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1.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-334362

ABSTRACT

No specific effective therapeutic drugs have been identified for COVID-19. Critically ill COVID-19 36 patients in the ICU experience high mortality. This project aims to study the effects of traditional 37 Chinese medicine (TCM) treatment on deadly outcomes caused by COVID-19. A total of 123 critically 38 ill COVID-19 patients who received close monitoring at the ICU of Vulcan Hill Hospital between 39 ICU patients received supportive management. Eighty-one patients were given additional TCM 41 treatment. Clinical characteristics during the treatment period (up to 39 days) and the clinical outcome 42 of each patient were closely monitored and analysed. We observed that patients treated with TCM had 43 lower mortality than the non-TCM treatment group (16 of 81 vs. 31 of 42;0.3 person/month vs. 2.9 44 person/month). In the adjusted Cox proportional hazards models, TCM treatment was associated with 45 improved survival [multivariate HR, 0.13;95% confidence interval (CI), 0.06–0.24;P < 0.001]. 46 Furthermore, we found that TCM treatment could partially improve the inflammation status by 47 reducing the levels of proinflammatory cytokines and recovering multiple organic functions. TCM 48 treatment may decrease inflammation status by reducing the level of proinflammatory cytokines and 49 allowing the recovery of multiple organic functions, which could improve the survival rate of critically 50 ill COVID-19 patients.

2.
Exp Ther Med ; 23(4): 249, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1690124

ABSTRACT

Over-inflammation and severe lung injury are major causes of morbidity and mortality in patients with coronavirus disease 2019 (COVID-19). With the COVID-19 pandemic, an increasing number of patients with preexisting lung injury and inflammation are undergoing surgery or artificial ventilation under sedation in intensive care units, where 2,6-diisopropylphenol (propofol) is a commonly used drug for sedation. The aim of the present study was to investigate whether post-inflammation treatment with propofol protects epithelial type II cells against inflammation in an in vitro model of inflammation. The A549 cell line, characterised as epithelial type II cells, were exposed to lipopolysaccharide (LPS) for 2 h and subsequently treated with different concentrations of propofol (0, 10, 25 or 50 µM) for 3 h. Western blot and reverse transcription-quantitative PCR analyses were used to detect the protein and mRNA expression levels, respectively, of CD14 and Toll-like receptor 4 (TLR4). Immunofluorescence staining was used to detect the in situ CD14 and TLR4 expression in epithelial type II cells. Tumor necrosis factor (TNF)-α production was also examined using ELISA. LPS significantly increased the expression of CD14 and TLR4, as well as the secretion of TNF-α. Post-treatment with 25 and 50 µM propofol of the LPS-treated cells significantly decreased CD14 and TLR4 expression, as well as TNF-α secretion, compared with the cells treated with LPS only, indicating that post-treatment with propofol alleviated inflammation and this effect was dose-dependent. The present study suggested that treatment with propofol after LPS administration has a protective effect on epithelial type II cells.

3.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-307712

ABSTRACT

Background: In December 2019, a cluster of cases of acute respiratory illness, novel coronavirus-infected pneumonia, occurred in Wuhan, Hubei Province, China. Health care workers exposure to a high density of patients are at extremely high risk of becoming infected at the early outbreak of this disease for not realizing the fact of human-to-human transmission among close contacts at that time. The false-negative nasopharyngeal swabs of SARS-CoV-2 caused the delayed diagnosis of COVID-19. The nosocomial transmission of SARS-CoV-2 in negative nasopharyngeal swabs cases were not reported previously. We wish to alert the potential transmission risk in COVID-19 patients with negative swab tests to the clinicians and stress the role of serological detection of anti-SARS-CoV-2.MethodsThis study evaluated a total of 6 cases and four of them were health care providers who worked in the same ward. All epidemiological and clinical information was collected. Respiratory samples of the patients were tested for influenza A, influenza B and respiratory syncytial virus (RSV) RNA The reverse-transcription–polymerase chain reaction (RT-PCR) assay of SARS-CoV-2 RNA was conducted and serological detection of anti-SARS-CoV-2-IgG/IgM is performed by chemiluminescence immunoassay kit.ResultsWe reported two related clusters of COVID-19 cases. The first cluster is a nosocomial infection of four health care providers at early January in one ward of university hospital. One of them made sequential familial cluster of infection. For total six cases, four of them (66.7%) showed negative RNA of SARS-CoV-2 by nasopharyngeal swabs. All patients received either self-quarantined at home or were admitted to hospital for isolated treatment. All recovered and had anti-SARS-CoV-2 IgG and/or IgM positive (100%) for serological detection of SARS-CoV-2 at recovery stage.ConclusionsOur study provides a cautionary warning that negative results of nasopharyngeal swabs of suspected SARS-CoV-2 infection can increase the risk of nosocomial infection among health care providers. Serologic detection for anti-SARS-CoV-2 IgG and/or IgM is an important test in the assistant diagnosis of COVID-19.

