interleukin-8 has been researched along with Pneumonia--Viral* in 30 studies
1 review(s) available for interleukin-8 and Pneumonia--Viral
1 trial(s) available for interleukin-8 and Pneumonia--Viral
29 other study(ies) available for interleukin-8 and Pneumonia--Viral
| Article | Year |
|---|---|
Threatening drug-drug interaction in a kidney transplant patient with coronavirus disease 2019 (COVID-19).
During the novel coronavirus pandemic, organ transplant recipients represent a frail susceptible category due to long-term immunosuppressive therapy. For this reason, clinical manifestations may differ from general population and different treatment approaches may be needed. We present the case of a 36-year-old kidney-transplanted woman affected by Senior-Loken syndrome diagnosed with COVID-19 pneumonia after a contact with her positive mother. Initial symptoms were fatigue, dry cough, and coryza; she never had fever nor oxygen supplementation. Hydroxychloroquine and lopinavir/ritonavir were started, and the antiviral drug was replaced with darunavir/cobicistat after 2 days for diarrhea. Immunosuppressant levels were closely monitored, and we observed very high tacrolimus trough levels despite initial dose reduction. The patient was left with steroid therapy alone. The peculiarity of clinical presentation and the management difficulties represent the flagship of our case report. We stress the need for guidelines in transplant recipients with COVID-19 infection with particular regard to the management of therapy. Topics: Adult; Antiviral Agents; Betacoronavirus; C-Reactive Protein; Ciliopathies; Cobicistat; Common Cold; Coronavirus Infections; Cough; COVID-19; COVID-19 Drug Treatment; Cytochrome P-450 CYP3A Inhibitors; Darunavir; Deprescriptions; Drug Combinations; Drug Interactions; Enzyme Inhibitors; Fatigue; Female; Glucocorticoids; Graft Rejection; Humans; Hydroxychloroquine; Immunocompromised Host; Immunosuppressive Agents; Interleukin-10; Interleukin-1beta; Interleukin-6; Interleukin-8; Kidney Diseases, Cystic; Kidney Failure, Chronic; Kidney Transplantation; Leber Congenital Amaurosis; Lopinavir; Methylprednisolone; Optic Atrophies, Hereditary; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2; Severity of Illness Index; Tacrolimus | 2020 |
Dapsone, colchicine and olanzapine as treatment adjuncts to prevent COVID-19 associated adult respiratory distress syndrome (ARDS).
Topics: Adult; Betacoronavirus; Chemotaxis, Leukocyte; Colchicine; Coronavirus Infections; COVID-19; Dapsone; Humans; Interleukin-8; Neutrophils; Olanzapine; Pandemics; Pneumonia, Viral; Respiratory Distress Syndrome; SARS-CoV-2 | 2020 |
Using IL-2R/lymphocytes for predicting the clinical progression of patients with COVID-19.
Effective laboratory markers for the estimation of disease severity and predicting the clinical progression of coronavirus disease-2019 (COVID-19) is urgently needed. Laboratory tests, including blood routine, cytokine profiles and infection markers, were collected from 389 confirmed COVID-19 patients. The included patients were classified into mild (n = 168), severe (n = 169) and critical groups (n = 52). The leukocytes, neutrophils, infection biomarkers [such as C-reactive protein (CRP), procalcitonin (PCT) and ferritin] and the concentrations of cytokines [interleukin (IL)-2R, IL-6, IL-8, IL-10 and tumor necrosis factor (TNF)-α] were significantly increased, while lymphocytes were significantly decreased with increased severity of illness. The amount of IL-2R was positively correlated with the other cytokines and negatively correlated with lymphocyte number. The ratio of IL-2R to lymphocytes was found to be remarkably increased in severe and critical patients. IL-2R/lymphocytes were superior compared with other markers for the identification of COVID-19 with critical illness, not only from mild but also from severe illness. Moreover, the cytokine profiles and IL-2R/lymphocytes were significantly decreased in recovered patients, but further increased in disease-deteriorated patients, which might be correlated with the outcome of COVID-19. Lymphopenia and increased levels of cytokines were closely associated with disease severity. The IL-2R/lymphocyte was a prominent biomarker for early identification of severe COVID-19 and predicting the clinical progression of the disease. Topics: Aged; Aged, 80 and over; Betacoronavirus; Biomarkers; C-Reactive Protein; China; Coronavirus Infections; COVID-19; Disease Progression; Female; Ferritins; Humans; Interleukin-10; Interleukin-2 Receptor alpha Subunit; Interleukin-6; Interleukin-8; Leukocyte Count; Male; Middle Aged; Neutrophils; Pandemics; Pneumonia, Viral; Procalcitonin; Prognosis; SARS-CoV-2; Severity of Illness Index; T-Lymphocytes; Tumor Necrosis Factor-alpha | 2020 |
Steroid-Responsive Encephalitis in Coronavirus Disease 2019.
