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1.
Aging (Albany NY) ; 13(undefined)2021 Dec 04.
Article in English | MEDLINE | ID: covidwho-1622953

ABSTRACT

Ongoing pandemic and potential resurgence of Coronavirus disease 2019 (COVID-19) has prompted urgent efforts to investigate the immunological memory of convalescent patients, especially in patients with active cancers. Here we performed single-cell RNA sequencing in peripheral blood samples of 3 healthy donors (HDs), 4 COVID-19 patients (Covs) and 4 COVID-19 patients with active gynecological tumor (TCs) pre- and post- anti-tumor treatment. All Covs patients had recovered from their acute infection. Interestingly, the molecular features of PBMCs in TCs are similar to that in Covs, suggesting that convalescent COVID-19 with gynecologic tumors do not have major immunological changes and may be protected against reinfection similar to COVID-19 patients without tumors. Moreover, the chemotherapy given to these patients mainly caused neutropenia, while having little effect on the proportion and functional phenotype of T and B cells, and T cell clonal expansion. Notably, anti-PD-L1 treatment massively increased cytotoxic scores of NK cells, and T cells, and facilitated clonal expansion of T cells in these patients. It is likely that T cells could protect patients from SARS-CoV-2 virus reinfection and anti-PD-L1 treatment can enhance the anti-viral activity of the T cells.

2.
Briefings in bioinformatics ; 2021.
Article in English | EuropePMC | ID: covidwho-1602648

ABSTRACT

Pneumonia, especially corona virus disease 2019 (COVID-19), can lead to serious acute lung injury, acute respiratory distress syndrome, multiple organ failure and even death. Thus it is an urgent task for developing high-efficiency, low-toxicity and targeted drugs according to pathogenesis of coronavirus. In this paper, a novel disease-related compound identification model–based capsule network (CapsNet) is proposed. According to pneumonia-related keywords, the prescriptions and active components related to the pharmacological mechanism of disease are collected and extracted in order to construct training set. The features of each component are extracted as the input layer of capsule network. CapsNet is trained and utilized to identify the pneumonia-related compounds in Qingre Jiedu injection. The experiment results show that CapsNet can identify disease-related compounds more accurately than SVM, RF, gcForest and forgeNet.

3.
Bioengineered ; 12(2): 12461-12469, 2021 12.
Article in English | MEDLINE | ID: covidwho-1585255

ABSTRACT

Severe mortality due to the COVID-19 pandemic resulted from the lack of effective treatment. Although COVID-19 vaccines are available, their side effects have become a challenge for clinical use in patients with chronic diseases, especially cancer patients. In the current report, we applied network pharmacology and systematic bioinformatics to explore the use of biochanin A in patients with colorectal cancer (CRC) and COVID-19 infection. Using the network pharmacology approach, we identified two clusters of genes involved in immune response (IL1A, IL2, and IL6R) and cell proliferation (CCND1, PPARG, and EGFR) mediated by biochanin A in CRC/COVID-19 condition. The functional analysis of these two gene clusters further illustrated the effects of biochanin A on interleukin-6 production and cytokine-cytokine receptor interaction in CRC/COVID-19 pathology. In addition, pathway analysis demonstrated the control of PI3K-Akt and JAK-STAT signaling pathways by biochanin A in the treatment of CRC/COVID-19. The findings of this study provide a therapeutic option for combination therapy against COVID-19 infection in CRC patients.


