Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 58
Filter
1.
ACS omega ; 7(22):18206-18212, 2022.
Article in English | EuropePMC | ID: covidwho-1872000

ABSTRACT

Over two years into the outbreak of COVID-19, the quest for effective and economical drugs has become starkly clear to reduce the risk of progression of coronavirus disease. A number of drugs have been investigated, and they can be taken orally at home and be used after exposure to SARS-CoV-2 or at the first sign of COVID-19. Fluorinated oral anti-COVID-19 drugs—including Paxlovid, the first oral tablet for the treatment of COVID-19—constitute an important subgroup. Fluorine has been widely used in the pharmaceutical market and can lead to improved selectivity indices, increased lipophilicity, greater metabolic stability, and improved anti-COVID-19 efficacy. In this mini-review, we will give an update on fluorinated anti-COVID-19 drugs by providing the key information and current knowledge of these drugs, including their molecular design, metabolism and pharmacokinetics, and mechanism of action.

2.
Viruses ; 14(6):1127, 2022.
Article in English | MDPI | ID: covidwho-1857857

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as the prime challenge facing public health safety since 2019. Correspondingly, coronavirus disease 2019 (COVID-19) vaccines have been developed and administered worldwide, varying in design strategies, delivery routes, immunogenicity and protective efficacy. Here, a replication-competent vesicular stomatitis virus (VSV) vectored recombinant COVID-19 vaccine was constructed and evaluated in BALB/c mice and Syrian golden hamsters. In BALB/c mice, intramuscular (i.m.) inoculation of recombinant vaccine induced significantly higher humoral immune response than that of the intranasal (i.n.) inoculation group. Analyses of cellular immunity revealed that a Th1-biased cellular immune response was induced in i.n. inoculation group while both Th1 and Th2 T cells were activated in i.m. inoculation group. In golden hamsters, i.n. inoculation of the recombinant vaccine triggered robust humoral immune response and conferred prominent protective efficacy post-SARS-CoV-2 challenge, indicating a better protective immunity in the i.n. inoculation group than that of the i.m. inoculation group. This study provides an effective i.n.-delivered recombinant COVID-19 vaccine candidate and elucidates a route-dependent manner of this vaccine candidate in two most frequently applied small animal models. Moreover, the golden hamster is presented as an economical and convenient small animal model that precisely reflects the immune response and protective efficacy induced by replication-competent COVID-19 vaccine candidates in other SARS-CoV-2 susceptible animals and human beings, especially in the exploration of i.n. immunization.

3.
Front Immunol ; 13: 869809, 2022.
Article in English | MEDLINE | ID: covidwho-1847173

ABSTRACT

Previous studies have shown that B.1.351 and other variants have extended the host range of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to mice. Sustained transmission is a prerequisite for viral maintenance in a population. However, no evidence of natural transmission of SARS-CoV-2 in wild mice has been documented to date. Here, we evaluated the replication and contact transmission of the B.1.351 variant in mice and rats. The B.1.351 variant could infect and replicate efficiently in the airways of mice and rats. Furthermore, the B.1.351 variant could not be transmitted in BALB/c or C57BL/6 mice but could be transmitted with moderate efficiency in rats by direct contact. Additionally, the B.1.351 variant did not transmit from inoculated Syrian hamsters to BALB/c mice. Moreover, the mouse-adapted SARS-CoV-2 strain C57MA14 did not transmit in mice. In summary, the risk of B.1.351 variant transmission in mice is extremely low, but the transmission risk in rats should not be neglected. We should pay more attention to the potential natural transmission of SARS-CoV-2 variants in rats and their possible spillback to humans.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Cricetinae , Humans , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Rats
4.
Front Cell Infect Microbiol ; 12: 897416, 2022.
Article in English | MEDLINE | ID: covidwho-1847157

