Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 51
Filter
1.
Biomed Res Int ; 2022: 3524090, 2022.
Article in English | MEDLINE | ID: covidwho-1854467

ABSTRACT

Biomedical named entity recognition (BioNER) from clinical texts is a fundamental task for clinical data analysis due to the availability of large volume of electronic medical record data, which are mostly in free text format, in real-world clinical settings. Clinical text data incorporates significant phenotypic medical entities (e.g., symptoms, diseases, and laboratory indexes), which could be used for profiling the clinical characteristics of patients in specific disease conditions (e.g., Coronavirus Disease 2019 (COVID-19)). However, general BioNER approaches mostly rely on coarse-grained annotations of phenotypic entities in benchmark text dataset. Owing to the numerous negation expressions of phenotypic entities (e.g., "no fever," "no cough," and "no hypertension") in clinical texts, this could not feed the subsequent data analysis process with well-prepared structured clinical data. In this paper, we developed Human-machine Cooperative Phenotypic Spectrum Annotation System (http://www.tcmai.org/login, HCPSAS) and constructed a fine-grained Chinese clinical corpus. Thereafter, we proposed a phenotypic named entity recognizer: Phenonizer, which utilized BERT to capture character-level global contextual representation, extracted local contextual features combined with bidirectional long short-term memory, and finally obtained the optimal label sequences through conditional random field. The results on COVID-19 dataset show that Phenonizer outperforms those methods based on Word2Vec with an F1-score of 0.896. By comparing character embeddings from different data, it is found that character embeddings trained by clinical corpora can improve F-score by 0.0103. In addition, we evaluated Phenonizer on two kinds of granular datasets and proved that fine-grained dataset can boost methods' F1-score slightly by about 0.005. Furthermore, the fine-grained dataset enables methods to distinguish between negated symptoms and presented symptoms. Finally, we tested the generalization performance of Phenonizer, achieving a superior F1-score of 0.8389. In summary, together with fine-grained annotated benchmark dataset, Phenonizer proposes a feasible approach to effectively extract symptom information from Chinese clinical texts with acceptable performance.


Subject(s)
COVID-19 , China , Electronic Health Records , Humans
3.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-336071

ABSTRACT

Summary The rising case numbers of the SARS-CoV-2 Omicron BA.4, BA.5, and BA.2.12.1 subvariants has generated serious concern about the course of the pandemic. Here we examine the neutralization resistance, infectivity, processing, and fusogenicity of spike from the BA.4/5 and BA.2.12.1 SARS-CoV-2 variants compared with other Omicron subvariants and Delta. Critically, we found that the new Omicron subvariants BA.4/5 and BA.2.12.1 were more resistant to neutralization by mRNA-vaccinated and boosted health care worker sera and Omicron-BA.1-wave patient sera than were the BA.1 and BA.2 variants. Interestingly, Delta-wave patient sera neutralized more efficiently against not only Delta but also BA.4/5 and BA.2.12.1 variants that also contain substitutions at position L452, similar to Delta. The BA.4/5 and BA.2.12.1 variants also exhibited higher fusogenicity, and increased spike processing, dependent on the L452 substitution. These results highlight the key role of the L452R and L452Q mutations in BA.4/5 and BA.2.12.1 subvariants.

4.
Cell Host Microbe ; 2022 Apr 25.
Article in English | MEDLINE | ID: covidwho-1803742

ABSTRACT

Recent reports of SARS-CoV-2 Omicron variant sub-lineages, BA.1, BA.1.1, and BA.2, have reignited concern over potential escape from vaccine- and infection-induced immunity. We examine the sensitivity of these sub-lineages and other major variants to neutralizing antibodies from mRNA-vaccinated and boosted individuals, as well as recovered COVID-19 patients, including those infected with Omicron. We find that all Omicron sub-lineages, especially BA.1 and BA.1.1, exhibit substantial immune escape that is largely overcome by mRNA vaccine booster doses. While Omicron BA.1.1 escapes almost completely from neutralization by early-pandemic COVID-19 patient sera and to a lesser extent from sera of Delta-infected patients, BA.1.1 is sensitive to Omicron-infected patient sera. Critically, all Omicron sub-lineages, including BA.2, are comparably neutralized by Omicron patient sera. These results highlight the importance of booster vaccine doses for protection against all Omicron variants and provide insight into the immunity from natural infection against Omicron sub-lineages.

