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1.
Cell Transplant ; 30: 9636897211054481, 2021.
Article in English | MEDLINE | ID: covidwho-1511642

ABSTRACT

Biological and cellular interleukin-6 (IL-6)-related therapies have been used to treat severe COVID-19 pneumonia with hyperinflammatory syndrome and acute respiratory failure, which prompted further exploration of the role of IL-6 in human umbilical cord mesenchymal stem cell (hUCMSC) therapy. Peripheral blood mononuclear cells (PBMCs) were responders cocultured with hUCMSCs or exogenous IL-6. A PBMC suppression assay was used to analyze the anti-inflammatory effects via MTT assay. The IL-6 concentration in the supernatant was measured using ELISA. The correlation between the anti-inflammatory effect of hUCMSCs and IL-6 levels and the relevant roles of IL-6 and IL-6 mRNA expression was analyzed using the MetaCore functional network constructed from gene microarray data. The location of IL-6 and IL-6 receptor (IL-6R) expression was further evaluated. We reported that hUCMSCs did not initially exert any inhibitory effect on PHA-stimulated proliferation; however, a potent inhibitory effect on PHA-stimulated proliferation was observed, and the IL-6 concentration reached approximately 1000 ng/mL after 72 hours. Exogenous 1000 ng/mL IL-6 inhibited PHA-stimulated inflammation but less so than hUCMSCs. The inhibitory effects of hUCMSCs on PHA-stimulated PBMCs disappeared after adding an IL-6 neutralizing antibody or pretreatment with tocilizumab (TCZ), an IL-6R antagonist. hUCMSCs exert excellent anti-inflammatory effects by inducing higher IL-6 levels, which is different from TCZ. High concentration of IL-6 cytokine secretion plays an important role in the anti-inflammatory effect of hUCMSC therapy. Initial hUCMSC therapy, followed by TCZ, seems to optimize the therapeutic potential to treat COVID-19-related acute respiratory distress syndrome (ARDS).


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/complications , Interleukin-6/biosynthesis , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/metabolism , Respiratory Distress Syndrome/therapy , SARS-CoV-2 , Antibodies, Monoclonal, Humanized/pharmacology , Antibodies, Neutralizing/immunology , Cells, Cultured , Coculture Techniques , Combined Modality Therapy , DNA, Complementary/genetics , Gene Expression Regulation/drug effects , Humans , Inflammation , Interleukin-6/genetics , Interleukin-6/pharmacology , Leukocytes, Mononuclear/cytology , Leukocytes, Mononuclear/drug effects , Leukocytes, Mononuclear/metabolism , Lymphocyte Activation/drug effects , Phytohemagglutinins/pharmacology , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Receptors, Interleukin-6/antagonists & inhibitors , Receptors, Interleukin-6/biosynthesis , Receptors, Interleukin-6/genetics , Respiratory Distress Syndrome/drug therapy , Respiratory Distress Syndrome/etiology , Umbilical Cord/cytology
2.
Cell Death Dis ; 12(11): 1019, 2021 10 29.
Article in English | MEDLINE | ID: covidwho-1493083

ABSTRACT

Clinical outcomes of COVID-19 patients are worsened by the presence of co-morbidities, especially cancer leading to elevated mortality rates. SARS-CoV-2 infection is known to alter immune system homeostasis. Whether cancer patients developing COVID-19 present alterations of immune functions which might contribute to worse outcomes have so far been poorly investigated. We conducted a multi-omic analysis of immunological parameters in peripheral blood mononuclear cells (PBMCs) of COVID-19 patients with and without cancer. Healthy donors and SARS-CoV-2-negative cancer patients were also included as controls. At the infection peak, cytokine multiplex analysis of blood samples, cytometry by time of flight (CyTOF) cell population analyses, and Nanostring gene expression using Pancancer array on PBMCs were performed. We found that eight pro-inflammatory factors (IL-6, IL-8, IL-13, IL-1ra, MIP-1a, IP-10) out of 27 analyzed serum cytokines were modulated in COVID-19 patients irrespective of cancer status. Diverse subpopulations of T lymphocytes such as CD8+T, CD4+T central memory, Mucosal-associated invariant T (MAIT), natural killer (NK), and γδ T cells were reduced, while B plasmablasts were expanded in COVID-19 cancer patients. Our findings illustrate a repertoire of aberrant alterations of gene expression in circulating immune cells of COVID-19 cancer patients. A 19-gene expression signature of PBMCs is able to discriminate COVID-19 patients with and without solid cancers. Gene set enrichment analysis highlights an increased gene expression linked to Interferon α, γ, α/ß response and signaling which paired with aberrant cell cycle regulation in cancer patients. Ten out of the 19 genes, validated in a real-world consecutive cohort, were specific of COVID-19 cancer patients independently from different cancer types and stages of the diseases, and useful to stratify patients in a COVID-19 disease severity-manner. We also unveil a transcriptional network involving gene regulators of both inflammation response and proliferation in PBMCs of COVID-19 cancer patients.


