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1.
biorxiv; 2024.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2024.03.18.584627

ABSTRACT

Background: During COVID-19 pandemic there emerged a need to efficiently monitor and process large volumes of scientific literature on the subject. Currently, as the pandemic is winding down, the clinicians encountered a novel syndrome - Post-acute Sequelae of COVID-19 (PASC) - that affects over 10% of those who contract SARS-CoV-2 and presents a significant and growing challenge in the medical field. The continuous influx of new research publications underscores a critical need for efficient tools for navigating the literature. Objectives: We aimed to develop an application which will allow monitoring and categorizing COVID-19-related literature through building publication networks and medical subject headings (MeSH) maps to be able to quickly identify key publications and publication networks. Methods: We introduce CORACLE (COVID-19 liteRAture CompiLEr), an innovative web application designed for the analysis of COVID-19-related scientific articles and the identification of research trends. CORACLE features three primary interfaces: The "Search" interface, which displays research trends and citation links; the "Citation Map" interface, allowing users to create tailored citation networks from PubMed Identifiers (PMIDs) to uncover common references among selected articles; and the "MeSH" interface, highlighting current MeSH trends and associations between MeSH terms. Results: Our web application, CORACLE, leverages regularly updated PubMed data to aggregate and categorize the extensive literature on COVID-19 and PASC, aiding in the identification of relevant research publication hubs. Using lung function in PASC patients as a search example, we demonstrate how to identify and visualize the interactions between the relevant publications. Conclusion: CORACLE proves to be an effective tool for the extraction and analysis of literature. Its functionalities, including the MeSH trends and customizable citation mapping, facilitate the discovery of relevant information and emerging trends in COVID-19 and PASC research.


Subject(s)
COVID-19
2.
J Glob Health ; 13: 03029, 2023 05 26.
Article in English | MEDLINE | ID: covidwho-20238634
3.
J Basic Microbiol ; 63(5): 519-529, 2023 May.
Article in English | MEDLINE | ID: covidwho-2312806

ABSTRACT

Bovine coronavirus (BCoV) is a member of pathogenic Betacoronaviruses that has been circulating for several decades in multiple host species. Given the similarity between BCoV and human coronaviruses, the current study aimed to review the complete genomes of 107 BCoV strains available on the GenBank database, collected between 1983 and 2017 from different countries. The maximum-likelihood based phylogenetic analysis revealed three main BCoV genogroups: GI, GII, and GIII. GI is further divided into nine subgenogroups: GI-a to GI-i. The GI-a to GI-d are restricted to Japan, and GI-e to GI-i to the USA. The evolutionary relationships were also inferred using phylogenetic network analysis, revealing two major distinct networks dominated by viruses identified in the USA and Japan, respectively. The USA strains-dominated Network Cluster includes two sub-branches: France/Germany and Japan/China in addition to the United States, while Japan strains-dominated Network Cluster is limited to Japan. Twelve recombination events were determined, including 11 intragenogroup (GI) and one intergenogroup (GII vs. GI-g). The breakpoints of the recombination events were mainly located in ORF1ab and the spike glycoprotein ORF. Interestingly, 10 of 12 recombination events occurred between Japan strains, one between the USA strains, and one from intercontinental recombination (Japan vs. USA). These findings suggest that geographical characteristics, and population density with closer contact, might significantly impact the BCoV infection and co-infection and boost the emergence of more complex virus lineages.


Subject(s)
Cattle Diseases , Coronavirus Infections , Coronavirus, Bovine , Animals , Cattle , Humans , Phylogeny , Likelihood Functions , Coronavirus Infections/epidemiology , Recombination, Genetic , Cattle Diseases/epidemiology
4.
Front Vet Sci ; 10: 1146648, 2023.
Article in English | MEDLINE | ID: covidwho-2320311

ABSTRACT

Transmissible gastroenteritis virus (TGEV) is a porcine coronavirus that threatens animal health and remains elusive despite years of research efforts. The systematical analysis of all available full-length genomes of TGEVs (a total of 43) and porcine respiratory coronaviruses PRCVs (a total of 7) showed that TGEVs fell into two independent evolutionary phylogenetic clades, GI and GII. Viruses circulating in China (until 2021) clustered with the traditional or attenuated vaccine strains within the same evolutionary clades (GI). In contrast, viruses latterly isolated in the USA fell into GII clade. The viruses circulating in China have a lower similarity with that isolated latterly in the USA all through the viral genome. In addition, at least four potential genomic recombination events were identified, three of which occurred in GI clade and one in GII clade. TGEVs circulating in China are distinct from the viruses latterly isolated in the USA at either genomic nucleotide or antigenic levels. Genomic recombination serves as a factor driving the expansion of TGEV genomic diversity.