5.
The Journal of Business & Industrial Marketing ; 37(5):1111-1126, 2022.
Article in English | ProQuest Central | ID: covidwho-1788594

ABSTRACT

Purpose>This study aims to investigate moderators affecting the impact of salesperson acquisition-retention (AR) ambidexterity on sales performance based on the motivation-opportunity-ability (MOA) framework.Design/methodology/approach>The authors collected triadic data through 391 questionnaires from salespeople, 50 questionnaires from sales managers and archival data about each salesperson’s performance. Hierarchical linear modeling was applied to test the hypotheses.Findings>The results indicate that salesperson AR ambidexterity positively affects sales performance. The positive effect is strengthened by capability control but weakened by outcome control and activity control. The authors also find that sales experience and market attractiveness hurt the effectiveness of salesperson AR ambidexterity.Research limitations/implications>First, this study does not examine the mediating mechanism underlying the effect of salesperson AR ambidexterity. Second, sales-service ambidexterity is another ambidextrous variable for salespeople. Future research can consider AR and sales-service ambidexterity together.Practical implications>First, managers should be cautious when encouraging experienced salespeople to conduct AR ambidexterity. Second, managers need to use capability control to motivate salespeople with AR ambidextrous behaviors. Third, AR ambidexterity could be not required in a market with many opportunities.Originality/value>Although some studies have examined the effectiveness of salesperson AR ambidexterity, they reveal inconsistent findings, which suggest contingent conditions on the effectiveness of salesperson AR ambidexterity. However, the attention on the contingent conditions is limited. Therefore, this paper systematically investigates the contingent conditions from the MOA framework. The findings provide some insights into when salesperson AR ambidexterity is effective.

6.
Front Public Health ; 9: 740800, 2021.
Article in English | MEDLINE | ID: covidwho-1775894

ABSTRACT

Background: Exposure to ambient particulate matter pollution (APMP) is a global health issue that directly affects the human respiratory system. Thus, we estimated the spatiotemporal trends in the burden of APMP-related respiratory diseases from 1990 to 2019. Methods: Based on the Global Burden of Disease Study 2019, data on the burden of APMP-related respiratory diseases were analyzed by age, sex, cause, and location. Joinpoint regression analysis was used to analyze the temporal trends in the burden of different respiratory diseases over the 30 years. Results: Globally, in 2019, APMP contributed the most to chronic obstructive pulmonary disease (COPD), with 695.1 thousand deaths and 15.4 million disability-adjusted life years (DALYs); however, the corresponding age-standardized death and DALY rates declined from 1990 to 2019. Similarly, although age-standardized death and DALY rates since 1990 decreased by 24% and 40%, respectively, lower respiratory infections (LRIs) still had the second highest number of deaths and DALYs attributable to APMP. This was followed by tracheal, bronchus, and lung (TBL) cancer, which showed increased age-standardized death and DALY rates during the past 30 years and reached 3.78 deaths per 100,000 persons and 84.22 DALYs per 100,000 persons in 2019. Among children aged < 5 years, LRIs had a huge burden attributable to APMP, whereas for older people, COPD was the leading cause of death and DALYs attributable to APMP. The APMP-related burdens of LRIs and COPD were relatively higher among countries with low and low-middle socio-demographic index (SDI), while countries with high-middle SDI showed the highest burden of TBL cancer attributable to APMP. Conclusions: APMP contributed substantially to the global burden of respiratory diseases, posing a significant threat to human health. Effective actions aimed at air pollution can potentially avoid an increase in the PM2.5-associated disease burden, especially in highly polluted areas.


