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1.
Neurology ; 99(14): e1486-e1498, 2022 Oct 04.
Статья в английский | MEDLINE | ID: covidwho-2109249

Реферат

BACKGROUND AND OBJECTIVES: Increased anxious-depressive symptomatology is observed in the preclinical stage of Alzheimer disease (AD), which may accelerate disease progression. We investigated whether ß-amyloid, cortical thickness in medial temporal lobe structures, neuroinflammation, and sociodemographic factors were associated with greater anxious-depressive symptoms during the COVID-19 confinement. METHODS: This retrospective observational study included cognitively unimpaired older adults from the Alzheimer's and Families cohort, the majority with a family history of sporadic AD. Participants performed the Hospital Anxiety and Depression Scale (HADS) during the COVID-19 confinement. A subset had available retrospective (on average: 2.4 years before) HADS assessment, amyloid [18F] flutemetamol PET and structural MRI scans, and CSF markers of neuroinflammation (interleukin-6 [IL-6], triggering receptor expressed on myeloid cells 2, and glial fibrillary acidic protein levels). We performed multivariable linear regression models to investigate the associations of prepandemic AD-related biomarkers and sociodemographic factors with HADS scores during the confinement. We further performed an analysis of covariance to adjust by participants' prepandemic anxiety-depression levels. Finally, we explored the role of stress and lifestyle changes (sleep patterns, eating, drinking, smoking habits, and medication use) on the tested associations and performed sex-stratified analyses. RESULTS: We included 921 (254 with AD biomarkers) participants. ß-amyloid positivity (B = 3.73; 95% CI = 1.1 to 6.36; p = 0.006), caregiving (B = 1.37; 95% CI 0.24-2.5; p = 0.018), sex (women: B = 1.95; 95% CI 1.1-2.79; p < 0.001), younger age (B = -0.12; 95% CI -0.18 to -0.052; p < 0.001), and lower education (B = -0.16; 95% CI -0.28 to -0.042; p = 0.008) were associated with greater anxious-depressive symptoms during the confinement. Considering prepandemic anxiety-depression levels, we further observed an association between lower levels of CSF IL-6 (B = -5.11; 95% CI -10.1 to -0.13; p = 0.044) and greater HADS scores. The results were independent of stress-related variables and lifestyle changes. Stratified analysis revealed that the associations were mainly driven by women. DISCUSSION: Our results link AD-related pathophysiology and neuroinflammation with greater anxious-depressive symptomatology during the COVID-19-related confinement, notably in women. AD pathophysiology may increase neuropsychiatric symptomatology in response to stressors. This association may imply a worse clinical prognosis in people at risk for AD after the pandemic and thus deserves to be considered by clinicians. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier NCT02485730.


Тема - темы
Alzheimer Disease , COVID-19 , Aged , Alzheimer Disease/metabolism , Amyloid beta-Peptides/metabolism , Anxiety , Biomarkers , Depression , Female , Glial Fibrillary Acidic Protein , Humans , Interleukin-6 , Male , Positron-Emission Tomography , Retrospective Studies , tau Proteins/metabolism
2.
BMJ Open ; 12(11): e063856, 2022 11 04.
Статья в английский | MEDLINE | ID: covidwho-2108284

Реферат

INTRODUCTION: Hypercoagulation is one the main features of COVID-19. It is induced by the hyperinflammatory response that shifts the balance of haemostasis towards pro-coagulation. Interleukin-6 (IL-6) antagonist therapy has been recommended in certain subgroups of critically ill patients with COVID-19 to modulate inflammatory response. The interaction between immune response and haemostasis is well recognised. Therefore, our objective is to evaluate whether the modulation of the inflammatory response by IL-6 antagonist inflicts any changes in whole blood coagulation as assessed by viscoelastic methods in critically ill patients with COVID-19. METHODS AND ANALYSIS: In this prospective observational study, we are going to collect data on inflammatory parameters and blood coagulation using the ClotPro® device. The primary outcome is the change of the fibrinolytic system measured by the Lysis Time and Lysis onset time before and after immunomodulation therapy. Data will be collected before the IL-6 antagonist administration at baseline (T0) then after 24, 48 hours, then on day 5 and 7 (T1-4, respectively). Secondary outcomes include changes in other parameters related to inflammation, blood coagulation and biomarkers of endothelial injury. ETHICS AND DISSEMINATION: Ethical approval was given by the Medical Research Council of Hungary (1405-3/2022/EÜG). All participants provided written consent. The results of the study will be disseminated through peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05218369; Clinicaltrials.gov.