5.
Int J Clin Pract ; 2022: 4763953, 2022.
Article in English | MEDLINE | ID: covidwho-2270119

ABSTRACT

Objectives: The clinical and imaging features of asymptomatic carriers of severe acute respiratory syndrome coronavirus 2 and symptomatic COVID-19 patients. Methods: The clinical and chest computed tomography imaging data of 47 asymptomatic carriers and 36 symptomatic COVID-19 patients were derived. All patients underwent 4-6 CT scans over a period of 2-5 days. Results: The bulk of asymptomatic carriers who developed symptoms and most of the COVID-19 patients were older than 18 years of age with a decreased lymphocyte count, abnormal hepatic and renal function, and increased D-dimer and C-reactive protein. In the early stage, the pulmonary lesion involved mostly 1-2 lobes at the peripheral area in asymptomatic carriers but more than three lobes at both the central and peripheral areas in COVID-19 patients. In the progression stage, the lesion of asymptomatic carriers extended from the peripheral to the central area, and no significant difference was found in the lesion range compared with the symptomatic control group. In early improvement stage, the lesion was rapidly absorbed, and lesions were located primarily at the peripheral area in asymptomatic carriers; contrastingly, lesions were primarily located at both the central and peripheral areas in symptomatic patients. Asymptomatic carriers reflected a significantly shorter duration from disease onset to peak progression stage compared with the symptomatic. Conclusions: Asymptomatic carriers are a potential source of transmission and may become symptomatic COVID-19 patients despite indicating less severe pulmonary damage, earlier improvement, and better prognosis. Early isolation and intervention can eliminate such carriers as potential sources of transmission and improve their prognosis.


Subject(s)
COVID-19 , Humans , Retrospective Studies , Lung/diagnostic imaging , SARS-CoV-2 , C-Reactive Protein
6.
Zhongguo Jishui Paishui = China Water & Wastewater ; - (22):130, 2022.
Article in Chinese | ProQuest Central | ID: covidwho-2204722

ABSTRACT

The continuous outbreak of COVID-19 results in a large number of therapeutic drugs inevitably entering water bodies through different pathways, and there are problems of accurate and rapid detection in the treatment and ecological evaluation of these drugs. Therefore, it is necessary to establish a method for simultaneous detection of multiple antiviral drugs for treatment of COVID-19 in water. A method for the simultaneous detection of 8 antiviral drugs(ribavirin, oseltamivir, nevirapine, lamivudine,abacavir, stavudine, acyclovir and penciclovir) in source water was developed by optimizing the determining parameters of liquid chromatography-tandem mass spectrometry(LC-MS/MS). The daughter ion response values of 8 antiviral drugs in this method were relatively high, which was beneficial to the detection of target compounds. The correlation coefficient(r) of the standard curve of 8 antiviral drugs was not less than 0.995 0, the method detection limit(MDL) and the lower limit of determination were in the range of 0.004-0.081 μg/L and 0.013-0.267 μg/L, respectively, and the spike recoveries and RSDs of actual water samples were 81.61%-113.03% and 0.84%-8.12%, respectively.

