Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 301
Filter
1.
PLoS One ; 17(7): e0264566, 2022.
Article in English | MEDLINE | ID: covidwho-1962989

ABSTRACT

Current medical guidelines consider pregnant women with COVID-19 to be a high-risk group. Since physiological gestation downregulates the immunological response to maintain "maternal-fetal tolerance", SARS-CoV-2 infection may constitute a potentially threatening condition to both the mother and the fetus. To establish the immune profile in pregnant COVID-19+ patients, a cross-sectional study was conducted. Pregnant women with COVID-19 (P-COVID-19+; n = 15) were analyzed and compared with nonpregnant women with COVID-19 (NP-COVID-19+; n = 15) or those with physiological pregnancy (P-COVID-19-; n = 13). Serological cytokine and chemokine concentrations, leucocyte immunophenotypes, and mononuclear leucocyte responses to polyclonal stimuli were analyzed in all groups. Higher concentrations of serological TNF-α, IL-6, MIP1b and IL-4 were observed within the P-COVID-19+ group, while cytokines and chemokines secreted by peripheral leucocytes in response to LPS, IL-6 or PMA-ionomicin were similar among the groups. Immunophenotype analysis showed a lower percentage of HLA-DR+ monocytes in P-COVID-19+ than in P-COVID-19- and a higher percentage of CD39+ monocytes in P-COVID-19+ than in NP-COVID-19+. After whole blood polyclonal stimulation, similar percentages of T cells and TNF+ monocytes between groups were observed. Our results suggest that P-COVID-19+ elicits a strong inflammatory response similar to NP-COVID19+ but also displays an anti-inflammatory response that controls the ATP/adenosine balance and prevents hyperinflammatory damage in COVID-19.


Subject(s)
COVID-19 , Monocytes , Apyrase/immunology , Cross-Sectional Studies , Cytokines , Female , Humans , Interleukin-6 , Pregnancy , SARS-CoV-2
2.
Signal Transduct Target Ther ; 7(1): 250, 2022 07 23.
Article in English | MEDLINE | ID: covidwho-1956395
3.
Int J Mol Sci ; 21(9)2020 Apr 30.
Article in English | MEDLINE | ID: covidwho-1934078

ABSTRACT

Severe acute respiratory syndrome-associated coronavirus (SARS-CoV) initiates the cytokine/chemokine storm-mediated lung injury. The SARS-CoV unique domain (SUD) with three macrodomains (N, M, and C), showing the G-quadruplex binding activity, was examined the possible role in SARS pathogenesis in this study. The chemokine profile analysis indicated that SARS-CoV SUD significantly up-regulated the expression of CXCL10, CCL5 and interleukin (IL)-1ß in human lung epithelial cells and in the lung tissues of the mice intratracheally instilled with the recombinant plasmids. Among the SUD subdomains, SUD-MC substantially activated AP-1-mediated CXCL10 expression in vitro. In the wild type mice, SARS-CoV SUD-MC triggered the pulmonary infiltration of macrophages and monocytes, inducing CXCL10-mediated inflammatory responses and severe diffuse alveolar damage symptoms. Moreover, SUD-MC actuated NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome-dependent pulmonary inflammation, as confirmed by the NLRP3 inflammasome inhibitor and the NLRP3-/- mouse model. This study demonstrated that SARS-CoV SUD modulated NLRP3 inflammasome-dependent CXCL10-mediated pulmonary inflammation, providing the potential therapeutic targets for developing the antiviral agents.


Subject(s)
Chemokine CXCL10/metabolism , Inflammasomes/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , SARS Virus/metabolism , Viral Proteins/metabolism , Animals , Bronchoalveolar Lavage Fluid/chemistry , Bronchoalveolar Lavage Fluid/immunology , Cell Line , Chemokine CXCL10/genetics , Disease Models, Animal , Humans , Lung/metabolism , Lung/pathology , Mice , Mice, Inbred C57BL , Mice, Knockout , Monocytes/immunology , Monocytes/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/deficiency , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Pneumonia/pathology , Pneumonia/virology , Promoter Regions, Genetic , SARS Virus/isolation & purification , Severe Acute Respiratory Syndrome/pathology , Severe Acute Respiratory Syndrome/virology , Up-Regulation , Viral Proteins/chemistry , Viral Proteins/genetics
4.
Ann Biol Clin (Paris) ; 80(2): 190-198, 2022 Mar 01.
Article in French | MEDLINE | ID: covidwho-1928339