Subject(s)
Air Pollution , Respiratory Tract Diseases , Adult , Aged , Air Pollution/adverse effects , Child , Child, Preschool , Global Burden of Disease , Humans , Particulate Matter/adverse effects , Quality-Adjusted Life Years , Respiratory Tract Diseases/epidemiology
7.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-329659

ABSTRACT

The emerging SARS-CoV-2 variants of concern (VOCs) exhibit enhanced transmission and immune escape, reducing the efficacy and effectiveness of the two FDA-approved mRNA vaccines currently in use. Here, we explored various strategies to develop mRNA vaccines that offer potentially safer and wider coverage of VOCs. The initial mouse vaccination results showed that the individual VOC mRNAs carrying furin cleavage mutation induced the generation of neutralizing antibody in a VOC-specific manner. Moreover, we discovered that the antibodies produced from mice immunized with Beta-Furin and Washington (WA)-Furin mRNAs cross-reacted with other VOCs. The broad spectrum of generated nAb was further confirmed when vaccinated mice were challenged with the respective live viruses. However, neither WA-Furin nor Beta-Furin mRNA elicited potent neutralizing activity against the omicron variant. Interestingly, in a mix-and-match booster experiment, omicron-Furin and WA-Furin mRNA elicited comparable protection against omicron. Finally, we tested the concept of bivalent vaccine by introducing the RBD of Delta strain into the intact S antigen of Omicron. The chimeric mRNA induces potent and broadly acting nAb against Omicron and Delta, which paves the way to develop vaccine candidate to target emerging variants in the future.

8.
Journal of clinical and translational science ; 5(Suppl 1):27-27, 2021.
Article in English | EuropePMC | ID: covidwho-1710533

ABSTRACT

IMPACT: Identifying differential COVID-19 progression across the disease continuum may help policymakers and service providers better identify or predict gaps in services and resources and develop precision strategies to support COVID-19 patients where the need is mostly needed. OBJECTIVES/GOALS: Single institution studies have documented COVID-19 disproportionally affected US racial and ethnic minority groups compared to Whites. However, few population-wide data studied severity and death in multiracial populations. We aim to examine the current disparity in the COVID-19 continuum, including hospitalizations, severity, and death. METHODS/STUDY POPULATION: Data on 67,094 laboratory documented COVID-19 cases nested from the state-wide ‘OneFlorida’ research consortium through August 3, 2020, were assessed to decide differences and disparities in COVID-19 outcomes. A COVID-19 outcome continuum outlining the proportions of cases transitioning from diagnosis to death was constructed (Figure 1). OneFlorida partners provide health care to more than 40% of Floridians in the nation’s third-largest and very diverse state. OneFlorida partners encompass hospitals, practice/clinic settings, and physicians, which provide care for 15 million patients across all of Florida’s 67 counties. It is part of the Patient-Centered Outcomes Research Institute (PCORI). RESULTS/ANTICIPATED RESULTS: Among cases, 25,443 (37.9%) were non-Hispanic Whites, 11,709 (17.5%) were non-Hispanic Blacks, and 16,119 (24.0%) were Hispanics. Among COVID-19 patients, Blacks and Hispanics had a higher frequency of emergency department (ED) visits (45.7% and 46.0%, respectively), whereas admission rates were higher in Blacks (15.6%) and Whites (15.9%) than in Hispanics (11.5%). Blacks had the highest rates of intubation (3.6%) and in-hospital deaths (2.7%) compared to Whites (2.5% and 2.3%, respectively) and Hispanics (1.3% and 1.4%, respectively), Figure 1. When rates were indexed to the state census data, Blacks had the worst rates across the disease continuum (infection to death). In comparison, Hispanics had higher rates of ED visits but lower rates of intubation and death, Table 1. DISCUSSION/SIGNIFICANCE OF FINDINGS: Outcomes continuum is a useful tool at an individual-level to assess care outcomes and at population-level as a framework to analyze the proportion of population with COVID-19 that progress to each successive disease stage. This will help policymakers to better identify gaps in services and develop precision strategies to support COVID-19 patients.

