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1.
Proc Natl Acad Sci U S A ; 118(52)2021 Dec 28.
Article in English | MEDLINE | ID: covidwho-1565770

ABSTRACT

The constant emergence of COVID-19 variants reduces the effectiveness of existing vaccines and test kits. Therefore, it is critical to identify conserved structures in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes as potential targets for variant-proof diagnostics and therapeutics. However, the algorithms to predict these conserved structures, which simultaneously fold and align multiple RNA homologs, scale at best cubically with sequence length and are thus infeasible for coronaviruses, which possess the longest genomes (∼30,000 nt) among RNA viruses. As a result, existing efforts on modeling SARS-CoV-2 structures resort to single-sequence folding as well as local folding methods with short window sizes, which inevitably neglect long-range interactions that are crucial in RNA functions. Here we present LinearTurboFold, an efficient algorithm for folding RNA homologs that scales linearly with sequence length, enabling unprecedented global structural analysis on SARS-CoV-2. Surprisingly, on a group of SARS-CoV-2 and SARS-related genomes, LinearTurboFold's purely in silico prediction not only is close to experimentally guided models for local structures, but also goes far beyond them by capturing the end-to-end pairs between 5' and 3' untranslated regions (UTRs) (∼29,800 nt apart) that match perfectly with a purely experimental work. Furthermore, LinearTurboFold identifies undiscovered conserved structures and conserved accessible regions as potential targets for designing efficient and mutation-insensitive small-molecule drugs, antisense oligonucleotides, small interfering RNAs (siRNAs), CRISPR-Cas13 guide RNAs, and RT-PCR primers. LinearTurboFold is a general technique that can also be applied to other RNA viruses and full-length genome studies and will be a useful tool in fighting the current and future pandemics.

2.
Infect Genet Evol ; 97: 105175, 2021 Dec 03.
Article in English | MEDLINE | ID: covidwho-1555685

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spreads all over the world and brings great harm to humans in many countries. Many new SARS-CoV-2 variants appeared during its transmission. In the present study, the Delta variants (B.1.617.2) of SARS-CoV-2, which have appeared in many countries, were considered for analysis. In order to evaluate the evolutionary divergence of the Delta variants(B.1.617.2), the codon usage divergence in Delta variants (B.1.617.2) of SARS-CoV-2 was compared to that of the SARS-CoV-2 genomes emerged before June 2020. All Delta variants (B.1.617.2) and 350 early genomes of SARS-CoV-2 in the NCBI database were downloaded. Codon usage pattern including the basic composition, the GC ratio of the third position (GC3) and the first two positions (GC12) in codons, overall GC contents, the effective number of codons (ENC), the codon bias index (CBI), the relative synonymous codon usage (RSCU) values, etc., of all concerned important gene sequences were all calculated. Codon usage divergence of them was calculated via summing their standard deviations. The results suggested that base compositions in both Delta variants (B.1.617.2) of SARS-CoV-2 and the early SARS-CoV-2 genomes were similar to each other. However, the internal codon usage divergence for most genes in Delta variants (B.1.617.2) was significantly wider than that of SARS-CoV-2. The RSCU values were further used to explore the synonymous and non-synonymous mutations in the sequences of the Delta variants (B.1.617.2), and the results showed the synonymous mutations are more obvious than the non-synonymous in the concerned sequences. The related codon usage divergence analysis is helpful for further study on the adaptability and disease prognosis of the SARS-CoV-2 variants.