ABSTRACT

INTRODUCTION: Le niveau d'expression des molécules HLA-DR à la surface des monocytes (mHLA-DR) est un marqueur diagnostique utilisé pour évaluer l'immunité des patients en réanimation (choc septique, polytraumatisés, brulures, greffe et plus récemment Covid-19). Il est également utilisé comme un outil de stratification dans les essais cliniques utilisant des thérapies immunostimulantes chez ces patients. L'objectif de cette étude était d'évaluer les performances analytiques d'une méthode de cytométrie en flux pour mesurer mHLA-DR afin de répondre aux exigences de la norme NF EN ISO 15189 dans le cadre de l'accréditation des laboratoires de biologie médicale. Matériels et méthodes. L'évaluation (performances de la technique, étendue de la mesure, comparaison de méthode) a été menée en suivant le SH GTA 04, guide recommandé par le Comité français d'accréditation (COFRAC). En complément, certaines conditions pré analytiques ont été ré-évaluées. Résultats. L'ensemble des coefficients de variation évaluant les performances étaient inférieurs à 10 % (répétabilité, reproductibilité, variabilité interopérateur). Les limites de quantification et de linéarité étaient adaptées à l'utilisation clinique du paramètre. Les résultats étaient identiques quel que soit le type et le fournisseur de cytomètre en flux. Les contraintes de conservation pré-analytiques des échantillons ont été confirmées. CONCLUSION: Les résultats étaient conformes aux exigences de qualité recommandées par le COFRAC. Ils permettent l'accréditation de la mesure de mHLA-DR par cytométrie en flux et son utilisation en soins courants.


Subject(s)
COVID-19 , HLA-DR Antigens , Monocytes , Flow Cytometry , HLA-DR Antigens/biosynthesis , HLA-DR Antigens/immunology , Humans , Monocytes/immunology , Monocytes/metabolism
5.
Medicine (Baltimore) ; 101(27): e29592, 2022 Jul 08.
Article in English | MEDLINE | ID: covidwho-1927460

ABSTRACT

Early predictors of severe coronavirus disease 2019 (COVID-19) would identify patients requiring intensive care. Recently, the monocyte distribution width (MDW) and presepsin level have been used for the early diagnosis of sepsis. Here, we assessed the utility of MDW and presepsin for the early assessment of COVID-19 severity. Eighty-seven inpatients with confirmed COVID-19 were enrolled and divided into 3 groups by the type of respiratory support: (1) mechanical ventilation or high-flow nasal cannula oxygen therapy (MVHF-OT), (2) conventional oxygen therapy, and (3) no oxygen therapy. We measured the complete blood count; MDW; erythrocyte sedimentation rate; and the levels of presepsin, C-reactive protein, procalcitonin, lactate dehydrogenase, ferritin, Krebs von den Lungen-6 (KL-6), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibody. Thirteen (14.9%) patients on MVHF-OT exhibited a significantly higher mortality and a longer hospital stay than did the others. The MDW and presepsin levels were significantly elevated on admission, and correlated with COVID-19 severity (both P < .001). Notably, only the MDW correlated significantly with symptoms in the no oxygen therapy group (P < .012). In the first week after admission, the MDW fell and no longer differed among the groups. The KL-6 level did not differ by disease severity at any time. Neutralizing antibodies were detected in 74 patients (91.4%) and the level of neutralization correlated significantly with COVID-19 severity (P < .001). The MDW and presepsin are useful indicators for early assessment of disease severity in COVID-19 patients.


Subject(s)
COVID-19 , Lipopolysaccharide Receptors , Monocytes , Peptide Fragments , Biomarkers , COVID-19/diagnosis , Critical Care , Humans , Lipopolysaccharide Receptors/analysis , Peptide Fragments/analysis , SARS-CoV-2 , Severity of Illness Index
6.
Nature ; 606(7914): 576-584, 2022 06.
Article in English | MEDLINE | ID: covidwho-1921629