ABSTRACT

The pandemic of respiratory diseases, such as coronavirus disease 2019 (COVID-19) and influenza, has imposed significant public health and economic burdens on the world. Wearing masks is an effective way to cut off the spread of the respiratory virus. However, due to cultural differences and uncomfortable wearing experiences, not everyone is willing to wear masks; there is an urgent need to find alternatives to masks. In this study, we tested the disinfection effect of a portable ionizer on pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (strain V34) and influenza A virus (strain CA04). Negative ions significantly reduced the concentration of particulate matter in the air above and effectively disinfected viruses stuck to the solid plate at the level of both nucleic acid and virus titer. The disinfection efficiency was >99.8% after 1-h exposure. Moreover, negative ions effectively disinfected aerosolized viruses; the disinfection efficiency was more than 87.77% after purification for 10 min. Furthermore, negative ions had a significant protective effect on susceptible animals exposed to viral aerosols. When the negative ionizer was switched from off to on, the inhalation 50% infective dose (ID50) for golden hamsters challenged with SARS-CoV-2 rose from 9.878 median tissue culture infective dose (TCID50) [95% confidence interval (CI), 6.727-14.013 TCID50] to 43.891 TCID50 (95% CI, 29.31-76.983 TCID50), and the inhalation ID50 for guinea pigs challenged with influenza A virus rose from 6.696 TCID50 (95% CI, 3.251-9.601 TCID50) to 28.284 TCID50 (95% CI, 19.705-40.599 TCID50). In the experiment of transmission between susceptible animals, negative ions 100% inhibited the aerosol transmission of SARS-CoV-2 and influenza A virus. Finally, we tested the safety of negative ion exposure. Balb/c mice exposed to negative ions for 4 weeks showed no abnormalities in body weight, blood routine analysis, and lung pathology. Our study demonstrates that air ions can be used as a safe and effective means of blocking respiratory virus transmission and contribute to pandemic prevention and control.


Subject(s)
COVID-19 , Influenza A virus , Aerosols , Animals , COVID-19/prevention & control , Cricetinae , Guinea Pigs , Ions , Mice , Pandemics/prevention & control , SARS-CoV-2
5.
iScience ; 25(6): 104350, 2022 Jun 17.
Article in English | MEDLINE | ID: covidwho-1819514

ABSTRACT

To date, intermediate hosts of SARS-CoV-2 remain obscure and controversial. Several studies have shown that SARS-CoV-2-related pangolin coronavirus (Pangolin-CoV) has a high sequence similarity to SARS-CoV-2 and might be the initial source of SARS-CoV-2; however, the biological characteristics of Pangolin-CoV are still largely unknown. In this study, we evaluated the pathogenicity and transmissibility of Pangolin-CoV in Syrian golden hamsters Mesocricetus auratus (Linnaeus, 1758) and compared it with SARS-CoV-2. Pangolin-CoV could effectively infect hamsters, showed similar tissue tropism to SARS-CoV-2 and replicated efficiently in the respiratory system and brain. The infected hamsters had no weight loss but had obvious viral shedding and lung pathological injury. Notably, Pangolin-CoV could transmit between hamsters by direct contact but not via aerosols, and the infected hamsters could exhale infectious viral aerosols (>1 µm). These results highlight the importance of continuous monitoring of coronaviruses in pangolins owing to the potential threat of Pangolin-CoV to human health.

7.
Am J Cardiol ; 170: 105-111, 2022 May 01.
Article in English | MEDLINE | ID: covidwho-1708135

ABSTRACT

Adverse events, including cardiac involvement, after vaccination for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported. We sought to evaluate trends of hospital encounters for vaccine recipients before and after vaccination. We analyzed patients who received the coronavirus disease 2019 (COVID-19) vaccine in the MedStar Health system (11 hospitals in Washington, District of Columbia and Maryland) from December 2020 through August 2021. We then compared hospital encounters (emergency department visits) of patients 60 days before a vaccine dose and 30 days after a vaccine dose, along with encounters related to the SARS-CoV-2 infection itself. The cohort included 5,217 patients who were vaccinated against COVID-19. Our analysis revealed a total of 6,751 emergency department visits, and we divided this total into 3 cohorts: fully vaccinated (n = 1,779), in vaccination window (n = 1,420), and before vaccination (n = 3,552). We found no significant association between vaccination and rate of presentation for acute coronary syndrome, pericarditis, myocarditis, heart failure, conduction abnormality, or noncardiac conditions. Further, encounters for complications related to SARS-CoV-2 infection decreased significantly from those before vaccination (5.4%) to those in vaccination window (4.2%) to those who were fully vaccinated (1.6%). These findings were consistent when all vaccinated encounters were combined into 1 cohort (fully vaccinated + in vaccination window). In conclusion, our analysis suggests that there is no significant association of COVID-19 vaccination with the rate of hospital encounters for cardiac disease, including acute coronary syndrome, pericarditis, myocarditis, congestive heart failure, and conduction abnormality. Further, administration of the vaccine resulted in a significant decrease in hospital encounters for SARS-CoV-2 infections and associated complications.