3.
Preprint in English | EuropePMC | ID: ppcovidwho-292884

ABSTRACT

Remarkable progress has been made in developing intramuscular vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2);however, they are limited with respect to eliciting local immunity in the respiratory tract, which is the primary infection site for SARS-CoV-2. To overcome the limitations of intramuscular vaccines, we constructed a nasal vaccine candidate based on an influenza vector by inserting a gene encoding the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2, named CA4-dNS1-nCoV-RBD (dNS1-RBD). A preclinical study showed that in hamsters challenged 1 day and 7 days after single-dose vaccination or 6 months after booster vaccination, dNS1-RBD largely mitigated lung pathology, with no loss of body weight, caused by either the prototype-like strain or beta variant of SARS-CoV-2. Lasted data showed that the animals could be well protected against beta variant challenge 9 months after vaccination. Notably, the weight loss and lung pathological changes of hamsters could still be significantly reduced when the hamster was vaccinated 24 h after challenge. Moreover, such cellular immunity is relatively unimpaired for the most concerning SARS-CoV-2 variants. The protective immune mechanism of dNS1-RBD could be attributed to the innate immune response in the nasal epithelium, local RBD-specific T cell response in the lung, and RBD-specific IgA and IgG response. Thus, this study demonstrates that the intranasally delivered dNS1-RBD vaccine candidate may offer an important addition to fight against the ongoing COVID-19 pandemic, compensating limitations of current intramuscular vaccines, particularly at the start of an outbreak.

4.
Front Microbiol ; 12: 770935, 2021.
Article in English | MEDLINE | ID: covidwho-1533681

ABSTRACT

Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a pandemic since March 2020 and led to significant challenges to over 200 countries and regions all over the world. The establishment of highly pathogenic coronavirus animal model is beneficial for the study of vaccines and pathogenic mechanism of the virus. Laboratory mice, Syrian hamsters, Non-human primates and Ferrets have been used to establish animal models of emerging coronavirus infection. Different animal models can reproduce clinical infection symptoms at different levels. Appropriate animal models are of great significance for the pathogenesis of COVID-19 and the research progress related to vaccines. This review aims to introduce the current progress about experimental animal models for SARS-CoV-2, and collectively generalize critical aspects of disease manifestation in humans and increase their usefulness in research into COVID-19 pathogenesis and developing new preventions and treatments.

5.
Inflammation ; 2021 Nov 25.
Article in English | MEDLINE | ID: covidwho-1530347

ABSTRACT

The emergence of severe acute syndrome coronavirus 2 (SARS-CoV-2) in December 2019 has led to the global COVID-19 pandemic. Although the symptoms of most COVID-19 patients are mild or self-curable, most of severe patients have sepsis caused by cytokine storms, which greatly increases the case fatality rate. Moreover, there is no effective drug that can limit the novel coronavirus thus far, so it is more needed to develop antiviral drugs for the SARS-CoV-2. In our research, we employed the techniques of molecular docking to screen 35 flavonoid compounds among which 29 compounds have Z-scores lower than - 6. Then, ( -)-gallocatechin gallate, ( +)-gallocatechin and baicalein were identified to have potent inhibitory activity against SARS-CoV-2 Mpro with IC50 values of 5.774 ± 0.805 µM, 13.14 ± 2.081 µM and 5.158 ± 0.928 µM respectively by FRET assay. Molecular docking results also showed that ( -)-gallocatechin gallate, ( +)-gallocatechin and baicalein can non-covalently bind to Mpro through π-π stacking and hydrogen bonds in the Cys145 catalytic site. We further evaluated the effect of ( -)-gallocatechin gallate and baicalein on cytokine storms using a mouse model of sepsis. ( -)-Gallocatechin gallate and baicalein significantly reduced sepsis of mouse models on weight, murine sepsis score, and survival rate and reduced the inflammatory factor levels, such as TNF-α, IL-1α, IL-4, and IL-10. Overall, ( -)-gallocatechin gallate and baicalein show certain potential of treatment against COVID-19.

