Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 256
Filter
1.
Int J Mol Sci ; 23(21)2022 Oct 22.
Article in English | MEDLINE | ID: covidwho-2081827

ABSTRACT

Systemic juvenile idiopathic arthritis (sJIA) and its complication, macrophage activation syndrome (sJIA-MAS), are rare but sometimes very serious or even critical diseases of childhood that can occasionally be characterized by nonspecific clinical signs and symptoms at onset-such as non-remitting high fever, headache, rash, or arthralgia-and are biologically accompanied by an increase in acute-phase reactants. For a correct positive diagnosis, it is necessary to rule out bacterial or viral infections, neoplasia, and other immune-mediated inflammatory diseases. Delays in diagnosis will result in late initiation of targeted therapy. A set of biomarkers is useful to distinguish sJIA or sJIA-MAS from similar clinical entities, especially when arthritis is absent. Biomarkers should be accessible to many patients, with convenient production and acquisition prices for pediatric medical laboratories, as well as being easy to determine, having high sensitivity and specificity, and correlating with pathophysiological disease pathways. The aim of this review was to identify the newest and most powerful biomarkers and their synergistic interaction for easy and accurate recognition of sJIA and sJIA-MAS, so as to immediately guide clinicians in correct diagnosis and in predicting disease outcomes, the response to treatment, and the risk of relapses. Biomarkers constitute an exciting field of research, especially due to the heterogeneous nature of cytokine storm syndromes (CSSs) in the COVID era. They must be selected with utmost care-a fact supported by the increasingly improved genetic and pathophysiological comprehension of sJIA, but also of CSS-so that new classification systems may soon be developed to define homogeneous groups of patients, although each with a distinct disease.


Subject(s)
Arthritis, Juvenile , COVID-19 , Macrophage Activation Syndrome , Humans , Child , Macrophage Activation Syndrome/diagnosis , Macrophage Activation Syndrome/drug therapy , Macrophage Activation Syndrome/etiology , Arthritis, Juvenile/diagnosis , Arthritis, Juvenile/drug therapy , COVID-19/diagnosis , Biomarkers
2.
J Leukoc Biol ; 111(6): 1159-1173, 2022 06.
Article in English | MEDLINE | ID: covidwho-2075036

ABSTRACT

Neutrophils play significant roles in immune homeostasis and as neutralizers of microbial infections. Recent evidence further suggests heterogeneity of neutrophil developmental and activation states that exert specialized effector functions during inflammatory disease conditions. Neutrophils can play multiple roles during viral infections, secreting inflammatory mediators and cytokines that contribute significantly to host defense and pathogenicity. However, their roles in viral immunity are not well understood. In this review, we present an overview of neutrophil heterogeneity and its impact on the course and severity of viral respiratory infectious diseases. We focus on the evidence demonstrating the crucial roles neutrophils play in the immune response toward respiratory infections, using influenza as a model. We further extend the understanding of neutrophil function with the studies pertaining to COVID-19 disease and its neutrophil-associated pathologies. Finally, we discuss the relevance of these results for future therapeutic options through targeting and regulating neutrophil-specific responses.


Subject(s)
COVID-19 , Virus Diseases , Cytokines , Humans , Inflammation Mediators , Neutrophil Activation , Neutrophils , Virus Diseases/pathology
3.
Int J Mol Sci ; 23(18)2022 Sep 09.
Article in English | MEDLINE | ID: covidwho-2071501