4.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-308913

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Alongside investigations into the virology of SARS-CoV-2, understanding the host–virus dependencies are vital for the identification and rational design of effective antiviral therapy. Here, we report the dominant SARS-CoV-2 entry receptor, ACE2, conjugates with small ubiquitin-like modifier 3 (SUMO3) through a proteome-wide protein interaction analysis. We further demonstrate that E3 SUMO ligase PIAS4 prompts the SUMOylation and stabilization of ACE2, whereas deSUMOylation enzyme SENP3 reverses this process. Conjugation of SUMO3 with ACE2 at lysine (K) 187 hampers the K48-linked ubiquitination of ACE2, thus suppressing its subsequent cargo receptor TOLLIP-dependent autophagic degradation. Pharmacological intervention of ACE2 SUMOylation blocks the entry of SARS-CoV-2 and viral infection-triggered immune responses. Collectively, our findings suggest selective autophagic degradation of ACE2 orchestrated by SUMOylation and ubiquitination can be targeted to future antiviral therapy of SARS-CoV-2.

5.
Antiviral Res ; 198: 105254, 2022 02.
Article in English | MEDLINE | ID: covidwho-1654045

ABSTRACT

Coronavirus disease 2019 (COVID-19) is a newly emerged infectious disease caused by a novel coronavirus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The rapid global emergence of SARS-CoV-2 highlights the importance and urgency for potential drugs to control the pandemic. The functional importance of RNA-dependent RNA polymerase (RdRp) in the viral life cycle, combined with structural conservation and absence of closely related homologs in humans, makes it an attractive target for designing antiviral drugs. Nucleos(t)ide analogs (NAs) are still the most promising broad-spectrum class of viral RdRp inhibitors. In this study, using our previously developed cell-based SARS-CoV-2 RdRp report system, we screened 134 compounds in the Selleckchemicals NAs library. Four candidate compounds, Fludarabine Phosphate, Fludarabine, 6-Thio-20-Deoxyguanosine (6-Thio-dG), and 5-Iodotubercidin, exhibit remarkable potency in inhibiting SARS-CoV-2 RdRp. Among these four compounds, 5-Iodotubercidin exhibited the strongest inhibition upon SARS-CoV-2 RdRp, and was resistant to viral exoribonuclease activity, thus presenting the best antiviral activity against coronavirus from a different genus. Further study showed that the RdRp inhibitory activity of 5-Iodotubercidin is closely related to its capacity to inhibit adenosine kinase (ADK).