6.
Preprint in English | EuropePMC | ID: ppcovidwho-291507

ABSTRACT

Messenger RNA (mRNA) vaccines have been successful for COVID-19, but still suffer from the critical issue of chemical instability and degradation of the mRNA molecule, which is a major obstacle in the storage, distribution, and efficiency of the vaccine. Previous work established a correlation between its chemical stability and thermodynamic folding stability, and longer half-life also leads to greater protein expression. Therefore, we aim to design mRNAs with optimal folding stability for more efficient mRNA vaccines. However, due to combinatorial explosion because of synonymous codons, the mRNA design space is prohibitively large, e.g., there are ~$2.4 \times 10

7.
IT Professional Magazine ; 23(5):31-37, 2021.
Article in English | ProQuest Central | ID: covidwho-1467515

ABSTRACT

COVID-19 has turned service-based business continuity into a hot issue, due to the survival of enterprises under long-tailed changes of business caused by various abnormal socioeconomic events and disruptions. We analyze how current techniques enable small and medium enterprises to be resilient and elastic. From observations of service disruptions during COVID-19 and problems with current technologies for resilience and elasticity, we recommend addressing resilience and elasticity requirements through contextual service information and hybrid services coordination programming and serving.

8.
Stem Cells Dev ; 30(19): 947-969, 2021 10 01.
Article in English | MEDLINE | ID: covidwho-1462261

ABSTRACT

Mesenchymal stem cell (MSC) therapy is considered one of the most promising treatments in the context of the coronavirus disease 2019 (COVID-19) pandemic. However, the safety and effectiveness of MSCs in the treatment of COVID-19-associated pneumonia patients need to be systematically reviewed and analyzed. Two independent researchers searched for relevant studies published between October 2019 and April 2021 in the PubMed, Embase, Cochrane Library, WAN FANG, and CNKI databases. All relevant randomized controlled trials, clinically controlled studies, retrospective studies, case reports, letters (with valid data), and case series were included in this meta-analysis. A fixed-effects model and 95% confidence interval (CI) were used to analyze the results. A total of 22 studies involving 371 patients were included in the present study. Allogeneic MSCs from umbilical cord, adipose tissue, menstrual blood, placental tissue, Wharton's jelly, or unreported sources were administered in 247 participants. Combined results revealed that MSC therapy significantly reduced the incidence of adverse events [AEs; odds ratio (OR) = 0.43, 95% CI = 0.22-0.84, P = 0.01] and mortality (OR = 0.17, 95% CI = 0.06-0.49, P < 0.01), and the difference compared with control group was statistically significant. No serious MSC treatment-related AEs were reported. Lung function, radiographic outcomes, and inflammation- and immunity-related biomarker levels all showed improving trends. Therefore, MSC therapy is an effective and safe method for the treatment of COVID-19-associated pneumonia and shows advantages in reducing AEs and mortality. However, a standard and effective MSC treatment program must be developed.


Subject(s)
COVID-19 , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/metabolism , SARS-CoV-2/metabolism , Allografts , COVID-19/metabolism , COVID-19/mortality , COVID-19/therapy , Humans
9.
Front Pharmacol ; 12: 692346, 2021.
Article in English | MEDLINE | ID: covidwho-1405423

ABSTRACT

Pulmonary fibrosis is a known sequela of severe or persistent lung damage. Existing clinical, imaging and autopsy studies have shown that the lungs exhibit a pathological pulmonary fibrosis phenotype after infection with coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Pulmonary fibrosis may be one of the most serious sequelae associated with coronavirus disease 2019 (COVID-19). In this study, we aimed to examine the preventative effects of the antiviral drug remdesivir on pulmonary fibrosis. We used a mouse model of bleomycin-induced pulmonary fibrosis to evaluate the effects of remdesivir on pulmonary fibrosis in vivo and further explored the potential pharmacological mechanisms of remdesivir in lung fibroblasts and alveolar epithelial cells in vitro. The preventive remdesivir treatment was started on the day of bleomycin installation, and the results showed that remdesivir significantly alleviated bleomycin-induced collagen deposition and improved pulmonary function. In vitro experiments showed that remdesivir dose-dependently suppressed TGF-ß1-induced lung fibroblast activation and improved TGF-ß1-induced alveolar epithelial to mesenchymal transition. Our results indicate that remdesivir can preventatively alleviate the severity of pulmonary fibrosis and provide some reference for the prevention of pulmonary fibrosis in patients with COVID-19.