Тема - темы
COVID-19 , Humans , Blood Coagulation , COVID-19/drug therapy , Critical Illness/therapy , Interleukin-6 , Multicenter Studies as Topic , Observational Studies as Topic , Prospective Studies
3.
Medicine (Baltimore) ; 101(44): e31294, 2022 Nov 04.
Статья в английский | MEDLINE | ID: covidwho-2107670

Реферат

To investigate the effect of transpyloric enteral nutrition (TEN) on NLRP1, inflammatory response and prognosis for patients with Corona Virus Disease-19 (COVID-19) in intensive care unit (ICU). The present prospective observational study included 29 cases of COVID-19 patients in ICU who admitted to our hospital during February 2020 to March 2020. All the patients were divided into gastrogavage groups (n = 16) and TEN group (n = 13) according to route of enteral nutrition. Serum levels of C-reactive protein (CRP), interleukin-1 ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and NLRP1 (NLR family pyrin domain containing 1) was detected by enzyme linked immunosorbent assay (ELISA). Serum levels of lymphocyte, albumin and hemoglobin was detected using an automatic biochemical analyzer. Patients' demographic and clinical characteristics were collected and analyzed. Kaplan-Meier (K-M) curve was conducted for survival analysis and receiver operating characteristic curve was used for the analysis of diagnostic value of biomarkers. All the patients were followed-up for 3 months. This study found that the survival group had higher rate of TEN therapies than the deceased. COVID-19 patients in ICU on TEN had lower APACHE II scores, frequency of feeding suspension and mortality, however, with higher content of albumin was found at 5th day. The incidence of nutritional intolerance including abdominal distension and gastric retention in patients on TEN was notably lower than those on gastrogavage. The serum levels of NLRP1, CRP, IL-1ß, IL-6 and TNF-α decreased in a time-dependent manner, but patients on TEN had lower levels of NLRP1, CRP and IL-1ß than patients on gastrogavage. A positive correlation was found among NLRP1 and inflammatory factors, and COVID-19 patients with lower NLRP1 had longer survival time. Serum NLRP1 also exhibited diagnostic value for the death of COVID-19 patients. TEN decreased inflammatory response and improved the prognosis for COVID-19 patients in ICU.


Тема - темы
COVID-19 , Enteral Nutrition , Humans , Interleukin-6/metabolism , Tumor Necrosis Factor-alpha/metabolism , COVID-19/therapy , Intensive Care Units , Prognosis , C-Reactive Protein
4.
Immunobiology ; 227(6): 152288, 2022 Nov.
Статья в английский | MEDLINE | ID: covidwho-2105124

Реферат

The clinical presentation of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), ranges between mild respiratory symptoms and a severe disease that shares many of the features of sepsis. Sepsis is a deregulated response to infection that causes life-threatening organ failure. During sepsis, the intestinal epithelial cells are affected, causing an increase in intestinal permeability and allowing microbial translocation from the intestine to the circulation, which exacerbates the inflammatory response. Here we studied patients with moderate, severe and critical COVID-19 by measuring a panel of molecules representative of the innate and adaptive immune responses to SARS-CoV-2, which also reflect the presence of systemic inflammation and the state of the intestinal barrier. We found that non-surviving COVID-19 patients had higher levels of low-affinity anti-RBD IgA antibodies than surviving patients, which may be a response to increased microbial translocation. We identified sFas and granulysin, in addition to IL-6 and IL-10, as possible early biomarkers with high sensitivity (>73 %) and specificity (>51 %) to discriminate between surviving and non-surviving COVID-19 patients. Finally, we found that the microbial metabolite d-lactate and the tight junction regulator zonulin were increased in the serum of patients with severe COVID-19 and in COVID-19 patients with secondary infections, suggesting that increased intestinal permeability may be a source of secondary infections in these patients. COVID-19 patients with secondary infections had higher disease severity and mortality than patients without these infections, indicating that intestinal permeability markers could provide complementary information to the serum cytokines for the early identification of COVID-19 patients with a high risk of a fatal outcome.


Тема - темы
COVID-19 , Coinfection , Sepsis , Humans , COVID-19/diagnosis , SARS-CoV-2 , Interleukin-6 , Interleukin-10 , Permeability , Biomarkers , Intestines
5.
Front Immunol ; 13: 882921, 2022.
Статья в английский | MEDLINE | ID: covidwho-2099139

Реферат

Invasive mucormycosis (IM) is a life-threatening infection caused by the fungal order Mucorales, its diagnosis is often delayed, and mortality rates range from 40-80% due to its rapid progression. Individuals suffering from hematological malignancies, diabetes mellitus, organ transplantations, and most recently COVID-19 are particularly susceptible to infection by Mucorales. Given the increase in the occurrence of these diseases, mucormycosis has emerged as one of the most common fungal infections in the last years. However, little is known about the host immune response to Mucorales. Therefore, we characterized the interaction among L. corymbifera-one of the most common causative agents of IM-and human monocytes, which are specialized phagocytes that play an instrumental role in the modulation of the inflammatory response against several pathogenic fungi. This study covered four relevant aspects of the host-pathogen interaction: i) The recognition of L. corymbifera by human monocytes. ii) The intracellular fate of L. corymbifera. iii) The inflammatory response by human monocytes against the most common causative agents of mucormycosis. iv) The main activated Pattern-Recognition Receptors (PRRs) inflammatory signaling cascades in response to L. corymbifera. Here, we demonstrate that L. corymbifera exhibits resistance to intracellular killing over 24 hours, does not germinate, and inflicts minimal damage to the host cell. Nonetheless, viable fungal spores of L. corymbifera induced early production of the pro-inflammatory cytokine IL-1ß, and late release of TNF-α and IL-6 by human monocytes. Moreover, we revealed that IL-1ß production predominantly depends on Toll-like receptors (TLRs) priming, especially via TLR4, while TNF-α is secreted via C-type lectin receptors (CTLs), and IL-6 is produced by synergistic activation of TLRs and CTLs. All these signaling pathways lead to the activation of NF-kB, a transcription factor that not only regulates the inflammatory response but also the apoptotic fate of monocytes during infection with L. corymbifera. Collectively, our findings provide new insights into the host-pathogen interactions, which may serve for future therapies to enhance the host inflammatory response to L. corymbifera.