Subject(s)
Anticarcinogenic Agents/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Colorectal Neoplasms/drug therapy , Gene Expression Regulation, Neoplastic/drug effects , Genistein/therapeutic use , Phytoestrogens/therapeutic use , Atlases as Topic , COVID-19/immunology , COVID-19/pathology , COVID-19/virology , Colorectal Neoplasms/immunology , Colorectal Neoplasms/pathology , Colorectal Neoplasms/virology , Cyclin D1/genetics , Cyclin D1/immunology , ErbB Receptors/genetics , ErbB Receptors/immunology , Humans , Interleukin-1alpha/genetics , Interleukin-1alpha/immunology , Interleukin-2/genetics , Interleukin-2/immunology , Janus Kinases/genetics , Janus Kinases/immunology , Metabolic Networks and Pathways/drug effects , Metabolic Networks and Pathways/genetics , Molecular Targeted Therapy/methods , Multigene Family , PPAR gamma/genetics , PPAR gamma/immunology , Pharmacogenetics/methods , Phosphatidylinositol 3-Kinases/genetics , Phosphatidylinositol 3-Kinases/immunology , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/immunology , Receptors, Interleukin-6/genetics , Receptors, Interleukin-6/immunology , SARS-CoV-2/drug effects , SARS-CoV-2/growth & development , SARS-CoV-2/pathogenicity , STAT Transcription Factors/genetics , STAT Transcription Factors/immunology , Signal Transduction
4.
BMC Microbiol ; 21(1): 351, 2021 12 18.
Article in English | MEDLINE | ID: covidwho-1582113

ABSTRACT

BACKGROUND: The 2019 novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 virus (SARS-CoV-2) is a current worldwide threat for which the immunological features after infection need to be investigated. The aim of this study was to establish a highly sensitive and quantitative detection method for SARS-CoV-2 IgG antibody and to compare the antibody reaction difference in patients with different disease severity. RESULTS: Recombinant SARS-CoV-2 nucleocapsid protein was expressed in Escherichia coli and purified to establish an indirect IgG ELISA detection system. The sensitivity of the ELISA was 100% with a specificity of 96.8% and a 98.3% concordance when compared to a colloidal gold kit, in addition, the sensitivity of the ELISA was 100% with a specificity of 98.9% and a 99.4% concordance when compared to a SARS-CoV-2 spike S1 protein IgG antibody ELISA kit. The increased sensitivity resulted in a higher rate of IgG antibody detection for COVID-19 patients. Moreover, the quantitative detection can be conducted with a much higher serum dilution (1:400 vs 1:10, 1:400 vs 1:100). The antibody titers of 88 patients with differing COVID-19 severity at their early convalescence ranged from 800 to 102,400, and the geometric mean titer for severe and critical cases, moderate cases, asymptomatic and mild cases was 51,203, 20,912, and 9590 respectively. CONCLUSION: The development of a highly sensitive ELISA system for the detection of SARS-CoV-2 IgG antibodies is described herein. This system enabled a quantitative study of rSARS-CoV-2-N IgG antibody titers in COVID-19 patients, the occurrence of higher IgG antibody titers were found to be correlated with more severe cases.


Subject(s)
Antibodies, Viral/blood , COVID-19/diagnosis , Coronavirus Nucleocapsid Proteins/immunology , Immunoglobulin G/blood , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/immunology , Child , Child, Preschool , China , Enzyme-Linked Immunosorbent Assay , Female , Humans , Infant , Male , Middle Aged , Phosphoproteins/immunology , SARS-CoV-2 , Sensitivity and Specificity , Young Adult
5.
Small ; : e2105832, 2021 Dec 16.
Article in English | MEDLINE | ID: covidwho-1574099

ABSTRACT

Recently, lipid nanoparticles (LNPs) have attracted attention due to their emergent use for COVID-19 mRNA vaccines. The success of LNPs can be attributed to ionizable lipids, which enable functional intracellular delivery. Previously, the authors established an automated high-throughput platform to screen ionizable lipids and identified that the LNPs generated using this automated technique show comparable or increased mRNA functional delivery in vitro as compared to LNPs prepared using traditional microfluidics techniques. In this study, the authors choose one benchmark lipid, DLin-MC3-DMA (MC3), and investigate whether the automated formulation technique can enhance mRNA functional delivery in vivo. Interestingly, a 4.5-fold improvement in mRNA functional delivery in vivo by automated LNPs as compared to LNPs formulated by conventional microfluidics techniques, is observed. Mechanistic studies reveal that particles with large size accommodate more mRNA per LNP, possess more hydrophobic surface, are more hemolytic, bind a larger protein corona, and tend to accumulate more in macropinocytosomes, which may quantitatively benefit mRNA cytosolic delivery. These data suggest that mRNA loading per particle is a critical factor that accounts for the enhanced mRNA functional delivery of automated LNPs. These mechanistic findings provide valuable insight underlying the enhanced mRNA functional delivery to accelerate future mRNA LNP product development.