10.
Phytomedicine ; 91: 153704, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1347789

ABSTRACT

BACKGROUND: COVID-19 (Coronavirus Disease-2019) has spread widely around the world and impacted human health for millions. The lack of effective targeted drugs and vaccines forces scientific world to search for new effective antiviral therapeutic drugs. It has reported that flavonoids have potential inhibitory activity on SARS-CoV-2 Mpro and anti-inflammatory properties. Dihydromyricetin, as a flavonol, also has antiviral and anti-inflammatory potential. However, the inhibition of dihydromyricetin on SARS-CoV-2 Mpro and the protective effect of dihydromyricetin on pulmonary inflammation and fibrosis have not been proved and explained. PURPOSE: The coronavirus main protease (Mpro) is essential for SARS-CoV-2 replication and to be recognized as an attractive drug target, we expect to find the inhibitor of Mpro. Novel coronavirus infection can cause severe inflammation and even sequelae of pulmonary fibrosis in critically ill patients. We hope to find a drug that can not only inhibit virus replication but also alleviate inflammation and pulmonary fibrosis in patients. METHODS: FRET-based enzymatic assay was used to evaluate the inhibit activity of dihydromyricetin on SARS-CoV-2 Mpro. Molecular docking was used to identify the binding pose of dihydromyricetin with SARS-CoV-2 Mpro. The protective effects of dihydromyricetin against BLM-induced pulmonary inflammation and fibrosis were investigated in C57BL6 mice. BALF and lung tissue were collected for inflammation cells count, ELISA, masson and HE staining, western blotting and immunohistochemistry to analyze the effects of dihydromyricetin on pulmonary inflammation and fibrosis. MTT, western blotting, reverse transcription-polymerase chain reaction (RT-PCR) and wound healing were used to analyze the effects of dihydromyricetin on lung fibrosis mechanisms in Mlg cells. RESULTS: In this study, we found that dihydromyricetin is a potent inhibitor targeting the SARS-CoV-2 Mpro with a half-maximum inhibitory concentration (IC50) of 1.716 ± 0.419 µM, using molecular docking and the FRET-based enzymatic assay. The binding pose of dihydromyricetin with SARS-CoV-2 Mpro was identified using molecular docking method. In the binding pocket of SARS-CoV-2 Mpro, the dihydrochromone ring of dihydromyricetin interact with the imidazole side chain of His163 through π-π stacking. The 1-oxygen of dihydromyricetin forms a hydrogen bond with the backbone nitrogen of Glu166. The 3-, 7-, 3'- and 4'-hydroxyl of dihydromyricetin interact with Gln189, Leu141, Arg188 and Thr190 through hydrogen bonds. Moreover, our results showed that dihydromyricetin can significantly alleviate BLM-induced pulmonary inflammation by inhibiting the infiltration of inflammation cells and the secretion of inflammation factors in the early process and also ameliorate pulmonary fibrosis by improving pulmonary function and down-regulate the expression of α-SMA and fibronectin in vivo. Our results also showed that dihydromyricetin inhibits the migration and activation of myofibroblasts and extracellular matrix production via transforming growth factor (TGF)-ß1/Smad signaling pathways. CONCLUSION: Dihydromyricetin is an effective inhibitor for SARS-CoV-2 Mpro and it prevents BLM-induced pulmonary inflammation and fibrosis in mice. Dihydromyricetin will be a potential medicine for the treatment of COVID-19 and its sequelae.


Subject(s)
Coronavirus 3C Proteases/antagonists & inhibitors , Flavonols/pharmacology , Protease Inhibitors , SARS-CoV-2 , Virus Replication , Animals , Antiviral Agents/pharmacology , COVID-19 , Fibrosis , Humans , Lung/pathology , Lung/virology , Mice , Mice, Inbred C57BL , Molecular Docking Simulation , Protease Inhibitors/pharmacology , SARS-CoV-2/drug effects , SARS-CoV-2/physiology , Virus Replication/drug effects
11.
Sci Transl Med ; 13(606)2021 08 11.
Article in English | MEDLINE | ID: covidwho-1319371