Тема - темы
COVID-19 , Mucorales , Mucormycosis , Humans , Mucormycosis/microbiology , Mucormycosis/pathology , NF-kappa B , Monocytes/pathology , Tumor Necrosis Factor-alpha , Interleukin-6 , Mucorales/physiology
6.
Infect Dis Clin North Am ; 36(4): 735-748, 2022 12.
Статья в английский | MEDLINE | ID: covidwho-2095433

Реферат

Both cytokine release syndrome (CRS) and sepsis are clinical syndromes rather than distinct diseases and share considerable overlap. It can often be challenging to distinguish between the two, but it is important given the availability of targeted treatment options. In addition, several other clinical syndromes overlap with CRS and sepsis, further making it difficult to differentiate them. This has particularly been highlighted in the recent coronavirus disease-2019 pandemic. As we start to understand the differences in the inflammatory markers and presentations in these syndromes, hopefully we will be able to enhance treatment and improve outcomes.


Тема - темы
COVID-19 , Sepsis , Humans , Cytokine Release Syndrome/etiology , Antibodies, Monoclonal, Humanized/therapeutic use , Interleukin-6 , Sepsis/drug therapy
7.
Cells ; 11(21)2022 Oct 28.
Статья в английский | MEDLINE | ID: covidwho-2090009

Реферат

Low back pain is a clinically highly relevant musculoskeletal burden and is associated with inflammatory as well as degenerative processes of the intervertebral disc. However, the pathophysiology and cellular pathways contributing to this devastating condition are still poorly understood. Based on previous evidence, we hypothesize that tissue renin-angiotensin system (tRAS) components, including the SARS-CoV-2 entry receptor angiotensin-converting enzyme 2 (ACE2), are present in human nucleus pulposus (NP) cells and associated with inflammatory and degenerative processes. Experiments were performed with NP cells from four human donors. The existence of angiotensin II, angiotensin II type 1 receptor (AGTR1), AGTR2, MAS-receptor (MasR), and ACE2 in human NP cells was validated with immunofluorescent staining and gene expression analysis. Hereafter, the cell viability was assessed after adding agonists and antagonists of the target receptors as well as angiotensin II in different concentrations for up to 48 h of exposure. A TNF-α-induced inflammatory in vitro model was employed to assess the impact of angiotensin II addition and the stimulation or inhibition of the tRAS receptors on inflammation, tissue remodeling, expression of tRAS markers, and the release of nitric oxide (NO) into the medium. Furthermore, protein levels of IL-6, IL-8, IL-10, and intracellular as well as secreted angiotensin II were assessed after exposing the cells to the substances, and inducible nitric oxide synthase (iNOS) levels were evaluated by utilizing Western blot. The existence of tRAS receptors and angiotensin II were validated in human NP cells. The addition of angiotensin II only showed a mild impact on gene expression markers. However, there was a significant increase in NO secreted by the cells. The gene expression ratios of pro-inflammatory/anti-inflammatory cytokines IL-6/IL-10, IL-8/IL-10, and TNF-α/IL-10 were positively correlated with the AGTR1/AGTR2 and AGTR1/MAS1 ratios, respectively. The stimulation of the AGTR2 MAS-receptor and the inhibition of the AGTR1 receptor revealed beneficial effects on the gene expression of inflammatory and tissue remodeling markers. This finding was also present at the protein level. The current data showed that tRAS components are expressed in human NP cells and are associated with inflammatory and degenerative processes. Further characterization of the associated pathways is warranted. The findings indicate that tRAS modulation might be a novel therapeutic approach to intervertebral disc disease.


Тема - темы
Nucleus Pulposus , Renin-Angiotensin System , Humans , Angiotensin II/metabolism , Angiotensin-Converting Enzyme 2 , Interleukin-10/metabolism , Interleukin-6/metabolism , Interleukin-8/metabolism , Nucleus Pulposus/cytology , Nucleus Pulposus/metabolism , Receptor, Angiotensin, Type 1/metabolism , Tumor Necrosis Factor-alpha/metabolism
8.
Rev Soc Bras Med Trop ; 55: e02392022, 2022.
Статья в английский | MEDLINE | ID: covidwho-2089509

Реферат

BACKGROUND: The inflammatory response plays a significant role in the outcome of coronavirus disease (COVID-19). METHODS: We investigated plasma cytokine and chemokine concentrations in non-infected (NI), asymptomatic severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2)-infected blood donors (AS), and patients with severe COVID-19 (SC). RESULTS: The SC group showed significantly higher levels of interleukin 6 (IL-6), IL-10, and CCL5 than the AS and NI groups. The SC and AS groups had considerably greater CXCL9 and CXCL10 concentrations than the NI group. Only NI and infected people showed separate clusters in the principal component analysis. CONCLUSIONS: SC, as well as AS was characterized by an inflammatory profile.