Subject(s)
Antibodies, Viral/blood , COVID-19/immunology , Cytokines/blood , Leukocytes, Mononuclear/immunology , Neoplasms/immunology , COVID-19/pathology , Case-Control Studies , Female , Humans , Leukocytes, Mononuclear/cytology , Male , Neoplasms/pathology
3.
Sci Rep ; 11(1): 20833, 2021 10 21.
Article in English | MEDLINE | ID: covidwho-1479812

ABSTRACT

Several single-cell RNA sequencing (scRNA-seq) studies analyzing immune response to COVID-19 infection have been recently published. Most of these studies have small sample sizes, which limits the conclusions that can be made with high confidence. By re-analyzing these data in a standardized manner, we validated 8 of the 20 published results across multiple datasets. In particular, we found a consistent decrease in T-cells with increasing COVID-19 infection severity, upregulation of type I Interferon signal pathways, presence of expanded B-cell clones in COVID-19 patients but no consistent trend in T-cell clonal expansion. Overall, our results show that the conclusions drawn from scRNA-seq data analysis of small cohorts of COVID-19 patients need to be treated with some caution.


Subject(s)
Biomarkers/metabolism , COVID-19/immunology , COVID-19/metabolism , RNA, Small Cytoplasmic , Single-Cell Analysis , Bronchoalveolar Lavage Fluid , Computational Biology , Databases, Factual , Gene Expression Profiling/methods , Genome, Human , Genome, Viral , Humans , Immunity , Leukocytes, Mononuclear/cytology , RNA-Seq , Reproducibility of Results , SARS-CoV-2 , Sequence Analysis, RNA/methods , Signal Transduction , Up-Regulation
4.
Int J Mol Sci ; 22(20)2021 Oct 18.
Article in English | MEDLINE | ID: covidwho-1470894

ABSTRACT

Infection caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2) in many cases is accompanied by the release of a large amount of proinflammatory cytokines in an event known as "cytokine storm", which is associated with severe coronavirus disease 2019 (COVID-19) cases and high mortality. The excessive production of proinflammatory cytokines is linked, inter alia, to the enhanced activity of receptors capable of recognizing the conservative regions of pathogens and cell debris, namely TLRs, TREM-1 and TNFR1. Here we report that peptides derived from innate immunity protein Tag7 inhibit activation of TREM-1 and TNFR1 receptors during acute inflammation. Peptides from the N-terminal fragment of Tag7 bind only to TREM-1, while peptides from the C-terminal fragment interact solely with TNFR1. Selected peptides are capable of inhibiting the production of proinflammatory cytokines both in peripheral blood mononuclear cells (PBMCs) from healthy donors and in vivo in the mouse model of acute lung injury (ALI) by diffuse alveolar damage (DAD). Treatment with peptides significantly decreases the infiltration of mononuclear cells to lungs in animals with DAD. Our findings suggest that Tag7-derived peptides might be beneficial in terms of the therapy or prevention of acute lung injury, e.g., for treating COVID-19 patients with severe pulmonary lesions.


Subject(s)
Acute Lung Injury/pathology , Cytokines/chemistry , Peptides/metabolism , Receptors, Tumor Necrosis Factor, Type I/metabolism , Triggering Receptor Expressed on Myeloid Cells-1/metabolism , Acute Lung Injury/metabolism , Animals , Cytokines/genetics , Cytokines/metabolism , Disease Models, Animal , Humans , Interferon-gamma/genetics , Interferon-gamma/metabolism , Leukocytes, Mononuclear/cytology , Leukocytes, Mononuclear/drug effects , Leukocytes, Mononuclear/metabolism , Lipopolysaccharides/pharmacology , Lung/metabolism , Lung/pathology , Lymphocyte Activation/drug effects , Male , Mice , Mice, Inbred ICR , Peptides/chemistry , Peptides/pharmacology , Protein Binding , Receptors, Tumor Necrosis Factor, Type I/antagonists & inhibitors , Triggering Receptor Expressed on Myeloid Cells-1/antagonists & inhibitors
5.
Front Immunol ; 12: 744799, 2021.
Article in English | MEDLINE | ID: covidwho-1448731