Coronavirus disease 2019 (COVID-19) infection has the potential for targeting the central nervous system, and several neurological symptoms have been described in patients with severe respiratory distress. Here, we described the case of a 60-year-old patient with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection but only mild respiratory abnormalities who developed an akinetic mutism attributable to encephalitis. Magnetic resonance imaging was negative, whereas electroencephalography showed generalized theta slowing. Cerebrospinal fluid analyses during the acute stage were negative for SARS-CoV-2, positive for pleocytosis and hyperproteinorrachia, and showed increased interleukin-8 and tumor necrosis factor-α concentrations. Other infectious or autoimmune disorders were excluded. A progressive clinical improvement along with a reduction of cerebrospinal fluid parameters was observed after high-dose steroid treatment, thus arguing for an inflammatory-mediated brain involvement related to COVID-19. ANN NEUROL 2020;88:423-427. Topics: Akinetic Mutism; Antiviral Agents; beta 2-Microglobulin; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Combinations; Electroencephalography; Encephalitis; Glucocorticoids; Humans; Hydroxychloroquine; Interleukin-6; Interleukin-8; Lopinavir; Magnetic Resonance Imaging; Male; Methylprednisolone; Middle Aged; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2; Treatment Outcome; Tumor Necrosis Factor-alpha | 2020 |
Viral and host factors related to the clinical outcome of COVID-19.
In December 2019, coronavirus disease 2019 (COVID-19), which is caused by the new coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified in Wuhan (Hubei province, China) Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aging; Animals; Asymptomatic Infections; Betacoronavirus; China; Cohort Studies; Coronavirus Infections; COVID-19; Critical Illness; Disease Progression; Evolution, Molecular; Female; Genetic Variation; Genome, Viral; Hospitalization; Host-Pathogen Interactions; Humans; Inflammation Mediators; Interleukin-6; Interleukin-8; Lymphocyte Count; Lymphopenia; Male; Middle Aged; Pandemics; Phylogeny; Pneumonia, Viral; Respiratory Distress Syndrome; SARS-CoV-2; T-Lymphocytes; Time Factors; Treatment Outcome; Virulence; Virus Shedding; Young Adult; Zoonoses | 2020 |
Pediatric Crohn Disease and Multisystem Inflammatory Syndrome in Children (MIS-C) and COVID-19 Treated With Infliximab.
Coronavirus disease 2019 (COVID-19) may lead to a severe inflammatory response referred to as a cytokine storm. We describe a case of severe COVID-19 infection in a recently diagnosed pediatric Crohn disease patient successfully treated with tumor necrosis factor-alpha (TNF-α) blockade. The patient presented with 5 days of fever, an erythematous maculopapular facial rash, and abdominal pain without respiratory symptoms. SARS-CoV-2 polymerase chain reaction was positive. Despite inpatient treatment for COVID-19 and a perianal abscess, the patient acutely decompensated, with worsening fever, tachycardia, fluid-refractory hypotension, elevation of liver enzymes, and transformation of the rash into purpura extending from the face to the trunk, upper and lower extremities, including the palmar and plantar surfaces of the hands and feet. Cytokine profile revealed rising levels of interleukin (IL)-6, IL-8, and TNF-α, higher than those described in either inflammatory bowel disease or severe COVID-19 alone. The patient was treated with infliximab for TNF-α blockade to address both moderately to severely active Crohn disease and multisystem inflammatory syndrome in children temporally related to COVID-19. Within hours of infliximab treatment, fever, tachycardia, and hypotension resolved. Cytokine profile improved with normalization of TNF-α, a decrease in IL-6, and IL-8 concentrations. This case supports a role for blockade of TNF-α in the treatment of COVID-19 inflammatory cascade. The role of anti-TNF agents in patients with multisystem inflammatory syndrome in children temporally related to COVID-19 requires further investigation. Topics: Abnormalities, Multiple; Adolescent; Antirheumatic Agents; Betacoronavirus; Coronavirus Infections; COVID-19; Crohn Disease; Genetic Diseases, X-Linked; Humans; Ichthyosiform Erythroderma, Congenital; Infliximab; Interleukin-6; Interleukin-8; Limb Deformities, Congenital; Male; Pandemics; Pneumonia, Viral; SARS-CoV-2; Tumor Necrosis Factor-alpha | 2020 |
IL-6 and CD8+ T cell counts combined are an early predictor of in-hospital mortality of patients with COVID-19.