Subject(s)
Acute Coronary Syndrome , COVID-19 , Heart Failure , Myocarditis , Pericarditis , Acute Coronary Syndrome/etiology , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines , Heart Failure/etiology , Hospitals , Humans , Myocarditis/etiology , Pericarditis/etiology , SARS-CoV-2 , Vaccination/adverse effects
8.
Environ Int ; 162: 107153, 2022 04.
Article in English | MEDLINE | ID: covidwho-1706132

ABSTRACT

Since December 2019, coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a great challenge to the world's public health system. Nosocomial infections have occurred frequently in medical institutions worldwide during this pandemic. Thus, there is an urgent need to construct an effective surveillance and early warning system for pathogen exposure and infection to prevent nosocomial infections in negative-pressure wards. In this study, visualization and construction of an infection risk assessment of SARS-CoV-2 through aerosol and surface transmission in a negative-pressure ward were performed to describe the distribution regularity and infection risk of SARS-CoV-2, the critical factors of infection, the air changes per hour (ACHs) and the viral variation that affect infection risk. The SARS-CoV-2 distribution data from this model were verified by field test data from the Wuhan Huoshenshan Hospital ICU ward. ACHs have a great impact on the infection risk from airborne exposure, while they have little effect on the infection risk from surface exposure. The variant strains demonstrated significantly increased viral loads and risks of infection. The level of protection for nurses and surgeons should be increased when treating patients infected with variant strains, and new disinfection methods, electrostatic adsorption and other air purification methods should be used in all human environments. The results of this study may provide a theoretical reference and technical support for reducing the occurrence of nosocomial infections.


Subject(s)
COVID-19 , SARS-CoV-2 , Aerosols , Humans , Patient Isolators , Risk Assessment
9.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-325198

ABSTRACT

Background: As we know, some patients with Coronavirus disease 2019 (COVID-19) may stay longer in the hospital, but whether the different hospitalization days are associated with different clinical features is not clear yet. Methods: : This study is a single-centered, observational and retrospective case series.97 patients with COVID-19 were divided into two groups:patients with hospitalization for more than 20 days (Group1,n=35)and those with hospitalization for less than 20 days (Group2,n=62).Data were collected Results Acute Respiratory Distress Syndrome(ARDS) and Hospital acquired pneumonia (HAP)were more common in Group1 than in Group2 . There were more patients administered quadruple antiviral therapy in Group1 than in Group2 . In group1, 14.3% patients’ specimens showed positive again after they were discharged from the hospital.Compared with Group2,Group1 had higher percentages of oxygenation index<300mmHg leucopenia and lymphopenia. In Group1, 19 patients were treated with chloroquine phosphate,whose nucleic acid tests were negative soon,but 5 patents who hadn’t used the medicine had positive testing again . Conclusions: : COVID-19 patients with longer hospitalization are more severe and need more quadruple antiviral therapy ;For patients who don't use chloroquine phosphate, the nucleic acid tests are more likely to return to positive again even if they have no symptoms at that time .