6.
Aging (Albany NY) ; 13(undefined)2021 Dec 04.
Article in English | MEDLINE | ID: covidwho-1551970

ABSTRACT

Ongoing pandemic and potential resurgence of Coronavirus disease 2019 (COVID-19) has prompted urgent efforts to investigate the immunological memory of convalescent patients, especially in patients with active cancers. Here we performed single-cell RNA sequencing in peripheral blood samples of 3 healthy donors (HDs), 4 COVID-19 patients (Covs) and 4 COVID-19 patients with active gynecological tumor (TCs) pre- and post- anti-tumor treatment. All Covs patients had recovered from their acute infection. Interestingly, the molecular features of PBMCs in TCs are similar to that in Covs, suggesting that convalescent COVID-19 with gynecologic tumors do not have major immunological changes and may be protected against reinfection similar to COVID-19 patients without tumors. Moreover, the chemotherapy given to these patients mainly caused neutropenia, while having little effect on the proportion and functional phenotype of T and B cells, and T cell clonal expansion. Notably, anti-PD-L1 treatment massively increased cytotoxic scores of NK cells, and T cells, and facilitated clonal expansion of T cells in these patients. It is likely that T cells could protect patients from SARS-CoV-2 virus reinfection and anti-PD-L1 treatment can enhance the anti-viral activity of the T cells.

7.
Building and Environment ; : 108555, 2021.
Article in English | ScienceDirect | ID: covidwho-1507723

ABSTRACT

Infectious diseases have caused significant physical harm to humans as well as enormous economic losses over the years. Effective ventilation and distribution of fresh air could help to reduce indoor cross-infection. The computational fluid dynamics (CFD) method was used in this paper to investigate airborne transmission with seven different air distribution methods. The revised Wells-Riley model, which took into account the non-uniform air distribution generated with the methods, was used to calculate the infection probability in an office room shared by ten occupants for 4 h. One of the occupants was an infector. The significance of the infector's location was studied. The obtained infection probability was compared to that obtained in the case of complete air mixing, which is uncommon in practice. Under specified conditions of this study, personalized ventilation (PV) performed the best in terms of preventing cross-infection, followed by displacement ventilation (DV), impinging jet ventilation (IJV), stratum ventilation (SV) and wall attachment ventilation (WAV). The number of infected occupants was reduced below the number obtained under the complete mixing assumption by using these air distribution methods. Mixing ventilation (MV) and diffuse ceiling ventilation (DCV) exhibited the worst performance. In comparison to the case of complete mixing the infection probability for seven out of nine susceptible occupants was higher with MV and for all occupants in the case of DCV. In SV, the position of the infector had a clear impact on the infection probability of susceptible individuals. WAV may perform better in practice if the system is well designed. The location of the exhaust outlets had a significant impact on the infection probability for DCV.

8.
Front Microbiol ; 12: 730807, 2021.
Article in English | MEDLINE | ID: covidwho-1468351

ABSTRACT

Three new tetramic acid derivatives (1-3) and a new polyketide (4) along with eight known compounds (5-12) were isolated from cultures of the deep-sea-derived fungus Penicillium sp. SCSIO06868. Four new structures were elucidated by analysis of one-dimensional/two-dimensional nuclear magnetic resonance (NMR) data and high-resolution electrospray ionization mass spectrometry. Their absolute configurations were established by X-ray crystallography analysis and comparison of the experimental and reported electronic circular dichroism (ECD) values or specific optical rotation. Compound 3 exhibited potent, selective inhibitory activities against Staphylococcus aureus and methicillin-resistant S. aureus with minimum inhibitory concentration values of both 2.5 µg/ml. Also, compound 3 showed weak antiviral activity against severe acute respiratory syndrome coronavirus 2 main protease, which was responsible for the coronavirus disease 2019 pandemic.