ABSTRACT

SARS-CoV-2 can cause acute respiratory distress and death in some patients1. Although severe COVID-19 is linked to substantial inflammation, how SARS-CoV-2 triggers inflammation is not clear2. Monocytes and macrophages are sentinel cells that sense invasive infection to form inflammasomes that activate caspase-1 and gasdermin D, leading to inflammatory death (pyroptosis) and the release of potent inflammatory mediators3. Here we show that about 6% of blood monocytes of patients with COVID-19 are infected with SARS-CoV-2. Monocyte infection depends on the uptake of antibody-opsonized virus by Fcγ receptors. The plasma of vaccine recipients does not promote antibody-dependent monocyte infection. SARS-CoV-2 begins to replicate in monocytes, but infection is aborted, and infectious virus is not detected in the supernatants of cultures of infected monocytes. Instead, infected cells undergo pyroptosis mediated by activation of NLRP3 and AIM2 inflammasomes, caspase-1 and gasdermin D. Moreover, tissue-resident macrophages, but not infected epithelial and endothelial cells, from lung autopsies from patients with COVID-19 have activated inflammasomes. Taken together, these findings suggest that antibody-mediated SARS-CoV-2 uptake by monocytes and macrophages triggers inflammatory cell death that aborts the production of infectious virus but causes systemic inflammation that contributes to COVID-19 pathogenesis.


Subject(s)
COVID-19 , Inflammation , Monocytes , Receptors, IgG , SARS-CoV-2 , COVID-19/virology , Caspase 1/metabolism , DNA-Binding Proteins , Humans , Inflammasomes/metabolism , Inflammation/metabolism , Inflammation/virology , Monocytes/metabolism , Monocytes/virology , NLR Family, Pyrin Domain-Containing 3 Protein , Phosphate-Binding Proteins , Pore Forming Cytotoxic Proteins , Receptors, IgG/metabolism
7.
Front Immunol ; 13: 812514, 2022.
Article in English | MEDLINE | ID: covidwho-1902973

ABSTRACT

The cell-mediated protective and pathogenic immune responses to SARS-CoV-2 infection remain largely elusive. Here we identified 76 distinct cell subsets in the PBMC samples that were associated with various clinical presentations of COVID-19 using scRNA-seq technology coupled with a deep and comprehensive analysis of unique cell surface markers and differentially expressed genes. We revealed that (TRAV1-2+CD8+)MAIT cells and (NCAM1hiCD160+)NK cells significantly enriched in the asymptomatic subjects whereas (LAG3+CD160+CD8+)NKT cells increased in the symptomatic patients. We also observed that (CD68-CSF1R-IL1BhiCD14+)classical monocytes were positively correlated with the disease severity. Moreover, (CD33-HLA-DMA-CD14+)classical monocytes and (CLEC10A-S100A9lo)pDC were associated with the viral persistence. The GO and KEGG analyses identified enriched pathways related to immune responses, inflammation, and apoptosis. These findings may enhance our understanding of the immunopathogenesis of COVID-19 and help develop novel strategies against SARS-CoV-2 infection.


Subject(s)
COVID-19/diagnosis , COVID-19/immunology , Killer Cells, Natural/immunology , Monocytes/immunology , Mucosal-Associated Invariant T Cells/immunology , Natural Killer T-Cells/immunology , SARS-CoV-2/physiology , Asymptomatic Infections , Female , Flow Cytometry , Humans , Immunophenotyping , Male , Middle Aged , Severity of Illness Index , Viral Load
8.
Sci Rep ; 12(1): 638, 2022 01 12.
Article in English | MEDLINE | ID: covidwho-1900549

ABSTRACT

COVID-19 can cause acute respiratory distress syndrome, leading to death in many individuals. Evidence of a deleterious role of the innate immune system is accumulating, but the precise mechanisms involved remain unclear. In this study, we investigated the links between circulating innate phagocytes and severity in COVID-19 patients. We performed in-depth phenotyping of neutrophil and monocyte subpopulations and measured soluble activation markers in plasma. Additionally, anti-microbial functions (phagocytosis, oxidative burst, and NETosis) were evaluated on fresh cells from patients. Neutrophils and monocytes had a strikingly disturbed phenotype, and elevated concentrations of activation markers (calprotectin, myeloperoxidase, and neutrophil extracellular traps) were measured in plasma. Critical patients had increased CD13low immature neutrophils, LOX-1 + and CCR5 + immunosuppressive neutrophils, and HLA-DRlow downregulated monocytes. Markers of immature and immunosuppressive neutrophils were strongly associated with severity. Moreover, neutrophils and monocytes of critical patients had impaired antimicrobial functions, which correlated with organ dysfunction, severe infections, and mortality. Together, our results strongly argue in favor of a pivotal role of innate immunity in COVID-19 severe infections and pleads for targeted therapeutic options.