ABSTRACT

In SARS-CoV-2-infected humans, disease progression is often associated with acute respiratory distress syndrome involving severe lung injury, coagulopathy, and thrombosis of the alveolar capillaries. The pathogenesis of these pulmonary complications in COVID-19 patients has not been elucidated. Autopsy study of these patients showed SARS-CoV-2 virions in pulmonary vessels and sequestrated leukocytes infiltrates associated with endotheliopathy and microvascular thrombosis. Since SARS-CoV-2 enters and infects target cells by binding its spike (S) protein to cellular angiotensin-converting enzyme 2 (ACE2), and there is evidence that vascular endothelial cells and neutrophils express ACE2, we investigated the effect of S-proteins and cell-cell communication on primary human lung microvascular endothelial cells (HLMEC) and neutrophils expression of thrombogenic factors and the potential mechanisms. Using S-proteins of two different SARS-CoV-2 variants (Wuhan and Delta), we demonstrate that exposure of HLMEC or neutrophils to S-proteins, co-culture of HLMEC exposed to S-proteins with non-exposed neutrophils, or co-culture of neutrophils exposed to S-proteins with non-exposed HLMEC induced transcriptional upregulation of tissue factor (TF), significantly increased the expression and secretion of factor (F)-V, thrombin, and fibrinogen and inhibited tissue factor pathway inhibitor (TFPI), the primary regulator of the extrinsic pathway of blood coagulation, in both cell types. Recombinant (r)TFPI and a thiol blocker (5,5'-dithio-bis-(2-nitrobenzoic acid)) prevented S-protein-induced expression and secretion of Factor-V, thrombin, and fibrinogen. Thrombomodulin blocked S-protein-induced expression and secretion of fibrinogen but had no effect on S-protein-induced expression of Factor-V or thrombin. These results suggests that following SARS-CoV-2 contact with the pulmonary endothelium or neutrophils and endothelial-neutrophil interactions, viral S-proteins induce coagulopathy via the TF pathway and mechanisms involving functional thiol groups. These findings suggest that using rTFPI and/or thiol-based drugs could be a viable therapeutic strategy against SARS-CoV-2-induced coagulopathy and thrombosis.


Subject(s)
Blood Coagulation Disorders , COVID-19 , Thrombosis , Angiotensin-Converting Enzyme 2 , Cell Communication , Endothelial Cells/metabolism , Endothelium/metabolism , Fibrinogen , Humans , Lipoproteins , Lung/metabolism , Neutrophils/metabolism , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/metabolism , Sulfhydryl Compounds , Thrombin , Thrombomodulin , Thromboplastin , Thrombosis/etiology
4.
Clin Neurol Neurosurg ; 222: 107467, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-2061005

ABSTRACT

OBJECTIVE: We explored the relationship between markers of infection and inflammation and mortality in patients with acute ischemic stroke who underwent thrombectomy. METHODS: We performed retrospective chart review of stroke patients who underwent thrombectomy at two tertiary academic centers between December 2018 and November 2020. Associations between discharge mortality, WBC count, neutrophil percentage, fever, culture data, and antibiotic treatment were analyzed using the Wilcoxon rank sum test, Student's t-test, and Fisher's exact test. Independent predictors of mortality were identified with multivariable analysis. Analyses were repeated excluding COVID-positive patients. RESULTS: Of 248 patients who underwent thrombectomy, 41 (17 %) died prior to discharge. Mortality was associated with admission WBC count (11 [8-14] vs. 9 [7-12], p = 0.0093), admission neutrophil percentage (78 % ± 11 vs. 71 % ± 14, p = 0.0003), peak WBC count (17 [13-22] vs. 12 [9-15], p < 0.0001), fever (71 % vs. 27 %, p < 0.0001), positive culture (44 % vs. 15 %, p < 0.0001), and days treated with antibiotics (3 [1-7] vs. 1 [0-4], p < 0.0001). After controlling for age, admission NIHSS and post-thrombectomy ASPECTS score, mortality was associated with admission WBC count (OR 13, CI 1.32-142, p = 0.027), neutrophil percentage (OR 1.03, CI 1.0-1.07, p = 0.045), peak WBC count (OR 301, CI 24-5008, p < 0.0001), fever (OR 24.2, CI 1.77-332, p < 0.0001), and positive cultures (OR 4.24, CI 1.87-9.62, p = 0.0006). After excluding COVID-positive patients (n = 14), peak WBC count, fever and positive culture remained independent predictors of mortality. CONCLUSION: Markers of infection and inflammation are associated with discharge mortality after thrombectomy. Further study is warranted to investigate the causal relationship of these markers with clinical outcome.


