Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 9 de 9
Filter
1.
Appl Microbiol Biotechnol ; 2022 Aug 11.
Article in English | MEDLINE | ID: covidwho-1990606

ABSTRACT

The coronavirus SARS-CoV-2 has caused a pandemic with > 550 millions of cases and > 6 millions of deaths worldwide. Medical management of COVID-19 relies on supportive care as no specific targeted therapies are available yet. Given its devastating effects on the economy and mental health, it is imperative to develop novel antivirals. An ideal candidate will be an agent that blocks the early events of viral attachment and cell entry, thereby preventing viral infection and spread. This work reports functionalized titanium dioxide (TiO2)-based nanoparticles adsorbed with flavonoids that block SARS-CoV-2 entry and fusion. Using molecular docking analysis, two flavonoids were chosen for their specific binding to critical regions of the SARS-CoV-2 spike glycoprotein that interacts with the host cell angiotensin-converting enzyme-2 (ACE-2) receptor. These flavonoids were adsorbed onto TiO2 functionalized nanoparticles (FTNP). This new nanoparticulate compound was assayed in vitro against two different coronaviruses; HCoV 229E and SARS-CoV-2, in both cases a clear antiviral effect was observed. Furthermore, using a reporter-based cell culture model, a potent antiviral activity is demonstrated. The adsorption of flavonoids to functionalized TiO2 nanoparticles induces a ~ threefold increase of that activity. These studies also indicate that FTNP interferes with the SARS-CoV-2 spike, impairing the cell fusion mechanism. KEY POINTS/HIGHLIGHTS: • Unique TiO2 nanoparticles displaying flavonoid showed potent anti-SARS-CoV-2 activity. • The nanoparticles precisely targeting SARS-CoV-2 were quantitatively verified by cell infectivity in vitro. • Flavonoids on nanoparticles impair the interactions between the spike glycoprotein and ACE-2 receptor.

2.
Diagnostics (Basel) ; 12(7)2022 Jul 05.
Article in English | MEDLINE | ID: covidwho-1917367

ABSTRACT

After more than two years, the COVID-19 pandemic is still ongoing and evolving all over the world; human herd immunity against SARS-CoV-2 increases either by infection or by unprecedented mass vaccination. A substantial change in population immunity is expected to contribute to the control of transmission. It is essential to monitor the extension and duration of the population's immunity to support the decisions of health authorities in each region and country, directed to chart the progressive return to normality. For this purpose, the availability of simple and cheap methods to monitor the levels of relevant antibodies in the population is a widespread necessity. Here, we describe the development of an RBD-based ELISA for the detection of specific antibodies in large numbers of samples. The recombinant expression of an RBD-poly-His fragment was carried out using either bacterial or eukaryotic cells in in vitro culture. After affinity chromatography purification, the performance of both recombinant products was compared by ELISA in similar trials. Our results showed that eukaryotic RBD increased the sensitivity of the assay. Interestingly, our results also support a correlation of the eukaryotic RBD-based ELISA with other assays aimed to test for neutralizing antibodies, which suggests that it provides an indication of protective immunity against SARS-CoV-2.

3.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-332231

ABSTRACT

In SARS-CoV-2, there is an overactivation of the immune system that triggers systemic hyperinflammation that causes lung damage;therefore, the use of convalescent plasma (CP) has been considered for its immunological mechanisms that could benefit patients in moderate and severe stages of the disease. This study evaluated the safety and efficacy of the use of convalescent donor plasma for COVID-19 to reduce mortality in patients with SARS-CoV-2 stage II (moderate) and stage III (severe) disease. Material: and methods A double-blind, randomized controlled clinical trial was conducted from May 20 to December 10, 2020. Thirty-nine participants with moderate (II) and severe (III) stage COVID-19 confirmed by RT-PCR and tomography were included. The study randomization rate was set at 3:1. Convalescent plasmas were chosen for application with a neutralizing antibody titer of ≥ 1:32. Patient follow-up included assessment by Sequential Organ Failure Assessment (SOFA) score and use of the Oxygenation Index (PAO 2 /FIO 2 ) index and monitoring of blood markers, such as C Reactive Protein (CRP), D-Dimer (DD), ferritin, IgG antibody titers against SARS-COV-2, and inflammatory cytokines at days three and seven post-treatment. Results: We observed a significantly lower 21-day post-transfusion mortality HR: 0.17 [95.0% CI 0.07-0.45, p<0.001] in the group receiving convalescent plasma compared to the control group;protective units (PU) in the group receiving convalescent plasma after seven days were significantly higher 512 (32-16384) vs 96 (32-256), p=0.01;the SOFA scale decreased to 3.7 ± 2.02 vs 7.1 ± 2.8, p<0.001 and the PAO 2 /FIO 2 index showed a significant improvement in the group receiving convalescent plasma 251.01 ± 109.4 vs 109.2 ± 62.4, p<0.001, vs the control group. In terms of safety, no adverse events related to the transfusion of convalescent plasma were observed. Conclusion: Convalescent plasma is safe and effective, as it decreases mortality in the convalescent plasma group compared to the control group.