Subject(s)
COVID-19/immunology , Immunity, Innate , Immunocompromised Host , Adult , Aged , Female , Humans , Male , Middle Aged , Monocytes/immunology , Neutrophils/immunology , Phagocytes/immunology , Prognosis , Severity of Illness Index , Young Adult
9.
BMC Infect Dis ; 22(1): 563, 2022 Jun 20.
Article in English | MEDLINE | ID: covidwho-1894421

ABSTRACT

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening complication that can develop weeks to months after an initial SARS-CoV-2 infection. A complex, time-consuming laboratory evaluation is currently required to distinguish MIS-C from other illnesses. New assays are urgently needed early in the evaluation process to expedite MIS-C workup and initiate treatment when appropriate. This study aimed to measure the performance of a monocyte anisocytosis index, obtained on routine complete blood count (CBC), to rapidly identify subjects with MIS-C at risk for cardiac complications. METHODS: We measured monocyte anisocytosis, quantified by monocyte distribution width (MDW), in blood samples collected from children who sought medical care in a single medical center from April 2020 to October 2020 (discovery cohort). After identifying an effective MDW threshold associated with MIS-C, we tested the utility of MDW as a tier 1 assay for MIS-C at multiple institutions from October 2020 to October 2021 (validation cohort). The main outcome was the early screening of MIS-C, with a focus on children with MIS-C who displayed cardiac complications. The screening accuracy of MDW was compared to tier 1 routine laboratory tests recommended for evaluating a child for MIS-C. RESULTS: We enrolled 765 children and collected 846 blood samples for analysis. In the discovery cohort, monocyte anisocytosis, quantified as an MDW threshold of 24.0, had 100% sensitivity (95% CI 78-100%) and 80% specificity (95% CI 69-88%) for identifying MIS-C. In the validation cohort, an initial MDW greater than 24.0 maintained a 100% sensitivity (95% CI 80-100%) and monocyte anisocytosis displayed a diagnostic accuracy greater that other clinically available hematologic parameters. Monocyte anisocytosis decreased with disease resolution to values equivalent to those of healthy controls. CONCLUSIONS: Monocyte anisocytosis detected by CBC early in the clinical workup improves the identification of children with MIS-C with cardiac complications, thereby creating opportunities for improving current practice guidelines.


Subject(s)
COVID-19 , COVID-19/complications , COVID-19/diagnosis , Child , Humans , Monocytes , SARS-CoV-2 , Systemic Inflammatory Response Syndrome/complications , Systemic Inflammatory Response Syndrome/diagnosis
10.
Molecules ; 27(12)2022 Jun 07.
Article in English | MEDLINE | ID: covidwho-1884287

ABSTRACT

The COVID-19 pandemic, caused by the rapidly spreading SARS-CoV-2 virus, led to the unprecedented mobilization of scientists, resulting in the rapid development of vaccines and potential pharmaceuticals. Although COVID-19 symptoms are moderately severe in most people, in some cases the disease can result in pneumonia and acute respiratory failure as well as can be fatal. The severe course of COVID-19 is associated with a hyperinflammatory state called a cytokine storm. One of the key cytokines creating a proinflammatory environment is IL-6, which is secreted mainly by monocytes and macrophages. Therefore, this cytokine has become a target for some therapies that inhibit its biological action; however, these therapies are expensive, and their availability is limited in poorer countries. Thus, new cheaper drugs that can overcome the severe infections of COVID-19 are needed. Here, we show that chlorpromazine inhibits the expression and secretion of IL-6 by monocytes activated by SARS-CoV-2 virus nucleocapsid protein and affects the activity of NF-κB and MEK/ERK signaling. Our results, including others, indicate that chlorpromazine, which has been used for several decades as a neuroleptic, exerts antiviral and immunomodulatory activity, is safe and inexpensive, and might be a desirable drug to support the therapy of patients with COVID-19.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/drug therapy , Chlorpromazine/pharmacology , Cytokines/metabolism , Humans , Interleukin-6 , Monocytes/metabolism , Nucleocapsid/metabolism , Pandemics
11.
Nature ; 607(7919): 578-584, 2022 07.
Article in English | MEDLINE | ID: covidwho-1873525