Тема - темы
COVID-19 , Humans , SARS-CoV-2 , Interleukin-10 , Interleukin-6 , Blood Donors , Chemokines , Cytokines
9.
ACS Appl Mater Interfaces ; 14(43): 48464-48475, 2022 Nov 02.
Статья в английский | MEDLINE | ID: covidwho-2087121

Реферат

Rapid and precise serum cytokine quantification provides immense clinical significance in monitoring the immune status of patients in rapidly evolving infectious/inflammatory disorders, examplified by the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. However, real-time information on predictive cytokine biomarkers to guide targetable immune pathways in pathogenic inflammation is critically lacking, because of the insufficient detection range and detection limit in current label-free cytokine immunoassays. In this work, we report a highly sensitive localized surface plasmon resonance imaging (LSPRi) immunoassay for label-free Interleukin 6 (IL-6) detection utilizing rationally designed peptide aptamers as the capture interface. Benefiting from its characteristically smaller dimension and direct functionalization on the sensing surface via Au-S bonding, the peptide-aptamer-based LSPRi immunoassay achieved enhanced label-free serum IL-6 detection with a record-breaking limit of detection down to 4.6 pg/mL, and a wide dynamic range of ∼6 orders of magnitude (values from 4.6 to 1 × 106 pg/mL were observed). The immunoassay was validated in vitro for label-free analysis of SARS-CoV-2 induced inflammation, and further applied in rapid quantification of serum IL-6 profiles in COVID-19 patients. Our peptide aptamer LSPRi immunoassay demonstrates great potency in label-free cytokine detection with unprecedented sensing capability to provide accurate and timely interpretation of the inflammatory status and disease progression, and determination of prognosis.


Тема - темы
Aptamers, Peptide , Biosensing Techniques , COVID-19 , Humans , SARS-CoV-2 , Cytokines/analysis , Interleukin-6 , Immunoassay/methods , Inflammation
10.
Biomed Pharmacother ; 156: 113946, 2022 Dec.
Статья в английский | MEDLINE | ID: covidwho-2085962

Реферат

Qingfei Paidu decoction (QFPDD) has been clinically proven to be effective in the treatment of coronavirus disease 2019 (COVID-19). However, the bioactive components and therapeutic mechanisms remain unclear. This study aimed to explore the effective components and underlying mechanisms of QFPDD in the treatment of COVID-19 by targeting the virus-host interactome and verifying the antiviral activities of its active components in vitro. Key active components and targets were identified by analysing the topological features of a compound-target-pathway-disease regulatory network of QFPDD for the treatment of COVID-19. The antiviral activity of the active components was determined by a live virus infection assay, and possible mechanisms were analysed by pseudotyped virus infection and molecular docking assays. The inhibitory effects of the components tested on the virus-induced release of IL-6, IL-1ß and CXCL-10 were detected by ELISA. Three components of QFPDD, oroxylin A, hesperetin and scutellarin, exhibited potent antiviral activities against live SARS-CoV-2 virus and HCoV-OC43 virus with IC50 values ranging from 18.68 to 63.27 µM. Oroxylin A inhibited the entry of SARS-CoV-2 pseudovirus into target cells and inhibited SARS-CoV-2 S protein-mediated cell-cell fusion by binding with the ACE2 receptor. The active components of QFPDD obviously inhibited the IL-6, IL-1ß and CXCL-10 release induced by the SARS-CoV-2 S protein. This study supports the clinical application of QFPDD and provides an effective analysis method for the in-depth study of the mechanisms of traditional Chinese medicine (TCM) in the prevention and treatment of COVID-19.


Тема - темы
COVID-19 , Humans , COVID-19/drug therapy , Molecular Docking Simulation , Interleukin-6 , SARS-CoV-2 , Phytochemicals/pharmacology , Phytochemicals/therapeutic use , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use
11.
Eur Rev Med Pharmacol Sci ; 26(19): 7297-7304, 2022 Oct.
Статья в английский | MEDLINE | ID: covidwho-2081434