10.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-325013

ABSTRACT

Identifying "superspreaders" of disease is a pressing concern for society during pandemics such as COVID-19. Superspreaders represent a group of people who have much more social contacts than others. The widespread deployment of WLAN infrastructure enables non-invasive contact tracing via people's ubiquitous mobile devices. This technology offers promise for detecting superspreaders. In this paper, we propose a general framework for WLAN-log-based superspreader detection. In our framework, we first use WLAN logs to construct contact graphs by jointly considering human symmetric and asymmetric interactions. Next, we adopt three vertex centrality measurements over the contact graphs to generate three groups of superspreader candidates. Finally, we leverage SEIR simulation to determine groups of superspreaders among these candidates, who are the most critical individuals for the spread of disease based on the simulation results. We have implemented our framework and evaluate it over a WLAN dataset with 41 million log entries from a large-scale university. Our evaluation shows superspreaders exist on university campuses. They change over the first few weeks of a semester, but stabilize throughout the rest of the term. The data also demonstrate that both symmetric and asymmetric contact tracing can discover superspreaders, but the latter performs better with daily contact graphs. Further, the evaluation shows no consistent differences among three vertex centrality measures for long-term (i.e., weekly) contact graphs, which necessitates the inclusion of SEIR simulation in our framework. We believe our proposed framework and these results may provide timely guidance for public health administrators regarding effective testing, intervention, and vaccination policies.

11.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-325008

ABSTRACT

Background: Since the end of December 2019, a pneumonia outbreak has occurred in Wuhan, Hubei Province, China. An epidemiological survey showed that the pneumovirus infection was closely related to the Huanan Seafood Wholesale Market in Wuhan, causing great panic among the general population. Through the isolation and whole-genome sequencing of the pneumovirus, an infection model of the pneumovirus in human airway epithelial cells was established, and the pneumovirus was identified as the 2019 novel coronavirus (2019-nCoV), which belongs to the β-coronavirus genus. This study focus on lethiferous processes of infections associated with the new virus. Methods: The data of 17 deaths from 13 hospitals in Wuhan were obtained, and the initial symptoms, clinical features during the progression of the disease, and treatment processes were well analyzed. Results: At the early phase of the outbreak of 2019-nCoV, the lack of effective drugs for pneumonia caused by the new coronavirus has led to lethal results in people who are often elderly with multiple diseases. Males were affected more than females. Fever, dry coughing, shortness of breath are the primary presentations, but not all. Chest images showed viral pneumonia. Symptomatic supportive treatment did not improve respiratory distress, leading to a sudden deterioration in the condition. The development of diseases are different from the other two cronoviruses. Conclusions: Older people are at high risk of death due to 2019-nCoV infection, and protecting high-risk groups is an effective way to reduce the number of deaths. A large number of viral pneumonia in Wuhan within a short period of time suggest the outbreak caused by a new virus, virus nucleic acid test will make accurate diagnosis, and the diagnosis based on clinical manifestations and imaging results provides a basis for early treatments.

12.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-325007

ABSTRACT

Background: Since the end of December 2019, a pneumonia outbreak has occurred in Wuhan, Hubei Province, China. An epidemiological survey showed that the pneumovirus infection was closely related to the Huanan Seafood Wholesale Market in Wuhan, causing great panic among the general population. Through isolation of the pneumovirus strain and whole-genome sequencing, an infection model of the pneumovirus in human airway epithelial cells was established, and the pneumovirus was identified as the 2019 novel coronavirus (2019-nCoV), which belongs to the β-coronavirus genus. This study focused on the different characteristics of 2019-nCoV, which we learned at the early stage of Covid-19 pandemic will help us to save more lives during the outbreak. Methods: The data of 17 deaths from 13 hospitals in Wuhan were obtained, and the initial symptoms, clinical features during the progression of the disease, and treatment processes were well analyzed. Results: At the initial phase of the outbreak of 2019-nCoV, the lack of effective drugs for pneumonia has led to lethal results in people who are often elderly with multiple underlying conditions. Males were affected more than females. Fever, dry coughing, shortness of breath were the primary presentations, but not all. Chest images showed typical features of viral pneumonia. Respiratory support treatment were needed, although sometimes did not improve respiratory distress. All the patients died of multiple organ failure caused by respiratory failure. Many treatments of covid-19 were done in ICU and lasted for a long time, the occupation of public medical resources will put pressure on the present medical system. Conclusions: COVID-19 is different from pneumonia caused by previous coronaviruses, it is more infectious and hard to manage. The initial death population were mainly elderly patients with underlying diseases. Protecting the elderly is an effective method to reduce the number of deaths. In the absence of nucleic acid detection reagents, relying on identifying typical symptoms and making full use of CT can increase the diagnosis of suspicious people. The condition of patients may deteriorate rapidly which increased the complexity of treatment. The increasing number of patients will put great pressure on the existing medical system.