ABSTRACT

The nervous and immune systems are intricately linked1. Although psychological stress is known to modulate immune function, mechanistic pathways linking stress networks in the brain to peripheral leukocytes remain poorly understood2. Here we show that distinct brain regions shape leukocyte distribution and function throughout the body during acute stress in mice. Using optogenetics and chemogenetics, we demonstrate that motor circuits induce rapid neutrophil mobilization from the bone marrow to peripheral tissues through skeletal-muscle-derived neutrophil-attracting chemokines. Conversely, the paraventricular hypothalamus controls monocyte and lymphocyte egress from secondary lymphoid organs and blood to the bone marrow through direct, cell-intrinsic glucocorticoid signalling. These stress-induced, counter-directional, population-wide leukocyte shifts are associated with altered disease susceptibility. On the one hand, acute stress changes innate immunity by reprogramming neutrophils and directing their recruitment to sites of injury. On the other hand, corticotropin-releasing hormone neuron-mediated leukocyte shifts protect against the acquisition of autoimmunity, but impair immunity to SARS-CoV-2 and influenza infection. Collectively, these data show that distinct brain regions differentially and rapidly tailor the leukocyte landscape during psychological stress, therefore calibrating the ability of the immune system to respond to physical threats.


Subject(s)
Brain , Fear , Leukocytes , Motor Neurons , Neural Pathways , Stress, Psychological , Animals , Bone Marrow Cells/cytology , Bone Marrow Cells/immunology , Brain/cytology , Brain/physiology , COVID-19/immunology , Chemokines/immunology , Disease Susceptibility , Fear/physiology , Glucocorticoids/metabolism , Humans , Leukocytes/cytology , Leukocytes/immunology , Lymphocytes/cytology , Lymphocytes/immunology , Lymphoid Tissue/cytology , Lymphoid Tissue/immunology , Mice , Monocytes/cytology , Monocytes/immunology , Motor Neurons/cytology , Motor Neurons/physiology , Neutrophils/cytology , Neutrophils/immunology , Optogenetics , Orthomyxoviridae Infections/immunology , Paraventricular Hypothalamic Nucleus/physiology , SARS-CoV-2/immunology , Stress, Psychological/immunology , Stress, Psychological/physiopathology
12.
Molecules ; 27(11)2022 May 26.
Article in English | MEDLINE | ID: covidwho-1869715

ABSTRACT

Impaired autophagy, responsible for increased inflammation, constitutes a risk factor for the more severe COVID-19 outcomes. Spermidine (SPD) is a known autophagy modulator and supplementation for COVID-19 risk groups (including the elderly) is recommended. However, information on the modulatory effects of eugenol (EUG) is scarce. Therefore, the effects of SPD and EUG, both singularly and in combination, on autophagy were investigated using different cell lines (HBEpiC, SHSY5Y, HUVEC, Caco-2, L929 and U937). SPD (0.3 mM), EUG (0.2 mM) and 0.3 mM SPD + 0.2 mM EUG, significantly increased autophagy using the hallmark measure of LC3-II protein accumulation in the cell lines without cytotoxic effects. Using Caco-2 cells as a model, several crucial autophagy proteins were upregulated at all stages of autophagic flux in response to the treatments. This effect was verified by the activation/differentiation and migration of U937 monocytes in a three-dimensional reconstituted intestinal model (Caco-2, L929 and U937 cells). Comparable benefits of SPD, EUG and SPD + EUG in inducing autophagy were shown by the protection of Caco-2 and L929 cells against lipopolysaccharide-induced inflammation. SPD + EUG is an innovative dual therapy capable of stimulating autophagy and reducing inflammation in vitro and could show promise for COVID-19 risk groups.