Реферат

OBJECTIVE: Pneumonia and hyperinflammatory state related to COVID-19 infection are fatal clinical conditions without definite treatment modalities. Interleukin-6 and Interleukin-1 targeted therapies have been proposed as treatment options. This study was conducted to investigate the efficacy of anakinra and tocilizumab added to corticosteroids in patients with COVID-19-associated pneumonia and hyper-inflammatory syndrome in our tertiary clinical center. PATIENTS AND METHODS: Patients with COVID-19-associated pneumonia and hyperinflammatory state who did not respond to initial treatments, including corticosteroids, were included in the study. The patients' electronic records were reviewed retrospectively and recorded according to a standardized data table. Univariate and multivariate regression analyses were used to identify risk factors associated with intubation. RESULTS: 388 patients were included in the study. 197 patients were intubated and most of them died (n=194/197, 98%). 67 patients received tocilizumab, and 97 patients received anakinra. Anakinra [OR: 0.440, 95% CI=0.244-0.794, p=0.006] and tocilizumab [OR: 0.491, 95% CI=0.256-0.943, p=0.033] were both associated with a decreased risk for intubation. However, having a neutrophil/lymphocyte ratio ≥ 10 [OR: 2.035, 95% CI=1.143-3.623, p=0.016], serum lactate dehydrogenase (LDH) level ≥ 400 [OR: 3.160, 95% CI=1.937-5.156, p<0.001] and age ≥ 50 [OR: 4.048, 95% CI=2.037-8.043, p < 0.001] was associated with an increased risk for intubation. CONCLUSIONS: Both anakinra and tocilizumab, added to initial standard COVID-19 treatments (including glucocorticoids) reduced the need for intubation in patients with COVID-19-associated severe pneumonia and hyperinflammatory syndrome. Given the high mortality rate of intubated patients with COVID-19, both treatments may have added benefits on mortality.


Тема - темы
COVID-19 , Humans , COVID-19/drug therapy , SARS-CoV-2 , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Interleukin-6 , Retrospective Studies , Treatment Outcome , Adrenal Cortex Hormones/therapeutic use , Interleukin-1 , Lactate Dehydrogenases
12.
Saudi Med J ; 43(10): 1120-1127, 2022 Oct.
Статья в английский | MEDLINE | ID: covidwho-2081103

Реферат

OBJECTIVES: To investigate the value of measuring the diaphragm thickness (DT) on thorax computed tomography (CT) at intensive care unit (ICU) admission for predicting intubation requirement and mortality among COVID-19 patients. METHODS: This study was carried out in Ankara City Hospital, Ankara, Turkey, from September 2020 to January 2021, with 94 critical COVID-19 patients. The patients' demographic characteristics, laboratory parameters, DT measurements, mechanical ventilation (MV) requirements, and mortality statuses were retrospectively screened. The relationships between DT on initial CT, MV requirement, and mortality were investigated. RESULTS: Diaphragm thickness was lower in patients who required intubation after ICU admission than in non-intubated patients (p=0.006); it was also lower in non-survivors (p=0.009). The threshold values for MV need was 3.35 mm (p=0.004) and 3.275 mm for mortality (p=0.006), according to the receiver operating characteristic analysis used to assess the predictive potential of DT. The non-survivor group had a greater neutrophil-to-lymphocyte ratio (p=0.026). Absolute neutrophil count (p=0.017), neutrophil-to-lymphocyte ratio (p=0.010), and interleukin-6 levels (p=0.027) were higher among patients requiring MV than among non-intubated patients. CONCLUSION: Mortality and MV requirements can be predicted from DT measurements. Diaphragm thickness can facilitate the identification of high-risk patients on CT evaluation at ICU admission.


Тема - темы
COVID-19 , Humans , Diaphragm/diagnostic imaging , Retrospective Studies , Interleukin-6 , Intubation, Intratracheal/adverse effects , Thorax
13.
Clin Lab ; 68(10)2022 Oct 01.
Статья в английский | MEDLINE | ID: covidwho-2080866

Реферат

BACKGROUND: In this retrospective study, we aimed to compare the laboratory and clinical results of cytokine hem-adsorption as an immunomodulation therapy in COVID-19 ICU patients with or without sepsis. METHODS: The levels of PCT, CRP, and ferritin were determined as indicators of infection/sepsis; the levels of in-terleukins (IL-6, IL-8 and IL-10, and TNF-α) were determined as indicators of cytokine storm were compared. APACHE score, SOFA score, and mortality rates were compared for the progression of the disease in 23 COVID-19 patients. RESULTS: The therapy was generally successful in reducing the levels of IL-6, IL-8, IL-10, and TNF-α but the levels measured after the procedure did not differ among the patients with or without sepsis, suggesting that the presence of sepsis did not affect the efficacy and function of the cytokine hemadsorption procedure in COVID-19 patients. All parameters were reduced after the procedure except the levels of PCT and ferritin and mortality rates of patients diagnosed with sepsis. The level of PCT was significantly higher in these patients compared with the patients without sepsis while the ferritin and mortality did not show any significant difference between the two groups, suggesting that the cytokine hemadsorption may be safe in the treatment of critical COVID-19 patients. CONCLUSIONS: As a result, the progression of sepsis in COVID-19 may be avoided with cytokine hemadsorption applied as an immunomodulator therapy. However, this therapy should be further explored and validated prior to its introduction to everyday clinical practice when the epidemic conditions end.