13.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-324240

ABSTRACT

Human steroid 5α-reductase 2 (SRD5α2) as a critical integral membrane enzyme in steroid metabolism catalyzes testosterone to dihydrotestosterone. Mutations on its gene have been linked to 5α-reductase deficiency and prostate cancer. Finasteride and dutasteride as SRD5α2 inhibitors are widely used anti-androgen drugs for benign prostate hyperplasia, which have recently been indicated in the treatment of COVID-19. The molecular mechanisms underlying enzyme catalysis and inhibition remained elusive for SRD5α2 and other eukaryotic integral membrane steroid reductases due to a lack of structural information. Here, we report a crystal structure of human SRD5α2 at 2.8 Å revealing a unique 7-TM structural topology and an intermediate adduct of finasteride and NADPH as NADP-dihydrofinasteride in a largely enclosed binding cavity inside the membrane. Structural analysis together with computational and mutagenesis studies reveals molecular mechanisms for the 5α-reduction of testosterone and the finasteride inhibition involving residues E57 and Y91. Molecular dynamics simulation results indicate high conformational dynamics of the cytosolic region regulating the NADPH/NADP + exchange. Mapping disease-causing mutations of SRD5α2 to our structure suggests molecular mechanisms for their pathological effects. Our results offer critical structural insights into the function of integral membrane steroid reductases and will facilitate drug development.

14.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-312180

ABSTRACT

Background: The aim of the study was to establish and validate nomograms to predict the mortality risk of patients with COVID-19 using routine clinical indicators. Method: This retrospective study included a development cohort enrolled 2119 hospitalized COVID-19 patients and a validation cohort included 1504 COVID-19 patients. The demographics, clinical manifestations, vital signs and laboratory test results of the patients at admission and outcome of in-hospital death were recorded. The independent factors associated with death were identified by a forward stepwise multivariate logistic regression analysis and used to construct two prognostic nomograms. The models were then tested in an external dataset. Results: Nomogram 1 is a full model included nine factors identified in the multivariate logistic regression and nomogram 2 is built by selecting four factors from nine to perform as a reduced model. Nomogram 1 and nomogram 2 established showed better performance in discrimination and calibration than the MuLBSTA score in training. In validation, Nomogram 1 performed better than nomogram 2 for calibration. Conclusion: Nomograms we established performed better than the MuLBSTA score. We recommend the application of nomogram 1 in general hospital which provide robust prognostic performance but more cumbersome;nomogram 2 in mobile cabin hospitals which depend on less laboratory examinations and more convenient. Both nomograms can help clinicians in identifying patients at risk of death with routine clinical indicators at admission, which may reduce the overall mortality of COVID-19.

15.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-315952

ABSTRACT

In this paper, we propose a new privacy-preserving, automated contact tracing system, ACOUSTIC-TURF, to fight COVID-19 using acoustic signals sent from ubiquitous mobile devices. At a high level, ACOUSTIC-TURF adaptively broadcasts inaudible ultrasonic signals with randomly generated IDs in the vicinity. Simultaneously, the system receives other ultrasonic signals sent from nearby (e.g., 6 feet) users. In such a system, individual user IDs are not disclosed to others and the system can accurately detect encounters in physical proximity with 6-foot granularity. We have implemented a prototype of ACOUSTIC-TURF on Android and evaluated its performance in terms of acoustic-signal-based encounter detection accuracy and power consumption at different ranges and under various occlusion scenarios. Experimental results show that ACOUSTIC-TURF can detect multiple contacts within a 6-foot range for mobile phones placed in pockets and outside pockets. Furthermore, our acoustic-signal-based system achieves greater precision than wireless-signal-based approaches when contact tracing is performed through walls. ACOUSTIC-TURF correctly determines that people on opposite sides of a wall are not in contact with one another, whereas the Bluetooth-based approaches detect nonexistent contacts among them.