Subject(s)
Brain Ischemia , COVID-19 , Ischemic Stroke , Stroke , Humans , Retrospective Studies , Treatment Outcome , Thrombectomy , Stroke/complications , Biomarkers , Inflammation , Anti-Bacterial Agents , Brain Ischemia/complications
5.
African Journal of Respiratory Medicine ; 15(2), 2020.
Article in English | EMBASE | ID: covidwho-2058658

ABSTRACT

Objective: Severe acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) seen in SARs-CoV-2 infection has been attributed to the disruption of the immune response in COVID-19 patients. Neutrophilia and marked lymphocyte reductions are associated with disease severity and seem predictive of disease outcome in moderate and severe COVID-19 patients. Herein, we aim to decipher possible mechanisms involved in extensive tissue injury observed in COVID-19 patients, accompanied by vasculopathy, coagulopathy, and a high incidence of thrombotic complications in severe patients. Method(s): We searched PubMED for keywords including COVID-19 pathogenesis, thrombosis, and vasculities. Result(s): Neutrophils can undergo a specialized form of apoptosis to yield thread-like extracellular structures termed neutrophil extracellular traps (NETs), termed NETosis, which form web-like scaffolds of DNA, histones, and toxic protein granules and enzymes, whose primary function is to trap and eliminate microbes. However, uncontrolled NET production can lead to ALI and ARDS, coagulopathy, multiple organ failure, and autoimmune disease. Dysregulation of NETs promotes production of anti-neutrophil cytoplasmic antibodies (ANCA) which affects small vessels through ANCA-associated vasculitis (AAV). Furthermore, NETs can also induce thrombosis via formation of scaffolds that trap platelets, RBCs, fibronectin, and other proteins, which can also induce coagulation. Conclusion(s): We suggest that NET production is central during SARS-CoV-2 infection and COVID-19 pathogenesis, associated with alveolar damage accumulation of edema, endothelial injury and coagulopathy, elevated platelet activation and thrombogenesis forming a NET production feed-forward loop, causing diffuse small vessel vasculitis in the lungs and other organs. Copyright © 2020 FSG Communications Ltd. All rights reserved.

6.
Journal of Guilan University of Medical Sciences ; 30(2), 2021.
Article in Persian | CAB Abstracts | ID: covidwho-2057029

ABSTRACT

The current study sought to examine the clinical, laboratory, and imaging aspects of COVID-19-positive critically sick patients who were admitted to the intensive care units (ICUs) at three hospitals in Rash City, Iran. The goal of this retrospective study was to examine 138 COVID-19 patients who had been hospitalized to the intensive care unit. Data on the study participants' demographics, underlying diseases, laboratory and imaging results, and prognosis of the diseases were taken from their medical records. 138 COVID-19 patients who were hospitalised to the intensive care unit were the subject of this retrospective analysis. Patient records were used to extract information about the patient, including demographic details, underlying diseases, laboratory and imaging results, and disease outcomes. The majority of the patients in this study were male and between the ages of 55 and 69. The most prevalent underlying conditions were diabetes mellitus, hypertension, and chronic heart disease;the most prevalent symptoms were shortness of breath, fever, and cough. The most prevalent lung Computer Tomography (CT) scan finding was ground glass opacities, and the most frequent laboratory findings in the study participants were an increase in LDH, ESR, CRP, neutrophil percentage, and lymphopenia. A 90.58% fatality rate was recorded. This study showed that the majority of patients with severe disease presentations were older, had a history of underlying disease, symptoms of shortness of breath, cough, and fever, substantial lung involvement in imaging, and altered laboratory findings. Despite medical treatment and mechanical ventilation, mortality remained high.