Тема - темы
COVID-19 , Sepsis , Cytokines , Ferritins , Hemadsorption , Humans , Immunologic Factors/therapeutic use , Interleukin-10 , Interleukin-6 , Interleukin-8 , Prognosis , ROC Curve , Retrospective Studies , Sepsis/diagnosis , Sepsis/drug therapy , Tumor Necrosis Factor-alpha
14.
Front Immunol ; 13: 1008438, 2022.
Статья в английский | MEDLINE | ID: covidwho-2080155

Реферат

Objectives: To determine the profile of cytokines in patients with severe COVID-19 who were enrolled in a trial of COVID-19 convalescent plasma (CCP). Methods: Patients were randomized to receive standard treatment and 3 CCP units or standard treatment alone (CAPSID trial, ClinicalTrials.gov NCT04433910). The primary outcome was a dichotomous composite outcome (survival and no longer severe COVID-19 on day 21). Time to clinical improvement was a key secondary endpoint. The concentrations of 27 cytokines were measured (baseline, day 7). We analyzed the change and the correlation between serum cytokine levels over time in different subgroups and the prediction of outcome in receiver operating characteristics (ROC) analyses and in multivariate models. Results: The majority of cytokines showed significant changes from baseline to day 7. Some were strongly correlated amongst each other (at baseline the cluster IL-1ß, IL-2, IL-6, IL-8, G-CSF, MIP-1α, the cluster PDGF-BB, RANTES or the cluster IL-4, IL-17, Eotaxin, bFGF, TNF-α). The correlation matrix substantially changed from baseline to day 7. The heatmaps of the absolute values of the correlation matrix indicated an association of CCP treatment and clinical outcome with the cytokine pattern. Low levels of IP-10, IFN-γ, MCP-1 and IL-1ß on day 0 were predictive of treatment success in a ROC analysis. In multivariate models, low levels of IL-1ß, IFN-γ and MCP-1 on day 0 were significantly associated with both treatment success and shorter time to clinical improvement. Low levels of IP-10, IL-1RA, IL-6, MCP-1 and IFN-γ on day 7 and high levels of IL-9, PDGF and RANTES on day 7 were predictive of treatment success in ROC analyses. Low levels of IP-10, MCP-1 and high levels of RANTES, on day 7 were associated with both treatment success and shorter time to clinical improvement in multivariate models. Conclusion: This analysis demonstrates a considerable dynamic of cytokines over time, which is influenced by both treatment and clinical course of COVID-19. Levels of IL-1ß and MCP-1 at baseline and MCP-1, IP-10 and RANTES on day 7 were associated with a favorable outcome across several endpoints. These cytokines should be included in future trials for further evaluation as predictive factors.


Тема - темы
COVID-19 , Cytokines , Humans , Interleukin 1 Receptor Antagonist Protein , Interleukin-17 , Chemokine CCL3 , Tumor Necrosis Factor-alpha , Interleukin-6 , Interleukin-4 , Capsid , COVID-19/therapy , Becaplermin , Chemokine CXCL10 , Interleukin-2 , Interleukin-8 , Interleukin-9 , Granulocyte Colony-Stimulating Factor
15.
Front Immunol ; 13: 985433, 2022.
Статья в английский | MEDLINE | ID: covidwho-2080149

Реферат

Multisystem inflammatory syndrome in children (MIS-C) is a rare, severe complication of COVID-19. A better knowledge of immunological, cellular, and genetic characteristics of MIS-C could help better understand the pathogenesis of the disease and contribute to identifying specific diagnostic biomarkers and develop targeted therapies. We studied 37 MIS-C children at hospital admission and 24 healthy controls analyzing serum cytokines (IFN-α, IFN-ß, IFN-γ, IL-6, IL-10, IL-17A, IL-12p70 and TNF), lymphocyte populations by flow cytometry and 386 genes related to autoimmune diseases, autoinflammation and primary immunodeficiencies by NGS. MIS-C patients showed a significant increase of serum IFNγ (despite a significant reduction of activated Th1) and ILs, even if with a great heterogeneity among patients, revealing different pathways involved in MIS-C pathogenesis and suggesting that serum cytokines at admission may help to select the inflammatory pathways to target in each patient. Flow cytometry demonstrated a relevant reduction of T populations while the percentage of B cell was increased in agreement with an autoimmune pathogenesis of MIS-C. Genetic analysis identified variants in 34 genes and 83.3% of patients had at least one gene variant. Among these, 9 were mutated in more patients. Most genes are related to autoimmune diseases like ATM, NCF1, MCM4, FCN3, and DOCK8 or to autoinflammatory diseases associated to the release of IFNγ like PRF1, NOD2, and MEF. Thus, an incomplete clearance of the Sars-CoV2 during the acute phase may induce tissue damage and self-antigen exposure and genetic variants can predispose to hyper-reactive immune dysregulation events of MIS-C-syndrome. Type II IFN activation and cytokine responses (mainly IL-6 and IL-10) may cause a cytokine storm in some patients with a more severe acute phase of the disease, lymphopenia and multisystemic organ involvement. The timely identification of such patients with an immunocytometric panel might be critical for targeted therapeutic management.