Subject(s)
Antiviral Agents/pharmacology , COVID-19/drug therapy , Nucleic Acid Synthesis Inhibitors/pharmacology , SARS-CoV-2/drug effects , Tubercidin/analogs & derivatives , Cell Line , Deoxyguanosine/analogs & derivatives , Deoxyguanosine/pharmacology , Drug Evaluation, Preclinical/methods , HEK293 Cells , Humans , Microbial Sensitivity Tests , RNA, Viral/biosynthesis , RNA-Dependent RNA Polymerase/antagonists & inhibitors , SARS-CoV-2/genetics , Thionucleosides/pharmacology , Tubercidin/pharmacology , Vidarabine/analogs & derivatives , Vidarabine/pharmacology , Vidarabine Phosphate/analogs & derivatives , Vidarabine Phosphate/pharmacology
6.
Signal Transduct Target Ther ; 6(1): 167, 2021 04 24.
Article in English | MEDLINE | ID: covidwho-1585891

ABSTRACT

The ongoing 2019 novel coronavirus disease (COVID-19) caused by SARS-CoV-2 has posed a worldwide pandemic and a major global public health threat. The severity and mortality of COVID-19 are associated with virus-induced dysfunctional inflammatory responses and cytokine storms. However, the interplay between host inflammatory responses and SARS-CoV-2 infection remains largely unknown. Here, we demonstrate that SARS-CoV-2 nucleocapsid (N) protein, the major structural protein of the virion, promotes the virus-triggered activation of NF-κB signaling. After binding to viral RNA, N protein robustly undergoes liquid-liquid phase separation (LLPS), which recruits TAK1 and IKK complex, the key kinases of NF-κB signaling, to enhance NF-κB activation. Moreover, 1,6-hexanediol, the inhibitor of LLPS, can attenuate the phase separation of N protein and restrict its regulatory functions in NF-κB activation. These results suggest that LLPS of N protein provides a platform to induce NF-κB hyper-activation, which could be a potential therapeutic target against COVID-19 severe pneumonia.


Subject(s)
COVID-19/metabolism , Coronavirus Nucleocapsid Proteins/metabolism , NF-kappa B/metabolism , RNA, Viral/metabolism , SARS-CoV-2/metabolism , Signal Transduction , A549 Cells , Acrylates/pharmacology , Animals , COVID-19/drug therapy , COVID-19/pathology , Chlorocebus aethiops , HEK293 Cells , HeLa Cells , Humans , Inflammation/drug therapy , Inflammation/metabolism , Inflammation/pathology , Phosphoproteins/metabolism , Vero Cells
7.
Antiviral Res ; 196: 105209, 2021 12.
Article in English | MEDLINE | ID: covidwho-1520691

ABSTRACT

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the causative agent of Coronavirus Disease 2019 (COVID-19) pandemic. Despite intensive and global efforts to discover and develop novel antiviral therapies, only Remdesivir has been approved as a treatment for COVID-19. Therefore, effective antiviral therapeutics are still urgently needed to combat and halt the pandemic. Viral RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 demonstrates high potential as a reliable target for the development of antivirals. We previously developed a cell-based assay to assess the efficiency of compounds that target SARS-CoV-2 RdRp, as well as their tolerance to viral exoribonuclease-mediated proof-reading. In our previous study, we discovered that 2-((1H-indol-3-yl)thio)-N-phenyl-acetamides specifically targets the RdRp of both respiratory syncytial virus (RSV) and influenza A virus. Thus, we hypothesize that 2-((1H-indol-3-yl)thio)-N-phenyl-acetamides may also have the ability to inhibit SARS-CoV-2 replication by targeting its RdRp activity. In this research, we test a compound library containing 103 of 2-((1H-indol-3-yl)thio)-N-phenyl-acetamides against SARS-CoV-2 RdRp, using our cell-based assay. Among these compounds, the top five candidates strongly inhibit SARS-CoV-2 RdRp activity while exhibiting low cytotoxicity and resistance to viral exoribonuclease. Compound 6-72-2a is the most promising candidate with the lowest EC50 value of 1.41 µM and highest selectivity index (CC50/EC50) (above 70.92). Furthermore, our data suggests that 4-46b and 6-72-2a also inhibit the replication of HCoV-OC43 and HCoV-NL63 virus in a dose-dependent manner. Compounds 4-46b and 6-72-2a exhibit EC50 values of 1.13 µM and 0.94 µM, respectively, on HCoV-OC43 viral replication. However, higher concentrations of these compounds are needed to effectively block HCoV-NL63 replication. Together, our findings successfully identified 4-46b and 6-72-2a as promising inhibitors against SARS-CoV-2 RdRp.


