li

    doi:10.21203/ Date: 2020-07-29 Source: ResearchSquare

    Background Coronavirus disease MESHD 2019 (COVID-19) is an emerging infection disease MESHD that rapidly spreads worldwide. Co-infection MESHD may occur in some cases of COVID-19, like influenza virus and so on. Clinical features and outcomes of severe COVID-19 patients with co-infection MESHD of influenza virus need to be noticed.Methods Retrospective cohort study was performed and total of 140 patients with severe COVID-19 was enrolled in designated wards of Sino-French New City Branch of Tongji Hospital between Feb 8th and March 15th in Wuhan, Hubei province, China. The demographic, clinical features, laboratory indices, treatment and outcomes of these patients were collected and analyzed.Results Of 140 severe COVID-19 hospitalized patients, 73 patients were with median age TRANS of 66 years old with identification of influenza virus IgM-positive and 67 patients were with median age TRANS of 62 years old in influenza virus IgM-negative. Nearly half of severe COVID-19 patients in this research are male TRANS. Majority of the severe COVID-19 patients had chronic underlying conditions. Wheeze HP was the clinical feature of severe COVID-19 patients with influenza IgM-positive (26.4% vs 9.0%, P = 0.008). On contrary, fatigue HP fatigue MESHD or myalgia HP myalgia MESHD was the feature of the COVID-19 patients without IgM-positive (38.4% vs 58.2%, P = 0.019). Increased levels of ferritin and prolonging APTT were showed in severe COVID-19 patients without influenza IgM-positive compared with patients in other group with significant differences. Death rate in the group of severe COVID-19 patients with influenza IgM-positive is lower than it in other group with significant differences (4.1% vs 14.9%, P = 0.040). In univariate regression analysis, several factors were associated with higher risk of death MESHD, which included LDH, troponin, NT-proBNP, D-dimer, PT, APTT, lymphocytes, platelet and eGFR. However, influenza virus IgM positive was associated with lower risk of death.Conclusions Characteristic features of patients with severe COVID-19 with influenza virus IgM-positive were described. Co-infection MESHD may occur during the pandemic of COVID-19, and we need to improve our understanding in order to confront this crisis in the future.

    Interferons and viruses induce a novel primate-specific isoform dACE2 and not the SARS-CoV-2 receptor ACE2

    Authors: Olusegun O Onabajo; A Rouf Banday; Wusheng Yan; Adeola Obajemu; Megan L Stanifer; Deanna M Santer; Oscar Florez-Vargas; Helen Piontkivska; Joselin Vargas; Carmon Kee; D Lorne Tyrrell; Juan L Mendoza; Steeve Boulant; Ludmila Prokunina-Olsson

    doi:10.1101/2020.07.19.210955 Date: 2020-07-20 Source: bioRxiv

    Severe acute respiratory syndrome coronavirus-2 MESHD (SARS-CoV-2), which causes COVID-19, utilizes angiotensin-converting enzyme 2 (ACE2) for entry into target cells. ACE2 has been proposed as an interferon-stimulated gene (ISG). Thus, interferon-induced variability in ACE2 expression levels could be important for susceptibility to COVID-19 or its outcomes. Here, we report the discovery of a novel, primate-specific isoform of ACE2, which we designate as deltaACE2 (dACE2). We demonstrate that dACE2, but not ACE2, is an ISG. In vitro, dACE2, which lacks 356 N-terminal amino acids, was non-functional in binding the SARS-CoV-2 spike protein and as a carboxypeptidase. Our results reconcile current knowledge on ACE2 expression and suggest that the ISG-type induction of dACE2 in IFN-high conditions created by treatments, inflammatory tumor MESHD microenvironment, or viral co-infections MESHD is unlikely to affect the cellular entry of SARS-CoV-2 and promote infection.

