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1.
Front Microbiol ; 12: 790714, 2021.
Article in English | MEDLINE | ID: covidwho-1594191

ABSTRACT

Virus infection has been consistently threatening public health. The cyclic GMP-AMP synthase (cGAS)-Stimulator of Interferon Genes (STING) pathway is a critical defender to sense various pathogens and trigger innate immunity of mammalian cells. cGAS recognizes the pathogenic DNA in the cytosol and then synthesizes 2'3'-cyclic GMP-AMP (2'3'cGAMP). As the second messenger, cGAMP activates STING and induces the following cascade to produce type I interferon (IFN-I) to protect against infections. However, viruses have evolved numerous strategies to hinder the cGAS-STING signal transduction, promoting their immune evasion. Here we outline the current status of the viral evasion mechanism underlying the regulation of the cGAS-STING pathway, focusing on how post-transcriptional modifications, viral proteins, and non-coding RNAs involve innate immunity during viral infection, attempting to inspire new targets discovery and uncover potential clinical antiviral treatments.

2.
Journal of Transportation Safety & Security ; : 1-21, 2021.
Article in English | Taylor & Francis | ID: covidwho-1585296
3.
Vaccines ; 10(1):72, 2022.
Article in English | MDPI | ID: covidwho-1580330

ABSTRACT

The emergence of SARS-CoV-2 variants may impact the effectiveness of vaccines, while heterologous vaccine strategy is considered to provide better protection. The immunogenicity of an mRNA-inactivated virus vaccine against the SARS-CoV-2 wild-type (WT) and variants was evaluated in the study. SARS-CoV-2 naïve adults (n = 123) were recruited and placed in the following groups: BNT162b2, CoronaVac or BNT162b2-CoronaVac (Combo) Group. Blood samples were collected to measure neutralization antibodies (NAb) by a live virus microneutralization assay (vMN) and surrogate NAb test. The day 56 vMN geometric mean titre (GMT) was 26.2 [95% confident interval (CI), [22.3–30.9] for Combo, 136.9 (95% CI, 104.2–179.7) for BNT162b2, and 14.7 (95% CI, 11.6–18.6) for CoronaVac groups. At 6 months post-first dose, the GMT declined to 8.0, 28.8 and 7.1 in the Combo, BNT162b2 and CoronaVac groups, respectively. Three groups showed reduced neutralizing activity against D614G, beta, theta and delta variants. At day 56 GMT (74.6) and month 6 GMT (22.7), the delta variant in the BNT162b2 group was higher than that in the Combo (day 56, 7.4;month 6, 5.5) and CoronaVac groups (day 56, 8.0;month 6, 5) (p < 0.0001). Furthermore, the mean surrogate NAb value on day 56 in the BNT162b2 group was 594.7 AU/mL and higher than 40.5 AU/mL in Combo and 38.8 AU/mL in CoronaVac groups (p < 0.0001). None of the participants developed severe adverse events, and all other adverse events were self-limiting. The Combo vaccination strategy was safe. The overall vaccine immunogenicity at day 56 and 6 months were comparable to the homologous CoronaVac group but inferior to the homologous BNT162b2 group, against both the WT and all variants. Furthermore, the antibody response of vaccines waned at 6 months and thereby, a third dose of the vaccine is needed for these vaccines.

4.
Electrochim Acta ; 404: 139766, 2022 Feb 01.
Article in English | MEDLINE | ID: covidwho-1587870

ABSTRACT

Tracking and monitoring of low concentrations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can effectively control asymptomatic transmission of current coronavirus disease 2019 (COVID-19) in the early stages of infection. Here, we highlight an electrochemical immunosensor for sensitive detection of SARS-CoV-2 antigen marker spike protein. The surface-clean Pd-Au nanosheets as a substrate for efficient sensing and signal output have been synthesized. The morphology, chemical states and excellent stable electrochemical properties of this surface-clean heterostructures have been studied. Functionalized superparamagnetic nanoparticles (MNPs) were introduced as sample separators and signal amplifiers. This biosensor was tested in phosphate buffered saline (PBS) and nasopharyngeal samples. The results showed that the sensor has a wide linear dynamic range (0.01 ng mL-1 to 1000 ng mL-1) with a low detection limit (0.0072 ng mL-1), which achieved stable and sensitive detection of the spike protein. Therefore, this immunosensing method provides a promising electrochemical measurement tool, which can furnish ideas for early screening and the reasonable optimization of detection methods of SARS-CoV-2.