Subject(s)
COVID-19 , Syzygium , Aged , Autophagy , COVID-19/drug therapy , Caco-2 Cells , Eugenol/pharmacology , Humans , Inflammation , Monocytes , Plant Oils , Spermidine/pharmacology , Triticum
13.
Cell Rep ; 39(11): 110945, 2022 Jun 14.
Article in English | MEDLINE | ID: covidwho-1866956

ABSTRACT

SARS-CoV-2-infected subjects are generally asymptomatic during initial viral replication but may suffer severe immunopathology after the virus has receded and monocytes have infiltrated the airways. In bronchoalveolar lavage fluid from severe COVID-19 patients, monocytes express mRNA encoding inflammatory mediators and contain SARS-CoV-2 transcripts. We leverage a human small airway model of infection and inflammation, whereby primary blood monocytes transmigrate across SARS-CoV-2-infected lung epithelium to characterize viral burden, gene expression, and inflammatory mediator secretion by epithelial cells and monocytes. In this model, lung-infiltrating monocytes acquire SARS-CoV-2 from the epithelium and upregulate expression and secretion of inflammatory mediators, mirroring in vivo data. Combined use of baricitinib (Janus kinase inhibitor) and remdesivir (nucleoside analog) enhances antiviral signaling and viral clearance by SARS-CoV-2-positive monocytes while decreasing secretion of proneutrophilic mediators associated with acute respiratory distress syndrome. These findings highlight the role of lung-infiltrating monocytes in COVID-19 pathogenesis and their importance as a therapeutic target.


Subject(s)
COVID-19 , Azetidines , COVID-19/drug therapy , Humans , Inflammation Mediators , Lung/pathology , Monocytes , Purines , Pyrazoles , SARS-CoV-2 , Sulfonamides
14.
Nat Immunol ; 23(5): 645, 2022 05.
Article in English | MEDLINE | ID: covidwho-1860383

Subject(s)
Monocytes
15.
J Cosmet Dermatol ; 21(5): 1809-1815, 2022 May.
Article in English | MEDLINE | ID: covidwho-1854043

ABSTRACT

INTRODUCTION: Telogen effluvium (TE) is one of the causes of non-scarring hair loss that occurred commonly 2-3 months after a triggering factor. It was reported that the incidence of TE increased during the COVID-19 (coronavirus disease 2019) pandemic. However, to date, there is no study evaluating the status of COVID-19 before the onset of hair loss in patients with TE. The aim of this study is to evaluate the patients with TE whether they had COVID-19 or not before the onset of their hair loss and to compare the demographic and clinical characteristics and laboratory parameters of those with and without a history of COVID-19. METHOD: We conducted an observational cohort study of TE patients. The diagnosis of TE depended on anamnesis and physical examination of the patients. Also, hair pull test was performed. Demographic data and the results of COVID-19 real-time polymerase chain reaction (RT-PCR) were recorded from the electronic medical records. RESULTS: Totally, 181 patients with TE were included in the study. Sixty-four of patients (35.4%) had been diagnosed with COVID-19 before the hair loss started. The median duration of development of hair loss was 2 months (range 1-11 months, IQR 3) after COVID-19 diagnosis. In this group, 87.5% of patients (n = 56) had acute TE and 12.5% of patients (n = 8) had chronic TE. The rate of acute TE and the use of vitamin supplements were ignificantly higher (p < 0.001 and p = 0.027, respectively) and the monocyte count in peripheral blood was lower (p = 0.041) in the group diagnosed with COVID-19. DISCUSSION AND CONCLUSION: It was stated that monocytes and macrophages infected by SARS-CoV-2 can produce pro-inflammatory cytokines that play a crucial role in the development of COVID-19-related complications. Also, it was suggested that the number of monocytes tends to be lower in the late recovery stage. The lower monocyte count in patients with a history of COVID-19 in our study may be related to evaluating the patients in the late period of recovery and the migration of circulating monocytes to hair follicles. The history of COVID-19 must be questioned in patients with TE. It should be kept in mind that hair loss that develops after COVID-19 may be presented as chronic TE form too. The exact mechanisms of hair loss induced by COVID-19 are not fully explained; the roles of monocytes on the hair follicles may be one of the responsible mechanisms.