4.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-308467

ABSTRACT

Background: CXCL17 is chemotactic for myeloid cells, exhibits broad-spectrum bactericidal activity, and is expressed in mucosal tissues. This chemokine is constitutively expressed in the respiratory tract, suggesting a role for CXCL17 in lung defenses. However, little is known about the possible participation of CXCL17 during respiratory infections in humans. Here, we evaluated the role of CXCL17 as a biomarker in patients with severe pandemic influenza A(H1N1) and coronavirus disease 2019 (COVID-19). MethodsWe conducted a prospective cohort study in hospitalized patients with severe influenza A(H1N1) and COVID-19 admitted to two national reference centers in Mexico City. Peripheral blood samples were obtained on admission for determinations of the serum levels of CXCL17 by enzyme-linked immunosorbent assay (ELISA). The expression of CXCL17 in lung autopsy specimens from patients that succumbed to both diseases was assessed by immunohistochemistry (IHQ). Serum CXCL17 levels were compared between patients grouped according to their disease and clinical outcome. The diagnostic and predictive value of serum CXCL17 levels was evaluated using machine-learning algorithms and regression analyses. ResultsA total of 92 patients were enrolled in the study, from which 68 were infected with influenza and 24 had COVID-19. Their clinical characteristics were similar, although dyspnea, rhinorrhea, and sputum production were more common during influenza, whereas dry cough and vomit were more frequent among COVID-19 patients. Both diseases induced the local expression of CXCL17 in the lung. However, serum levels of CXCL17 were increased only in patients with influenza but not COVID-19. CXCL17 not only differentiates influenza from COVID-19 but serves as a prognostic biomarker associated with mortality and renal failure in influenza patients. Using cell culture assays, we also identified that human alveolar A549 cells and peripheral blood monocyte-derived macrophages produce CXCL17 after influenza A(H1N1) pdm09 virus infection. ConclusionsOur results suggest a possible role for CXCL17 in the pathogenesis of influenza A(H1N1), supporting the use of this molecule as a prognostic biomarker. Future studies on the role of CXCL17 in COVID-19 are warranted.

5.
BMC Infect Dis ; 21(1): 1170, 2021 Nov 20.
Article in English | MEDLINE | ID: covidwho-1526605

ABSTRACT

BACKGROUND: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX ). METHODS: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. RESULTS: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. CONCLUSIONS: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care.


Subject(s)
COVID-19 , COVID-19/therapy , Humans , Immunization, Passive , Randomized Controlled Trials as Topic , SARS-CoV-2 , Treatment Outcome
8.
Front Immunol ; 12: 593595, 2021.
Article in English | MEDLINE | ID: covidwho-1229174

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), is a global health threat with the potential to cause severe disease manifestations in the lungs. Although COVID-19 has been extensively characterized clinically, the factors distinguishing SARS-CoV-2 from other respiratory viruses are unknown. Here, we compared the clinical, histopathological, and immunological characteristics of patients with COVID-19 and pandemic influenza A(H1N1). We observed a higher frequency of respiratory symptoms, increased tissue injury markers, and a histological pattern of alveolar pneumonia in pandemic influenza A(H1N1) patients. Conversely, dry cough, gastrointestinal symptoms and interstitial lung pathology were observed in COVID-19 cases. Pandemic influenza A(H1N1) was characterized by higher levels of IL-1RA, TNF-α, CCL3, G-CSF, APRIL, sTNF-R1, sTNF-R2, sCD30, and sCD163. Meanwhile, COVID-19 displayed an immune profile distinguished by increased Th1 (IL-12, IFN-γ) and Th2 (IL-4, IL-5, IL-10, IL-13) cytokine levels, along with IL-1ß, IL-6, CCL11, VEGF, TWEAK, TSLP, MMP-1, and MMP-3. Our data suggest that SARS-CoV-2 induces a dysbalanced polyfunctional inflammatory response that is different from the immune response against pandemic influenza A(H1N1). Furthermore, we demonstrated the diagnostic potential of some clinical and immune factors to differentiate both diseases. These findings might be relevant for the ongoing and future influenza seasons in the Northern Hemisphere, which are historically unique due to their convergence with the COVID-19 pandemic.