Subject(s)
Acetamides/pharmacology , COVID-19/drug therapy , RNA-Dependent RNA Polymerase , Antiviral Agents/pharmacology , Drug Delivery Systems , Humans , RNA, Viral/biosynthesis , RNA-Dependent RNA Polymerase/antagonists & inhibitors , RNA-Dependent RNA Polymerase/drug effects , SARS-CoV-2/drug effects , Viral Proteins/antagonists & inhibitors , Viral Proteins/drug effects , Virus Replication/drug effects
8.
Signal Transduct Target Ther ; 5(1): 221, 2020 10 06.
Article in English | MEDLINE | ID: covidwho-1387195
9.
Appl Math ; 36(2): 287-303, 2021.
Article in English | MEDLINE | ID: covidwho-1274931

ABSTRACT

OBJECTIVES: Firstly, according to the characteristics of COVID-19 epidemic and the control measures of the government of Shaanxi Province, a general population epidemic model is established. Then, the control reproduction number of general population epidemic model is obtained. Based on the epidemic model of general population, the epidemic model of general population and college population is further established, and the control reproduction number is also obtained. METHODS: For the established epidemic model, firstly, the expression of the control reproduction number is obtained by using the next generation matrix. Secondly, the real-time reported data of COVID-19 in Shaanxi Province is used to fit the epidemic model, and the parameters in the model are estimated by least square method and MCMC. Thirdly, the Latin hypercube sampling method and partial rank correlation coefficient (PRCC) are adopted to analyze the sensitivity of the model. CONCLUSIONS: The control reproduction number remained at 3 from January 23 to January 31, then gradually decreased from 3 to slightly greater than 0.2 by using the real-time reports on the number of COVID-19 infected cases from Health Committee of Shaanxi Province in China. In order to further control the spread of the epidemic, the following measures can be taken: (i) reducing infection by wearing masks, paying attention to personal hygiene and limiting travel; (ii) improving isolation of suspected patients and treatment of symptomatic individuals. In particular, the epidemic model of the college population and the general population is established, and the control reproduction number is given, which will provide theoretical basis for the prevention and control of the epidemic in the colleges.

10.
ACS Infect Dis ; 7(6): 1535-1544, 2021 06 11.
Article in English | MEDLINE | ID: covidwho-1243273

ABSTRACT

Coronavirus disease 2019 (COVID-19) is a fatal respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The identification of potential drugs is urgently needed to control the pandemic. RNA dependent RNA polymerase (RdRp) is a conserved protein within RNA viruses and plays a crucial role in the viral life cycle, thus making it an attractive target for development of antiviral drugs. In this study, 101 quinoline and quinazoline derivatives were screened against SARS-CoV-2 RdRp using a cell-based assay. Three compounds I-13e, I-13h, and I-13i exhibit remarkable potency in inhibiting RNA synthesis driven by SARS-CoV-2 RdRp and relatively low cytotoxicity. Among these three compounds, I-13e showed the strongest inhibition upon RNA synthesis driven by SARS-CoV-2 RdRp, the resistance to viral exoribonuclease activity and the inhibitory effect on the replication of CoV, thus holding potential of being drug candidate for treatment of SARS-CoV-2.


Subject(s)
Quinazolines , Quinolines , RNA-Dependent RNA Polymerase/antagonists & inhibitors , SARS-CoV-2/drug effects , Humans , Quinazolines/pharmacology , Quinolines/pharmacology , RNA, Viral/biosynthesis
11.
Signal Transduct Target Ther ; 6(1): 167, 2021 04 24.
Article in English | MEDLINE | ID: covidwho-1203416