ABSTRACT

Multiple safe and effective vaccines that elicit immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are necessary to respond to the ongoing coronavirus disease 2019 (COVID-19) pandemic. Here, we developed a protein subunit vaccine composed of spike ectodomain protein (StriFK) plus a nitrogen bisphosphonate-modified zinc-aluminum hybrid adjuvant (FH002C). StriFK-FH002C generated substantially higher neutralizing antibody titers in mice, hamsters, and cynomolgus monkeys than those observed in plasma isolated from COVID-19 convalescent individuals. StriFK-FH002C also induced both TH1- and TH2-polarized helper T cell responses in mice. In hamsters, StriFK-FH002C immunization protected animals against SARS-CoV-2 challenge, as shown by the absence of virus-induced weight loss, fewer symptoms of disease, and reduced lung pathology. Vaccination of hamsters with StriFK-FH002C also reduced within-cage virus transmission to unvaccinated, cohoused hamsters. In summary, StriFK-FH002C represents an effective, protein subunit-based SARS-CoV-2 vaccine candidate.


Subject(s)
COVID-19 , Animals , Antibodies, Neutralizing , Antibodies, Viral , COVID-19 Vaccines , Cricetinae , Humans , Mice , Protein Subunits , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/genetics
12.
Genes Genomics ; 43(11): 1351-1359, 2021 11.
Article in English | MEDLINE | ID: covidwho-1296973

ABSTRACT

BACKGROUND: COVID-19, as a novel coronavirus disease caused by new coronavirus SARS-CoV-2, spreads all over the world, and brings harm to human in many countries. Humans suffered a lot from both SARS-CoV-2 now and by SARS-CoV in the year 2003. It is important to understand the differences and the relationships between these two types of viruses. OBJECTIVE: To compare relative synonymous codon usage of ORF1ab gene in SARS-CoV-2 and SARS-CoV, relative synonymous codon usage of their genomes are studied in this paper from the bioinformatics perspective. METHODS: The ORF1ab gene, which is an important non-structural polyprotein coding gene and now used for nucleic acid detection markers in many measurement method, in both SARS-CoV-2 (30 strains) and SARS-CoV (20 strains) are considered to be the research object in the present paper. The relative synonymous codon usage values of the ORF1ab gene are calculated to characterize the differences and the evolutionary characteristics among 50 strains. RESULTS: There is a significant difference between SARS-CoV and SARS-CoV-2 when the relative synonymous codon usage value of ORF1ab genes is concerned. The results suggest that codon usage pattern of SARS-CoV is more similar to human than that of the SARS-CoV-2, and that the inner difference in SARS-CoV-2 strains is larger than that of SARS-CoV, which denote the larger diversity exits in the SARS-CoV-2 virus. CONCLUSION: These results show that the relative synonymous codon usage values in the coronavirus could be used for further research on their evolutionary phenomenon.


Subject(s)
Codon Usage/genetics , Polyproteins/genetics , SARS Virus/genetics , SARS-CoV-2/genetics , Viral Proteins/genetics , COVID-19 , Computational Biology , Evolution, Molecular , Genome, Viral , Humans , Open Reading Frames , Phylogeny , SARS-CoV-2/classification
13.
Natural Product Research and Development ; 32(7):1099-1103, 2020.
Article in Chinese | CAB Abstracts | ID: covidwho-1237008

ABSTRACT

To explore the active compounds of Chinese herbal medicine Paris polyphylla in the treatment of SARS-CoV-2. SARS-CoV-2 mainly binds to the angiotensin-converting enzyme 2 (ACE2) receptor on the surface of human cells through its S protein.In this study, the molecular docking simulation method was used to predict the binding affinity of ACE2 and three kinds of polyphyllin (I, VI, VII) rich in Paris polyphylla. The results show that the three polyphyllin can bind well with ACE2, and the binding free energy is lower than -8 kcal/mol. The amino acid residues combined by the three compounds include: Pro-346, Thr-347, Ala-348, Asp-350, Asn-394, His-401, Glu-402. The core structure shared by the three drugs plays a key role in binding the above sites.In addition, the energy required for the binding of polyphyllin I to ACE2 is the lowest, while the number of key amino acids and the number of hydrogen bonds formed by the interaction of polyphyllin VI with the target protein are the largest. Therefore, structural design based on these three active ingredients is expected to obtain highly effective SARS-CoV-2 inhibitors, in order to provide a research basis for the discovery of COVID-19 therapeutic drugs.