7.
BMC Vet Res ; 18(1): 444, 2022 Dec 22.
Article in English | MEDLINE | ID: covidwho-2196274

ABSTRACT

The emergence and rapid spread of the acute respiratory syndrome coronavirus-2 have confirmed that animal coronaviruses represent a potential zoonotic source. Porcine deltacoronavirus is a worldwide evolving enteropathogen of swine, detected first in Hong Kong, China, before its global identification. Following the recent detection of PDCoV in humans, we attempted in this report to re-examine the status of PDCoV phylogenetic classification and evolutionary characteristics. A dataset of 166 complete PDCoV genomes was analyzed using the Maximum Likelihood method in IQ-TREE with the best-fitting model GTR + F + I + G4, revealing two major genogroups (GI and GII), with further seven and two sub-genogroups, (GI a-g) and (GII a-b), respectively. PDCoV strains collected in China exhibited the broadest genetic diversity, distributed in all subgenotypes. Thirty-one potential natural recombination events were identified, 19 of which occurred between China strains, and seven involved at least one China strain as a parental sequence. Importantly, we identified a human Haiti PDCoV strain as recombinant, alarming a possible future spillover that could become a critical threat to human health. The similarity and recombination analysis showed that PDCoV spike ORF is highly variable compared to ORFs encoding other structural proteins. Prediction of linear B cell epitopes of the spike glycoprotein and the 3D structural mapping of amino acid variations of two representative strains of GI and GII showed that the receptor-binding domain (RBD) of spike glycoprotein underwent a significant antigenic drift, suggesting its contribution in the genetic diversity and the wider spread of PDCoV.


Subject(s)
COVID-19 , Swine Diseases , Humans , Swine , Animals , Phylogeny , COVID-19/veterinary , Biological Evolution , Glycoproteins , Swine Diseases/epidemiology
8.
Tianjin Medical Journal ; 50(10):1083-1087, 2022.
Article in Chinese | GIM | ID: covidwho-2168217

ABSTRACT

Objective: To investigate the epidemiological, clinical and imaging characteristics of SARS-CoV-2 infection caused by Omicron variant.

9.
Front Immunol ; 13: 1041860, 2022.
Article in English | MEDLINE | ID: covidwho-2163023

ABSTRACT

Accurate detection of SARS-CoV-2 neutralizing antibody (nAb) is critical for assessing the immunity levels after virus infection or vaccination. As fast, cost-effective alternatives to viral infection-based assays, competitive binding (CB) assays were developed to quantitate nAb by monitoring the ability of sera to inhibit the binding of viral spike (S) protein to the angiotensin converting enzyme 2 (ACE2) receptor. Herein, we established a bead-based flow cytometric CB assay and tested the detection performance of six combination models, i.e. immobilized ACE2 and soluble Fc-tagged S1 subunit of S protein (iACE2/S1-Fc), immobilized ACE2 and soluble Fc-tagged receptor binding domain (RBD) of S protein (iACE2/RBD-Fc), immobilized S1 and soluble Fc-tagged ACE2 (iS1/ACE2-Fc), immobilized S1 and soluble His-tagged ACE2 (iS1/ACE2-His), immobilized RBD and soluble Fc-tagged ACE2 (iRBD/ACE2-Fc), and immobilized RBD and soluble His-tagged ACE2 (iRBD/ACE2-His). Using SARS-CoV-2 monoclonal antibodies and sera of convalescent COVID-19 patients and vaccinated subjects, the combination models iACE2/RBD-Fc, iACE2/S1-Fc and iS1/ACE2-His were identified to be able to specifically detect SARS-CoV-2 nAb, among which iACE2/RBD-Fc model showed the highest sensitivity, superior to a commercial SARS-CoV-2 surrogate virus neutralization test (sVNT) ELISA kit. Further studies demonstrated that the sensitivity and specificity of CB assays were affected by the tag of ACE2, type of spike and method of measuring binding rate between ACE2 and spike. Moreover, the iACE2/RBD-Fc model showed good performance in detecting kinetic development of nAb against both the prototype SARS-CoV-2 strain and an omicron variant of SARS-CoV-2 in people immunized by an inactivated SARS-CoV-2 vaccine, and the results of iACE2/RBD-Fc model are correlated well with those of live virus-based and pseudovirus-based neutralization tests, demonstrating the potential to be developed into a highly sensitive, specific, versatile and high-throughput method for detecting SARS-CoV-2 nAb in clinical practice.