9.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-308237

ABSTRACT

Background: With the spread of SARS-CoV-2 around the world, a rising number of studies have been conducted on the epidemiological and clinical characteristics of COVID-19. However, studies about the effect of SARS-CoV-2 on coagulation function are rare. Hence, we aimed to assess the differences and dynamic changes of blood coagulation function in ordinary, severe and critical patients with COCID-19. Methods: A retrospective study was conducted. Clinical information, including age, routine blood and blood coagulation function, was collected from medical records of COVID-19 patients from January 24 to March 25, 2020 in Huangshi, Hubei Province. According to new pneumonia diagnosis and treatment of COVID-19 (trial version seventh), the patients were divided into ordinary, severe and critical groups. Results: 261 COVID-19 patients (186 ordinary, 45 severe and 30 critical ones) were enrolled. Average age in critical group (71.47±11.48 years) was the oldest of three subgroups. At admission, statistically differences could be observed for D-dimer, FDP, Platelet and lymphocyte count among three subgroups (P<0.05). During hospitalization, the peak values of coagulation and valley values of blood routine were monitored, and there were significant differences among ordinary, severe and critical patients in D-dimer (0.26±0.46, 1.39±1.51 and 2.89±1.68 mg/L), FDP (3.29±5.52, 23.68±39.07 and 56.11±49.94 μg/ml), platelet [(164±55.53), (171±69.96) and (84±57.80) ×109/L)] and lymphocyte counts [(1.10±0.46), (0.65±0.35) and (0.55±0.31) ×109/L)], respectively (P<0.001). In the critical group, D-dimer and FDP were significantly increased, while platelet count and lymphocyte count were obviously decreased. D-dimer and FDP in the course of disease in severe/critical groups showed a first upward and then downward trend. Conclusions: Close monitoring of coagulation function could help predict the severity of COVID-19, and guide treatment.

10.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-323913

ABSTRACT

Background: Novel coronavirus disease 2019 (COVID-19) has spread around the world;therefore, more attention should be paid to the clinical features of COVID-19, with the aim of improving the diagnosis and treatment of patients. Methods: By 15 February 2020, 60 patients diagnosed with COVID-19 had been admitted to Nanjing Second Hospital. We analyzed the clinical features of different age segments infected with COVID-19 prospectively, including epidemiological, clinical, laboratory, and radiological characteristics;treatment, clinical outcomes, and prognosis of this cohort of patients. Results: The cohort comprised 29 male and 31 female patients (median age = 46.18 years old (range: 18–97). Fifty-five (91.7%) patients had a clear epidemiological contact history. The average incubation period was 7.92 days. The most common clinical manifestations were fever (85%) and cough (75%). Peripheral white blood cell counts were mostly normal at admission, 7 days, and 14 days, with no differences among patients of different ages. The lymphocyte counts of all patients were in the normal range on admission, and after 7 days and 14 days of treatment;however, the lymphocyte count in > 65-year-old patients was less than that in the < 40 and 40–65-year-old groups after 7 and 14 days of treatment ( P < 0.05, respectively). At admission, the CD4 T lymphocyte count was within the normal range;however, the CD4 T lymphocyte count in >65-year-old group was less than that in the < 40 and 40–65-years-old groups after 14 days of treatment. The CD4 T lymphocyte counts were 723.46 ± 243.82/ml (< 40), 640.00 ± 242.30/ml (40–65), and 399.88 ± 256.16/ml (> 65) ( P =0.0075). The > 65-years-old group had higher levels of lactate dehydrogenase (269.83 ± 73.36 vs . 208.52 ± 35.67 and 243.83 ± 76.66) after 14 days ( P = 0.0496). Imaging revealed more lesions in the 40–65 and > 65-year-old groups ( P < 0.0001). The days after the nucleic acid detection turned negative in the three age groups were: 9.19 ± 3.93 (< 40), 10.04 ± 4.10 (40–65), and 13.57 ± 2.76 (> 65) ( P = 0.0373). After antiviral treatment, together with anti-infection regimen if the patient with lung infection and continuous oxygen inhalation if the patient is hypoxic, all patients achieved total recovery and were discharged with follow-up. Conclusion: Patients with COVID-19 pneumonia generally had an epidemiological history. Older patients showed more extensive lesions upon admission, more severe illness, slower recovery of immune function, the longer viral nucleic acid persistence.