14.
Remote Sensing ; 13(8):1423, 2021.
Article in English | MDPI | ID: covidwho-1178409

ABSTRACT

The lockdown of cities in the Yangtze River Delta (YRD) during COVID-19 has provided many natural and typical test sites for estimating the potential of air pollution control and reduction. To evaluate the reduction of PM2.5 concentration in the YRD region by the epidemic lockdown policy, this study employs big data, including PM2.5 observations and 29 independent variables regarding Aerosol Optical Depth (AOD), climate, terrain, population, road density, and Gaode map Point of interesting (POI) data, to build regression models and retrieve spatially continuous distributions of PM2.5 during COVID-19. Simulation accuracy of multiple machine learning regression models, i.e., random forest (RF), support vector regression (SVR), and artificial neural network (ANN) were compared. The results showed that the RF model outperformed the SVR and ANN models in the inversion of PM2.5 in the YRD region, with the model-fitting and cross-validation coefficients of determination R2 reached 0.917 and 0.691, mean absolute error (MAE) values were 1.026 μg m−3 and 2.353 μg m−3, and root mean square error (RMSE) values were 1.413 μg m−3, and 3.144 μg m−3, respectively. PM2.5 concentrations during COVID-19 in 2020 have decreased by 3.61 μg m−3 compared to that during the same period of 2019 in the YRD region. The results of this study provide a cost-effective method of air pollution exposure assessment and help provide insight into the atmospheric changes under strong government controlling strategies.

15.
Radiol Cardiothorac Imaging ; 2(2): e200092, 2020 Apr.
Article in English | MEDLINE | ID: covidwho-1155974

ABSTRACT

Purpose: To evaluate the performance of chest CT regarding the initial presentation of patients suspected of having coronavirus disease 2019 (COVID-19). Materials and Methods: Data from 103 patients who were under investigation for COVID-19 based on inclusion criteria according to the World Health Organization Interim Guidance were retrospectively collected from January 21, 2020, to February 14, 2020. All patients underwent chest CT scanning and reverse-transcription polymerase chain reaction (RT-PCR) testing for COVID-19 at hospital presentation. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) (with 95% confidence intervals) were calculated to evaluate the performance of CT. Subgroup analyses were also performed based on the geographical distribution of these cases in the province of Henan, China. Results: There were 88/103 (85%) patients with COVID-19 confirmed by RT-PCR testing. The overall sensitivity, specificity, PPV, and NPV were 93% (85%, 97%), 53% (27%, 77%), 92% (83%, 96%), and 42% (18%, 70%), respectively. Similar results were shown in both geographic regions. The respective sensitivity, specificity, PPV, and NPV for chest CT in the districts of Xinyang and Zhumadian (n = 56) were 92% (80%, 97%), 63% (26%, 90%), 93% (81%, 98%), and 56% (23%, 85%), while these indicators in the district of Anyang (n = 47) were 95% (81%, 99%), 43% (12%, 80%), 90% (76%, 97%), and 60% (17%-93%). There were no significant differences in the prevalence of positive examinations in the two geographic subgroups for CT (P = .423) or RT-PCR (P = .931). Conclusion: Although initial chest CT obtained at hospital presentation showed high sensitivity in patients under investigation for COVID-19 in the two geographic regions in Henan Province, the NPV was only modest, suggesting a low value of CT as a screening tool.© RSNA, 2020.