BACKGROUNDFatal cases of COVID-19 are increasing globally. We retrospectively investigated the potential of immunologic parameters as early predictors of COVID-19.METHODSA total of 1018 patients with confirmed COVID-19 were enrolled in our 2-center retrospective study. Clinical feature, laboratory test, immunological test, radiological findings, and outcomes data were collected. Univariate and multivariable logistic regression analyses were performed to evaluate factors associated with in-hospital mortality. Receiver operator characteristic (ROC) curves and survival curves were plotted to evaluate their clinical utility.RESULTSThe counts of all T lymphocyte subsets were markedly lower in nonsurvivors than in survivors, especially CD8+ T cells. Among all tested cytokines, IL-6 was elevated most significantly, with an upward trend of more than 10-fold. Using multivariate logistic regression analysis, IL-6 levels of more than 20 pg/mL and CD8+ T cell counts of less than 165 cells/μL were found to be associated with in-hospital mortality after adjusting for confounding factors. Groups with IL-6 levels of more than 20 pg/mL and CD8+ T cell counts of less than 165 cells/μL had a higher percentage of older and male patients as well as a higher proportion of patients with comorbidities, ventilation, intensive care unit admission, shock, and death. Furthermore, the receiver operating curve of the model combining IL-6 (>20 pg/mL) and CD8+ T cell counts (<165 cells/μL) displayed a more favorable discrimination than that of the CURB-65 score. The Hosmer-Lemeshow test showed a good fit of the model, with no statistical significance.CONCLUSIONIL-6 (>20 pg/mL) and CD8+ T cell counts (<165 cells/μL) are 2 reliable prognostic indicators that accurately stratify patients into risk categories and predict COVID-19 mortality.FundingThis work was supported by funding from the National Natural Science Foundation of China (no. 81772477 and 81201848). Topics: Aged; Area Under Curve; Betacoronavirus; CD8-Positive T-Lymphocytes; Coronavirus Infections; COVID-19; Female; Hospital Mortality; Humans; Interleukin-10; Interleukin-6; Interleukin-8; Logistic Models; Lymphocyte Count; Lymphopenia; Male; Middle Aged; Multivariate Analysis; Pandemics; Pneumonia, Viral; Prognosis; Receptors, Interleukin-2; Retrospective Studies; ROC Curve; SARS-CoV-2; Tumor Necrosis Factor-alpha | 2020 |
Characterization of the Inflammatory Response to Severe COVID-19 Illness.
Topics: Acute-Phase Reaction; Adult; Aged; alpha 1-Antitrypsin; Betacoronavirus; Blotting, Western; Carrier Proteins; Case-Control Studies; Community-Acquired Infections; Coronavirus Infections; COVID-19; Critical Illness; Cytokines; Electrophoresis, Polyacrylamide Gel; Enzyme-Linked Immunosorbent Assay; Female; Hospitalization; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Intensive Care Units; Interleukin-10; Interleukin-1beta; Interleukin-6; Interleukin-8; Lactic Acid; Length of Stay; Male; Membrane Proteins; Middle Aged; Neutrophils; Pandemics; Phosphorylation; Pneumonia; Pneumonia, Viral; Receptors, Tumor Necrosis Factor, Type I; SARS-CoV-2; Severity of Illness Index; Thyroid Hormone-Binding Proteins; Thyroid Hormones | 2020 |
Use of inhaled corticosteroids in asthma and coronavirus disease 2019: Keep calm and carry on.
Topics: Administration, Inhalation; Adrenal Cortex Hormones; Angiotensin-Converting Enzyme 2; Anti-Asthmatic Agents; Asthma; Betacoronavirus; Coronavirus Infections; COVID-19; Cytokine Release Syndrome; Dexamethasone; Endoribonucleases; Gene Expression Regulation; Host-Pathogen Interactions; Humans; Interleukin-6; Interleukin-8; Pandemics; Peptidyl-Dipeptidase A; Pneumonia, Viral; Receptors, Virus; SARS-CoV-2; Serine Endopeptidases; Severity of Illness Index; Tumor Necrosis Factor-alpha; Viral Nonstructural Proteins | 2020 |
Gene expression pattern differences in primary human pulmonary epithelial cells infected with MERS-CoV or SARS-CoV-2.