Subject(s)
Angiotensin-Converting Enzyme 2 , COVID-19 , Humans , Angiotensin-Converting Enzyme 2/metabolism , SARS-CoV-2 , Antibodies, Neutralizing , COVID-19 Vaccines , Binding, Competitive , COVID-19/diagnosis , Antibodies, Viral
10.
Resources Policy ; 80:103147, 2023.
Article in English | ScienceDirect | ID: covidwho-2132239

ABSTRACT

Risk and return are two fundamentals that have an impact on an investor’s or hedger’s investing choices. Based on the proposed synchronous movement intensity index, this paper aims to improve the hedging performance by adjusting the model-driven hedge ratio and realize the trade-off between return and risk in futures hedging. First, without loss of generality, we forecast crude oil spot and futures volatility using 10 GARCH-type models, including three linear models and seven nonlinear models, to obtain the ex-ante hedging ratio under the minimum variance framework. Then, we develop a novel and tractable method to identify the market state based on the index of consistency intensity, in which the index portrays the synchronous degree of stock price movements in the energy sector. Last but not least, we propose the hedge ratio adjustment criteria based on the identified state, and adjust the ratio driven by GARCH-type models of futures in accordance with the market state. Empirical results of crude oil futures markets indicate that the proposed state-dependent hedging model is superior to the commonly used models in terms of three criteria including mean of returns, variance, and ratio of mean to variance of returns for measuring hedging effect. We apply the DM test to make a statistical inference and discover that while the mean and the ratio of mean to variance of returns are increasing, the variance and hedging effectiveness of the hedged portfolio based on the modified methods are not significantly affected. Furthermore, the superiority of the proposed method is robust to different market conditions, including significant rising or falling trends, large basis, and COVID-19 pandemic. We also test the robustness of the proposed method with respect to the baseline model, quantile, and evaluation window. Overall, this paper provides a more realistic approach for crude oil risk managers to hedge crude oil price risk, some corresponding implications are also concluded.

11.
International Review of Financial Analysis ; : 102412, 2022.
Article in English | ScienceDirect | ID: covidwho-2086328

ABSTRACT

The complexity and uncertainty of the financial market mainly stem from the rich market internal transaction information and a wide range effect of external factors. To this end, this paper proposes the combination factors-driven forecasting method to predict realized volatilities of the CSI 300 index and index futures. Based on the volatilities predicted by the proposed method, we further evaluate the ex-ante hedging performance in comparison to the conventional HAR model as well as GARCH-type models. The empirical results indicate that the factors-driven realized volatility model significantly dominates the other commonly used models in terms of hedging effectiveness. Furthermore, the superiority of the proposed method is robust in different market conditions, including significant rising or falling and abnormal market fluctuations in the COVID-19 pandemic, and in different index markets. Therefore, this paper improves the prediction accuracy of volatility by integrating market internal transaction information and external factor information, and the proposed method in this paper can be used by investors to obtain an excellent hedging effect.

12.
Curr Med Sci ; 2022 Oct 17.
Article in English | MEDLINE | ID: covidwho-2075541

ABSTRACT

With the deepening of China's health-care reform, an integrated delivery system has gradually emerged with the function of improving the efficiency of the health-care delivery system. For China's integrated delivery system, a medical consortium plays an important role in integrating public hospitals and primary care facilities. The first medical consortium policy issued after the COVID-19 pandemic apparently placed hope on accelerating the implementation of a medical consortium and tiered health-care delivery system. This paper illustrates the possible future pathway of China's medical consortium through retrospection of the 10-year process, changes of the series of policies, and characteristics of the policy issued in 2020. We considered that a fully integrated medical consortium would be a major phenomenon in China's medical industry, which would lead to the formation of a dualistic care pattern in China.

13.
Atmosphere ; 13(7):1042, 2022.
Article in English | ProQuest Central | ID: covidwho-1963693

ABSTRACT

Previous studies have determined biomass burning as a major source of air pollutants in the ambient air in Thailand. To analyse the impacts of meteorological parameters on the variation of carbonaceous aerosols and water-soluble ionic species (WSIS), numerous statistical models, including a source apportionment analysis with the assistance of principal component analysis (PCA), hierarchical cluster analysis (HCA), and artificial neural networks (ANNs), were employed in this study. A total of 191 sets of PM2.5 samples were collected from the three monitoring stations in Chiang-Mai, Bangkok, and Phuket from July 2020 to June 2021. Hotspot numbers and other meteorological parameters were obtained using NOAA-20 weather satellites coupled with the Global Land Data Assimilation System. Although PCA revealed that crop residue burning and wildfires are the two main sources of PM2.5, ANNs highlighted the importance of wet deposition as the main depletion mechanism of particulate WSIS and carbonaceous aerosols. Additionally, Mg2+ and Ca2+ were deeply connected with albedo, plausibly owing to their strong hygroscopicity as the CCNs responsible for cloud formation.