11.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-321465

ABSTRACT

Background: Previous studies showed that the effect of antivirals for COVID-19 was promising but varied across patient population, and was modest among severe cases. Chinese Medicine (CM) was extensively used and reported effective in China, awaiting further evidence support. We aimed to evaluate the real-world effectiveness of add-on semi-individualized.Methods: A retrospective total sampling cohort of 1788 adult confirmed COVID-19 patients were recruited from all 2235 consecutive records retrieved from 5 hospitals in Wuhan during15 January to 13 March 2020. Consultation notes, laboratory/imaging investigations, pharmacy and prognosis records were linked by an electronic medical record system and verified by at least 2 researchers independently. The mortality of add-on semi-individualized CM users and non-users was compared by weighted hazard ratios of multivariable Cox regression and by propensity score matching. Change of biomarkers was compared between groups and the frequency of CMs used was analysed. Subgroup analysis was performed to stratify disease severity and dose of CM exposure. Sensitivity analyses were conducted to test the robustness.Findings: The crude mortality was 3.8% in the semi-individualized CM user group and 17.0% among the non-users. Add-on CM was associated with a significant mortality reduction of 58% (HR=0.42, 95%CI: 0.23 to 0.77, p=0.005) and 66% (HR=0.34, 95%CI: 0.15 to 0.76, p=0.009) among all and severe/critical COVID-19 cases with dose-dependent response, after inversely weighted with propensity score calculated by age, gender, history of hypertension, diabetes, coronary artery disease and disease severity. The result was robust in various stratified, weighted, matched, adjusted and sensitivity analyses. Severe/critical patients received add-on CM had a trend of stabilized D-dimer level after 3-7 days of admission compared to baseline.Interpretation: Add-on semi-individualized CM was associated with reduced mortality demonstrating dose-dependent response, especially among severe/critical COVID-19 patients. Chinese medicine could be considered as an add-on regimen for trial use.Funding Statement: This work is partially supported by the National Key Research and Development Program (2017YFC1703506 and 2020YFC0841600). Declaration of Interests: No financial relationships with any organisations that might have an interest in the submitted work in the previous three years;no other relationships or activities that could appear to have influenced the submitted work.Ethics Approval Statement: This study was approved by the ethics review board of Hubei Provincial Hospital of Traditional Chinese Medicine (HBZY2020-C01-01). Written consent was waived due to the retrospective nature.

12.
Signal transduction and targeted therapy ; 7(1), 2022.
Article in English | EuropePMC | ID: covidwho-1652408

ABSTRACT

As a highly pathogenic human coronavirus, SARS-CoV-2 has to counteract an intricate network of antiviral host responses to establish infection and spread. The nucleic acid-induced stress response is an essential component of antiviral defense and is closely related to antiviral innate immunity. However, whether SARS-CoV-2 regulates the stress response pathway to achieve immune evasion remains elusive. In this study, SARS-CoV-2 NSP5 and N protein were found to attenuate antiviral stress granule (avSG) formation. Moreover, NSP5 and N suppressed IFN expression induced by infection of Sendai virus or transfection of a synthetic mimic of dsRNA, poly (I:C), inhibiting TBK1 and IRF3 phosphorylation, and restraining the nuclear translocalization of IRF3. Furthermore, HEK293T cells with ectopic expression of NSP5 or N protein were less resistant to vesicular stomatitis virus infection. Mechanistically, NSP5 suppressed avSG formation and disrupted RIG-I–MAVS complex to attenuate the RIG-I–mediated antiviral immunity. In contrast to the multiple targets of NSP5, the N protein specifically targeted cofactors upstream of RIG-I. The N protein interacted with G3BP1 to prevent avSG formation and to keep the cofactors G3BP1 and PACT from activating RIG-I. Additionally, the N protein also affected the recognition of dsRNA by RIG-I. This study revealed the intimate correlation between SARS-CoV-2, the stress response, and innate antiviral immunity, shedding light on the pathogenic mechanism of COVID-19.