Coronaviruses such as MERS-CoV and SARS-CoV-2 infect the human respiratory tract and can cause severe pneumonia. Disease severity and outcomes are different for these two infections: the human mortality rate for MERS-CoV and SARS-CoV-2 is over 30% and less than 10%, respectively. Here, using microarray assay, we analyzed the global alterations in gene expression induced by MERS-CoV or SARS-CoV-2 infections in primary human pulmonary epithelial cells. Overall, the number of differentially expressed genes was higher in human lung cells infected with MERS-CoV than in cells with SARS-CoV-2. Out of 44,556 genes analyzed, 127 and 50 were differentially expressed in cells infected with MERS-CoV and SARS-CoV-2, respectively (> 2-fold increase, compared to uninfected cells). Of these, only eight genes, including the one coding for CXCL8, were similarly modulated (upregulated or downregulated) by the two coronaviruses. Importantly, these results were virus-specific and not conditioned by differences in viral load, and viral growth curves were similar in human lung cells infected with both viruses. Our results suggest that these distinct gene expression profiles, detected early after infection by these two coronaviruses, may help us understand the differences in clinical outcomes of MERS-CoV and SARS-CoV-2 infections. Topics: Betacoronavirus; Cells, Cultured; Chemokine CXCL6; Coronavirus Infections; COVID-19; Down-Regulation; Epithelial Cells; Gene Expression Profiling; Host Microbial Interactions; Humans; Interleukin-8; Lung; Middle East Respiratory Syndrome Coronavirus; Pandemics; Pneumonia, Viral; SARS-CoV-2; Species Specificity; Up-Regulation | 2020 |
Cytokine prediction of mortality in COVID19 patients.
Coronavirus disease 2019 (COVID19) is a life-threatening infection with uncertain progression and outcome. Assessing the severity of the disease for worsening patients is of importance in making decisions related to supportive mechanical ventilation and aggressive treatments. This was a prospective, non-randomized study that included hospitalized patients diagnosed with COVID19. Pro-inflammatory cytokines were assessed during hospitalization, and we calculated a prediction paradigm for 30-day mortality based on the serum levels of interleukin1β (IL1β), interleukin6 (IL6), interleukin8 (IL8), and tumor necrosis factor alpha (TNFα) measured by next-generation ELISA. Data of 71 COVID19 patients, mean age 62 years, SD13.8, 50 males, 21 females, were analyzed. Twelve (16.9%) patients died within 7-39 days of their first COVID19 positive nasopharyngeal test. Levels of IL6 and TNFα were significantly higher in patients that did not survive. IL6 predicted mortality at the cut-off value of 163.4 pg/ml, with a sensitivity of 91.7% and specificity of 57.6%. Our findings demonstrate that IL6 expression is significant for the prediction of 30-day mortality in hospitalized COVID19 patients and, therefore, may assist in treatment decisions. Topics: Betacoronavirus; Coronavirus Infections; COVID-19; Cytokine Release Syndrome; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-1beta; Interleukin-6; Interleukin-8; Kaplan-Meier Estimate; Male; Middle Aged; Pandemics; Pneumonia, Viral; Prognosis; Prospective Studies; SARS-CoV-2; Tumor Necrosis Factor-alpha | 2020 |
Cytokine profile in plasma of severe COVID-19 does not differ from ARDS and sepsis.
BACKGROUNDElevated levels of inflammatory cytokines have been associated with poor outcomes among COVID-19 patients. It is unknown, however, how these levels compare with those observed in critically ill patients with acute respiratory distress syndrome (ARDS) or sepsis due to other causes.METHODSWe used a Luminex assay to determine expression of 76 cytokines from plasma of hospitalized COVID-19 patients and banked plasma samples from ARDS and sepsis patients. Our analysis focused on detecting statistical differences in levels of 6 cytokines associated with cytokine storm (IL-1β, IL-1RA, IL-6, IL-8, IL-18, and TNF-α) between patients with moderate COVID-19, severe COVID-19, and ARDS or sepsis.RESULTSFifteen hospitalized COVID-19 patients, 9 of whom were critically ill, were compared with critically ill patients with ARDS (n = 12) or sepsis (n = 16). There were no statistically significant differences in baseline levels of IL-1β, IL-1RA, IL-6, IL-8, IL-18, and TNF-α between patients with COVID-19 and critically ill controls with ARDS or sepsis.CONCLUSIONLevels of inflammatory cytokines were not higher in severe COVID-19 patients than in moderate COVID-19 or critically ill patients with ARDS or sepsis in this small cohort. Broad use of immunosuppressive therapies in ARDS has failed in numerous Phase 3 studies; use of these therapies in unselected patients with COVID-19 may be unwarranted.FUNDINGFunding was received from NHLBI K23 HL125663 (AJR); The Bill and Melinda Gates Foundation OPP1113682 (AJR and CAB); Burroughs Wellcome Fund Investigators in the Pathogenesis of Infectious Diseases #1016687 NIH/NIAID U19AI057229-16; Stanford Maternal Child Health Research Institute; and Chan Zuckerberg Biohub (CAB). Topics: Adult; Aged; Case-Control Studies; Coronavirus Infections; COVID-19; Cytokine Release Syndrome; Cytokines; Female; Humans; Interleukin 1 Receptor Antagonist Protein; Interleukin-18; Interleukin-1beta; Interleukin-6; Interleukin-8; Male; Middle Aged; Pandemics; Pneumonia, Viral; Respiratory Distress Syndrome; Sepsis; Severity of Illness Index; Tumor Necrosis Factor-alpha | 2020 |
Tobacco, but Not Nicotine and Flavor-Less Electronic Cigarettes, Induces ACE2 and Immune Dysregulation.