7.
Br J Haematol ; 2022 Oct 06.
Article in English | MEDLINE | ID: covidwho-2052308

ABSTRACT

Numerous studies have shown peculiar morphological anomalies in COVID-19 patients' smears. We searched all the peer-reviewed scientific publications that explicitly reference the cytomorphological alterations on peripheral blood smears of patients with COVID-19. We extracted data from sixty-five publications (case reports, patient group studies, reviews, and erythrocyte morphology studies). The results show that frequent alterations concern the morphology of lymphocytes (large lymphocytes with weakly basophilic cytoplasm, plasmacytoid lymphocytes, large granular lymphocytes). Neutrophils display abnormal nuclei and cytoplasm in a distinctive cytomorphological picture. Besides a left shift in maturation, granulations can be increased (toxic type) or decreased with areas of basophilia. Nuclei are often hyposegmented (pseudo-Pelger-Huёt anomaly). Apoptotic or pycnotic cells are not uncommon. Monocytes typically have a large cytoplasm loaded with heterogeneous and coalescing vacuoles. Platelets show large and giant shapes. The presence of erythrocyte fragments and schistocytes is especially evident in the forms of COVID-19 that are associated with thrombotic microangiopathies. Such atypia of blood cells reflects the generalized activation in severe COVID-19, which has been demonstrated with immunophenotypic, molecular, genetic, and functional methods. Neutrophils, in particular, are involved in the pathophysiology of hyperinflammation with cytokine storm, which characterizes the most unfavorable evolution.

8.
Front Immunol ; 13: 996637, 2022.
Article in English | MEDLINE | ID: covidwho-2043454

ABSTRACT

Increased neutrophils and elevated level of circulating calprotectin are hallmarks of severe COVID-19 and they contribute to the dysregulated immune responses and cytokine storm in susceptible patients. However, the precise mechanism controlling calprotectin production during SARS-CoV-2 infection remains elusive. In this study, we showed that Dok3 adaptor restrains calprotectin production by neutrophils in response to SARS-CoV-2 spike (S) protein engagement of TLR4. Dok3 recruits SHP-2 to mediate the de-phosphorylation of MyD88 at Y257, thereby attenuating downstream JAK2-STAT3 signaling and calprotectin production. Blocking of TLR4, JAK2 and STAT3 signaling could prevent excessive production of calprotectin by Dok3-/- neutrophils, revealing new targets for potential COVID-19 therapy. As S protein from SARS-CoV-2 Delta and Omicron variants can activate TLR4-driven calprotectin production in Dok3-/- neutrophils, our study suggests that targeting calprotectin production may be an effective strategy to combat severe COVID-19 manifestations associated with these emerging variants.


Subject(s)
Adaptor Proteins, Signal Transducing , COVID-19 , Spike Glycoprotein, Coronavirus , Adaptor Proteins, Signal Transducing/metabolism , Humans , Leukocyte L1 Antigen Complex , Myeloid Differentiation Factor 88/metabolism , Neutrophils/metabolism , SARS-CoV-2 , Toll-Like Receptor 4/metabolism
9.
Front Immunol ; 13: 995886, 2022.
Article in English | MEDLINE | ID: covidwho-2043453

ABSTRACT

Kawasaki disease (KD), a multisystem inflammatory syndrome that occurs in children, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or COVID-19) may share some overlapping mechanisms. The purpose of this study was to analyze the differences in single-cell RNA sequencing between KD and COVID-19. We performed single-cell RNA sequencing in KD patients (within 24 hours before IVIG treatment) and age-matched fever controls. The single-cell RNA sequencing data of COVID-19, influenza, and health controls were downloaded from the Sequence Read Archive (GSE149689/PRJNA629752). In total, 22 single-cell RNA sequencing data with 102,355 nuclei were enrolled in this study. After performing hierarchical and functional clustering analyses, two enriched gene clusters demonstrated similar patterns in severe COVID-19 and KD, heightened neutrophil activation, and decreased MHC class II expression. Furthermore, comparable dysregulation of neutrophilic granulopoiesis representing two pronounced hyperinflammatory states was demonstrated, which play a critical role in the overactivated and defective aging program of granulocytes, in patients with KD as well as those with severe COVID-19. In conclusion, both neutrophil activation and MHC class II reduction play a crucial role and thus may provide potential treatment targets for KD and severe COVID-19.