14.
biorxiv; 2022.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2022.07.23.501235

ABSTRACT

T lymphocyte reduction and immunosenescence frequently occur in severe and critical coronavirus disease 2019 (COVID-19) patients, which may cause immunothrombosis and numerous sequelae. This study integrated analyzed multi-omics data from healthy donors, pneumonia, COVID-19 patients (mild & moderate, severe, and critical), and convalescences, including clinical, laboratory test, PBMC bulk RNA-seq, PBMC scRNA-seq and TCR-seq, BAL scRNA-seq, and lung proteome. We revealed that there are certain associations among T lymphocyte reduction, CD8+ T cell senescence, Th17 immune activation, and immunothrombosis. A specific phenotype (S. P.) CD8+ T cells were identified in severe and critical COVID-19 patients in both PBMC and BAL scRNA-seq, which showed highly TCR homology with terminal effector CD8+ T cells and senescent CD8+ T cells. Pseudotime analysis showed that the S. P. CD8+ T cells were located in the transition trajectory from mild to severe disease. Which may be activated by terminal effector CD8+ T cells or senescent CD8+ T cells, thereby promoting Th17 cell differentiation. This phenomenon was absent in healthy donors, mild and moderate COVID-19 patients, or convalescences. Our findings are an important reference for avoiding the conversion of patients with mild to severe diseases and provide insight into the future prevention and control of COVID-19 and its variants.


Subject(s)
Coronavirus Infections , Pneumonia , COVID-19 , Disease
15.
Front Microbiol ; 13: 860851, 2022.
Article in English | MEDLINE | ID: covidwho-1775716

ABSTRACT

Porcine hemagglutinating encephalomyelitis virus (PHEV) is a Betacoronavirus characterized by neurological symptoms and a worldwide prevalence. Although PHEV is one of the earliest discovered porcine coronaviruses, it remains poorly studied. The full-length genome of the earliest PHEV strain collected in 1970 in the United States (PHEV/67 N/US/1970) was determined in October 2020. Using this virus as a prototype, we comparatively analyzed all available PHEV full-length sequences during 1970-2015. In phylogenetic trees based on PHEV full-length or spike glycoprotein open reading frame genomic sequences, PHEV/67 N/US/1970 was sorted into a clade different from that of viruses isolated in the United States in 2015. Intriguingly, United States and Belgium viruses isolated in 2015 and 2005, respectively, revealed multiple deletion mutation patterns compared to the strain PHEV/67 N/US/1970, leading to a truncated or a non-functional NS2A coding region. In addition, the genomic similarity analysis showed a hypervariability of the spike glycoprotein coding region, which can affect at least eight potential linear B cell epitopes located in the spike glycoprotein. This report indicates that PHEVs in the United States underwent a significant genetic drift, which might influence PHEV surveillance in other countries.