The COVID-19 pandemic caused by the SARS-CoV-2 virus, overlaps with the ongoing epidemics of cigarette smoking and electronic cigarette (e-cig) vaping. However, there is scarce data relating COVID-19 risks and outcome with cigarette or e-cig use. In this study, we mined three independent RNA expression datasets from smokers and vapers to understand the potential relationship between vaping/smoking and the dysregulation of key genes and pathways related to COVID-19. We found that smoking, but not vaping, upregulates ACE2, the cellular receptor that SARS-CoV-2 requires for infection. Both smoking and use of nicotine and flavor-containing e-cigs led to upregulation of pro-inflammatory cytokines and inflammasome-related genes. Specifically, chemokines including CCL20 and CXCL8 are upregulated in smokers, and CCL5 and CCR1 are upregulated in flavor/nicotine-containing e-cig users. We also found genes implicated in inflammasomes, such as CXCL1, CXCL2, NOD2, and ASC, to be upregulated in smokers and these e-cig users. Vaping flavor and nicotine-less e-cigs, however, did not lead to significant cytokine dysregulation and inflammasome activation. Release of inflammasome products, such as IL-1B, and cytokine storms are hallmarks of COVID-19 infection, especially in severe cases. Therefore, our findings demonstrated that smoking or vaping may critically exacerbate COVID-19-related inflammation or increase susceptibility to COVID-19. Topics: Adult; Angiotensin-Converting Enzyme 2; Betacoronavirus; Bronchi; Chemokine CCL20; Coronavirus Infections; COVID-19; Electronic Nicotine Delivery Systems; Epithelial Cells; Humans; Immune System; Interleukin-1beta; Interleukin-8; Middle Aged; Nod2 Signaling Adaptor Protein; Pandemics; Peptidyl-Dipeptidase A; Pneumonia, Viral; SARS-CoV-2; Tobacco Smoking; Up-Regulation; Young Adult | 2020 |
An inflammatory cytokine signature predicts COVID-19 severity and survival.
Several studies have revealed that the hyper-inflammatory response induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major cause of disease severity and death. However, predictive biomarkers of pathogenic inflammation to help guide targetable immune pathways are critically lacking. We implemented a rapid multiplex cytokine assay to measure serum interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α and IL-1β in hospitalized patients with coronavirus disease 2019 (COVID-19) upon admission to the Mount Sinai Health System in New York. Patients (n = 1,484) were followed up to 41 d after admission (median, 8 d), and clinical information, laboratory test results and patient outcomes were collected. We found that high serum IL-6, IL-8 and TNF-α levels at the time of hospitalization were strong and independent predictors of patient survival (P < 0.0001, P = 0.0205 and P = 0.0140, respectively). Notably, when adjusting for disease severity, common laboratory inflammation markers, hypoxia and other vitals, demographics, and a range of comorbidities, IL-6 and TNF-α serum levels remained independent and significant predictors of disease severity and death. These findings were validated in a second cohort of patients (n = 231). We propose that serum IL-6 and TNF-α levels should be considered in the management and treatment of patients with COVID-19 to stratify prospective clinical trials, guide resource allocation and inform therapeutic options. Topics: Aged; Betacoronavirus; Coronavirus Infections; COVID-19; Cytokines; Female; Hospitalization; Humans; Interleukin-1beta; Interleukin-6; Interleukin-8; Male; Middle Aged; Pandemics; Pneumonia, Viral; SARS-CoV-2; Severity of Illness Index; Survival Rate; Tumor Necrosis Factor-alpha | 2020 |
Re-analysis of Single Cell Transcriptome Reveals That the NR3C1-CXCL8-Neutrophil Axis Determines the Severity of COVID-19.