13.
Annals of Operations Research ; : 1-16, 2022.
Article in English | EuropePMC | ID: covidwho-1615240

ABSTRACT

The novel coronavirus pneumonia brings new opportunities for the webcast. The characteristics of webcast and incentive types are two important potential variables that may affect user attitudes. Therefore, from this perspective, we test the mechanism of the two potential variables on the attitude of webcast users under the framework of ECM-ISC. Structural equation model analysis shows that: the interest of webcast has a significant positive impact on the cognitive attitude and emotional attitude of users;the explicit stimulation of webcast has a significant positive impact on the cognitive attitude and emotional attitude of users;the implicit incentive of webcast has a significant positive impact. The results show significant positive effects on users' cognitive attitude, emotional attitude, and behavior attitude;the interaction of live network characteristics and incentive types has a significant positive impact on users' cognitive attitude and emotional attitude.

14.
J Immunol ; 208(3): 753-761, 2022 02 01.
Article in English | MEDLINE | ID: covidwho-1614089

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has seriously threatened global public health. Severe COVID-19 has been reported to be associated with an impaired IFN response. However, the mechanisms of how SARS-CoV-2 antagonizes the host IFN response are poorly understood. In this study, we report that SARS-CoV-2 helicase NSP13 inhibits type I IFN production by directly targeting TANK-binding kinase 1 (TBK1) for degradation. Interestingly, inhibition of autophagy by genetic knockout of Beclin1 or pharmacological inhibition can rescue NSP13-mediated TBK1 degradation in HEK-293T cells. Subsequent studies revealed that NSP13 recruits TBK1 to p62, and the absence of p62 can also inhibit TBK1 degradation in HEK-293T and HeLa cells. Finally, TBK1 and p62 degradation and p62 aggregation were observed during SARS-CoV-2 infection in HeLa-ACE2 and Calu3 cells. Overall, our study shows that NSP13 inhibits type I IFN production by recruiting TBK1 to p62 for autophagic degradation, enabling it to evade the host innate immune response, which provides new insights into the transmission and pathogenesis of SARS-CoV-2 infection.


Subject(s)
Autophagy , COVID-19/immunology , Interferon Type I/biosynthesis , Methyltransferases/physiology , RNA Helicases/physiology , SARS-CoV-2/physiology , Sequestosome-1 Protein/metabolism , Viral Nonstructural Proteins/physiology , Beclin-1/antagonists & inhibitors , Cell Line , Down-Regulation , Humans , Immune Evasion , Immunity, Innate , Immunoprecipitation , Interferon Type I/genetics , Multiprotein Complexes , Protein Aggregates , Protein Interaction Mapping
16.
Proc Natl Acad Sci U S A ; 119(1)2022 01 04.
Article in English | MEDLINE | ID: covidwho-1599544

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible coronavirus responsible for the global COVID-19 pandemic. Herein, we provide evidence that SARS-CoV-2 spreads through cell-cell contact in cultures, mediated by the spike glycoprotein. SARS-CoV-2 spike is more efficient in facilitating cell-to-cell transmission than is SARS-CoV spike, which reflects, in part, their differential cell-cell fusion activity. Interestingly, treatment of cocultured cells with endosomal entry inhibitors impairs cell-to-cell transmission, implicating endosomal membrane fusion as an underlying mechanism. Compared with cell-free infection, cell-to-cell transmission of SARS-CoV-2 is refractory to inhibition by neutralizing antibody or convalescent sera of COVID-19 patients. While angiotensin-converting enzyme 2 enhances cell-to-cell transmission, we find that it is not absolutely required. Notably, despite differences in cell-free infectivity, the authentic variants of concern (VOCs) B.1.1.7 (alpha) and B.1.351 (beta) have similar cell-to-cell transmission capability. Moreover, B.1.351 is more resistant to neutralization by vaccinee sera in cell-free infection, whereas B.1.1.7 is more resistant to inhibition by vaccinee sera in cell-to-cell transmission. Overall, our study reveals critical features of SARS-CoV-2 spike-mediated cell-to-cell transmission, with important implications for a better understanding of SARS-CoV-2 spread and pathogenesis.