Subject(s)
COVID-19 , Cytokines , Influenza A Virus, H1N1 Subtype , Influenza, Human , Matrix Metalloproteinase 1 , Matrix Metalloproteinase 3 , Receptors, Immunologic , Adult , Aged , COVID-19/blood , COVID-19/epidemiology , COVID-19/immunology , Cytokines/blood , Cytokines/immunology , Female , Humans , Influenza A Virus, H1N1 Subtype/immunology , Influenza A Virus, H1N1 Subtype/metabolism , Influenza, Human/blood , Influenza, Human/epidemiology , Influenza, Human/immunology , Male , Matrix Metalloproteinase 1/blood , Matrix Metalloproteinase 1/immunology , Matrix Metalloproteinase 3/blood , Matrix Metalloproteinase 3/immunology , Middle Aged , Prospective Studies , Receptors, Immunologic/blood , Receptors, Immunologic/immunology , Th1 Cells/immunology , Th2 Cells/immunology
9.
Front Immunol ; 12: 633297, 2021.
Article in English | MEDLINE | ID: covidwho-1133913

ABSTRACT

The C-X-C motif chemokine ligand 17 (CXCL17) is chemotactic for myeloid cells, exhibits bactericidal activity, and exerts anti-viral functions. This chemokine is constitutively expressed in the respiratory tract, suggesting a role in lung defenses. However, little is known about the participation of CXCL17 against relevant respiratory pathogens in humans. Here, we evaluated the serum levels and lung tissue expression pattern of CXCL17 in a cohort of patients with severe pandemic influenza A(H1N1) from Mexico City. Peripheral blood samples obtained on admission and seven days after hospitalization were processed for determinations of serum CXCL17 levels by enzyme-linked immunosorbent assay (ELISA). The expression of CXCL17 was assessed by immunohistochemistry (IHQ) in lung autopsy specimens from patients that succumbed to the disease. Serum CXCL17 levels were also analyzed in two additional comparative cohorts of coronavirus disease 2019 (COVID-19) and pulmonary tuberculosis (TB) patients. Additionally, the expression of CXCL17 was tested in lung autopsy specimens from COVID-19 patients. A total of 122 patients were enrolled in the study, from which 68 had pandemic influenza A(H1N1), 24 had COVID-19, and 30 with PTB. CXCL17 was detected in post-mortem lung specimens from patients that died of pandemic influenza A(H1N1) and COVID-19. Interestingly, serum levels of CXCL17 were increased only in patients with pandemic influenza A(H1N1), but not COVID-19 and PTB. CXCL17 not only differentiated pandemic influenza A(H1N1) from other respiratory infections but showed prognostic value for influenza-associated mortality and renal failure in machine-learning algorithms and regression analyses. Using cell culture assays, we also identified that human alveolar A549 cells and peripheral blood monocyte-derived macrophages increase their CXCL17 production capacity after influenza A(H1N1) pdm09 virus infection. Our results for the first time demonstrate an induction of CXCL17 specifically during pandemic influenza A(H1N1), but not COVID-19 and PTB in humans. These findings could be of great utility to differentiate influenza and COVID-19 and to predict poor prognosis specially at settings of high incidence of pandemic A(H1N1). Future studies on the role of CXCL17 not only in severe pandemic influenza, but also in seasonal influenza, COVID-19, and PTB are required to validate our results.


Subject(s)
Biomarkers/metabolism , Chemokines, CXC/metabolism , Influenza A Virus, H1N1 Subtype/physiology , Influenza, Human/diagnosis , Lung/metabolism , Mycobacterium tuberculosis/physiology , SARS-CoV-2/physiology , Adult , Aged , COVID-19/diagnosis , COVID-19/mortality , Chemokines, CXC/genetics , Chemokines, CXC/immunology , Cohort Studies , Disease Progression , Female , Humans , Influenza, Human/mortality , Lung/pathology , Male , Mexico , Middle Aged , Pandemics , Patient Outcome Assessment , Prognosis , Survival Analysis , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/mortality , Young Adult
SELECTION OF CITATIONS
SEARCH DETAIL