SARS-CoV-2 infection has recently been declared a pandemic. Some patients showing severe symptoms exhibit drastic inflammation and airway damage. In this study, we re-analyzed published scRNA-seq data of COVID-19 patient bronchoalveolar lavage fluid to further classify and compare immunological features according to the patient's disease severity. Patients with severe symptoms showed DNA damage and apoptotic features of epithelial cells. Our results suggested that epithelial damage was associated with neutrophil infiltration. Myeloid cells of severe patients showed higher expression of proinflammatory cytokines and chemokines such as CXCL8. As a result, neutrophils were abundant in lungs of patients from the severe group. Furthermore, recruited neutrophils highly expressed genes related to neutrophil extracellular traps. Neutrophil-mediated inflammation was regulated by glucocorticoid receptor expression and activity. Based on these results, we suggest that severe COVID-19 symptoms may be determined by differential expression of glucocorticoid receptors and neutrophils. Topics: Adult; Aged; Betacoronavirus; Bronchoalveolar Lavage Fluid; Coronavirus Infections; COVID-19; Epithelial Cells; Extracellular Traps; Female; Gene Expression Profiling; Humans; Inflammation; Interleukin-8; Male; Middle Aged; Myeloid Cells; Neutrophil Infiltration; Neutrophils; Pandemics; Pneumonia, Viral; Receptors, Glucocorticoid; RNA-Seq; SARS-CoV-2; Severity of Illness Index; Single-Cell Analysis; Transcriptome | 2020 |
Immune characteristics distinguish patients with severe disease associated with SARS-CoV-2.
Topics: Adult; Aged; Betacoronavirus; Biomarkers; Coronavirus Infections; COVID-19; Cytokine Release Syndrome; Female; Humans; Interleukin-2 Receptor alpha Subunit; Interleukin-6; Interleukin-8; Length of Stay; Lymphocyte Count; Male; Middle Aged; Neutrophils; Pandemics; Pneumonia, Viral; Retrospective Studies; SARS-CoV-2; Severity of Illness Index; Treatment Outcome; Young Adult | 2020 |
SARS-CoV-2 triggers inflammatory responses and cell death through caspase-8 activation.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can lead to respiratory illness and multi-organ failure in critically ill patients. Although the virus-induced lung damage and inflammatory cytokine storm are believed to be directly associated with coronavirus disease 2019 (COVID-19) clinical manifestations, the underlying mechanisms of virus-triggered inflammatory responses are currently unknown. Here we report that SARS-CoV-2 infection activates caspase-8 to trigger cell apoptosis and inflammatory cytokine processing in the lung epithelial cells. The processed inflammatory cytokines are released through the virus-induced necroptosis pathway. Virus-induced apoptosis, necroptosis, and inflammation activation were also observed in the lung sections of SARS-CoV-2-infected HFH4-hACE2 transgenic mouse model, a valid model for studying SARS-CoV-2 pathogenesis. Furthermore, analysis of the postmortem lung sections of fatal COVID-19 patients revealed not only apoptosis and necroptosis but also massive inflammatory cell infiltration, necrotic cell debris, and pulmonary interstitial fibrosis, typical of immune pathogenesis in the lung. The SARS-CoV-2 infection triggered a dual mode of cell death pathways and caspase-8-dependent inflammatory responses may lead to the lung damage in the COVID-19 patients. These discoveries might assist the development of therapeutic strategies to treat COVID-19. Topics: Animals; Apoptosis; Betacoronavirus; Caspase 8; Cell Line, Tumor; Chemokine CCL5; Chemokine CXCL10; Coronavirus Infections; COVID-19; Cytokine Release Syndrome; Disease Models, Animal; Epithelial Cells; Gene Expression Regulation; Humans; Interleukin-1beta; Interleukin-7; Interleukin-8; Lung; Mice; Mice, Transgenic; Necroptosis; Pandemics; Pneumonia, Viral; Pulmonary Fibrosis; SARS-CoV-2; Tumor Necrosis Factor-alpha | 2020 |
Age-severity matched cytokine profiling reveals specific signatures in Covid-19 patients.