Subject(s)
Alopecia Areata , COVID-19 , COVID-19/epidemiology , COVID-19 Testing , Cohort Studies , Humans , Monocytes , Pandemics , SARS-CoV-2
16.
Front Immunol ; 13: 871592, 2022.
Article in English | MEDLINE | ID: covidwho-1809407

ABSTRACT

Background: CD163, a haptoglobin-hemoglobin scavenger receptor mostly expressed by monocytes and macrophages, is involved in the regulation of inflammatory processes. Following proteolytic cleavage after pro-inflammatory stimulation, CD163 is shed from the cell surface and its soluble form in plasma, sCD163, is a biomarker of monocyte/macrophage lineage activation.The assessment of sCD163 plasmatic levels in an early stage of the disease could have clinical utility in predicting the severity of COVID-19 pneumonia. The use of tocilizumab (monoclonal antibody anti-IL-6 receptor) in COVID-19 patients reduces lethality rate at 30 days. The aim of the study was to investigate the effect of tocilizumab on sCD163 plasmatic levels in a cohort of COVID-19 patients. Methods: In COVID-19 patients, on hospital admission (T0), after 7 days from hospitalization (T7) and after 45 days from discharge (T45) sCD163 plasmatic levels were evaluated, along with other laboratory parameters. COVID-19 patients were stratified into tocilizumab (TCZ) and non-tocilizumab (non-TCZ) groups. TCZ group was further divided into responder (R) and non-responder (NR) groups. Patients who died or required mechanical ventilation were defined as NR. As control group, healthy donors (HD) were enrolled. Results: Seventy COVID-19 patients and 47 HD were enrolled. At T0, sCD163 plasmatic levels were higher in COVID-19 patients compared to HD (p<0.0001) and the longitudinal evaluation showed a reduction in sCD163 plasmatic levels at T7 compared to T0 (p=0.0211). At T0, both TCZ and non-TCZ groups showed higher sCD163 plasmatic levels compared to HD (p<0.0001 and p=0.0147, respectively). At T7, the longitudinal evaluation showed a significant reduction in sCD163 plasmatic levels (p=0.0030) only in the TCZ group, reaching levels comparable to those of HD. Conversely, not statistically significance in non-TCZ group was observed and, at T7, a statistically significance was found comparing non-TCZ group to HD (p=0.0019). At T0, R and NR groups showed not statistically significance in sCD163 plasmatic levels and both groups showed higher levels compared to HD (p=0.0001 and p=0.0340, respectively). The longitudinal evaluation showed significant reductions in both groups (R: p=0.0356; NR: p=0.0273) independently of the outcome. After 45 days of follow-up sCD163 plasmatic levels remain stable. Conclusion: sCD163 plasmatic levels are increased in COVID-19 pneumonia and is efficiently down-regulated by tocilizumab treatment regardless of the clinical outcome.


Subject(s)
COVID-19 , Antibodies, Monoclonal, Humanized/metabolism , Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/drug therapy , Humans , Monocytes
17.
Int Immunopharmacol ; 109: 108781, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1796624

ABSTRACT

OBJECT: The study aimed to utilize the peripheral blood immunological parameters and resulting individual and combined inflammatory indices [neutrophil/lymphocyte ratio (NLR), lymphocyte/monocyte ratio (LMR) and C-reactive protein/lymphocyte ratio (CLR)] in predicting the prognosis and mortality in COVID-19 patients. MATERIALS AND METHODS: The measurements of individual and combined inflammatory indices (NLR, LMR and CLR) were performed at hospital admission and at last day of hospitalization for COVID-19 patients. RESULTS: Prominent elevation of NLR and CLR among patients with refractory disease admitted to Intensive Care Unit (ICU) and deceased patients was found when compared with moderate ill patients and healthy controls. Interestingly, NLR and CLR typically returned to near normal value as patients recover from severe infection. By contrast, deceased patients had persistent increased NLR and CLR until last day of hospitalization in ICU. ROC obtained for the above parameters showed that NLR and CLR were the most associated immunological parameters with the severity of COVID-19 disease. Using multivariate logistic regression analysis, CLR > 69.46 is an independent prognostic factors in identifying critically ill COVID-19 cases. Study of the combined markers NLR and CLR showed that most of patients admitted in ICU were characterized with high NLR combined with high CLR, while most of healthy subjects and non-ICU group have low NLR combined with low CLR. CONCLUSION: The combination of NLR and CLR could improve the predictive efficacy compared to individual markers to segregate patients who will develop a severe disease from those with a mild pathology.