    Optimized Laboratory Detection Strategy for COVID-19 Patients Reduces the Rate of Missed Diagnosis

    Authors: Wenjiao Chang; Yuru Shi; Yingjie Qi; Jiaxing Liu; Ting Liu; Zhaowu Chen; Dongfeng Liu; Ming Yin; Jing Xu; Yun Yang; Jing Ge; Shu Zhu; Yong Gao; Xiaoling Ma

    doi:10.21203/ Date: 2020-07-13 Source: ResearchSquare

    Background: Novel coronavirus pneumonia MESHD pneumonia HP (NCP) is an emerging, highly contagious community acquired pneumonia HP pneumonia MESHD (CAP) caused by severe acute SARS-CoV-2. Nucleic acid test currently played a crucial role in diagnosis of suspected COVID-19 patients. However, a high false-negative rate of this “gold standard” test has been reported and posed a major setback in blocking the spread of the virus. We here aim to describe an optimized laboratory detection strategy to reduce the false negative rate. Methods: Suspected NCP patients were asked to collect both coughed HP up specimen and pharyngeal swab. Samples from the same patient were mixed and tested at a single pool. SARS-CoV-2 was then detected by real-time RT-PCR using two different detection kits. Only if both results were negative was the test reported as negative. The patients will be excluded after two consecutive negative tests at 24 hour intervals. We also used multiplex PCR to detect 13 common respiratory tract pathogens (RTP). Results: Using this strategy, we confirmed 85 SARS-CoV-2 infections MESHD from 181 suspected patients, and 94.12% of patients were positive in the first test. The 96 excluded patients were followed up, and no additional NCP was found. We also found that 31.25% patients in 96 non-NCP patients were infected MESHD with at least one RTP that may cause CAP. Conclusion: Our studies suggest that dual reagents screening with pooled coughed HP up specimen and pharyngeal swab samples reduced the false negative rate of nucleic acid testing. During the epidemic of NCP in Anhui province, there was a certain proportion of infection and co-infection MESHD of other common pathogens of CAP. In comparison with SARS-CoV-2 detection alone, combining multiple pathogen detection reduces the rate of miss diagnosis.

    Characterization of Microbial Co-infections MESHD infections in the Respiratory Tract HP of hospitalized COVID-19 patients

    Authors: Huanzi Zhong; Yanqun Wang; Zhun Shi; Lu Zhang; Huahui Ren; Weiqun He; Zhaoyong Zhang; Airu Zhu; Jingxian Zhao; Fei Xiao; Fangming Yang; Tianzhu Liang; Feng Ye; Bei Zhong; Shicong Ruan; Mian Gan; Jiahui Zhu; Fang Li; Fuqiang Li; Daxi Wang; Jiandong Li; Peidi Ren; Shida Zhu; Huanming Yang; Jian Wang; Karsten Kristiansen; Hein M Tun; Weijun Chen; Nanshan Zhong; Xun Xu; Yi-min Li; Junhua LI; Jincun Zhao

    doi:10.1101/2020.07.02.20143032 Date: 2020-07-05 Source: medRxiv

    Summary Background Severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) has caused a global pandemic of Coronavirus disease MESHD 2019 (COVID-19). However, microbial composition of the respiratory tract and other infected tissues, as well as their possible pathogenic contributions to varying degrees of disease severity in COVID-19 patients remain unclear. Method Between January 27 and February 26, 2020, serial clinical specimens (sputum, nasal and throat swab, anal swab and feces) were collected from a cohort of hospitalized COVID-19 patients, including 8 mildly and 15 severely ill patients (requiring ICU admission and mechanical ventilation), in the Guangdong province, China. Total RNA was extracted and ultra-deep metatranscriptomic sequencing was performed in combination with laboratory diagnostic assays. Co-infection MESHD rates, the prevalence SERO and abundance of microbial communities in these COVID-19 patients were determined. Findings Notably, respiratory microbial co-infections MESHD were exclusively found in 84.6% of severely ill patients (11/13), among which viral and bacterial co-infections MESHD were detected by sequencing in 30.8% (4/13) and 69.2% (9/13) of the patients, respectively. In addition, for 23.1% (3/13) of the patients, bacterial co-infections MESHD with Burkholderia cepacia complex (BCC) and Staphylococcus epidermidis MESHD were also confirmed by bacterial culture. Further, a time-dependent, secondary infection of B. cenocepacia with expressions of multiple virulence genes in one severely ill patient was demonstrated, which might be the primary cause of his disease deterioration and death MESHD one month after ICU admission. Interpretation Our findings identified distinct patterns of co-infections MESHD with SARS-CoV-2 and various respiratory pathogenic microbes in hospitalized COVID-19 patients in relation to disease severity. Detection and tracking of BCC-associated nosocomial infections MESHD are recommended to improve the pre-emptive treatment regimen and reduce fatal outcomes of hospitalized patients infected with SARS-CoV-2. Funding National Science and Technology Major Project of China, National Major Project for Control and Prevention of Infectious Disease MESHD in China, the emergency grants for prevention and control of SARS-CoV-2 of Ministry of Science and Technology and Guangdong province, Guangdong Provincial Key Laboratory of Genome Read and Write, Guangdong Provincial Academician Workstation of BGI Synthetic Genomics, and Shenzhen Engineering Laboratory for Innovative Molecular Diagnostics.