5.
Preprint | EuropePMC | ID: ppcovidwho-296805

ABSTRACT

The Omicron (B.1.1.529) variant of SARS-CoV-2 was only recently detected in southern Africa, but its subsequent spread has been extensive, both regionally and globally1. It is expected to become dominant in the coming weeks2, probably due to enhanced transmissibility. A striking feature of this variant is the large number of spike mutations3 that pose a threat to the efficacy of current COVID-19 vaccines and antibody therapies4. This concern is amplified by the findings from our study. We found B.1.1.529 to be markedly resistant to neutralization by serum not only from convalescent patients, but also from individuals vaccinated with one of the four widely used COVID-19 vaccines. Even serum from persons vaccinated and boosted with mRNA-based vaccines exhibited substantially diminished neutralizing activity against B.1.1.529. By evaluating a panel of monoclonal antibodies to all known epitope clusters on the spike protein, we noted that the activity of 18 of the 19 antibodies tested were either abolished or impaired, including ones currently authorized or approved for use in patients. In addition, we also identified four new spike mutations (S371L, N440K, G446S, and Q493R) that confer greater antibody resistance to B.1.1.529. The Omicron variant presents a serious threat to many existing COVID-19 vaccines and therapies, compelling the development of new interventions that anticipate the evolutionary trajectory of SARS-CoV-2.

7.
Signal Transduct Target Ther ; 6(1): 414, 2021 Dec 06.
Article in English | MEDLINE | ID: covidwho-1556321

ABSTRACT

Azvudine (FNC) is a nucleoside analog that inhibits HIV-1 RNA-dependent RNA polymerase (RdRp). Recently, we discovered FNC an agent against SARS-CoV-2, and have taken it into Phase III trial for COVID-19 patients. FNC monophosphate analog inhibited SARS-CoV-2 and HCoV-OC43 coronavirus with an EC50 between 1.2 and 4.3 µM, depending on viruses or cells, and selective index (SI) in 15-83 range. Oral administration of FNC in rats revealed a substantial thymus-homing feature, with FNC triphosphate (the active form) concentrated in the thymus and peripheral blood mononuclear cells (PBMC). Treating SARS-CoV-2 infected rhesus macaques with FNC (0.07 mg/kg, qd, orally) reduced viral load, recuperated the thymus, improved lymphocyte profiles, alleviated inflammation and organ damage, and lessened ground-glass opacities in chest X-ray. Single-cell sequencing suggested the promotion of thymus function by FNC. A randomized, single-arm clinical trial of FNC on compassionate use (n = 31) showed that oral FNC (5 mg, qd) cured all COVID-19 patients, with 100% viral ribonucleic acid negative conversion in 3.29 ± 2.22 days (range: 1-9 days) and 100% hospital discharge rate in 9.00 ± 4.93 days (range: 2-25 days). The side-effect of FNC is minor and transient dizziness and nausea in 16.12% (5/31) patients. Thus, FNC might cure COVID-19 through its anti-SARS-CoV-2 activity concentrated in the thymus, followed by promoted immunity.