ABSTRACT

Sepsis is a global health emergency, which is caused by various sources of infection that lead to changes in gene expression, protein-coding, and metabolism. Advancements in "omics" technologies have provided valuable tools to unravel the mechanisms involved in the pathogenesis of this disease. In this study, we performed shotgun mass spectrometry in peripheral blood mononuclear cells (PBMC) from septic patients (N=24) and healthy controls (N=9) and combined these results with two public microarray leukocytes datasets. Through combination of transcriptome and proteome profiling, we identified 170 co-differentially expressed genes/proteins. Among these, 122 genes/proteins displayed the same expression trend. Ingenuity Pathway Analysis revealed pathways related to lymphocyte functions with decreased status, and defense processes that were predicted to be strongly increased. Protein-protein interaction network analyses revealed two densely connected regions, which mainly included down-regulated genes/proteins that were related to the transcription of RNA, translation of proteins, and mitochondrial translation. Additionally, we identified one module comprising of up-regulated genes/proteins, which were mainly related to low-density neutrophils (LDNs). LDNs were reported in sepsis and in COVID-19. Changes in gene expression level were validated using quantitative real-time PCR in PBMCs from patients with sepsis. To further support that the source of the upregulated module of genes/proteins found in our results were derived from LDNs, we identified an increase of this population by flow cytometry in PBMC samples obtained from the same cohort of septic patients included in the proteomic analysis. This study provides new insights into a reprioritization of biological functions in response to sepsis that involved a transcriptional and translational shutdown of genes/proteins, with exception of a set of genes/proteins related to LDNs and host-defense system.


Subject(s)
Leukocytes, Mononuclear/metabolism , Neutrophils/metabolism , Sepsis/metabolism , Databases, Factual , Gene Expression Profiling , Gene Expression Regulation , Humans , Leukocytes, Mononuclear/cytology , Myeloid-Derived Suppressor Cells/cytology , Myeloid-Derived Suppressor Cells/metabolism , Neutrophils/cytology , Protein Interaction Maps , Proteomics , Sepsis/genetics , Sepsis/immunology
6.
Cells ; 10(10)2021 10 03.
Article in English | MEDLINE | ID: covidwho-1444118

ABSTRACT

The PD-L1/PD-1 immune checkpoint axis is the strongest T cell exhaustion inducer. As immune dysfunction occurs during obesity, we analyzed the impact of obesity on PD-L1/PD-1 expression in white adipose tissue (WAT) in mice and in human white adipocytes. We found that PD-L1 was overexpressed in WAT of diet-induced obese mice and was associated with increased expression of PD-1 in visceral but not subcutaneous WAT. Human in vitro cocultures with adipose-tissue-derived mesenchymal stem cells (ASC) and mononuclear cells demonstrated that the presence of ASC harvested from obese WAT (i) enhanced PD-L1 expression as compared with ASC from lean WAT, (ii) decreased Th1 cell cytokine secretion, and (iii) resulted in decreased cytolytic activity towards adipocytes. Moreover, (iv) the implication of PD-L1 in obese ASC-mediated T cell dysfunction was demonstrated through PD-L1 blockade. Finally, (v) conditioned media gathered from these cocultures enhanced PD-L1 expression in freshly differentiated adipocytes, depending on IFNγ. Altogether, our results suggest that PD-L1 is overexpressed in the WAT of obese individuals during IFNγ secretion, leading to T cell dysfunction and notably reduced cytolytic activity. Such a mechanism could shed light on why adipose-tissue-infiltrating viruses, such as SARS-CoV-2, can worsen disease in obese individuals.