Subject(s)
COVID-19/immunology , COVID-19/transmission , SARS-CoV-2/immunology , Virus Internalization , Angiotensin-Converting Enzyme 2 , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral , COVID-19/therapy , Cell Fusion , Chlorocebus aethiops , HEK293 Cells , Humans , Immunization, Passive , Spike Glycoprotein, Coronavirus/immunology , Vero Cells
17.
[Unspecified Source]; 2020.
Preprint in English | [Unspecified Source] | ID: ppcovidwho-292812

ABSTRACT

Rapid and specific antibody testing is crucial for improved understanding, control, and treatment of COVID-19 pathogenesis. Herein, we describe and apply a rapid, sensitive, and accurate virus neutralization assay for SARS-CoV-2 antibodies. The new assay is based on an HIV-1 lentiviral vector that contains a secreted intron Gaussia luciferase or secreted Nano-luciferase reporter cassette, pseudotyped with the SARS-CoV-2 spike (S) glycoprotein, and is validated with a plaque reduction assay using an authentic, infectious SARS-CoV-2 strain. The new assay was used to evaluate SARS-CoV-2 antibodies in serum from individuals with a broad range of COVID-19 symptoms, including intensive care unit (ICU) patients, health care workers (HCWs), and convalescent plasma donors. The highest neutralizing antibody titers were observed among ICU patients, followed by general hospitalized patients, HCWs and convalescent plasma donors. Our study highlights a wide phenotypic variation in human antibody responses against SARS-CoV-2, and demonstrates the efficacy of a novel lentivirus pseudotype assay for high-throughput serological surveys of neutralizing antibody titers in large cohorts.

18.
Int J Biol Macromol ; 193(Pt B): 1124-1129, 2021 Dec 15.
Article in English | MEDLINE | ID: covidwho-1487744

ABSTRACT

Thrombotic complication has been an important symptom in critically ill patients with COVID-19. It has not been clear whether the virus spike (S) protein can directly induce blood coagulation in addition to inflammation. Heparan sulfate (HS)/heparin, a key factor in coagulation process, was found to bind SARS-CoV-2 S protein with high affinity. Herein, we found that the S protein can competitively inhibit the bindings of antithrombin and heparin cofactor II to heparin/HS, causing abnormal increase in thrombin activity. SARS-CoV-2 S protein at a similar concentration (~10 µg/mL) as the viral load in critically ill patients can cause directly blood coagulation and thrombosis in zebrafish model. Furthermore, exogenous heparin/HS can significantly reduce coagulation caused by S protein, pointing to a potential new direction to elucidate the etiology of the virus and provide fundamental support for anticoagulant therapy especially for the COVID-19 critically ill patients.


Subject(s)
Blood Coagulation , Heparitin Sulfate , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Thrombosis/metabolism , Animals , Heparitin Sulfate/chemistry , Heparitin Sulfate/metabolism , Humans , Mice , Protein Binding , SARS-CoV-2/chemistry , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/metabolism
19.
ACS Infect Dis ; 7(11): 3096-3110, 2021 11 12.
Article in English | MEDLINE | ID: covidwho-1483084

