scholarly journals Targeting of the CD80/86 proinflammatory axis as a therapeutic strategy to prevent severe COVID-19

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Antonio Julià ◽  
Irene Bonafonte-Pardàs ◽  
Antonio Gómez ◽  
María López-Lasanta ◽  
Mireia López-Corbeto ◽  
...  
Keyword(s):  
Therapeutic Approach ◽  
Therapeutic Strategy ◽  
Bronchoalveolar Lavage Fluid ◽  
Functional Results ◽  
Lavage Fluid ◽  
Rna Seq ◽  
Epidemiological Evidence ◽  
Systemic Level ◽  
The Usa ◽  
Early Cohort

AbstractAn excessive immune response known as cytokine storm is the hallmark of severe COVID-19. The cause of this cytokine rampage is yet not known. Based on recent epidemiological evidence, we hypothesized that CD80/86 signaling is essential for this hyperinflammation, and that blocking this proinflammatory axis could be an effective therapeutic approach to protect against severe COVID-19. Here we provide exploratory evidence that abatacept, a drug that blocks CD80/86 co-stimulation, produces changes at the systemic level that are highly antagonistic of the proinflammatory processes elicited by COVID-19. Using RNA-seq from blood samples from a longitudinal cohort of n = 38 rheumatic patients treated with abatacept, we determined the immunological processes that are significantly regulated by this treatment. We then analyzed available blood RNA-seq from two COVID19 patient cohorts, a very early cohort from the epicenter of the pandemic in China (n = 3 COVID-19 cases and n = 3 controls), and a recent and larger cohort from the USA (n = 49 severe and n = 51 mild COVD-19 patients). We found a highly significant antagonism between SARS-CoV-2 infection and COVID-19 severity with the systemic response to abatacept. Analysis of previous single-cell RNA-seq data from bronchoalveolar lavage fluid from mild and severe COVID-19 patients and controls, reinforce the implication of the CD80/86 proinflammatory axis. Our functional results further support abatacept as a candidate therapeutic approach to prevent severe COVID-19.

scholarly journals COVID-19 Hyperinflammation: What about Neutrophils?

mSphere ◽  
2020 ◽  
Vol 5 (3) ◽  
Author(s):  
Athanasios Didangelos
Keyword(s):  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Published Data ◽  
Data Sets ◽  
Rna Seq ◽  
Inflammatory Genes ◽  
Infected Cells ◽  
Neutrophil Response ◽  
Druggable Targets

ABSTRACT COVID-19 is often related to hyperinflammation that drives lung or multiorgan injury. The immunopathological mechanisms that cause excessive inflammation are under investigation and constantly updated. Here, a gene network approach was used on recently published data sets to identify possible COVID-19 inflammatory mechanisms and bioactive genes. First, network analysis of putative SARS-CoV-2 cellular receptors led to the mining of a neutrophil-response signature and relevant inflammatory genes. Second, analysis of RNA-seq data sets of lung cells infected with SARS-CoV-2 revealed that infected cells expressed neutrophil-attracting chemokines. Third, analysis of RNA-seq data sets of bronchoalveolar lavage fluid cells from COVID-19 patients identified upregulation of neutrophil genes and chemokines. Different inflammatory genes mined here, including TNFR, IL-8, CXCR1, CXCR2, ADAM10, GPR84, MME, ANPEP, and LAP3, might be druggable targets in efforts to limit SARS-CoV-2 inflammation in severe clinical cases. The possible role of neutrophils in COVID-19 inflammation needs to be studied further.

scholarly journals E-cigarette or vaping product use-associated lung injury

2020 ◽  
Vol 81 (4) ◽  
pp. 1-9 ◽  
Author(s):  
Philip W Ind
Keyword(s):  
Respiratory Failure ◽  
Lung Injury ◽  
Bronchoalveolar Lavage Fluid ◽  
Recent Literature ◽  
Lavage Fluid ◽  
Probable Case ◽  
Product Use ◽  
Vitamin E Acetate ◽  
The Usa ◽  
The Uk

E-cigarette or vaping product use-associated lung injury is a recently recognised, acute pulmonary syndrome which has been reported (particularly from June to October 2019) throughout the USA, but not in Europe (although one probable case, in the UK, has been reported; Medicines and Healthcare products Regulatory Agency, 2020 ). It presents acutely, most often in young men, as severe pulmonary consolidation, usually with respiratory failure. The mortality is around 2%. The cause(s) are unknown, but it is associated with vaping, particularly using unlicensed cannabis-containing products with tetrahydrocannabinol. Vitamin E acetate, often present in tetrahydrocannabinol-containing vape products as a solvent, has been implicated, as it has been identified in the bronchoalveolar lavage fluid of patients with e-cigarette or vaping product use-associated lung injury. This article reviews the recent literature, including clinical features, presentation and investigations, and possible mechanisms, in the context of vaping practices in the USA and the UK.