8.
Preprint in English | EuropePMC | ID: ppcovidwho-296435

ABSTRACT

OBJECTIVE : To assess the efficacy and safety of tenecteplase in patients with pulmonary embolism (PE). METHODS : We completed the literature search on May 31, 2021 using PubMed, EMBASE and the Web of Science. Analyses were conducted according to PE risk stratification, study design and duration of follow-up. The pooled risk ratios (RRs) and its 95% confident intervals (CIs) for death and major bleeding were calculated using a random-effect model. RESULTS : A total of six studies, with four randomized controlled trials (RCTs) and two cohort studies, were included in this study out of the 160 studies retrieved. For patients with high-risk PE, tenecteplase increased 30-day survival rate (16% vs 6%;P=0.005) and did not increase the incidence of bleeding (6% vs 5%;P=0.73). For patients with intermediate-risk PE, four RCTs suggested that tenecteplase reduced right ventricular insufficiency at 24h early in the onset and the incidence of hemodynamic failure without affecting mortality in a short/long-term [<30 days RR=0.83, 95% CI (0.47, 1.46);≥30 days RR=1.04, 95% CI (0.88, 1.22)]. However, tenecteplase was associated with high bleeding risk [<30 days RR=1.79, 95% CI (1.61, 2.00);≥30 days RR=1.28, 95% CI (0.62, 2.64)]. CONCLUSIONS : Tenecteplase may represent a promising candidate for patients with intermediate/high risk PE. Furthermore, tenecteplase may be preferable in the COVID-19 pandemic due to its all-at-once administration.

9.
Preprint in English | EuropePMC | ID: ppcovidwho-296366

ABSTRACT

Background: Assessing the humoral immunity of patients with underlying diseases after being infected with SARS-CoV-2 is essential for determining effective prevention and control strategies. The purpose of this study is to investigate whether underlying disease is a risk factor for SARS-CoV-2 infection, reveal the seroprevalence of people with underlying disease and the characteristics of dynamic changes in anti-SARS-CoV-2 antibodies, and provide evidence for the scientific formulation of COVID-19 vaccination strategies. Methods: : The probability ratio sampling method was adopted to systematically select 100 communities from 13 districts in Wuhan, China, followed by a random selection of households from 100 communities according to a list provided by the local government. Individuals who have lived in Wuhan for at least 14 days since December 2019 and were ≥40 years old were included. Individuals with other serious diseases besides COVID-19, from whom a sample could not be obtained or refused to participate, were excluded. All eligible subjects signed a written informed consent form and completed a standardized electronic questionnaire before being enrolled in the group. From April 9–13, 2020, venous blood samples were collected from all individuals;from June 11–13, 2020, and from October 9–December 5, 2020, all positive and matched negative families were followed up. Results: : The seroprevalence of SARS-CoV-2 in people with underlying diseases was 6.30% (95% CI [5.09-7.52]), and that of people without underlying diseases was 6.12% (95% CI [5.33-6.91]). Among people with underlying diseases, retirees, health workers, and people who have been exposed to fever or respiratory symptoms since December 2019 were more likely to be infected with SARS-CoV-2. The IgG titer of people with underlying disease decreased significantly over time (P <0.05), but the neutralizing antibody titer remained relatively stable throughout the follow-up period. There was no significant difference between the IgG titer decline rate of people with underlying disease and those without. The IgG titer of people with underlying disease and asymptomatic infection was lower than that in symptomatic infection. Conclusion: These findings imply that vaccination strategies for people with and without underlying diseases may not require special adjustments.

10.
Water ; 13(22):3183, 2021.
Article in English | MDPI | ID: covidwho-1512755

ABSTRACT

In this study, the product attributes of cruise tours are distinguished into on-board activities, leisure space, cabin comfort, Michelin restaurant, and refund mechanism, and the multi-attribute utility model of cruise tours is constructed using the choice experiment (CE) method. Of the 575 questionnaires distributed, 439 were valid, with an effective recovery rate of 76.3%. The results revealed the following: (1) when cruisers travel, what they value the most is the quality of service on board, followed by the facilities on board;(2) passengers’ preferences for comfortable pool space and more activities on board are negatively significant, indicating that they do not prefer to add these amenities and experiences to the cruise ship;(3) passengers are willing to pay extra to upgrade the interior cabin to one with a view and to experience the Michelin restaurant;and (4) influenced by the COVID-19 pandemic, cruisers are more willing to manage their own health. Moreover, the pandemic does not reduce their willingness to travel by cruise.