ABSTRACT

The ongoing 2019 novel coronavirus disease (COVID-19) caused by SARS-CoV-2 has posed a worldwide pandemic and a major global public health threat. The severity and mortality of COVID-19 are associated with virus-induced dysfunctional inflammatory responses and cytokine storms. However, the interplay between host inflammatory responses and SARS-CoV-2 infection remains largely unknown. Here, we demonstrate that SARS-CoV-2 nucleocapsid (N) protein, the major structural protein of the virion, promotes the virus-triggered activation of NF-κB signaling. After binding to viral RNA, N protein robustly undergoes liquid-liquid phase separation (LLPS), which recruits TAK1 and IKK complex, the key kinases of NF-κB signaling, to enhance NF-κB activation. Moreover, 1,6-hexanediol, the inhibitor of LLPS, can attenuate the phase separation of N protein and restrict its regulatory functions in NF-κB activation. These results suggest that LLPS of N protein provides a platform to induce NF-κB hyper-activation, which could be a potential therapeutic target against COVID-19 severe pneumonia.


Subject(s)
COVID-19/metabolism , Coronavirus Nucleocapsid Proteins/metabolism , NF-kappa B/metabolism , RNA, Viral/metabolism , SARS-CoV-2/metabolism , Signal Transduction , A549 Cells , Acrylates/pharmacology , Animals , COVID-19/drug therapy , COVID-19/pathology , Chlorocebus aethiops , HEK293 Cells , HeLa Cells , Humans , Inflammation/drug therapy , Inflammation/metabolism , Inflammation/pathology , Phosphoproteins/metabolism , Vero Cells
12.
Antiviral Res ; 190: 105078, 2021 06.
Article in English | MEDLINE | ID: covidwho-1198616

ABSTRACT

Antiviral therapeutics is one effective avenue to control and end this devastating COVID-19 pandemic. The viral RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 has been recognized as a valuable target of antivirals. However, the cell-free SARS-CoV-2 RdRp biochemical assay requires the conversion of nucleotide prodrugs into the active triphosphate forms, which regularly occurs in cells yet is a complicated multiple-step chemical process in vitro, and thus hinders the utility of this cell-free assay in the rapid discovery of RdRp inhibitors. In addition, SARS-CoV-2 exoribonuclease provides the proof-reading capacity to viral RdRp, thus creates relatively high resistance threshold of viral RdRp to nucleotide analog inhibitors, which must be examined and evaluated in the development of this class of antivirals. Here, we report a cell-based assay to evaluate the efficacy of nucleotide analog compounds against SARS-CoV-2 RdRp and assess their tolerance to viral exoribonuclease-mediated proof-reading. By testing seven commonly used nucleotide analog viral polymerase inhibitors, Remdesivir, Molnupiravir, Ribavirin, Favipiravir, Penciclovir, Entecavir and Tenofovir, we found that both Molnupiravir and Remdesivir showed the strong inhibition of SARS-CoV-2 RdRp, with EC50 value of 0.22 µM and 0.67 µM, respectively. Moreover, our results suggested that exoribonuclease nsp14 increases resistance of SARS-CoV-2 RdRp to nucleotide analog inhibitors. We also determined that Remdesivir presented the highest resistance to viral exoribonuclease activity in cells. Therefore, we have developed a cell-based SARS-CoV-2 RdRp assay which can be deployed to discover SARS-CoV-2 RdRp inhibitors that are urgently needed to treat COVID-19 patients.


Subject(s)
Antiviral Agents/pharmacology , COVID-19/drug therapy , Drug Discovery , RNA-Dependent RNA Polymerase/antagonists & inhibitors , SARS-CoV-2/drug effects , SARS-CoV-2/enzymology , A549 Cells , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/pharmacology , Alanine/analogs & derivatives , Alanine/pharmacology , COVID-19/virology , Cell Survival/drug effects , Exoribonucleases/antagonists & inhibitors , HEK293 Cells , High-Throughput Screening Assays , Humans , RNA, Viral/genetics , SARS-CoV-2/genetics , Viral Nonstructural Proteins/antagonists & inhibitors
13.
J Med Virol ; 93(1): 456-462, 2021 01.
Article in English | MEDLINE | ID: covidwho-1196396