9.
mBio ; 12(5): e0137221, 2021 10 26.
Article in English | MEDLINE | ID: covidwho-1462899

ABSTRACT

Interleukin6 (IL-6) is a key driver of hyperinflammation in COVID-19, and its level strongly correlates with disease progression. To investigate whether variability in COVID-19 severity partially results from differential IL-6 expression, functional single-nucleotide polymorphisms (SNPs) of IL-6 were determined in Chinese COVID-19 patients with mild or severe illness. An Asian-common IL-6 haplotype defined by promoter SNP rs1800796 and intronic SNPs rs1524107 and rs2066992 correlated with COVID-19 severity. Homozygote carriers of C-T-T variant haplotype were at lower risk of developing severe symptoms (odds ratio, 0.256; 95% confidence interval, 0.088 to 0.739; P = 0.007). This protective haplotype was associated with lower levels of IL-6 and its antisense long noncoding RNA IL-6-AS1 by cis-expression quantitative trait loci analysis. The differences in expression resulted from the disturbance of stimulus-dependent bidirectional transcription of the IL-6/IL-6-AS1 locus by the polymorphisms. The protective rs2066992-T allele disrupted a conserved CTCF-binding locus at the enhancer elements of IL-6-AS1, which transcribed antisense to IL-6 and induces IL-6 expression in inflammatory responses. As a result, carriers of the protective allele had significantly reduced IL-6-AS1 expression and attenuated IL-6 induction in response to acute inflammatory stimuli and viral infection. Intriguingly, this low-producing variant that is endemic to present-day Asia was found in early humans who had inhabited mainland Asia since ∼40,000 years ago but not in other ancient humans, such as Neanderthals and Denisovans. The present study suggests that an individual's IL-6 genotype underlies COVID-19 outcome and may be used to guide IL-6 blockade therapy in Asian patients. IMPORTANCE Overproduction of cytokine interleukin-6 (IL-6) is a hallmark of severe COVID-19 and is believed to play a critical role in exacerbating the excessive inflammatory response. Polymorphisms in IL-6 account for the variability of IL-6 expression and disparities in infectious diseases, but its contribution to the clinical presentation of COVID-19 has not been reported. Here, we investigated IL-6 polymorphisms in severe and mild cases of COVID-19 in a Chinese population. The variant haplotype C-T-T, represented by rs1800796, rs1524107, and rs2066992 at the IL-6 locus, was reduced in patients with severe illness; in contrast, carriers of the wild-type haplotype G-C-G had higher risk of severe illness. Mechanistically, the protective variant haplotype lost CTCF binding at the IL-6 intron and responded poorly to inflammatory stimuli, which may protect the carriers from hyperinflammation in response to acute SARS-CoV-2 infection. These results point out the possibility that IL-6 genotypes underlie the differential viral virulence during the outbreak of COVID-19. The risk loci we identified may serve as a genetic marker to screen high-risk COVID-19 patients.


Subject(s)
COVID-19/metabolism , COVID-19/prevention & control , Interleukin-6/metabolism , A549 Cells , Genotype , Haplotypes/genetics , HeLa Cells , Humans , Polymorphism, Single Nucleotide/genetics , Real-Time Polymerase Chain Reaction , Software
10.
J Med Virol ; 92(9): 1681-1683, 2020 09.
Article in English | MEDLINE | ID: covidwho-1384206

ABSTRACT

As an emerging infectious disease, the clinical course and virological course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remain to be further investigated. In this case report, we described a case of SARS-CoV-2 infection with the clinical course for more than 2 months. This patient had recovered from pneumonia after treatment. The viral RNA of throat swabs became negative and the viral-specific antibodies were produced during the recovery period. However, the viral RNA reappeared and additionally persisted in throat swabs for more than 40 days. In addition, the viral RNA was detected in multiple types of specimens with extremely high titers in the saliva. In conclusion, these findings indicate that SARS-CoV-2 can cause a long clinical course. The coexistence of viral RNA and viral-specific antibodies may imply an immune evasion of SARS-CoV-2 from the host's immune system.