Тема - темы
Autoimmune Diseases , COVID-19 , Immunologic Deficiency Syndromes , Child , Humans , Interleukin-10 , SARS-CoV-2 , Interleukin-17 , Interleukin-6 , RNA, Viral , Cytokines/metabolism , Biomarkers , Autoantigens , Guanine Nucleotide Exchange Factors
16.
Front Immunol ; 13: 928979, 2022.
Статья в английский | MEDLINE | ID: covidwho-2080133

Реферат

Purpose: A characteristic problem occurring in COVID-19 is excessive elevations of pro-inflammatory cytokines (e.g. IL-6 and CRP) which are associated with worse clinical outcomes. Stimulation of the vagally-mediated cholinergic anti-inflammatory reflex by slow paced breathing with prolonged exhalation may present a clinically relevant way to reduce circulating IL-6. Method: Single-center randomized controlled clinical trial with enrolment of 46 patients hospitalized with confirmed severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) infection and moderate COVID-19 pneumonia (primary diagnosis). Differences between intervention (4sec inhalation, 6sec exhalation for 20 minutes 3x daily) and control group in IL-6 calculated using multilevel mixed-effect linear regression models with random slope including the covariates relevant comorbidities, COVID-19 medication, and age. Both groups received standard care. Results: Mean age was 57 years ± 13 years, N= 28 (60%) male, N=30 (65%) with relevant comorbidities. The model including group-by-time interaction revealed a significantly lower trajectory of IL-6 in the intervention group (effect size Cohens f2 = 0.11, LR-test p=.040) in the intention-to-treat sample, confirmed by per-protocol analysis (f2 = 0.15, LR-test p=.022). Exploratory analysis using the median split of practice time to predict IL-6 of the next morning indicated a dose-response relationship with beneficial effects of practice time above 45 minutes per day. Oxygen saturation remained unchanged during slow-paced breathing (95.1% ± 2.1% to 95.4% ± 1.6%). Conclusion: Patients practicing slow-paced breathing had significantly lower IL-6 values than controls with a small to medium effect size and without relevant side effects. Further trials should evaluate clinical outcomes and an earlier start of the intervention. Slow-paced breathing could be an easy to implement, low-cost, safe and feasible adjuvant therapeutic approach to reduce circulating IL-6 in moderate COVID-19 pneumonia. Clinical Trial Registration: https://www.drks.de, identifier DRKS00023971, Universal Trial Number (UTN) U1111-1263-8658.


Тема - темы
COVID-19 , Humans , Male , Middle Aged , Female , Neuroimmunomodulation , SARS-CoV-2 , Interleukin-6 , Cytokines
17.
Eur Cytokine Netw ; 33(2): 1-12, 2022 06 01.
Статья в английский | MEDLINE | ID: covidwho-2079880

Реферат

Treatment of severe and critical cases of coronavirus disease 2019 (COVID-19) is still a top priority in public health. Previously, we reported distinct Th1 cytokines related to the pathophysiology of severe COVID-19 condition. In the present study, we investigated the association of Th1 and Th2 cytokine/chemokine endotypes with cell-mediated immunity via multiplex immunophenotyping, single-cell RNA-Seq analysis of peripheral blood mononuclear cells, and analysis of the clinical features of COVID-19 patients. Based on serum cytokine and systemic inflammatory markers, COVID-19 cases were classified into four clusters of increasing (I-IV) severity. Two prominent clusters were of interest and could be used as prognostic reference for a targeted treatment of severe COVID-19 cases. Cluster III reflected severe/critical pathology and was characterized by decreased in CCL17 levels and increase in IL-6, C-reactive protein CXCL9, IL-18, and IL-10 levels. The second cluster (Cluster II) showed mild to moderate pathology and was characterized by predominated CXCL9 and IL-18 levels, levels of IL-6 and CRP were relatively low. Cluster II patients received anti-inflammatory treatment in early-stage, which may have led prevent disease prognosis which is accompanied to IL-6 and CRP induction. In Cluster III, a decrease in the proportion of effector T cells with signs of T cell exhaustion was observed. This study highlights the mechanisms of endotype clustering based on specific inflammatory markers in related the clinical outcome of COVID-19.


Тема - темы
COVID-19 , Cytokines , Humans , Interleukin-10 , Interleukin-18 , C-Reactive Protein , Interleukin-6 , Leukocytes, Mononuclear , Chemokines , Biomarkers
18.
Medicine (Baltimore) ; 101(41): e31102, 2022 Oct 14.
Статья в английский | MEDLINE | ID: covidwho-2077961