Subject(s)
Adipose Tissue, White/metabolism , B7-H1 Antigen/biosynthesis , Gene Expression Regulation , Mesenchymal Stem Cells/cytology , Obesity/metabolism , T-Lymphocytes/immunology , Animals , COVID-19/immunology , Cell Differentiation , Coculture Techniques , Humans , Immunohistochemistry , Inflammation , Interferon-gamma/metabolism , Leukocytes, Mononuclear/cytology , Male , Mice , Mice, Inbred C57BL , Obesity/immunology , SARS-CoV-2 , T-Lymphocytes/cytology
7.
Elife ; 102021 08 23.
Article in English | MEDLINE | ID: covidwho-1369909

ABSTRACT

The exact immunopathophysiology of community-acquired pneumonia (CAP) caused by SARS-CoV-2 (COVID-19) remains clouded by a general lack of relevant disease controls. The scarcity of single-cell investigations in the broader population of patients with CAP renders it difficult to distinguish immune features unique to COVID-19 from the common characteristics of a dysregulated host response to pneumonia. We performed integrated single-cell transcriptomic and proteomic analyses in peripheral blood mononuclear cells from a matched cohort of eight patients with COVID-19, eight patients with CAP caused by Influenza A or other pathogens, and four non-infectious control subjects. Using this balanced, multi-omics approach, we describe shared and diverging transcriptional and phenotypic patterns-including increased levels of type I interferon-stimulated natural killer cells in COVID-19, cytotoxic CD8 T EMRA cells in both COVID-19 and influenza, and distinctive monocyte compositions between all groups-and thereby expand our understanding of the peripheral immune response in different etiologies of pneumonia.


Subject(s)
COVID-19/immunology , Community-Acquired Infections/immunology , Influenza, Human/immunology , Single-Cell Analysis , Adult , Female , Humans , Leukocytes, Mononuclear/cytology , Leukocytes, Mononuclear/immunology , Male , Middle Aged
8.
J Cell Mol Med ; 25(12): 5823-5827, 2021 06.
Article in English | MEDLINE | ID: covidwho-1221608

ABSTRACT

The long non-coding RNAs (lncRNAs) play a critical regulatory role in the host response to the viral infection. However, little is understood about the transcriptome architecture, especially lncRNAs pattern during the SARS-CoV-2 infection. In the present study, using publicly available RNA sequencing data of bronchoalveolar lavage fluid (BALF) and peripheral blood mononuclear cells (PBMC) samples from COVID-19 patients and healthy individuals, three interesting findings highlighted: (a) More than half of the interactions between lncRNAs-PCGs of BALF samples established by three trans-acting lncRNAs (HOTAIRM1, PVT1 and AL392172.1), which also exhibited the high affinity for binding to the SARS-CoV-2 genome, suggesting the major regulatory role of these lncRNAs during the SARS-CoV-2 infection. (b) lncRNAs of MALAT1 and NEAT1 are possibly contributed to the inflammation development in the SARS-CoV-2 infected cells. (c) In contrast to the 3' part of the SARS-CoV-2 genome, the 5' part can interact with many human lncRNAs. Therefore, the mRNA-based vaccines will not show any side effects because of the off-label interactions with the human lncRNAs. Overall, the putative functionalities of lncRNAs can be promising to design the non-coding RNA-based drugs and to inspect the efficiency of vaccines to overcome the current pandemic.


Subject(s)
COVID-19 , RNA, Long Noncoding/metabolism , RNA, Viral/metabolism , SARS-CoV-2/genetics , Bronchoalveolar Lavage Fluid/immunology , Bronchoalveolar Lavage Fluid/virology , COVID-19/immunology , COVID-19/virology , Databases, Nucleic Acid , Humans , Leukocytes, Mononuclear/cytology , Leukocytes, Mononuclear/immunology , Leukocytes, Mononuclear/virology
9.
Arch Med Res ; 51(7): 645-653, 2020 10.
Article in English | MEDLINE | ID: covidwho-1023467

