65 research outputs found
Phenotype of BTKâlacking myeloid cells during prolonged COVIDâ19 and upon convalescent plasma
© 2022 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.XLA patient with 7-month course of COVID-19 with persistent plasma SARS-CoV-2 load revealed a sustained non-inflammatory profile of myeloid cells in association with contained severity of disease, arguing in favor of the use of BTK inhibitors in SARS-COV-2 infection.This work was funded by the following grants from Fundação para a CiĂȘncia e a Tecnologia (FCT), Portugal, through âApoio Especial Research4COVID-19,â project numbers 125 and 803. AndrĂ© M. C. Gomes and Guilherme B. Farias received Fellowships funded by FCT (Doctorates4COVID-19, 2020.10202.BD), and Janssen-Cilag FarmacĂȘutica, respectively.info:eu-repo/semantics/publishedVersio
Acute HIV-1 and SARS-CoV-2 infections Share Slan+ Monocyte Depletion - evidence from an hyperacute HIV-1 case report
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).Monocytes are key modulators in acute viral infections, determining both inflammation and development of specific B- and T-cell responses. Recently, these cells were shown to be associated to different SARS-CoV-2 infection outcome. However, their role in acute HIV-1 infection remains unclear. We had the opportunity to evaluate the mononuclear cell compartment in an early hyper-acute HIV-1 patient in comparison with an untreated chronic HIV-1 and a cohort of SARS-CoV-2 infected patients, by high dimensional flow cytometry using an unsupervised approach. A distinct polarization of the monocyte phenotype was observed in the two viral infections, with maintenance of pro-inflammatory M1-like profile in HIV-1, in contrast to the M2-like immunosuppressive shift in SARS-CoV-2. Noticeably, both acute infections had reduced CD14low/-CD16+ non-classical monocytes, with depletion of the population expressing Slan (6-sulfo LacNac), which is thought to contribute to immune surveillance through pro-inflammatory properties. This depletion indicates a potential role of these cells in acute viral infection, which has not previously been explored. The inflammatory state accompanied by the depletion of Slan+ monocytes may provide new insights on the critical events that determine the rate of viral set-point in acute HIV-1 infection and subsequent impact on transmission and reservoir establishment.This work was funded by the following grants from Fundação para a CiĂȘncia e a Tecnologia (FCT), Portugal, through âApoio Especial Research4COVID-19â, project numbers 125 to S.M.F. and 803 to A.C.T. Fellowships funded by FCT (Doctorates4COVID-19, 2020.10202.BD), and Janssen-Cilag FarmacĂȘutica were received by A.M.C.G. and G.B.F., respectively.info:eu-repo/semantics/publishedVersio
Severe COVID-19 recovery is associated with timely acquisition of a myeloid cell immune-regulatory phenotype
Copyright © 2021 Trombetta, Farias, Gomes, Godinho-Santos, Rosmaninho, Conceição, Laia, Santos, Almeida, Mota, Gomes, Serrano, Veldhoen, Sousa and Fernandes. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.After more than one year since the COVID-19 outbreak, patients with severe disease still constitute the bottleneck of the pandemic management. Aberrant inflammatory responses, ranging from cytokine storm to immune-suppression, were described in COVID-19 and no treatment was demonstrated to change the prognosis significantly. Therefore, there is an urgent need for understanding the underlying pathogenic mechanisms to guide therapeutic interventions. This study was designed to assess myeloid cell activation and phenotype leading to recovery in patients surviving severe COVID-19. We evaluated longitudinally patients with COVID-19 related respiratory insufficiency, stratified according to the need of intensive care unit admission (ICU, n = 11, and No-ICU, n = 9), and age and sex matched healthy controls (HCs, n = 11), by flow cytometry and a wide array of serum inflammatory/immune-regulatory mediators. All patients featured systemic immune-regulatory myeloid cell phenotype as assessed by both unsupervised and supervised analysis of circulating monocyte and dendritic cell subsets. Specifically, we observed a reduction of CD14lowCD16+ monocytes, and reduced expression of CD80, CD86, and Slan. Moreover, mDCs, pDCs, and basophils were significantly reduced, in comparison to healthy subjects. Contemporaneously, both monocytes and DCs showed increased expression of CD163, CD204, CD206, and PD-L1 immune-regulatory markers. The expansion of M2-like monocytes was significantly higher at admission in patients featuring detectable SARS-CoV-2 plasma viral load and it was positively correlated with the levels of specific antibodies. In No-ICU patients, we observed a peak of the alterations at admission and a progressive regression to a phenotype similar to HCs at discharge. Interestingly, in ICU patients, the