    Non-coronavirus Genome Sequences Identified from Metagenomic Analysis of Clinical Samples from COVID-19 Infected Patients: An Evidence for Co-infection MESHD

    Authors: Mohamed Abouelkhair

    id:10.20944/preprints202005.0505.v2 Date: 2020-06-18 Source:

    In December 2019, pneumonia HP pneumonia MESHD caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection MESHD emerged in Wuhan City, Hubei Province, China. Early in 2020, the World Health Organization (WHO) announced a new name for the 2019-nCoV-caused epidemic disease MESHD: coronavirus disease MESHD 2019 (COVID-19) and declared COVID-19 to be the sixth international public health emergency. Cellular co-infection MESHD is a critical determinant of both viral fitness and infection MESHD outcome and plays a crucial role in shaping the host immune response to infections. In this study, sixty-eight public next-generation sequencing libraries from SARS-CoV-2 infected MESHD patients were retrieved from the NCBI Sequence Read Archive database using SRA-Toolkit. Using an alignment-free method based on K-mer mapping and extension, SARS-CoV-2 was identified in all except three patients. Influenza A H7N9 (3/68), Human immunodeficiency virus MESHD immunodeficiency HP virus 1 (1/68), rhabdovirus isolate (3/68), Human metapneumovirus (1/68), coronaviruses NL63 (1/68), Parvovirus (1/68), Simian virus 40 (1/68), and hepatitis HP hepatitis MESHD virus (1/68) genome sequences were detected in SARS-CoV-2 infected MESHD patients.

    Impact of recent influenza A virus infection MESHD on clinical characteristics and outcomes in severe coronavirus disease MESHD 2019 adult TRANS inpatients

    Authors: Chang Gao; Xianjun Yang; Long Chen; Hongyang Xu; Jialin Liu; Shanshan Wang; Haitao Niu; Wenkui Yu; Jian-an Huang; Xiuqin Zhang; Bo Shen; Alpaslan Tasdogan; Jessalyn M. Ubellacker; Jiahao Chen; Ling Yang; Qingyuan Zhan; Qiang Guo

    doi:10.21203/ Date: 2020-06-14 Source: ResearchSquare

    Background: Coronavirus disease 2019 (COVID-19) is a current global pandemic. However, impact of recent influenza A virus infection on the clinical course and outcomes of severe COVID-19 adult TRANS inpatients needs to be further explored.Methods: In this retrospective cohort study, severe, laboratory confirmed COVID-19 adult TRANS patients from Wuhan Tongji Hospital were included. Data were obtained from electronic medical records and compared between patients with and without recent influenza A virus infection MESHD.Results: 200 patients were included, 51.5% with recent influenza A virus infection MESHD. Recent influenza A virus infection group presented with longer persistence of cough HP and sputum from illness onset (35.0 vs. 27.0 days, P = 0.018) and (33.0 vs. 26.0 days, P = 0.015), respectively. Median time of progression to critical illness from illness onset was shorter (day 11.5 vs. day 16.0, P = 0.034). Time to clinical improvement and length of hospital stay were longer in recent infection group (23.0 vs. 19.0 days, P = 0.044) and (22.0 vs. 18.0 days, P = 0.030), respectively.Conclusions: Patients with recent influenza A virus infection showed a delay in time to clinical improvement and increased length of hospital stay. There is a high clinical need to improve the detection of common respiratory pathogens to identify co-infection MESHD during the epidemic of COVID-19.

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MeSH Disease
Human Phenotype

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