Subject(s)
COVID-19 , Neutrophils , Biomarkers , Humans , Lymphocytes/pathology , Monocytes , Neutrophils/pathology , Prognosis , ROC Curve , Retrospective Studies , Severity of Illness Index
18.
Genome Biol ; 23(1): 96, 2022 04 14.
Article in English | MEDLINE | ID: covidwho-1793837

ABSTRACT

Genome-wide association studies have identified 3p21.31 as the main risk locus for severe COVID-19, although underlying mechanisms remain elusive. We perform an epigenomic dissection of 3p21.31, identifying a CTCF-dependent tissue-specific 3D regulatory chromatin hub that controls the activity of several chemokine receptor genes. Risk SNPs colocalize with regulatory elements and are linked to increased expression of CCR1, CCR2 and CCR5 in monocytes and macrophages. As excessive organ infiltration of inflammatory monocytes and macrophages is a hallmark of severe COVID-19, our findings provide a rationale for the genetic association of 3p21.31 variants with elevated risk of hospitalization upon SARS-CoV-2 infection.


Subject(s)
COVID-19 , Monocytes , COVID-19/genetics , Genome-Wide Association Study , Humans , Macrophages/metabolism , Monocytes/metabolism , Receptors, CCR5/genetics , Receptors, CCR5/metabolism , Receptors, Chemokine/genetics , Receptors, Chemokine/metabolism , SARS-CoV-2
19.
Viruses ; 14(4)2022 04 15.
Article in English | MEDLINE | ID: covidwho-1792417

ABSTRACT

Monocytes play a role in viral biology, but little is known about the monocyte subpopulation in the course of COVID-19 disease. The aim of the study was the analysis of classical, intermediate and non-classical monocytes with expression of PD-L1 and CD62L, TIM-3 and CD86 molecules in peripheral blood (PB) to distinguish patients with SARS-CoV-2 infection from convalescent patients. The study group consisted of 55 patients with SARS-CoV-2 infection and 51 convalescent patients. The cells were analyzed by flow cytometry. The number and proportion of monocytes were lower in patients with COVID-19 than convalescent patients. We observed a lower proportion of non-classical monocytes in COVID-19 patients than convalescent ones. There was a higher proportion of PDL-1-positive intermediate monocytes in COVID-19 patients than convalescent ones. We noticed a higher geometric mean fluorescence intensity (GeoMean) of PD-L1 on intermediate monocytes in COVID-19 patients than convalescent patients, and a higher proportion of CD62L-positive monocytes in COVID-19 patients in comparison with convalescent ones. We found a higher GeoMean of CD62L on monocytes in COVID-19 patients than convalescent ones. Assessment of PD-L1- and CD62L-positive monocyte subsets may identify patients with a possible predisposition for rapid recovery. The monitoring of monocyte subsets in PB might be a useful test in COVID-19 patients.


Subject(s)
B7-H1 Antigen , COVID-19 , L-Selectin , Monocytes , B7-H1 Antigen/genetics , B7-H1 Antigen/metabolism , COVID-19/genetics , COVID-19/metabolism , Flow Cytometry , Humans , L-Selectin/genetics , L-Selectin/metabolism , Monocytes/metabolism , SARS-CoV-2
20.
PLoS One ; 17(4): e0264979, 2022.
Article in English | MEDLINE | ID: covidwho-1789178

ABSTRACT

The global COVID-19 pandemic has claimed the lives of more than 750,000 US citizens. Dysregulation of the immune system underlies the pathogenesis of COVID-19, with inflammation mediated tissue injury to the lung in the setting of suppressed systemic immune function. To define the molecular mechanisms of immune dysfunction in COVID-19 we utilized a systems immunology approach centered on the circulating leukocyte phosphoproteome measured by mass cytometry. We find that although COVID-19 is associated with wholesale activation of a broad set of signaling pathways across myeloid and lymphoid cell populations, STAT3 phosphorylation predominated in both monocytes and T cells. STAT3 phosphorylation was tightly correlated with circulating IL-6 levels and high levels of phospho-STAT3 was associated with decreased markers of myeloid cell maturation/activation and decreased ex-vivo T cell IFN-γ production, demonstrating that during COVID-19 dysregulated cellular activation is associated with suppression of immune effector cell function. Collectively, these data reconcile the systemic inflammatory response and functional immunosuppression induced by COVID-19 and suggest STAT3 signaling may be the central pathophysiologic mechanism driving immune dysfunction in COVID-19.


Subject(s)
COVID-19 , Humans , Monocytes/metabolism , Pandemics , STAT3 Transcription Factor/metabolism , Signal Transduction , T-Lymphocytes
SELECTION OF CITATIONS
SEARCH DETAIL