ABSTRACT

The development of vaccines against coronaviruses has focused on the spike (S) protein, which is required for the recognition of host-cell receptors and thus elicits neutralizing antibodies. Targeting conserved epitopes on the S protein offers the potential for pan-beta-coronavirus vaccines that could prevent future pandemics. We displayed five B-cell epitopes, originally identified in the convalescent sera from recovered severe acute respiratory syndrome (SARS) patients, on the surface of the cowpea mosaic virus (CPMV) and evaluated these formulations as vaccines. Prime-boost immunization of mice with three of these candidate vaccines, CPMV-988, CPMV-1173, and CPMV-1209, elicited high antibody titers that neutralized the severe acute respiratory syndrome coronavirus (SARS-CoV) in vitro and showed an early Th1-biased profile (2-4 weeks) transitioning to a slightly Th2-biased profile just after the second boost (6 weeks). A pentavalent slow-release implant comprising all five peptides displayed on the CPMV elicited anti-S protein and epitope-specific antibody titers, albeit at a lower magnitude compared to the soluble formulations. While the CPMV remained intact when released from the PLGA implants, processing results in loss of RNA, which acts as an adjuvant. Loss of RNA may be a reason for the lower efficacy of the implants. Finally, although the three epitopes (988, 1173, and 1209) that were found to be neutralizing the SARS-CoV were 100% identical to the SARS-CoV-2, none of the vaccine candidates neutralized the SARS-CoV-2 in vitro suggesting differences in the natural epitope perhaps caused by conformational changes or the presence of N-linked glycans. While a cross-protective vaccine candidate was not developed, a multivalent SARS vaccine was developed. The technology discussed here is a versatile vaccination platform that can be pivoted toward other diseases and applications that are not limited to infectious diseases.


Subject(s)
COVID-19 , Comovirus , Nanoparticles , Vaccines , Animals , COVID-19/therapy , Comovirus/genetics , Epitopes, B-Lymphocyte , Humans , Immunization, Passive , Mice , Peptides , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
20.
Eur Geriatr Med ; 12(5): 1045-1055, 2021 10.
Article in English | MEDLINE | ID: covidwho-1474202

ABSTRACT

AIMS: To evaluate the efficacy of multi-component interventions for prevention of hospital-acquired pneumonia in older patients hospitalized in geriatric wards. METHODS: A randomized, parallel-group, controlled trial was undertaken in patients aged 65 and above who were admitted to a tertiary hospital geriatric unit from January 1, 2016 to June 30, 2018 for an acute non-respiratory illness. Participants were randomized by to receive either a multi-component intervention (consisting of reverse Trendelenburg position, dysphagia screening, oral care and vaccinations), or usual care. The outcome measures were the proportion of patients who developed hospital-acquired pneumonia during hospitalisation, and mean time from randomization to the next hospitalisation due to respiratory infections in 1 year. RESULTS: A total of 123 participants (median age, 85; 43.1% male) were randomized, (n = 59) to intervention group and (n = 64) to control group. The multi-component interventions did not significantly reduce the incidence of hospital-acquired pneumonia but did increase the mean time to next hospitalisation due to respiratory infection (11.5 months vs. 9.5 months; P = 0.049), and reduced the risk of hospitalisation in 1 year (18.6% vs. 34.4%; P = 0.049). Implementation of multi-component interventions increased diagnoses of oropharyngeal dysphagia (35.6% vs. 20.3%; P < 0.001) and improved the influenza (54.5% vs 17.2%; P < 0.001) and pneumococcal vaccination rates (52.5% vs. 20.3%; P < 0.001). CONCLUSIONS: The nosocomial pneumonia multi-component intervention did not significantly reduce the incidence of hospital-acquired pneumonia during hospitalisation but reduce subsequent hospitalisations for respiratory infections. CLINICAL TRIAL REGISTRATION: ClinicalTrial.gov, NCT04347395.


Subject(s)
COVID-19 , Cross Infection , Healthcare-Associated Pneumonia , Aged , Aged, 80 and over , Cross Infection/epidemiology , Female , Healthcare-Associated Pneumonia/epidemiology , Humans , Male , SARS-CoV-2 , Treatment Outcome
SELECTION OF CITATIONS
SEARCH DETAIL