16.
Mol Biol Evol ; 39(2)2022 02 03.
Article in English | MEDLINE | ID: covidwho-1594013

ABSTRACT

The ongoing SARS (severe acute respiratory syndrome)-CoV (coronavirus)-2 pandemic has exposed major gaps in our knowledge on the origin, ecology, evolution, and spread of animal coronaviruses. Porcine epidemic diarrhea virus (PEDV) is a member of the genus Alphacoronavirus in the family Coronaviridae that may have originated from bats and leads to significant hazards and widespread epidemics in the swine population. The role of local and global trade of live swine and swine-related products in disseminating PEDV remains unclear, especially in developing countries with complex swine production systems. Here, we undertake an in-depth phylogeographic analysis of PEDV sequence data (including 247 newly sequenced samples) and employ an extension of this inference framework that enables formally testing the contribution of a range of predictor variables to the geographic spread of PEDV. Within China, the provinces of Guangdong and Henan were identified as primary hubs for the spread of PEDV, for which we estimate live swine trade to play a very important role. On a global scale, the United States and China maintain the highest number of PEDV lineages. We estimate that, after an initial introduction out of China, the United States acted as an important source of PEDV introductions into Japan, Korea, China, and Mexico. Live swine trade also explains the dispersal of PEDV on a global scale. Given the increasingly global trade of live swine, our findings have important implications for designing prevention and containment measures to combat a wide range of livestock coronaviruses.


Subject(s)
Coronavirus , Porcine epidemic diarrhea virus , Swine Diseases , Animals , China , Pandemics , Phylogeny , Phylogeography , Porcine epidemic diarrhea virus/genetics , Swine , Swine Diseases/epidemiology , United States
17.
Front Immunol ; 12: 733171, 2021.
Article in English | MEDLINE | ID: covidwho-1559118

ABSTRACT

Background: COVID-19, caused by SARS-CoV-2 virus, is a global pandemic with high mortality and morbidity. Limited diagnostic methods hampered the infection control. Since the direct detection of virus mainly by RT-PCR may cause false-negative outcome, host response-dependent testing may serve as a complementary approach for improving COVID-19 diagnosis. Objective: Our study discovered a highly-preserved transcriptional profile of Type I interferon (IFN-I)-dependent genes for COVID-19 complementary diagnosis. Methods: Computational language R-dependent machine learning was adopted for mining highly-conserved transcriptional profile (RNA-sequencing) across heterogeneous samples infected by SARS-CoV-2 and other respiratory infections. The transcriptomics/high-throughput sequencing data were retrieved from NCBI-GEO datasets (GSE32155, GSE147507, GSE150316, GSE162835, GSE163151, GSE171668, GSE182569). Mathematical approaches for homological analysis were as follows: adjusted rand index-related similarity analysis, geometric and multi-dimensional data interpretation, UpsetR, t-distributed Stochastic Neighbor Embedding (t-SNE), and Weighted Gene Co-expression Network Analysis (WGCNA). Besides, Interferome Database was used for predicting the transcriptional factors possessing IFN-I promoter-binding sites to the key IFN-I genes for COVID-19 diagnosis. Results: In this study, we identified a highly-preserved gene module between SARS-CoV-2 infected nasal swab and postmortem lung tissue regulating IFN-I signaling for COVID-19 complementary diagnosis, in which the following 14 IFN-I-stimulated genes are highly-conserved, including BST2, IFIT1, IFIT2, IFIT3, IFITM1, ISG15, MX1, MX2, OAS1, OAS2, OAS3, OASL, RSAD2, and STAT1. The stratified severity of COVID-19 may also be identified by the transcriptional level of these 14 IFN-I genes. Conclusion: Using transcriptional and computational analysis on RNA-seq data retrieved from NCBI-GEO, we identified a highly-preserved 14-gene transcriptional profile regulating IFN-I signaling in nasal swab and postmortem lung tissue infected by SARS-CoV-2. Such a conserved biosignature involved in IFN-I-related host response may be leveraged for COVID-19 diagnosis.