Реферат

BACKGROUND: To study the changes and effects of angiotensin-converting enzyme 2 (ACE2)/angiotensin 1-7 (Ang1-7) and ACE/AngII in people with different glucose metabolisms and to explore the possible mechanisms underlying the severity of COVID-19 infection in diabetic patients. METHODS: A total of 88 patients with type 2 diabetes, 72 patients with prediabetes (impaired fasting glucose, 30 patients; impaired glucose regulation, 42 patients), and 50 controls were selected. Changes and correlations of ACE2, Ang1-7 and other indicators were detected among the three groups. Patients were divided into four groups according to the course of diabetes: <1 year, 1-5 years, 5-10 years, and >10 years. ACE2 and Ang1-7 levels were compared and analyzed. RESULTS: ACE2 and Ang1-7 increased with the severity of diabetes (P0 < .05 or P < .01). The levels of ACE2 and Ang1-7 in the longer course group were lower than those in the shorter course group, whereas the levels of ACE, Ang II, and interleukin-6 (IL-6) gradually increased (P < .05). Pearson correlation analysis showed that ACE2 was positively correlated with IL-6, FBG, and 2hPBG levels in the prediabetes group. In the diabetic group, ACE2 was positively correlated with Ang1-7 and negatively correlated with ACE, AngII, IL-6, and C-reactive protein levels. Multiple linear regression analysis showed that IL-6 and ACE were the main factors influencing ACE2 in the diabetic group. CONCLUSION SUBSECTIONS: ACE2/Ang1-7 and ACE/AngII systems are activated, and inflammatory cytokine release increases in prediabetes. With the prolongation of the disease course, the effect of ACE2/Ang1-7 decreased gradually, while the effect of ACE/AngII increased significantly. Dysfunctions of ACE2/Ang1-7 may be one of the important mechanisms underlying the severity of COVID-19 infection in patients with diabetes.


Тема - темы
Angiotensin-Converting Enzyme 2 , COVID-19 , Diabetes Mellitus, Type 2 , Prediabetic State , Humans , Angiotensin I/metabolism , Angiotensin II , Angiotensin-Converting Enzyme 2/metabolism , C-Reactive Protein , Glucose , Interleukin-6 , Peptide Fragments/metabolism
19.
Vet Microbiol ; 274: 109553, 2022 Nov.
Статья в английский | MEDLINE | ID: covidwho-2076830

Реферат

Infection induces the production of proinflammatory cytokines and chemokines such as interleukin-8 (IL-8) and interleukin-6 (IL-6). Although they facilitate local antiviral immunity, their excessive release leads to life-threatening cytokine release syndrome, exemplified by the severe cases of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In the present study, we found that interleukin-8 (IL-8) was upregulated by PDCoV infection. We then demonstrated that PDCoV E protein induced IL-8 production and that the TM domain and the C-terminal domain of the E protein were important for IL-8 production. Subsequently, we showed here that deleting the AP-1 and NF-κB binding motif in porcine IL-8 promoter abrogated its activation, suggesting that IL-8 expression was dependent on AP-1 and NF-κB. Furthermore, PDCoV E induced IL-8 production, which was also dependent on the NF-κB pathway through activating nuclear factor p65 phosphorylation and NF-κB inhibitor alpha (IκBα) protein phosphorylation, as well as inducing the nuclear translocation of p65, eventually resulting in the promotion of IL-8 production. PDCoV E also activated c-fos and c-jun, both of which are members of the AP-1 family. These findings provide new insights into the molecular mechanisms of PDCoV-induced IL-8 production and help us further understand the pathogenesis of PDCoV infection.


Тема - темы
COVID-19 , Swine Diseases , Swine , Animals , NF-kappa B/metabolism , NF-KappaB Inhibitor alpha , Interleukin-6/genetics , Transcription Factor AP-1/genetics , Transcription Factor AP-1/metabolism , Interleukin-8/genetics , Interleukin-8/metabolism , SARS-CoV-2 , COVID-19/veterinary , Cytokines , Antiviral Agents/pharmacology
20.
Nutrients ; 14(20)2022 Oct 13.
Статья в английский | MEDLINE | ID: covidwho-2071661

Реферат

Overweight and obesity are associated with chronic low-grade inflammation and represent risk factors for various diseases, including COVID-19. However, most published studies on COVID-19 defined obesity by the body mass index (BMI), which does not encounter adipose tissue distribution, thus neglecting immunometabolic high-risk patterns. Therefore, we comprehensively analyzed baseline anthropometry (BMI, waist-to-height-ratio (WtHR), visceral (VAT), epicardial (EAT), subcutaneous (SAT) adipose tissue masses and liver fat, inflammation markers (CRP, ferritin, interleukin-6), and immunonutritional scores (CRP-to-albumin ratio (CAR), modified Glasgow prognostic score, neutrophile-to-lymphocyte ratio, prognostic nutritional index)) in 58 consecutive COVID-19 patients of the early pandemic phase with regard to the necessity of invasive mechanical ventilation (IMV). Here, metabolically high-risk adipose tissues represented by increased VAT, liver fat, and WtHR strongly correlated with higher levels of inflammation, pathologic immunonutritional scores, and the need for IMV. In contrast, the prognostic value of BMI was inferior and absent with regard to SAT. Multivariable logistic regression analysis identified an optimized IMV risk prediction model employing liver fat, WtHR, and CAR. In summary, we suggest an immunometabolically risk-adjusted model to predict COVID-19-induced respiratory failure better than BMI-based stratification, which warrants prospective validation.


Тема - темы
COVID-19 , Respiratory Insufficiency , Humans , Body Mass Index , Interleukin-6 , Obesity/complications , Obesity/pathology , Inflammation/complications , Respiratory Insufficiency/complications , Albumins , Ferritins , Risk Assessment , Intra-Abdominal Fat/pathology , Risk Factors
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