ABSTRACT

In the past several months, the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-associated infection (coronavirus disease 2019 [COVID-19]) developed rapidly and has turned into a global pandemic. Although SARS-CoV-2 mainly attacks respiratory systems, manifestations of multiple organs have been observed. A great concern was raised about whether COVID-19 may affect male reproductive functions. In this study, we collected semen specimens from 12 male COVID-19 patients for virus detection and semen characteristics analysis. No SARS-CoV-2 was found in semen specimens. Eight out of 12 patients had normal semen quality. We also compared the sex-related hormone levels between 119 reproductive-aged men with SARS-CoV-2 infection and 273 age-matched control men. A higher serum luteinizing hormone (LH) and a lower ratio of testosterone (T) to LH were observed in the COVID-19 group. Multiple regression analysis indicated that serum T: LH ratio was negatively associated with white blood cell counts and C-reactive protein levels in COVID-19 patients. It's the first report about semen assessment and sex-hormone evaluation in reproductive-aged male COVID-19 patients. Although further study is needed to clarify the reasons and underlying mechanisms, our study presents an abnormal sex hormone secretion among COVID-19 patients, suggesting that attention should be paid to reproductive function evaluation in the follow-up.


Subject(s)
COVID-19/complications , Gonadal Steroid Hormones/analysis , Gonadal Steroid Hormones/blood , Semen Analysis , Semen/chemistry , Adult , Humans , Male , Middle Aged , Testosterone/blood , Young Adult
14.
Front Public Health ; 8: 599769, 2020.
Article in English | MEDLINE | ID: covidwho-1045484

ABSTRACT

The COVID-19 pandemic has put labor-intensive industries at risk, among which the construction industry is a typical one. Practitioners in the construction industry are facing high probabilities of COVID-19 transmission, while their knowledge, attitudes, and practices (KAP) are critical to the prevention of virus spread. This study seeks to investigate the KAP of construction industry practitioners in China through an online questionnaire survey conducted from 15 to 30 June 2020. A total of 702 effective responses were received and analyzed. The results revealed that: (1) although an overwhelming percentage of respondents had the correct knowledge about COVID-19, there were significant respondents (15% of all) who were unsure or wrong about the human-to-human transmission of the virus; (2) practitioners generally showed an optimistic attitude about winning the battle against the COVID-19 pandemic and were satisfied with the governments' contingency measures; (3) practitioners tended to actively take preventive measures, although checking body temperature, wearing face masks, and keeping safe social distance still needs to be reinforced. This research is among the first to identify the KAP of construction industry practitioners toward the COVID-19 pandemic in China. Results presented here have implications for enhancing strategies to reduce and prevent COVID-19 spread in the construction industry.


Subject(s)
COVID-19/prevention & control , Construction Industry/statistics & numerical data , Health Knowledge, Attitudes, Practice , Adult , COVID-19/transmission , China , Cross-Sectional Studies , Female , Humans , Male , Masks , Middle Aged , Surveys and Questionnaires
15.
Jpn J Infect Dis ; 73(6): 399-403, 2020 Nov 24.
Article in English | MEDLINE | ID: covidwho-976562

ABSTRACT

In December 2019, a cluster of cases of acute respiratory illness, novel coronavirus-infected pneumonia, occurred in Wuhan, Hubei Province, China. The false-negative nasopharyngeal swabs for SARS-CoV-2 caused delayed diagnosis of COVID-19, which hindered the prevention and control of the pandemic. The transmission risk of SARS-CoV-2 in negative nasopharyngeal swabs cases has rarely been addressed previously. This study evaluated two clusters of COVID-19 in six patients, four of whom (66.7%) tested negative for RNA of SARS-CoV-2 on RT-PCR of nasopharyngeal swabs. All epidemiological, clinical, and laboratory data were collected. The first cluster was a nosocomial infection of four health care providers in early January. One case resulted in a sequential familial cluster of infection. All patients either self-quarantined at home or were admitted to hospital for isolated treatment. All recovered and were anti-SARS-CoV-2 IgG- and/or IgM-positive (100%) for serological detection of SARS-CoV-2 at the recovery stage. Our study provides a cautionary warning that negative results for nasopharyngeal swabs of suspected SARS-CoV-2 infection can increase the risk of nosocomial infection among health care providers. Serologic detection for anti-SARS-CoV-2 IgG and/or IgM is an important test in the diagnosis of COVID-19.