Subject(s)
COVID-19 Testing/methods , COVID-19/diagnosis , Interferon Type I/metabolism , SARS-CoV-2/isolation & purification , COVID-19/genetics , COVID-19/metabolism , Diagnosis, Differential , Gene Expression Profiling , Gene Regulatory Networks , Humans , Lung/metabolism , Machine Learning , Nasopharynx/metabolism , Respiratory Tract Infections , Severity of Illness Index , Transcriptome
18.
Biosens Bioelectron ; 198: 113823, 2022 Feb 15.
Article in English | MEDLINE | ID: covidwho-1520727

ABSTRACT

Direct in situ fluorescent enzyme-linked immunosorbent assay (ELISA) is rarely investigated and reported. Herein, a direct in situ high-performance HRP-labeled fluorescent immunoassay platform was constructed. The platform was developed based on a rapid in situ fluorogenic reaction between Polyethyleneimine (PEI) and p-Phenylenediamine (PPD) analogues to generate fluorescent copolymer nanoparticles (FCNPs). The formation mechanism of FCNPs was found to be the oxidation of •OH radicals, which was further proved by nitrogen protection and scavenger of •OH radicals. Meantime, the fluorescence wavelength of FCNPs could be adjusted from 471 to 512 nm by introducing various substitution groups into the PPD structure. Using cardiac troponin I (cTnI) and SARS-CoV-2 nucleocapsid protein (N-protein) as the model antigens, the proposed fluorescent ELISA exhibited a wide dynamic range of 5-180 ng/mL and a low limit of detection (LOD) of 0.19 ng/mL for cTnI, and dynamic range of 0-120 ng/mL and a LOD of 0.33 ng/mL for SARS-CoV-2 N protein, respectively. Noteworthy, the proposed method was successful applied to evaluate the cTnI and SARS-CoV-2 N protein levels in serum with satisfied results. Therefore, the proposed platform paved ways for developing novel fluorescence-based HRP-labeled ELISA technologies and broadening biomarker related clinical diagnostics.


Subject(s)
Biosensing Techniques , COVID-19 , Enzyme-Linked Immunosorbent Assay , Horseradish Peroxidase , Humans , Immunoassay , Nucleocapsid Proteins , SARS-CoV-2 , Troponin I
20.
Front Med (Lausanne) ; 8: 706380, 2021.
Article in English | MEDLINE | ID: covidwho-1502327

ABSTRACT

This study aimed to establish and validate the nomograms to predict the mortality risk of patients with coronavirus disease 2019 (COVID-19) using routine clinical indicators. This retrospective study included a development cohort enrolled 2,119 hospitalized patients with COVID-19 and a validation cohort included 1,504 patients with COVID-19. The demographics, clinical manifestations, vital signs, and laboratory tests of the patients at admission and outcome of in-hospital death were recorded. The independent factors associated with death were identified by a forward stepwise multivariate logistic regression analysis and used to construct the two prognostic nomograms. The nomogram 1 was a full model to include nine factors identified in the multivariate logistic regression and nomogram 2 was built by selecting four factors from nine to perform as a reduced model. The nomogram 1 and nomogram 2 showed better performance in discrimination and calibration than the Multilobular infiltration, hypo-Lymphocytosis, Bacterial coinfection, Smoking history, hyper-Tension and Age (MuLBSTA) score in training. In validation, nomogram 1 performed better than nomogram 2 for calibration. We recommend the application of nomogram 1 in general hospitals which provide robust prognostic performance though more cumbersome; nomogram 2 in the out-patient, emergency department, and mobile cabin hospitals, which depend on less laboratory examinations to make the assessment more convenient. Both the nomograms can help the clinicians to identify the patients at risk of death with routine clinical indicators at admission, which may reduce the overall mortality of COVID-19.

SELECTION OF CITATIONS
SEARCH DETAIL