11.
Preprint in English | EuropePMC | ID: ppcovidwho-291992

ABSTRACT

Federated learning is an emerging privacy-preserving AI technique where clients (i.e., organisations or devices) train models locally and formulate a global model based on the local model updates without transferring local data externally. However, federated learning systems struggle to achieve trustworthiness and embody responsible AI principles. In particular, federated learning systems face accountability and fairness challenges due to multi-stakeholder involvement and heterogeneity in client data distribution. To enhance the accountability and fairness of federated learning systems, we present a blockchain-based trustworthy federated learning architecture. We first design a smart contract-based data-model provenance registry to enable accountability. Additionally, we propose a weighted fair data sampler algorithm to enhance fairness in training data. We evaluate the proposed approach using a COVID-19 X-ray detection use case. The evaluation results show that the approach is feasible to enable accountability and improve fairness. The proposed algorithm can achieve better performance than the default federated learning setting in terms of the model's generalisation and accuracy.

12.
Eur Respir J ; 58(1)2021 07.
Article in English | MEDLINE | ID: covidwho-1496128

ABSTRACT

OBJECTIVE: To evaluate pulmonary function and clinical symptoms in coronavirus disease 2019 (COVID-19) survivors within 3 months after hospital discharge, and to identify risk factors associated with impaired lung function. METHODS AND MATERIAL: COVID-19 patients were prospectively followed-up with pulmonary function tests and clinical characteristics for 3 months following discharge from a hospital in Wuhan, China between January and February 2020. RESULTS: 647 patients were included. 87 (13%) patients presented with weakness, 63 (10%) with palpitations and 56 (9%) with dyspnoea. The prevalence of each of the three symptoms were markedly higher in severe patients than nonsevere patients (19% versus 10% for weakness, p=0.003; 14% versus 7% for palpitations, p=0.007; 12% versus 7% for dyspnoea, p=0.014). Results of multivariable regression showed increased odds of ongoing symptoms among severe patients (OR 1.7, 95% CI 1.1-2.6; p=0.026) or patients with longer hospital stays (OR 1.03, 95% CI 1.00-1.05; p=0.041). Pulmonary function test results were available for 81 patients, including 41 nonsevere and 40 severe patients. In this subgroup, 44 (54%) patients manifested abnormal diffusing capacity of the lung for carbon monoxide (D LCO) (68% severe versus 42% nonsevere patients, p=0.019). Chest computed tomography (CT) total severity score >10.5 (OR 10.4, 95% CI 2.5-44.1; p=0.001) on admission and acute respiratory distress syndrome (ARDS) (OR 4.6, 95% CI 1.4-15.5; p=0.014) were significantly associated with impaired D LCO. Pulmonary interstitial damage may be associated with abnormal D LCO. CONCLUSION: Pulmonary function, particularly D LCO, declined in COVID-19 survivors. This decrease was associated with total severity score of chest CT >10.5 and ARDS occurrence. Pulmonary interstitial damage might contribute to the imparied D LCO.


Subject(s)
COVID-19 , Carbon Monoxide , China , Follow-Up Studies , Humans , Lung/diagnostic imaging , SARS-CoV-2
14.
Engineering (Beijing) ; 2021 Oct 23.
Article in English | MEDLINE | ID: covidwho-1474517