Subject(s)
COVID-19 Testing/methods , COVID-19/diagnosis , COVID-19/transmission , Disease Outbreaks , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2/isolation & purification , Adult , Antibodies, Viral/blood , COVID-19/epidemiology , COVID-19/prevention & control , China/epidemiology , Cross Infection , False Negative Reactions , Female , Humans , Male , Middle Aged , Nasopharynx/virology , Retrospective Studies , SARS-CoV-2/genetics , SARS-CoV-2/immunology
16.
J Med Internet Res ; 22(11): e23128, 2020 11 11.
Article in English | MEDLINE | ID: covidwho-976118

ABSTRACT

BACKGROUND: Patients with COVID-19 in the intensive care unit (ICU) have a high mortality rate, and methods to assess patients' prognosis early and administer precise treatment are of great significance. OBJECTIVE: The aim of this study was to use machine learning to construct a model for the analysis of risk factors and prediction of mortality among ICU patients with COVID-19. METHODS: In this study, 123 patients with COVID-19 in the ICU of Vulcan Hill Hospital were retrospectively selected from the database, and the data were randomly divided into a training data set (n=98) and test data set (n=25) with a 4:1 ratio. Significance tests, correlation analysis, and factor analysis were used to screen 100 potential risk factors individually. Conventional logistic regression methods and four machine learning algorithms were used to construct the risk prediction model for the prognosis of patients with COVID-19 in the ICU. The performance of these machine learning models was measured by the area under the receiver operating characteristic curve (AUC). Interpretation and evaluation of the risk prediction model were performed using calibration curves, SHapley Additive exPlanations (SHAP), Local Interpretable Model-Agnostic Explanations (LIME), etc, to ensure its stability and reliability. The outcome was based on the ICU deaths recorded from the database. RESULTS: Layer-by-layer screening of 100 potential risk factors finally revealed 8 important risk factors that were included in the risk prediction model: lymphocyte percentage, prothrombin time, lactate dehydrogenase, total bilirubin, eosinophil percentage, creatinine, neutrophil percentage, and albumin level. Finally, an eXtreme Gradient Boosting (XGBoost) model established with the 8 important risk factors showed the best recognition ability in the training set of 5-fold cross validation (AUC=0.86) and the verification queue (AUC=0.92). The calibration curve showed that the risk predicted by the model was in good agreement with the actual risk. In addition, using the SHAP and LIME algorithms, feature interpretation and sample prediction interpretation algorithms of the XGBoost black box model were implemented. Additionally, the model was translated into a web-based risk calculator that is freely available for public usage. CONCLUSIONS: The 8-factor XGBoost model predicts risk of death in ICU patients with COVID-19 well; it initially demonstrates stability and can be used effectively to predict COVID-19 prognosis in ICU patients.


Subject(s)
COVID-19/epidemiology , Machine Learning/standards , Algorithms , Female , Humans , Intensive Care Units , Male , Prognosis , Reproducibility of Results , Retrospective Studies , Risk Factors
17.
SSRN; 2020.
Preprint | SSRN | ID: ppcovidwho-543

ABSTRACT

Background: Since December 8, 2019, China is experiencing an outbreak of pneumonia caused by 2019 novel coronavirus (COVID-19). The purpose of this study is to