expression of immuno-suppressive markers progressively increased until discharge. Notably, an increase of M2-like HLA-DRhighPD-L1+ cells in CD14++CD16- monocytes and in dendritic cell subsets was observed at ICU discharge. Furthermore, IFN-Îł and IL-12p40 showed a decline over time in ICU patients, while high values of IL1RA and IL-10 were maintained. In conclusion, these results support that timely acquisition of a myeloid cell immune-regulatory phenotype might contribute to recovery in severe systemic SARS-CoV-2 infection and suggest that therapeutic agents favoring an innate immune system regulatory shift may represent the best strategy to be implemented at this stage.The Research was funded by Fundação para a CiĂȘncia e Tecnologia (FCT), âAPOIO ESPECIAL RESEARCH 4COVID-19â projects 803, 125, 231_596873172, and 729. AMCG and GF received fellowships funded by FCT (DOCTORATES4COVID-19, 2020.10202.BD), and JANSSEN- CILAG FARMACĂUTICA, respectively. The funder was not involved in the study design, collection, analysis, interpretation of data, writing of the article or decision to submit it for publication. MV was supported by the European Union H2020 ERA project (No 667824 â EXCELLtoINNOV). This project has received funding from the European Unionâs Horizon 2020 research and innovation programme under grant agreement No 667824.info:eu-repo/semantics/publishedVersio
SARSâCoV2 pneumonia recovery is linked to expansion of innate lymphoid cells type 2 expressing CCR10
© 2021 The Authors. European Journal of Immunology published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.Accelerate lung repair in SARS-CoV-2 pneumonia is essential for pandemic handling. Innate lymphoid cells (ILCs) are likely players, given their role in mucosal protection and tissue homeostasis. We studied ILC subpopulations at two time points in a cohort of patients admitted in the hospital due to SARS-CoV-2 infection. COVID-19 patients with moderate/severe respiratory failure featured profound depletion of circulating ILCs at hospital admission, in agreement with overall lymphocyte depletion. However, ILCs recovered in direct correlation with lung function improvement as measured by oxygenation index and in negative association with inflammatory and lung/endothelial damage markers like RAGE. While both ILC1 and ILC2 expanded, ILC2 showed the most striking phenotype changes, with CCR10 upregulation in strong correlation with these parameters. Overall, CCR10+ ILC2 emerge as relevant contributors to SARS-CoV-2 pneumonia recovery.This work was funded by the following grants from Fundação para a CiĂȘncia e a Tecnologia (FCT), Portugal, through âAPOIO ESPECIAL RESEARCH4COVID-19,â project numbers 125 to SMF and 803 to ACT. AMCG and GBF received fellowships funded by FCT (DOCTORATES4COVID-19, 2020.10202.BD) and JANSSEN- CILAG FARMACĂUTICA, respectively.info:eu-repo/semantics/publishedVersio
A New Approach for Heparin Standardization: Combination of Scanning UV Spectroscopy, Nuclear Magnetic Resonance and Principal Component Analysis
The year 2007 was marked by widespread adverse clinical responses to heparin use, leading to a global recall of potentially affected heparin batches in 2008. Several analytical methods have since been developed to detect impurities in heparin preparations; however, many are costly and dependent on instrumentation with only limited accessibility. A method based on a simple UV-scanning assay, combined with principal component analysis (PCA), was developed to detect impurities, such as glycosaminoglycans, other complex polysaccharides and aromatic compounds, in heparin preparations. Results were confirmed by NMR spectroscopy. This approach provides an additional, sensitive tool to determine heparin purity and safety, even when NMR spectroscopy failed, requiring only standard laboratory equipment and computing facilities
Pervasive gaps in Amazonian ecological research
Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4
While the increasing availability of global databases on ecological communities has advanced our knowledge
of biodiversity sensitivity to environmental changes,5â7 vast areas of the tropics remain understudied.8â11 In
the American tropics, Amazonia stands out as the worldâs most diverse rainforest and the primary source of
Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13â15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazonâs biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus
crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced
environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian
Amazonia, while identifying the regionâs vulnerability to environmental change. 15%â18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by
2050. This means that unless we take immediate action, we will not be able to establish their current status,
much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio
- âŠ