Subject(s)
COVID-19 , Mucocutaneous Lymph Node Syndrome , COVID-19/complications , Child , Humans , Immunoglobulins, Intravenous , Neutrophils , SARS-CoV-2 , Systemic Inflammatory Response Syndrome
10.
Vestnik Rossiyskoy voyenno meditsinskoy akademii ; 4:105-112, 2021.
Article in Russian | GIM | ID: covidwho-2040520

ABSTRACT

Features of variation of peripheral blood leukocyte formula parameters in 86 patients with coronavirus pneumonia with leukocytosis with a background of glucocorticoid treatment were investigated. All patients were divided into 2 groups. Group 1 was 22 individuals who showed clinical signs of the bacterial infection (purulent sputum cough in combination with neutrophilic leukocytosis at hospital the admission). The 2nd group was made up of 64 patients with the glucocorticoids developed against the background of treatment with glucocorticoids (dexamethasone 20 mg/day or prednisolone 150 mg/day, intravenously for 3 days) leukocytosis >10 x109/l without signs of a bacterial infection. It was found that in patients of the 1st group compared to the 2nd group, levels of the white blood cells and neutrophils were significantly (p < 0.001) exceeded the reference values in the absence of a significant change in the number of monocytes. In patients of the 2nd group after a three-day intravenous application of the glucocorticoids on the 4th day of hospitalization, a statistically significant (p < 0.001) increase in the number of neutrophils and monocytes was established. When comparing the quantitative parameters of the leukocyte formula between the 2nd group on the 4th day of the hospitalization and the 1st group at admission, there were no differences in the level of leukocytes and neutrophils. Number of monocytes in group 2 (1.11 (0.90;1.34) x 109/l), on the contrary, statistically significantly (p < 0.001) exceeded their level in the 1st group (0.59 (0.50;0.77) x 109/l). Thus, an indicator of the number of monocytes in the peripheral blood could be a promising differential diagnostic criterion for the genesis of the leukocytosis in patients with the COVID-19. This parameter may be one of the factors influencing the decision to prescribe the antibacterial therapy.

11.
Antioxidants (Basel) ; 11(9)2022 Sep 09.
Article in English | MEDLINE | ID: covidwho-2032829

ABSTRACT

Lonicerae japonicae flos (LJ) is an Asian traditional herb that is used as a dietary supplement, tea, and beverage to clear heat and quench thirst. However, no studies investigated its effect on activated human neutrophils, which played a crucial role in the bad prognosis of coronavirus disease of 2019 (COVID-19) patients by aggravating lung inflammation and respiratory failure. Herein, we evaluated the anti-inflammatory effect of LJ ethanol extract (LJEE) on human neutrophils activated by N-formyl-methionyl-leucyl-phenylalanine (fMLF). Our experimental results indicated that LJEE suppressed fMLF-activated superoxide anion (O2•-) generation, the expression of CD11b, and cell adhesion and migration, as well as the formation of neutrophil extracellular traps in human neutrophils. Further in-depth mechanical investigation revealed that pretreatment with LJEE accelerated the Ca2+ clearance, but did not affect the phosphorylation of mitogen-activated protein kinases (MAPKs) and protein kinase B (Akt) in activated human neutrophils. In addition, LJEE displayed a dose-dependent reactive oxygen species (ROS) scavenger activity, which assisted its anti-inflammatory activity. From the bioassay-coupled chromatographic profile, chlorogenic acids were found to dominate the anti-inflammatory effects of LJEE. Moreover, LJ water extract (LJWE) demonstrated an interrupting effect on the severe acute respiratory syndrome coronavirus-2 spike protein (SARS-CoV-2-Spike)/angiotensin-converting enzyme 2 (ACE2) binding. In conclusion, the obtained results not only supported the traditional use of LJ for heat-clearance, but also suggested its potential application in daily health care during the COVID-19 pandemic.