16.
Cell Rep Med ; 2(4): 100242, 2021 Apr 20.
Article in English | MEDLINE | ID: covidwho-1155661

ABSTRACT

Severe SARS-CoV-2 infection often leads to the development of acute respiratory distress syndrome (ARDS), with profound pulmonary patho-histological changes post-mortem. It is not clear whether ARDS from SARS-CoV-2 is similar to that observed in influenza H1N1, another common viral cause of lung injury. Here, we analyze specific ARDS regions of interest utilizing a spatial transcriptomic platform on autopsy-derived lung tissue from patients with SARS-CoV-2 (n = 3), H1N1 (n = 3), and a dual infected individual (n = 1). Enhanced gene signatures in alveolar epithelium, vascular tissue, and lung macrophages identify not only increased regional coagulopathy but also increased extracellular remodeling, alternative macrophage activation, and squamous metaplasia of type II pneumocytes in SARS-CoV-2. Both the H1N1 and dual-infected transcriptome demonstrated an enhanced antiviral response compared to SARS-CoV-2. Our results uncover regional transcriptional changes related to tissue damage/remodeling, altered cellular phenotype, and vascular injury active in SARS-CoV-2 and present therapeutic targets for COVID-19-related ARDS.

17.
Sci Rep ; 11(1): 4145, 2021 02 18.
Article in English | MEDLINE | ID: covidwho-1091456

ABSTRACT

The pandemic of Coronavirus Disease 2019 (COVID-19) is causing enormous loss of life globally. Prompt case identification is critical. The reference method is the real-time reverse transcription PCR (RT-PCR) assay, whose limitations may curb its prompt large-scale application. COVID-19 manifests with chest computed tomography (CT) abnormalities, some even before the onset of symptoms. We tested the hypothesis that the application of deep learning (DL) to 3D CT images could help identify COVID-19 infections. Using data from 920 COVID-19 and 1,073 non-COVID-19 pneumonia patients, we developed a modified DenseNet-264 model, COVIDNet, to classify CT images to either class. When tested on an independent set of 233 COVID-19 and 289 non-COVID-19 pneumonia patients, COVIDNet achieved an accuracy rate of 94.3% and an area under the curve of 0.98. As of March 23, 2020, the COVIDNet system had been used 11,966 times with a sensitivity of 91.12% and a specificity of 88.50% in six hospitals with PCR confirmation. Application of DL to CT images may improve both efficiency and capacity of case detection and long-term surveillance.


Subject(s)
COVID-19/diagnostic imaging , COVID-19/diagnosis , Tomography, X-Ray Computed/methods , COVID-19/epidemiology , COVID-19/metabolism , China/epidemiology , Data Accuracy , Deep Learning , Humans , Lung/pathology , Pneumonia/diagnostic imaging , Retrospective Studies , SARS-CoV-2/isolation & purification , Sensitivity and Specificity
18.
BMC Infect Dis ; 21(1): 176, 2021 Feb 15.
Article in English | MEDLINE | ID: covidwho-1085167

ABSTRACT

BACKGROUND: Epidemiological and clinical features of patients with corona virus disease 2019 (COVID-19) were well delineated. However, no researches described the patients complicated with pleural effusion (PE). In the present study, we aimed to clinically characterize the COVID-19 patients complicated with PE and to create a predictive model on the basis of PE and other clinical features to identify COVID-19 patients who may progress to critical condition. METHODS: This retrospective study examined 476 COVID-19 inpatients, involving 153 patients with PE and 323 without PE. The data on patients' past history, clinical features, physical checkup findings, laboratory results and chest computed tomography (CT) findings were collected and analyzed. LASSO regression analysis was employed to identify risk factors associated with the severity of COVID-19. RESULTS: Laboratory findings showed that patients with PE had higher levels of white blood cells, neutrophils, lactic dehydrogenase, C-reactive protein and D-dimer, and lower levels of lymphocytes, platelets, hemoglobin, partial pressure of oxygen and oxygen saturation. Meanwhile, patients with PE had higher incidence of severe or critical illness and mortality rate, and longer hospital stay time compared to their counterparts without pleural effusion. Moreover, LASSO regression analysis exhibited that pleural effusion, lactic dehydrogenase (LDH), D-dimer and total bilirubin (TBIL) might be risk factors for critical COVID-19. CONCLUSIONS: Pleural effusion could serve as an indicator for severe inflammation and poor clinical outcomes, and might be a complementary risk factor for critical type of COVID-19.