18.
Infect Drug Resist ; 13: 3045-3053, 2020.
Article in English | MEDLINE | ID: covidwho-738463

ABSTRACT

PURPOSE: To differentiate between respiratory infections caused by SARS-CoV-2 and other respiratory pathogens during the COVID-19 outbreak in Wuhan, we simultaneously tested for SARS-CoV-2 and pathogens associated with CAP to determine the incidence and impact of respiratory coinfections in COVID-19 patients. PATIENTS AND METHODS: We included 250 patients who were diagnosed with COVID-19. RT-PCR was used to detect influenza A, influenza B and respiratory syncytial viruses. Chemiluminescence immunoassays were used to detect IgM antibodies for adenovirus, Chlamydia pneumoniae and Mycoplasma pneumoniae in the serum of patients. Based on these results, we divided the patients into two groups, the simple SARS-CoV-2-infected group and the coinfected SARS-COV-2 group. Coinfected patients were then further categorized as having a coinfection of viral pathogen (CoIV) or coinfection of atypical bacterial pathogen (CoIaB). RESULTS: No statistically significant differences were found in age, gender, the time taken to return negative SARS-CoV-2 nucleic acid test results, length of hospital stays, and mortality between the simple SARS-CoV-2 infection group and the coinfection group. Of the 250 hospitalized COVID-19 patients, 39 (15.6%) tested positive for at least one respiratory pathogen in addition to SARS-CoV-2. A third of these pathogens were detected as early as the 1st week after symptom onset and another third were identified after more than three weeks. The most detected CAP pathogen was C. pneumoniae (5.2%), followed by the respiratory syncytial virus (4.8%), M. pneumoniae (4.4%) and adenovirus (2.8%). Patients coinfected with viral pathogens (CoIV) (n=18) had longer hospital stays when compared to patients coinfected with atypical bacterial pathogens (CoIaB) (n=21). Except for one fatality, the remaining 38 coinfected patients all recovered with favourable outcomes. CONCLUSION: Coinfections in COVID-19 patients are common. The coinfecting pathogens can be detected at variable intervals during COVID-19 disease course and remain an important consideration in targeted treatment strategies for COVID-19 patients.

19.
Eur Respir J ; 55(6)2020 06.
Article in English | MEDLINE | ID: covidwho-595496

ABSTRACT

BACKGROUND: The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), infected over 3300 healthcare workers in early 2020 in China. Little information is known about nosocomial infections of healthcare workers in the initial period. We analysed data from healthcare workers with nosocomial infections in Wuhan Union Hospital (Wuhan, China) and their family members. METHODS: We collected and analysed data on exposure history, illness timelines and epidemiological characteristics from 25 healthcare workers with laboratory-confirmed coronavirus disease 2019 (COVID-19) and two healthcare workers in whom COVID-19 was highly suspected, as well as 10 of their family members with COVID-19, between 5 January and 12 February 2020. The demographics and clinical features of the 35 laboratory-confirmed cases were investigated and viral RNA of 12 cases was sequenced and analysed. RESULTS: Nine clusters were found among the patients. All patients showed mild to moderate clinical manifestation and recovered without deterioration. The mean period of incubation was 4.5 days, the mean±sd clinical onset serial interval (COSI) was 5.2±3.2 days, and the median virus shedding time was 18.5 days. Complete genomic sequences of 12 different coronavirus strains demonstrated that the viral structure, with small irrelevant mutations, was stable in the transmission chains and showed remarkable traits of infectious traceability. CONCLUSIONS: SARS-CoV-2 can be rapidly transmitted from person to person, regardless of whether they have symptoms, in both hospital settings and social activities, based on the short period of incubation and COSI. The public health service should take practical measures to curb the spread, including isolation of cases, tracing close contacts, and containment of severe epidemic areas. Besides this, healthcare workers should be alert during the epidemic and self-quarantine if self-suspected of infection.


Subject(s)
Coronavirus Infections/epidemiology , Disease Outbreaks , Family , Health Personnel , Infectious Disease Transmission, Patient-to-Professional/statistics & numerical data , Pneumonia, Viral/epidemiology , Adult , Aged , Aged, 80 and over , Betacoronavirus/genetics , COVID-19 , China/epidemiology , Coronavirus Infections/transmission , Female , Hospitals , Humans , Infectious Disease Incubation Period , Length of Stay , Male , Middle Aged , Pandemics , Pneumonia, Viral/transmission , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2 , Virus Shedding , Whole Genome Sequencing
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