12.
Immune Netw ; 22(4): e36, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-2024870

ABSTRACT

Dexamethasone (DEX) was the first drug shown to save lives of critically ill coronavirus disease 2019 (COVID-19) patients suffering from respiratory distress. A hyperactivated state of neutrophils was found in COVID-19 patients compared to non-COVID pneumonia cases. Given the beneficial effects of DEX in COVID-19 patients, we investigated the effects of DEX and of other immunomodulatory drugs vitamin D3 (VD3) and retinoic acid (RA) on neutrophil function. DEX, but not VD3 or RA, significantly inhibited all tested aspects of neutrophil function, e.g., degranulation, intracellular ROS production, CXCL8 release and NETosis. Interestingly, RA displayed the opposite effect by significantly increasing both CXCL8 and NET release by neutrophils. Taken together, these data suggest that the lower COVID-19 mortality in DEX-treated patients may in part be due to the dampening effect of DEX on the inflammatory neutrophil response, which could prevent neutrophil plugs with NETS in the lungs and other inflamed organs of patients.

13.
Mech Ageing Dev ; 204: 111667, 2022 06.
Article in English | MEDLINE | ID: covidwho-2015813

ABSTRACT

The COVID-19 pandemic caused by SARS-CoV-2 infection has been of unprecedented clinical and socio-economic worldwide relevance. The case fatality rate for COVID-19 grows exponentially with age and the presence of comorbidities. In the older patients, COVID-19 manifests predominantly as a systemic disease associated with immunological, inflammatory, and procoagulant responses. Timely diagnosis and risk stratification are crucial steps to define appropriate therapies and reduce mortality, especially in the older patients. Chronically and systemically activated innate immune responses and impaired antiviral responses have been recognized as the results of a progressive remodeling of the immune system during aging, which can be described by the words 'immunosenescence' and 'inflammaging'. These age-related features of the immune system were highlighted in patients affected by COVID-19 with the poorest clinical outcomes, suggesting that the mechanisms underpinning immunosenescence and inflammaging could be relevant for COVID-19 pathogenesis and progression. Increasing evidence suggests that senescent myeloid and endothelial cells are characterized by the acquisition of a senescence-associated pro-inflammatory phenotype (SASP), which is considered as the main culprit of both immunosenescence and inflammaging. Here, we reviewed this evidence and highlighted several circulating biomarkers of inflammaging that could provide additional prognostic information to stratify COVID-19 patients based on the risk of severe outcomes.


Subject(s)
COVID-19 , Aging , Biomarkers , COVID-19/diagnosis , Endothelial Cells , Humans , Inflammation , Pandemics , SARS-CoV-2
15.
Respirology Case Reports ; 10(9), 2022.
Article in English | ProQuest Central | ID: covidwho-2013740

ABSTRACT

Disseminated primary varicella infection can carry risks of significant morbidity and mortality particularly in immunocompromised populations. Routine, funded childhood vaccination against varicella has significantly reduced associated hospitalization and deaths, however, uptake and efficacy among adults is unknown. We present a case of disseminated primary varicella infection (including rash, pneumonitis, hepatitis and thrombocytopenia) in an immunocompetent patient on long term inhaled corticosteroids for asthma. This case highlights potential risk factors for severe varicella which require further study in adults and raises the need to discuss vaccination in at risk groups including appropriate counselling in those who may be at higher risk.

16.
Salud i Ciencia ; 24(6):316-317, 2021.
Article in Portuguese | GIM | ID: covidwho-2012860

ABSTRACT

In patients with acute ischemic stroke and COVID-19, the highest ratio between neutrophils and lymphocytes and increased serum levels of C-reactive protein, ferritin, D-dimer and fibrinogen are associated with poor neurological prognosis;75% of these patients die or survive with significant disability. At the moment, however, they cannot be established firm conclusions about the long-term evolution of these patients. Thus, the objective of this systematic review was to identify and correlate clinical and biochemical findings in patients with infection confirmed by SARS-CoV-2 and acute ischemic stroke.