ABSTRACT

Current knowledge of the risk factors predicting the progression to severe coronavirus disease 2019 (COVID-19) among patients in community isolation who either are asymptomatic or only suffer from mild COVID-19 is very limited. Using a multivariable competing risk survival analysis, we herein identify several important predictors of progression to severe COVID-19-rather than to recovery-among patients in community isolation. A competing risk survival analysis was performed on time-to-event data from a cohort study of all COVID-19 patients (n = 1753) in the largest community isolation center in Wuhan, China, from opening to closing. The exposures were age, sex, respiratory symptoms, gastrointestinal symptoms, general symptoms, and computed tomography (CT) scan signs. The main outcomes were time to COVID-19 deterioration or recovery. The factors predicting progression to severe COVID-19 among the patients in community isolation were: male sex (hazard ratio (HR) = 1.29, 95% confidence interval (95%CI), 1.04-1.58, p = 0.018), young and old age, dyspnea (HR = 1.58, 95%CI, 1.24-2.01, p < 0.001), and CT signs of ground-glass opacity (HR = 1.39, 95%CI, 1.04-1.86, p = 0.024) and infiltrating shadows (HR= 1.84, 95%CI, 1.22-2.78, p = 0.004). The risk of progression was found to be lower among patients with nausea or vomiting (HR = 0.53, 95%CI, 0.30-0.96, p = 0.036) and headaches (HR = 0.54, 95%CI, 0.29-0.99, p = 0.046). Based on the results of this study, resource-poor settings, dyspnea, sex, and age can easily be used to identify mild COVID-19 patients who are at increased risk of progression. Looking for CT signs of ground-glass opacity and infiltrating shadows may be an affordable option to support triage decisions in resource-rich settings. Common and unspecific symptoms including headaches, nausea, and vomiting likely induced the selection for community isolation of COVID-19 patients who were relatively unlikely to deteriorate. Triage and prioritization outcomes could be boosted if strategies are incorporated to minimize the inefficient prioritization of harmless comorbidities.

15.
Nat Med ; 27(6): 1012-1024, 2021 06.
Article in English | MEDLINE | ID: covidwho-1472229

ABSTRACT

Age is the dominant risk factor for infectious diseases, but the mechanisms linking age to infectious disease risk are incompletely understood. Age-related mosaic chromosomal alterations (mCAs) detected from genotyping of blood-derived DNA, are structural somatic variants indicative of clonal hematopoiesis, and are associated with aberrant leukocyte cell counts, hematological malignancy, and mortality. Here, we show that mCAs predispose to diverse types of infections. We analyzed mCAs from 768,762 individuals without hematological cancer at the time of DNA acquisition across five biobanks. Expanded autosomal mCAs were associated with diverse incident infections (hazard ratio (HR) 1.25; 95% confidence interval (CI) = 1.15-1.36; P = 1.8 × 10-7), including sepsis (HR 2.68; 95% CI = 2.25-3.19; P = 3.1 × 10-28), pneumonia (HR 1.76; 95% CI = 1.53-2.03; P = 2.3 × 10-15), digestive system infections (HR 1.51; 95% CI = 1.32-1.73; P = 2.2 × 10-9) and genitourinary infections (HR 1.25; 95% CI = 1.11-1.41; P = 3.7 × 10-4). A genome-wide association study of expanded mCAs identified 63 loci, which were enriched at transcriptional regulatory sites for immune cells. These results suggest that mCAs are a marker of impaired immunity and confer increased predisposition to infections.


Subject(s)
Aging/genetics , Communicable Diseases/genetics , Pneumonia/genetics , Sepsis/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Aging/pathology , Biological Specimen Banks , Chromosome Aberrations , Communicable Diseases/complications , Communicable Diseases/microbiology , Digestive System Diseases/epidemiology , Digestive System Diseases/genetics , Digestive System Diseases/microbiology , Female , Genetic Predisposition to Disease , Genome-Wide Association Study , Genotype , Hematologic Neoplasms/complications , Hematologic Neoplasms/genetics , Hematologic Neoplasms/microbiology , Humans , Male , Middle Aged , Mosaicism , Pneumonia/epidemiology , Pneumonia/microbiology , Risk Factors , Sepsis/epidemiology , Sepsis/microbiology , Urogenital Abnormalities/epidemiology , Urogenital Abnormalities/genetics , Urogenital Abnormalities/microbiology , Young Adult
16.
J Med Chem ; 64(19): 14887-14894, 2021 10 14.
Article in English | MEDLINE | ID: covidwho-1428719