Subject(s)
COVID-19/diagnosis , COVID-19/virology , RNA, Viral , SARS-CoV-2/genetics , Virus Shedding , Adult , Biomarkers , Disease Management , Humans , Male , Symptom Assessment , Time Factors , Tomography, X-Ray Computed
11.
Signal Transduct Target Ther ; 6(1): 289, 2021 07 29.
Article in English | MEDLINE | ID: covidwho-1333903

ABSTRACT

Pregnant women are generally more susceptible to viral infection. Although the impact of SARS-CoV-2 in pregnancy remains to be determined, evidence indicates that the risk factors for severe COVID-19 are similar in pregnancy to the general population. Here we systemically analyzed the clinical characteristics of pregnant and non-pregnant female COVID-19 patients who were hospitalized during the same period and found that pregnant patients developed marked lymphopenia and higher inflammation evident by higher C-reactive protein and IL-6. To elucidate the pathways that might contribute to immunopathology or protective immunity against COVID-19 during pregnancy, we applied single-cell mRNA sequencing to profile peripheral blood mononuclear cells from four pregnant and six non-pregnant female patients after recovery along with four pregnant and three non-pregnant healthy donors. We found normal clonal expansion of T cells in the pregnant patients, heightened activation and chemotaxis in NK, NKT, and MAIT cells, and differential interferon responses in the monocyte compartment. Our data present a unique feature in both innate and adaptive immune responses in pregnant patients recovered from COVID-19.


Subject(s)
Adaptive Immunity , COVID-19/immunology , Immunity, Innate , Lymphocytes/immunology , Pregnancy Complications, Infectious/immunology , SARS-CoV-2/immunology , Adult , C-Reactive Protein/immunology , Female , Humans , Interleukin-6/immunology , Pregnancy , Retrospective Studies , Sequence Analysis, RNA , Single-Cell Analysis
12.
Nat Commun ; 12(1): 4543, 2021 07 27.
Article in English | MEDLINE | ID: covidwho-1328844

ABSTRACT

The outbreak of coronavirus disease 2019 (COVID-19) is a global health emergency. Various omics results have been reported for COVID-19, but the molecular hallmarks of COVID-19, especially in those patients without comorbidities, have not been fully investigated. Here we collect blood samples from 231 COVID-19 patients, prefiltered to exclude those with selected comorbidities, yet with symptoms ranging from asymptomatic to critically ill. Using integrative analysis of genomic, transcriptomic, proteomic, metabolomic and lipidomic profiles, we report a trans-omics landscape for COVID-19. Our analyses find neutrophils heterogeneity between asymptomatic and critically ill patients. Meanwhile, neutrophils over-activation, arginine depletion and tryptophan metabolites accumulation correlate with T cell dysfunction in critical patients. Our multi-omics data and characterization of peripheral blood from COVID-19 patients may thus help provide clues regarding pathophysiology of and potential therapeutic strategies for COVID-19.


Subject(s)
COVID-19/genetics , COVID-19/metabolism , Critical Illness , Genomics/methods , Humans , Lipidomics/methods , Metabolomics/methods , Neutrophils/metabolism , Transcriptome/genetics
13.
Nat Commun ; 12(1): 3501, 2021 06 09.
Article in English | MEDLINE | ID: covidwho-1263489

ABSTRACT

The characteristics of COVID-19 patients with persistent SARS-CoV-2 infection are not yet well described. Here, we compare the clinical and molecular features of patients with long duration of viral shedding (LDs) with those from patients with short duration patients (SDs), and healthy donors (HDs). We find that several cytokines and chemokines, such as interleukin (IL)-2, tumor necrosis factor (TNF) and lymphotoxin α (LT-α) are present at lower levels in LDs than SDs. Single-cell RNA sequencing shows that natural killer (NK) cells and CD14+ monocytes are reduced, while regulatory T cells are increased in LDs; moreover, T and NK cells in LDs are less activated than in SDs. Importantly, most cells in LDs show reduced expression of ribosomal protein (RP) genes and related pathways, with this inversed correlation between RP levels and infection duration further validated in 103 independent patients. Our results thus indicate that immunosuppression and low RP expression may be related to the persistence of the viral infection in COVID-19 patients.