16.
Nat Microbiol ; 7(3): 423-433, 2022 03.
Article in English | MEDLINE | ID: covidwho-1671570

ABSTRACT

Elucidating the dynamics of the neutralizing antibody (nAb) response in coronavirus disease 2019 (COVID-19) convalescents is crucial in controlling the pandemic and informing vaccination strategies. Here we measured nAb titres across 411 sequential plasma samples collected during 1-480 d after illness onset or laboratory confirmation (d.a.o.) from 214 COVID-19 convalescents, covering the clinical spectrum of disease and without additional exposure history after recovery or vaccination against SARS-CoV-2, using authentic SARS-CoV-2 microneutralization (MN) assays. Forty-eight samples were also tested for neutralizing activities against the circulating variants using pseudotyped neutralization assay. Results showed that anti-RBD IgG and MN titres peaked at ~120 d.a.o. and subsequently declined, with significantly reduced nAb responses found in 91.67% of COVID-19 convalescents (≥50% decrease in current MN titres compared with the paired peak MN titres). Despite this decline, majority of the COVID-19 convalescents maintained detectable anti-RBD IgG and MN titres at 400-480 d.a.o., with undetectable neutralizing activity found in 14.41% (16/111) of the mild and 50% (5/10) of the asymptomatic infections at 330-480 d.a.o. Persistent antibody-dependent immunity could provide protection against circulating variants after one year, despite significantly decreased neutralizing activities against Beta, Delta and Mu variants. In conclusion, these data show that despite a marked decline in neutralizing activity over time, nAb responses persist for up to 480 d in most convalescents of symptomatic COVID-19, whereas a high rate of undetectable nAb responses was found in convalescents from asymptomatic infections.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , SARS-CoV-2/physiology , Adolescent , Adult , Aged , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Asymptomatic Infections/epidemiology , COVID-19/blood , COVID-19/epidemiology , COVID-19/virology , Child , Child, Preschool , Cohort Studies , Female , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Immunoglobulin M/blood , Immunoglobulin M/immunology , Male , Middle Aged , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Young Adult
18.
Curr Med Imaging ; 18(8): 869-875, 2022.
Article in English | MEDLINE | ID: covidwho-1533548

ABSTRACT

INTRODUCTION: To investigate the Computed Tomography (CT) imaging characteristics and dynamic changes of COVID-19 pneumonia at different stages. METHODS: Forty-six patients infected with COVID-19 who had chest CT scans were enrolled, and CT scans were performed 4-6 times with an interval of 2-5 days. RESULTS: At the early stage (n=25), ground glass opacity was presented in 11 patients (11/25 or 44.0 %) and ground glass opacity mixed with consolidation in 13 (13/25 or 52.0 %) in the lung CT images. At the progressive stage (n=38), ground glass opacity was presented in only one patient (1/38 or 2.6 %) and ground glass opacity mixed with consolidation in 33 (33/38 or 86.8 %). In the early improvement stage (n=38), the imaging presentation was ground glass opacity alone in three patients (3/38 or 7.9 %) and ground glass opacity mixed with consolidation in 34 (34/38 or 89.5 %). In the late improvement (absorption) stage (n=33), the primary imaging presentation was ground glass presentation in eight patients (8/33 or 24.2 %) and ground glass opacity mixed with consolidation in 23 (23/33 or 69.7 %). The lesion reached the peak at 4-16 days after disease onset, and 26 (26/38 or 68.4 %) patients reached the disease peak within ten days. Starting from 6 to 20 days after onset, the disease began to be improved, with 30 (30/38 or 78.9 %) patients being improved within 15 days. CONCLUSION: COVID-19 pneumonia will progress to the peak stage at a mediate time of seven days and enter the improvement stage at twelve days. Computed tomography imaging of the pulmonary lesion has a common pattern from disease onset to improvement and recovery and provides important information for evaluation of the disease course and treatment effect.


Subject(s)
COVID-19 , COVID-19/diagnostic imaging , Disease Progression , Humans , Lung/diagnostic imaging , SARS-CoV-2 , Tomography, X-Ray Computed/methods
19.
Brief Bioinform ; 23(1)2022 01 17.
Article in English | MEDLINE | ID: covidwho-1522119

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for millions of deaths around the world. To help contribute to the understanding of crucial knowledge and to further generate new hypotheses relevant to SARS-CoV-2 and human protein interactions, we make use of the information abundant Biomine probabilistic database and extend the experimentally identified SARS-CoV-2-human protein-protein interaction (PPI) network in silico. We generate an extended network by integrating information from the Biomine database, the PPI network and other experimentally validated results. To generate novel hypotheses, we focus on the high-connectivity sub-communities that overlap most with the integrated experimentally validated results in the extended network. Therefore, we propose a new data analysis pipeline that can efficiently compute core decomposition on the extended network and identify dense subgraphs. We then evaluate the identified dense subgraph and the generated hypotheses in three contexts: literature validation for uncovered virus targeting genes and proteins, gene function enrichment analysis on subgraphs and literature support on drug repurposing for identified tissues and diseases related to COVID-19. The major types of the generated hypotheses are proteins with their encoding genes and we rank them by sorting their connections to the integrated experimentally validated nodes. In addition, we compile a comprehensive list of novel genes, and proteins potentially related to COVID-19, as well as novel diseases which might be comorbidities. Together with the generated hypotheses, our results provide novel knowledge relevant to COVID-19 for further validation.