ABSTRACT

BACKGROUND: The SARS-CoV-2 is the etiological agent causing COVID-19 which has infected more than 2 million people with more than 200000 deaths since its emergence in December 2019. In the majority of cases patients are either asymptomatic or show mild to moderate symptoms and signs of a common cold. A subset of patients, however, develop a severe atypical pneumonia, with the characteristic ground-glass appearance on chest x-ray and computerized tomography, which evolves into an acute respiratory distress syndrome, that requires mechanical ventilation and eventually results in multiple organ failure and death. The Molecular pathogenesis of COVID-19 is still unknown. AIM OF THE STUDY: In the present work we performed a stringent metanalysis from the publicly available RNAseq data from bronchoalveolar cells and peripheral blood mononuclear cells to elucidate molecular alterations and cellular deconvolution to identify immune cell profiles. RESULTS: Alterations in genes involved in hyaluronan, glycosaminoglycan and mucopolysaccharides metabolism were over-represented in bronchoalveolar cells infected by SARS-CoV-2, as well as potential lung infiltration with neutrophils, T CD4+ cell and macrophages. The blood mononuclear cells presented a proliferative state. Dramatic reduction of NK and T lymphocytes, whereas an exacerbated increase in monocytes. CONCLUSIONS: In summary our results revealed molecular pathogenesis of the SARS-CoV-2 infection to bronchoalveolar cells inducing the hyaluronan and glycosaminoglycan metabolism that could shape partially the components of the ground-glass opacities observed in CT. And the potential immune response profile in COVID-19.


Subject(s)
COVID-19 , Glycosaminoglycans , Bronchoalveolar Lavage Fluid/cytology , COVID-19/diagnostic imaging , COVID-19/genetics , COVID-19/metabolism , COVID-19/pathology , Glycosaminoglycans/genetics , Glycosaminoglycans/metabolism , Humans , Hyaluronic Acid/genetics , Hyaluronic Acid/metabolism , Leukocytes, Mononuclear/cytology , Lung/diagnostic imaging , Lung/pathology , SARS-CoV-2
10.
Cell Death Dis ; 11(11): 957, 2020 11 06.
Article in English | MEDLINE | ID: covidwho-912894

ABSTRACT

A global effort is currently undertaken to restrain the COVID-19 pandemic. Host immunity has come out as a determinant for COVID-19 clinical outcomes, and several studies investigated the immune profiling of SARS-CoV-2 infected people to properly direct the clinical management of the disease. Thus, lymphopenia, T-cell exhaustion, and the increased levels of inflammatory mediators have been described in COVID-19 patients, in particular in severe cases1. Age represents a key factor in COVID-19 morbidity and mortality2. Understanding age-associated immune signatures of patients are therefore important to identify preventive and therapeutic strategies. In this study, we investigated the immune profile of COVID-19 hospitalized patients identifying a distinctive age-dependent immune signature associated with disease severity. Indeed, defined circulating factors - CXCL8, IL-10, IL-15, IL-27, and TNF-α - positively correlate with older age, longer hospitalization, and a more severe form of the disease and may thus represent the leading signature in critical COVID-19 patients.


Subject(s)
Coronavirus Infections/pathology , Cytokines/metabolism , Pneumonia, Viral/pathology , Age Factors , Aged , Aged, 80 and over , Antibodies, Viral/blood , Betacoronavirus/immunology , Betacoronavirus/isolation & purification , COVID-19 , Cluster Analysis , Coronavirus Infections/immunology , Coronavirus Infections/virology , Female , Humans , Immunoglobulin G/blood , Interleukin-10/metabolism , Interleukin-8/metabolism , Length of Stay , Leukocytes, Mononuclear/cytology , Leukocytes, Mononuclear/metabolism , Male , Middle Aged , Pandemics , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , SARS-CoV-2 , Severity of Illness Index , Tumor Necrosis Factor-alpha/metabolism
11.
Am J Physiol Lung Cell Mol Physiol ; 320(1): L84-L98, 2021 01 01.
Article in English | MEDLINE | ID: covidwho-910283

ABSTRACT

Coronavirus disease 2019 (COVID-19), driven by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was declared a global pandemic in March 2020. Pathogenic T cells and inflammatory monocytes are regarded as the central drivers of the cytokine storm associated with the severity of COVID-19. In this study, we explored the characteristic peripheral cellular profiles of patients with COVID-19 in both acute and convalescent phases by single-cell mass cytometry (CyTOF). Using a combination of algorithm-guided data analyses, we identified peripheral immune cell subsets in COVID-19 and revealed CD4+ T-cell depletion, T-cell differentiation, plasma cell expansion, and the reduced antigen presentation capacity of innate immunity. Notably, COVID-19 induces a dysregulation in the balance of monocyte populations by the expansion of the monocyte subsets. Collectively, our results represent a high-dimensional, single-cell profile of the peripheral immune response to SARS-CoV-2 infection.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , COVID-19/immunology , Leukocytes, Mononuclear/immunology , Monocytes/immunology , SARS-CoV-2/immunology , Adult , Aged , Antigen Presentation/immunology , CD4-Positive T-Lymphocytes/cytology , COVID-19/pathology , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/pathology , Cytokines/immunology , Dendritic Cells/cytology , Dendritic Cells/immunology , Female , Humans , Killer Cells, Natural/cytology , Killer Cells, Natural/immunology , Leukocytes, Mononuclear/cytology , Lymphocyte Depletion , Male , Middle Aged , Monocytes/cytology , Plasma Cells/cytology , Single-Cell Analysis
12.
Bioorg Chem ; 105: 104429, 2020 12.
Article in English | MEDLINE | ID: covidwho-893618