17.
Molecules ; 27(18)2022 Sep 08.
Article in English | MEDLINE | ID: covidwho-2010215

ABSTRACT

The prevalence of novel SARS-CoV-2 variants is also accompanied by an increased turnover rate and additional cleavage sites at the positions necessary for priming the Spike (S) protein. Of these priming sites, the proteolytically sensitive polybasic sequence of the activation loop at the S1/S2 interface and the S2' location within the S2 subunit of the S protein are cleaved by furin and TMPRSS2, which are important for the infection of the target cell. Neutrophils, migrating to the site of infection, secrete serine proteases to fight against pathogens. The serine proteases encompass neutrophil elastase (NE), proteinase 3 (PR3), and cathepsin G (CatG), which can hydrolyze the peptide bond adjacent to the S1/S2 interface. SARS-CoV-2 might take the opportunity to hijack proteases from an immune response to support viral entry to the cell. The region near S704L within the S2 subunit, a novel amino acid substitution of SARS-CoV-2 Omicron sublineage BA.2.12.1, is located close to the S1/S2 interface. We found that NE, PR3, and CatG digested the peptide within this region; however, the S704L amino acid substitution altered cleavage sites for PR3. In conclusion, such an amino acid substitution modifies S2 antigen processing and might further impact the major histocompatibility complex (MHC) binding and T cell activation.


Subject(s)
COVID-19 , SARS-CoV-2 , Cathepsin G , Furin/genetics , Humans , Leukocyte Elastase , Myeloblastin , Peptide Hydrolases/metabolism , Peptides , Spike Glycoprotein, Coronavirus/metabolism
18.
Bionanoscience ; : 1-9, 2022 Sep 02.
Article in English | MEDLINE | ID: covidwho-2007281

ABSTRACT

In recovered COVID-19 patients, the state of mucosal immunity remains understudied. Cytological, functional, and metabolic characteristics of neutrophils and the interleukin status will help to correctly assess the need for immunorehabilitation measures. The study objective is to assess the state of mucosal immunity after COVID-19. A comprehensive study of mucosal immunity included the assessment of nasal mucosal neutrophils with the monitoring of destructive and apoptotic changes as well as examination of the functional and metabolic activity of neutrophils entering the nasal secretions. Phagocytic activity was assessed using microbial suspension of Staphylococcus aureus, as well as intracellular oxygen-dependent biocidity, the functions of capturing, absorbing, and killing pathogens. Study of the secretory component included assessment of interleukin levels (TNF-α, IL-10, IFN-γ) and the content of sCD95 (sAPO-1/FAS), membrane marker of apoptosis, in the nasal secretions. Cell wall neutrophils in recovered COVID-19 patients show enhanced destructive and apoptotic processes within the cells. Functional disorders due to inhibited phagocytosis of autoflora are recorded. Functionally defective cells are brought into the nasal secretions; they demonstrate severely inhibited oxygen-dependent biocidity, rapid depletion of reserves, incomplete phagocytosis, and limited ability to capture pathogens, which can contribute to the growth of various pathogenic viruses and bacteria. In the nasal secretions, the concentration of sCD95 (sAPO-1/FAS), the membrane marker of apoptosis, is increased. Elevated level of pro- and anti-inflammatory cytokines (TNF-α, IL-10) downregulates IFN-γ, thus directly contributing to the formation of functionally defective neutrophils. Compensatory increase in the IL-10 anti-inflammatory cytokine under the influence of SARS-CoV-2 virus proteins downregulates IFN-γ and is a cofactor of depression of intracellular biocidity of neutrophils. An increased level of the TNF-α pro-inflammatory cytokine increases apoptotic and destructive changes in neutrophils entering the nasal secretion. Virus-induced, functional, and metabolic impairment of neutrophils of the mucosal immunity system develop in recovered COVID-19 patients, thus providing a scientific rationale for immunomodulatory therapy.