Subject(s)
COVID-19/immunology , SARS-CoV-2/pathogenicity , B-Lymphocytes/metabolism , B-Lymphocytes/pathology , COVID-19/virology , Cytokines/blood , Gene Expression Profiling , Humans , Killer Cells, Natural/metabolism , Killer Cells, Natural/pathology , Leukocytes, Mononuclear/pathology , Lymphocyte Activation/genetics , Lymphocyte Subsets/metabolism , Lymphocyte Subsets/pathology , Ribosomal Proteins/genetics , SARS-CoV-2/isolation & purification , Signal Transduction/genetics , T-Lymphocytes/metabolism , T-Lymphocytes/pathology , Virus Shedding
14.
Zhongguo Huanjing Kexue = China Environmental Science ; 41(5):2056, 2021.
Article in English | ProQuest Central | ID: covidwho-1257729

ABSTRACT

Based on the OMI satellite data, the characteristics of atmospheric ozone sensitivity in Fujian province and its nice municipalities during the period of COVID-19 epidemic were assessed with HCHO and NO2 vertical column densities as proxies for ozone sensitivity. The results showed that Fujian Province was dominated by VOCs-limited regime before the pandemic with the controlled area proportion of 46.5%. The other two regimes: NOx-VOCs-limited regime and NOx-limited regime, controlled 25.0% and 28.5% of the area, respectively. The area proportion controlled by VOXs-limited regime was highest in Xiamen and lowest in Nanping. During the period with strict pandemic control policies, VOXs-limited regime, NOx-VOCs-limited regime and NOx-limited regime controlled 29.5%, 21.1%, and 49.4% of the area, respectively. The area proportion controlled by NOx-limited regime was highest in Ningde and lowest in Putian. During the stable period, VOXs-limited regime, NOx-VOCs-limited regime and NOx-limited regime controlled 23.1%, 29.1%, and 47.8% of the area, respectively. NOx-limited regime was the dominant regime with highest area proportion controlled in Nanping and lowest area proportion in Xiamen. Compared with the before pandemic period, the area proportion of Xiamen controlled by VOCs-limited regime was obviously reduced(38.1% less) during the period with strict control policies, and the lowest reduction was in Sanming with a moderate decrease of 7.9%. According to the conversion results, Putian, Quanzhou, and Xiamen were categorized into the first city group where changes in ozone sensitivity were jointly influenced by its precursors including formaldehyde(HCHO) and nitrogen dioxide(NO2), while other cities could be categorized into the second group where ozone sensitivities were mainly affected by NO2 column concentrations. Therefore, effective strategies for ozone reduction would be more complex in the first group of cities.

16.
Front Immunol ; 12: 675476, 2021.
Article in English | MEDLINE | ID: covidwho-1236675

ABSTRACT

Pregnant women are generally more susceptible to viral infection. Although the impact of SARS-CoV-2 on pregnant women remains to be determined, evidence indicates that risks of adverse clinical outcomes are similar in pregnancy to the general population. Here we analyzed clinical symptoms and outcomes of 20 pregnant and 299 reproductive-aged non-pregnant female COVID-19 patients who were hospitalized during the same period. Laboratory measurements were compared among mild cases and healthy pregnant women. Our study found that pregnant patients showed enhanced innate immune response evident by higher neutrophils and C-reactive protein. Cytokines, chemokines, and growth factors (CCGFs) profiles from 11 pregnant and 4 non-pregnant COVID-19 patients and 10 healthy pregnant female patients, and lymphocyte subsets analysis of 7 pregnant patients and 19 non-pregnant patients, indicate suppressed cytokine storm and potential enhanced CD8+ T cell and NK cell activity in pregnant patients with COVID-19, which may be essential in contributing to the unique anti-SARS-CoV-2 response in pregnancy.


Subject(s)
COVID-19/immunology , Pregnancy Complications, Infectious/immunology , Adult , COVID-19/diagnosis , COVID-19/pathology , COVID-19/virology , Cytokines/immunology , Female , Hospitalization , Humans , Lymphocyte Subsets/immunology , Pregnancy , Pregnancy Complications, Infectious/diagnosis , Pregnancy Complications, Infectious/pathology , Pregnancy Complications, Infectious/virology , SARS-CoV-2
17.
Computers & Industrial Engineering ; : 107386, 2021.
Article in English | ScienceDirect | ID: covidwho-1213084