ABSTRACT

Human serum albumin (HSA) as the most abundant protein in human blood plasma, can be a good indicator for evaluating severity of some diseases in the clinic. HSA can be find in two forms: reduced albumin (human mercaptalbumin (HMA)) and oxidized albumin (human non-mercaptalbumin (HNA)). The rate of oxidized albumin to total albumin can be enhanced in multiple diseases. Increase in HNA level have been demonstrated in liver, diabetes plus fatigue and coronary artery diseases. In liver patients, this enhancement can reach to 50-200 percent which can then lead to bacterial/viral infections and eventually death in severe conditions. Due to the induction of cytokine storm, we can say that the level of HNA in serum of coronavirus disease 2019 (COVID-19) patients may be a positive predictor of mortality, especially in patients with underlying diseases such as cardiovascular disease (CVD), diabetes, aging and other inflammatory diseases. We suggest that checking oxidized albumin in COVID-19 patients may provide new therapeutic and diagnostic opportunities to better combat COVID-19.


Subject(s)
COVID-19/diagnosis , Serum Albumin, Human/analysis , COVID-19/therapy , COVID-19/virology , Humans , Leukocytes, Mononuclear/cytology , Leukocytes, Mononuclear/metabolism , Liver/metabolism , Oxidation-Reduction , Reactive Oxygen Species/chemistry , Reactive Oxygen Species/metabolism , SARS-CoV-2/isolation & purification , Serum Albumin/analysis , Serum Albumin/chemistry , Serum Albumin, Human/chemistry
13.
EMBO Mol Med ; 12(10): e13038, 2020 10 07.
Article in English | MEDLINE | ID: covidwho-722035

ABSTRACT

Early in the COVID-19 pandemic, type 2 diabetes (T2D) was marked as a risk factor for severe disease and mortality. Inflammation is central to the aetiology of both conditions where variations in immune responses can mitigate or aggravate disease course. Identifying at-risk groups based on immunoinflammatory signatures is valuable in directing personalised care and developing potential targets for precision therapy. This observational study characterised immunophenotypic variation associated with COVID-19 severity in T2D. Broad-spectrum immunophenotyping quantified 15 leucocyte populations in peripheral circulation from a cohort of 45 hospitalised COVID-19 patients with and without T2D. Lymphocytopenia and specific loss of cytotoxic CD8+ lymphocytes were associated with severe COVID-19 and requirement for intensive care in both non-diabetic and T2D patients. A morphological anomaly of increased monocyte size and monocytopenia restricted to classical CD14Hi CD16- monocytes was specifically associated with severe COVID-19 in patients with T2D requiring intensive care. Increased expression of inflammatory markers reminiscent of the type 1 interferon pathway (IL6, IL8, CCL2, INFB1) underlaid the immunophenotype associated with T2D. These immunophenotypic and hyperinflammatory changes may contribute to increased voracity of COVID-19 in T2D. These findings allow precise identification of T2D patients with severe COVID-19 as well as provide evidence that the type 1 interferon pathway may be an actionable therapeutic target for future studies.


Subject(s)
COVID-19/pathology , Diabetes Mellitus, Type 2/pathology , Monocytes/physiology , Aged , COVID-19/complications , COVID-19/virology , Chemokine CCL2/genetics , Chemokine CCL2/metabolism , Diabetes Mellitus, Type 2/complications , Female , Humans , Immunophenotyping , Inflammation/etiology , Interleukin-6/genetics , Interleukin-6/metabolism , Leukocytes, Mononuclear/cytology , Leukocytes, Mononuclear/metabolism , Lipopolysaccharide Receptors/metabolism , Lymphopenia/diagnosis , Male , Middle Aged , Monocytes/cytology , Monocytes/pathology , Risk Factors , SARS-CoV-2/isolation & purification , Severity of Illness Index
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