19.
Antioxidants (Basel) ; 11(9)2022 Aug 29.
Article in English | MEDLINE | ID: covidwho-2005919

ABSTRACT

The formation of microthrombi in lung autopsies indicates the involvement of NETs in the immunopathogenesis of severe COVID-19. Therefore, supplements inhibiting NET formation, in association with drugs with fewer adverse effects, should be a relevant strategy to attenuate the disease. Resveratrol (RESV) is a natural polyphenol with an important antiviral and antioxidant role. To modulate neutrophils from patients infected with SARS-CoV-2, we evaluated the in vitro effect of RESV on NET formation. Herein, we investigated 190 patients hospitalized with moderate, severe, and critical symptoms at Hospital das Clínicas, Brazil. We observed that neutrophilia in patients with severe COVID-19 infection is composed of neutrophils with activated profile able to release NET spontaneously. Notably, RESV decreased the neutrophil-activated status and the release of free DNA, inhibiting NET formation even under the specific PMA stimulus. At present, there is no evidence of the role of RESV in neutrophils from patients with COVID-19 infection. These findings suggest that adjunctive therapies with RESV may help decrease the inflammation of viral or bacterial infection, improving patient outcomes.

20.
BMC Pulm Med ; 22(1): 314, 2022 Aug 15.
Article in English | MEDLINE | ID: covidwho-2002160

ABSTRACT

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a rapidly progressive and fatal respiratory failure disease that often occurs in critically ill patients. Since ARDS is associated with immune dysregulation and coagulation abnormalities, it is necessary to identify an appropriate predictor that can accurately predict ARDS mortality based on its pathophysiology. Therefore, this study aimed to evaluate the clinical value of neutrophils to lymphocytes and platelets ratio (N/LPR) in predicting 28-day mortality in ARDS patients. METHODS: From July 2018 to October 2021, the medical records of ARDS patients were retrospective reviewed. Neutrophil count, lymphocyte count, and platelet count were collected, and the neutrophil-to-lymphocyte ratio (NLR) and N/LPR were calculated. Multivariate logistic regression analyses were performed to identify independent predictors of 28-day mortality in ARDS. Receiver operating characteristic (ROC) curve with the area under curve (AUC) was used to evaluate optimal cut-off values for 28-day mortality in ARDS. Kaplan-Meier analysis was used to estimate the 28-day survival probabilities stratified by optimal cut-off values of N/LPR and NLR. RESULTS: A total of 136 ARDS patients were included in this study and were further divided into survivors (n = 69) and non-survivors (n = 67) groups according to their survival status on day 28. There were no significant differences between the two groups in age, sex, history of smoking and drinking, comorbidities, and reasons of admission (P > 0.05). Non-survivors had significantly higher neutrophil counts, NLR and N/LPR and had significantly lower platelet counts than survivors (P < 0.05). Multivariate regression analysis revealed that N/LPR, NLR and platelet counts were independent predictors for 28-day mortality in ARDS (P < 0.05). The ROC analyses showed that N/LPR with optimal cut-off value of 10.57 (sensitivity: 74.6%; specificity: 72.5%) is a more reliable predictor for 28-day mortality in ARDS than NLR and platelet count (AUC: 0.785 vs. 0.679 vs. 0.326). Further subgroup analysis confirmed that ARDS patients with N/LPR < 10.57 had significantly lower 28-day mortality than patients with N/LPR ≥ 10.57 (P < 0.001). Kaplan-Meier analysis also confirmed that ARDS patients with N/LPR < 10.57 had significantly longer survival. CONCLUSION: N/LPR is an independent risk factor associated with 28-day mortality in ARDS patients and shows better performance in predicting mortality rate than NLR.


Subject(s)
Neutrophils , Respiratory Distress Syndrome , Humans , Lymphocytes , Prognosis , ROC Curve , Retrospective Studies
SELECTION OF CITATIONS
SEARCH DETAIL