scholarly journals Blockade of glutamate receptor ameliorates lipopolysaccharide-induced sepsis through regulation of neuropeptides

2018 ◽  
Vol 38 (3) ◽  
Author(s):  
Zhai Zhe ◽  
Bi Hongyuan ◽  
Qiao Wenjuan ◽  
Wang Peng ◽  
Liu Xiaowei ◽  
...  
Keyword(s):  
Animal Models ◽  
Glutamate Receptor ◽  
Therapeutic Strategy ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Control Group ◽  
Protective Effects ◽  
Mk 801 ◽  
Aspartate Receptor ◽  
The Central Nervous System

Glutamate receptors (N-methyl-d-aspartate receptor (NMDAR)) are expressed mainly in the central nervous system (CNS), but several potentially important exceptions are worth mentioning. Recently, NMDAR, a glutamate receptor, has been reported to be found in the lungs. NMDAR is activated in acute lung injury (ALI). Here, the present experiment was designed to examine whether NMDAR blockade (MK-801) ameliorates ALI through affecting neuropeptides in LPS-induced sepsis animal models. Male Kunming mice were divided into control group, LPS group, control + MK-801 group, and LPS + MK-801 group. Bronchoalveolar lavage fluid (BALF) was collected and evaluated. The lung histological pathology was assayed by immunocytochemistry staining. Western blot was used to measure PGP9.5, substance P (SP), and vasoactive intestinal polypeptide (VIP). Results showed that LPS-induced mice animal models were ameliorated by co-treatment with the MK-801, an uncompetitive NMDAR antagonist. Moreover, the protective effects of MK-801 attributed to the increased secretion of VIP and decreased secretion of SP. The results of the present study indicated that the blockade of NMDAR may represent a promising therapeutic strategy for the treatment of sepsis-associated ALI through regulation of neuropeptides.

Identification of neutrophil chemotactic factors in bronchoalveolar lavage fluid of asthmatic patients

1997 ◽  
Vol 27 (4) ◽  
pp. 396-405 ◽  
Author(s):  
L. M. TERAN ◽  
M. G. CAMPOS ◽  
B. T. BEGISHVILLI ◽  
J.-M. SCHRODER ◽  
R. DJUKANOVIC ◽  
...  
Keyword(s):  
Bronchoalveolar Lavage ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Asthmatic Patients ◽  
Chemotactic Factors

scholarly journals Identification of Lung and Blood Microbiota Implicated in COVID-19 Prognosis

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1452
Author(s):  
Kypros Dereschuk ◽  
Lauren Apostol ◽  
Ishan Ranjan ◽  
Jaideep Chakladar ◽  
Wei Tse Li ◽  
...  
Keyword(s):  
Peripheral Blood Mononuclear Cell ◽  
Lung Biopsy ◽  
Bronchoalveolar Lavage Fluid ◽  
Human Microbiome ◽  
Lavage Fluid ◽  
Immune Dysregulation ◽  
Peripheral Blood Mononuclear ◽  
Inflammatory Pathways ◽  
Immune Therapies ◽  
Blood Microbiota

The implications of the microbiome on Coronavirus disease 2019 (COVID-19) prognosis has not been thoroughly studied. In this study we aimed to characterize the lung and blood microbiome and their implication on COVID-19 prognosis through analysis of peripheral blood mononuclear cell (PBMC) samples, lung biopsy samples, and bronchoalveolar lavage fluid (BALF) samples. In all three tissue types, we found panels of microbes differentially abundant between COVID-19 and normal samples correlated to immune dysregulation and upregulation of inflammatory pathways, including key cytokine pathways such as interleukin (IL)-2, 3, 5-10 and 23 signaling pathways and downregulation of anti-inflammatory pathways including IL-4 signaling. In the PBMC samples, six microbes were correlated with worse COVID-19 severity, and one microbe was correlated with improved COVID-19 severity. Collectively, our findings contribute to the understanding of the human microbiome and suggest interplay between our identified microbes and key inflammatory pathways which may be leveraged in the development of immune therapies for treating COVID-19 patients.

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