Subject(s)
COVID-19 , Computer Simulation , Models, Biological , Protein Interaction Maps , COVID-19/genetics , COVID-19/metabolism , Humans , SARS-CoV-2/chemistry , SARS-CoV-2/genetics , SARS-CoV-2/metabolism
20.
JAMA ; 323(16): 1582-1589, 2020 04 28.
Article in English | MEDLINE | ID: covidwho-1453469

ABSTRACT

Importance: Coronavirus disease 2019 (COVID-19) is a pandemic with no specific therapeutic agents and substantial mortality. It is critical to find new treatments. Objective: To determine whether convalescent plasma transfusion may be beneficial in the treatment of critically ill patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Design, Setting, and Participants: Case series of 5 critically ill patients with laboratory-confirmed COVID-19 and acute respiratory distress syndrome (ARDS) who met the following criteria: severe pneumonia with rapid progression and continuously high viral load despite antiviral treatment; Pao2/Fio2 <300; and mechanical ventilation. All 5 were treated with convalescent plasma transfusion. The study was conducted at the infectious disease department, Shenzhen Third People's Hospital in Shenzhen, China, from January 20, 2020, to March 25, 2020; final date of follow-up was March 25, 2020. Clinical outcomes were compared before and after convalescent plasma transfusion. Exposures: Patients received transfusion with convalescent plasma with a SARS-CoV-2-specific antibody (IgG) binding titer greater than 1:1000 (end point dilution titer, by enzyme-linked immunosorbent assay [ELISA]) and a neutralization titer greater than 40 (end point dilution titer) that had been obtained from 5 patients who recovered from COVID-19. Convalescent plasma was administered between 10 and 22 days after admission. Main Outcomes and Measures: Changes of body temperature, Sequential Organ Failure Assessment (SOFA) score (range 0-24, with higher scores indicating more severe illness), Pao2/Fio2, viral load, serum antibody titer, routine blood biochemical index, ARDS, and ventilatory and extracorporeal membrane oxygenation (ECMO) supports before and after convalescent plasma transfusion. Results: All 5 patients (age range, 36-65 years; 2 women) were receiving mechanical ventilation at the time of treatment and all had received antiviral agents and methylprednisolone. Following plasma transfusion, body temperature normalized within 3 days in 4 of 5 patients, the SOFA score decreased, and Pao2/Fio2 increased within 12 days (range, 172-276 before and 284-366 after). Viral loads also decreased and became negative within 12 days after the transfusion, and SARS-CoV-2-specific ELISA and neutralizing antibody titers increased following the transfusion (range, 40-60 before and 80-320 on day 7). ARDS resolved in 4 patients at 12 days after transfusion, and 3 patients were weaned from mechanical ventilation within 2 weeks of treatment. Of the 5 patients, 3 have been discharged from the hospital (length of stay: 53, 51, and 55 days), and 2 are in stable condition at 37 days after transfusion. Conclusions and Relevance: In this preliminary uncontrolled case series of 5 critically ill patients with COVID-19 and ARDS, administration of convalescent plasma containing neutralizing antibody was followed by improvement in their clinical status. The limited sample size and study design preclude a definitive statement about the potential effectiveness of this treatment, and these observations require evaluation in clinical trials.


Subject(s)
Antibodies, Neutralizing/therapeutic use , Antibodies, Viral/therapeutic use , Betacoronavirus/immunology , Coronavirus Infections/therapy , Pneumonia, Viral/therapy , Respiratory Distress Syndrome/therapy , Adult , Aged , Antibodies, Viral/blood , Antiviral Agents/therapeutic use , Blood Donors , COVID-19 , Coronavirus Infections/drug therapy , Coronavirus Infections/physiopathology , Critical Illness , Female , Glucocorticoids/therapeutic use , Humans , Immunization, Passive , Immunoglobulin G/blood , Immunoglobulin M/blood , Male , Methylprednisolone/therapeutic use , Middle Aged , Organ Dysfunction Scores , Pandemics , Pneumonia, Viral/drug therapy , Pneumonia, Viral/physiopathology , SARS-CoV-2 , COVID-19 Serotherapy
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