ABSTRACT

Service platform has developed rapidly in car-sharing, consumers often buy or own cars but not fully utilize and share them. Since the coronavirus pandemic has affected sales and people’s attitudes towards car-sharing, which brought both opportunities and challenges to the platform and changed the operating mode of manufacturers, some traditional manufacturers have motivated to cooperate with third-party platform. In this paper, we develop an analytical framework to examine the pricing decisions and optimal mode selection of manufacturer under the COVID-19 epidemic. Considering the supply chain consists of a manufacturer and a third-party sharing platform. We analyze three scenarios including no sharing, customers-to-customers, and mixed sharing, then employ a game theoretic approach to get equilibrium solutions and analytically derive the optimal mode choice. Our analysis shows that when the operation and maintenance cost is low, manufacturer will join the third-party platform, and the sharing price increase in operation and maintenance cost, while the selling price decrease in operation and maintenance cost. When the value perception factor less than the threshold, the manufacturer will retain sales channel, and the selling demand decrease in value perception factor in the growing market, the sharing demand has the same trend, vice versa. Furthermore, we find that if the operation and maintenance cost is low and value perception factor is high, mixed sharing is the best choice for the manufacturer, while the manufacturer will choose no car-sharing when the value perception factor is relatively low.

18.
Ann Intern Med ; 174(4): 453-461, 2021 04.
Article in English | MEDLINE | ID: covidwho-1201442

ABSTRACT

BACKGROUND: The understanding of viral positivity and seroconversion during the course of coronavirus disease 2019 (COVID-19) is limited. OBJECTIVE: To describe patterns of viral polymerase chain reaction (PCR) positivity and evaluate their correlations with seroconversion and disease severity. DESIGN: Retrospective cohort study. SETTING: 3 designated specialty care centers for COVID-19 in Wuhan, China. PARTICIPANTS: 3192 adult patients with COVID-19. MEASUREMENTS: Demographic, clinical, and laboratory data. RESULTS: Among 12 780 reverse transcriptase PCR tests for severe acute respiratory syndrome coronavirus 2 that were done, 24.0% had positive results. In 2142 patients with laboratory-confirmed COVID-19, the viral positivity rate peaked within the first 3 days. The median duration of viral positivity was 24.0 days (95% CI, 18.9 to 29.1 days) in critically ill patients and 18.0 days (CI, 16.8 to 19.1 days) in noncritically ill patients. Being critically ill was an independent risk factor for longer viral positivity (hazard ratio, 0.700 [CI, 0.595 to 0.824]; P < 0.001). In patients with laboratory-confirmed COVID-19, the IgM-positive rate was 19.3% in the first week, peaked in the fifth week (81.5%), and then decreased steadily to around 55% within 9 to 10 weeks. The IgG-positive rate was 44.6% in the first week, reached 93.3% in the fourth week, and then remained high. Similar antibody responses were seen in clinically diagnosed cases. Serum inflammatory markers remained higher in critically ill patients. Among noncritically ill patients, a higher proportion of those with persistent viral positivity had low IgM titers (<100 AU/mL) during the entire course compared with those with short viral positivity. LIMITATION: Retrospective study and irregular viral and serology testing. CONCLUSION: The rate of viral PCR positivity peaked within the initial few days. Seroconversion rates peaked within 4 to 5 weeks. Dynamic laboratory index changes corresponded well to clinical signs, the recovery process, and disease severity. Low IgM titers (<100 AU/mL) are an independent risk factor for persistent viral positivity. PRIMARY FUNDING SOURCE: None.


Subject(s)
COVID-19 Testing , COVID-19/diagnosis , Pneumonia, Viral/diagnosis , Pneumonia, Viral/virology , SARS-CoV-2 , Viral Load , Adult , Aged , Antibodies, Viral/blood , COVID-19/epidemiology , China/epidemiology , Critical Illness , Female , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/epidemiology , Retrospective Studies , Seroconversion , Severity of Illness Index
19.
Front Psychiatry ; 12: 653709, 2021.
Article in English | MEDLINE | ID: covidwho-1181405

ABSTRACT

[This corrects the article DOI: 10.3389/fpsyt.2020.00386.].

20.
Front Psychiatry ; 12: 653709, 2021.
Article in English | MEDLINE | ID: covidwho-1178046

ABSTRACT

[This corrects the article DOI: 10.3389/fpsyt.2020.00386.].

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