Subject(s)
COVID-19/pathology , Pleural Effusion/pathology , Adult , C-Reactive Protein/analysis , COVID-19/diagnostic imaging , COVID-19/physiopathology , China , Exudates and Transudates , Female , Humans , Male , Middle Aged , Pleural Effusion/physiopathology , Retrospective Studies , Risk Factors , SARS-CoV-2/physiology , Severity of Illness Index , Tomography, X-Ray Computed
19.
Environ Res ; 195: 110831, 2021 04.
Article in English | MEDLINE | ID: covidwho-1084272

ABSTRACT

The present work summarizes the major research findings related to wastewater-based epidemiology (WBE) study of COVID-19 and puts forward a conceptual framework, termed as "Surveillance of Wastewater for Early Epidemic Prediction (SWEEP)" for implementation of WBE. SWEEP framework is likely to tackle few practical issues related to WBE and simultaneously proposes refinements to the approach for better outcome and efficiency to save precious lives around the globe. It is observed that the present pandemic offers an opportunity for SWEEP to get included in routine urban water management to put the humankind at front to stop such pandemic in future or at least be prepared to fight against it. With global collaboration, SWEEP can be fine-tuned to meet diverse needs, making the present and future generations resilient to future viral outbreaks. Recent WBE studies conducted to check for the presence of SARS-CoV-2 in wastewater revealed that raw sewage samples tested positive to PCR-based assays while the treated samples showed absence of viral titers. Moreover, the lockdown had a positive impact on decreasing the viral loading in sewage. The proposed SWEEP protocol has an advantage over testifying individuals for predicting the stage of pandemic.


Subject(s)
COVID-19 , Communicable Disease Control , Humans , SARS-CoV-2 , Waste Water , Wastewater-Based Epidemiological Monitoring
20.
Front Immunol ; 12: 626235, 2021.
Article in English | MEDLINE | ID: covidwho-1082695

ABSTRACT

Objectives: The coordinated immune response of the host is the key of the successful combat of the body against SARS-CoV-2 infection and is decisive for the development and progression of COVID-19. In this study, we aimed to investigate whether the immunological phenotype of patients are associated with duration of illness in patients with severe COVID-19. Method: In this single-center study, 69 patients with severe or critical COVID-19 were recruited retrospectively. Immunological parameters including counts of white blood cells, neutrophils, lymphocytes, the neutrophil-to-lymphocyte ratio, and levels of circulating cytokines and cytokine receptors were screened for their association with disease severity, survival and duration of illness of COVID-19. Results: Our data confirmed previous results that neutrophil-to-lymphocyte ratio and circulating levels of IL-6 represent prominent biomarker for the prediction of disease severity and survival of COVID-19. However, this study shows for the first time that duration of illness in patients with severe COVID-19 is positively associated with serum levels of IL-8 (P=0.004) and soluble IL-2Rα (P=0.025). Conclusion: The significant association of duration of illness with circulating levels of IL-8 and soluble IL-2Rα in patients with severe COVID-19 implicates that neutrophils and T cells are involved in the evolution of COVID-19.


Subject(s)
COVID-19/blood , Interleukin-8/blood , Receptors, Interleukin-2/blood , Adult , Aged , Aged, 80 and over , Biomarkers/blood , COVID-19/immunology , Cytokines/blood , Cytokines/immunology , Female , Humans , Interleukin-8/immunology , Leukocyte Count , Lymphocyte Count , Lymphocytes/immunology , Male , Middle Aged , Neutrophils/immunology , Receptors, Interleukin-2/immunology , Retrospective Studies , SARS-CoV-2/isolation & purification , Severity of Illness Index
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