A global effort is currently undertaken to restrain the COVID-19 pandemic. Host immunity has come out as a determinant for COVID-19 clinical outcomes, and several studies investigated the immune profiling of SARS-CoV-2 infected people to properly direct the clinical management of the disease. Thus, lymphopenia, T-cell exhaustion, and the increased levels of inflammatory mediators have been described in COVID-19 patients, in particular in severe cases Topics: Age Factors; Aged; Aged, 80 and over; Antibodies, Viral; Betacoronavirus; Cluster Analysis; Coronavirus Infections; COVID-19; Cytokines; Female; Humans; Immunoglobulin G; Interleukin-10; Interleukin-8; Length of Stay; Leukocytes, Mononuclear; Male; Middle Aged; Pandemics; Pneumonia, Viral; SARS-CoV-2; Severity of Illness Index; Tumor Necrosis Factor-alpha | 2020 |
Broncho-alveolar inflammation in COVID-19 patients: a correlation with clinical outcome.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly reached pandemic proportions. Given that the main target of SARS-CoV-2 are lungs leading to severe pneumonia with hyperactivation of the inflammatory cascade, we conducted a prospective study to assess alveolar inflammatory status in patients with moderate to severe COVID-19.. Diagnostic bronchoalveolar lavage (BAL) was performed in 33 adult patients with SARS-CoV-2 infection by real-time PCR on nasopharyngeal swab admitted to the Intensive care unit (ICU) (n = 28) and to the Intermediate Medicine Ward (IMW) (n = 5). We analyze the differential cell count, ultrastructure of cells and Interleukin (IL)6, 8 and 10 levels.. ICU patients showed a marked increase in neutrophils (1.24 × 10. Alveolitis, associated with COVID-19, is mainly sustained by innate effectors which showed features of extensive activation. The burden of pro-inflammatory cytokines IL6 and IL8 in the broncho-alveolar environment is associated with clinical outcome. Topics: Adenosine Monophosphate; Adrenal Cortex Hormones; Aged; Alanine; Antibodies, Monoclonal, Humanized; Antiviral Agents; Betacoronavirus; Bronchoalveolar Lavage; Bronchoalveolar Lavage Fluid; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Combinations; Female; Humans; Hydroxychloroquine; Inflammation; Intensive Care Units; Interleukin-10; Interleukin-6; Interleukin-8; Italy; Leukocytes; Leukocytes, Mononuclear; Lopinavir; Lung; Lymphocytes; Macrophages, Alveolar; Male; Microscopy, Electron, Transmission; Middle Aged; Neutrophils; Pandemics; Pneumonia, Viral; Prognosis; Prospective Studies; Respiration, Artificial; Ritonavir; SARS-CoV-2; Spike Glycoprotein, Coronavirus; Survival Rate; Virion | 2020 |
Human metapneumovirus infection activates the TSLP pathway that drives excessive pulmonary inflammation and viral replication in mice.
Human metapneumovirus (hMPV) is a leading cause of acute respiratory tract infections in children and the elderly. The mechanism by which this virus triggers an inflammatory response still remains unknown. Here, we evaluated whether the thymic stromal lymphopoietin (TSLP) pathway contributes to lung inflammation upon hMPV infection. We found that hMPV infection promotes TSLP expression both in human airway epithelial cells and in the mouse lung. hMPV infection induced lung infiltration of OX40L(+) CD11b(+) DCs. Mice lacking the TSLP receptor deficient mice (tslpr(-/-) ) showed reduced lung inflammation and hMPV replication. These mice displayed a decreased number of neutrophils as well a reduction in levels of thymus and activation-regulated chemokine/CCL17, IL-5, IL-13, and TNF-α in the airways upon hMPV infection. Furthermore, a higher frequency of CD4(+) and CD8(+) T cells was found in tslpr(-/-) mice compared to WT mice, which could contribute to controlling viral spread. Depletion of neutrophils in WT and tslpr(-/-) mice decreased inflammation and hMPV replication. Remarkably, blockage of TSLP or OX40L with specific Abs reduced lung inflammation and viral replication following hMPV challenge in mice. Altogether, these results suggest that activation of the TSLP pathway is pivotal in the development of pulmonary pathology and pulmonary hMPV replication. Topics: Animals; Antibodies, Monoclonal; Cell Line; Cytokines; Dendritic Cells; Disease Models, Animal; Epithelial Cells; Gene Expression; Humans; Interleukin-33; Interleukin-8; Interleukins; Macrophages, Alveolar; Metapneumovirus; Mice; Neutrophils; OX40 Ligand; Paramyxoviridae Infections; Pneumonia, Viral; Receptors, Cytokine; Signal Transduction; T-Lymphocyte Subsets; Thymic Stromal Lymphopoietin; Virus Replication | 2015 |
Recently emerged swine influenza A virus (H2N3) causes severe pneumonia in Cynomolgus macaques.