ABSTRACT

Antiviral treatments of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been extensively pursued to conquer the pandemic. To inhibit the viral entry to the host cell, we designed and obtained three peptide sequences via quartz crystal microbalance measurement screening, which showed high affinity at nanomole to the S1 subunit of the spike protein and wild-type SARS-CoV-2 pseudovirus. Circular dichroism spectroscopy measurements revealed significant conformation changes of the S1 protein upon encounter with the three peptides. The peptides were able to effectively block the infection of a pseudovirus to 50% by inhibiting the host cell lines binding with the S1 protein, evidenced by the results from Western blotting and pseudovirus luciferase assay. Moreover, the combination of the three peptides could increase the inhibitory rate to 75%. In conclusion, the three chemically synthetic neutralizing peptides and their combinations hold promising potential as effective therapeutics in the prevention and treatment of COVID-19.


Subject(s)
Peptides/metabolism , Spike Glycoprotein, Coronavirus/metabolism , A549 Cells , Angiotensin-Converting Enzyme 2/chemistry , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/pathology , COVID-19/virology , Cell Survival/drug effects , Circular Dichroism , Humans , Neutralization Tests , Peptides/chemistry , Peptides/pharmacology , Protein Binding , Protein Subunits/chemistry , Protein Subunits/metabolism , SARS-CoV-2/isolation & purification , Spike Glycoprotein, Coronavirus/chemistry , Virus Internalization/drug effects
17.
Matern Fetal Med ; 2(2): 65-67, 2020 Apr.
Article in English | MEDLINE | ID: covidwho-1410265
18.
Chin Med J (Engl) ; 134(17): 2045-2047, 2021 Aug 23.
Article in English | MEDLINE | ID: covidwho-1405072
19.
Pharmacological Research - Modern Chinese Medicine ; : 100007, 2021.
Article in English | ScienceDirect | ID: covidwho-1401788

ABSTRACT

Targeted therapeutics for SARS-CoV-2 virus caused COVID-19 are in urgent need. Cinobufacini has been reported to have broad-spectrum antiviral effects and widely used in Southeast Asian countries. This study aims to assess the efficacy of Cinobufacini injection in treating patients with severe COVID-19. A randomized preliminary clinical trial was conducted and eligible patients were allocated to receive general treatment plus Cinobufacini injection or only general treatment as control for 7 days. The primary outcomes of the oxygenation index PaO2/FiO2 and ROX, secondary outcomes of white blood cell count, respiratory support step-down time (RSST), safety indicators, etc were monitored. After 7 days of treatment, the oxygenation index was improved in 95.2% patients in the treatment group compared with 68.4% in the control group. The PaO2/FiO2 and ROX indices in the treatment group (mean, 226.27±67.35 and 14.01±3.99 respectively) were significantly higher than the control group (mean, 143.23±51.29 and 9.64±5.54 respectively). The RSST was 1 day shorter in the treatment group. Multivariate regression analysis suggested that Cinobufacini injection contributed the most to the outcome of PaO2/FiO2. No obvious adverse effects were observed. The preliminary data showed that Cinobufacini injection had apparent efficacy in improving the respiratory function of patients with severe COVID-19.

20.
Curr Pharm Biotechnol ; 2021 Sep 06.
Article in English | MEDLINE | ID: covidwho-1399059

ABSTRACT

Mesenchymal stem cells (MSCs) are multipotent progenitor cells that play crucial roles in the microenvironment of injured tissues. The potential therapeutics of MSCs have attracted extensive attention for several diseases such as acute respiratory distress syndrome (ARDS) and novel coronavirus disease 2019 (COVID-19) pneumonia. MSC-extracellular vesicles have been isolated from MSC-conditioned media (MSC-CM) with similar functional effects as parent MSCs. The therapeutic role of MSCs can be achieved through the balance between the inflammatory and regenerative microenvironments. Clinical settings of MSCs and their extracellular vesicles remain promising for many diseases, such as ARDS and pneumonia. However, their clinical applications remain limited due to the cost of growing and storage facilities of MSCs with a lack of standardized MSC-CM. This review highlights the proposed role of MSCs in pulmonary diseases and discusses the recent advances of MSC application for pneumonia and other lung disorders.

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