The triple reassortant H2N3 virus isolated from diseased pigs in the United States in 2006 is pathogenic for certain mammals without prior adaptation and transmits among swine and ferrets. Adaptation, in the H2 hemagglutinin derived from an avian virus, includes the ability to bind to the mammalian receptor, a significant prerequisite for infection of mammals, in particular humans, which poses a big concern for public health. Here we investigated the pathogenic potential of swine H2N3 in Cynomolgus macaques, a surrogate model for human influenza infection. In contrast to human H2N2 virus, which served as a control and largely caused mild pneumonia similar to seasonal influenza A viruses, the swine H2N3 virus was more pathogenic causing severe pneumonia in nonhuman primates. Both viruses replicated in the entire respiratory tract, but only swine H2N3 could be isolated from lung tissue on day 6 post infection. All animals cleared the infection whereas swine H2N3 infected macaques still presented with pathologic changes indicative of chronic pneumonia at day 14 post infection. Swine H2N3 virus was also detected to significantly higher titers in nasal and oral swabs indicating the potential for animal-to-animal transmission. Plasma levels of IL-6, IL-8, MCP-1 and IFNγ were significantly increased in swine H2N3 compared to human H2N2 infected animals supporting the previously published notion of increased IL-6 levels being a potential marker for severe influenza infections. In conclusion, the swine H2N3 virus represents a threat to humans with the potential for causing a larger outbreak in a non-immune or partially immune population. Furthermore, surveillance efforts in farmed pig populations need to become an integral part of any epidemic and pandemic influenza preparedness. Topics: Animals; Chemokine CCL2; Female; Humans; Influenza A virus; Influenza A Virus, H2N2 Subtype; Interferon-gamma; Interleukin-6; Interleukin-8; Lung; Macaca fascicularis; Male; Orthomyxoviridae Infections; Pneumonia, Viral; Reassortant Viruses; Severity of Illness Index; Swine; Swine Diseases | 2012 |
Effects of intrapulmonary viral tropism and cytokine expression on the histological patterns of cytomegalovirus pneumonia.
Pulmonary cytomegalovirus (CMV) infection causes fatal CMV pneumonia (CMVp) in immunocompromised patients; however, the mechanisms underlying CMV-infection-induced pulmonary lesion development remain largely unknown. We examined the relationship between CMVp patterns and intrapulmonary viral tropism, including expression of inflammatory cytokines and related molecules. Double immunohistochemistry of CMV antigen and cellular markers showed that epithelial tropism was associated with a diffuse alveolar damage (DAD) pattern (CMVp-DAD) while stromal tropism was associated with a predominantly interstitial inflammation/fibrosis (IIF) (CMVp-IIF) or a combination of DAD and IIF (CMVp-complex). Transforming growth factor (TGF)-β1 expression was relevant to CMV-induced tissue injury, and its expression was higher in CMVp-complex and CMVp-IIF than in CMVp-DAD. Expression of integrin β6 (ITGB6), an adhesion molecule and important activator of TGF-β1 in interstitial pneumonia, was lost in CMV-infected pneumocytes, especially CMVp-DAD, whereas CMV-negative pneumocytes in CMVp-complex and CMVp-IIF showed overexpression. Diffuse interleukin (IL)-8 up-regulation and strong expression were present in both CMV-infected pneumocytes and stromal cells only in CMVp-IIF cases with marked interstitial neutrophilic infiltration. On the basis of viral tropism and the expression of TGF-β1, ITGB6, and IL-8, we conclude that CMV-infected pulmonary cells play an important role in the development of diverse CMVp patterns. Topics: Adult; Aged; Aged, 80 and over; Antigens, Viral; Cytokines; Cytomegalovirus; Cytomegalovirus Infections; Fatal Outcome; Female; Humans; Integrin beta Chains; Interleukin-8; Male; Middle Aged; Pneumonia, Viral; Transforming Growth Factor beta1; Viral Tropism | 2012 |
Respiratory syncitial virus in children with acute respiratory infections.
To study the nutritional status of children with Respiratory Syncitial virus infection.. One hundred and twenty six children with acute respiratory infection, between the age of 4-24 months, were investigated for RSV infection with bronchiolitis, pneumonia and upper respiratory tract infection. Nasopharyngeal aspirates were collected and cytokine responses were determined by ELISA. Upper respiratory tract infections were detected in 16.66%, bronchiolitis in 30.15% and Pneumonia in 53.17% children.. Of the 126 patients, 46.66% children were positive for RSV while 58.33% were negative for RSV. Children with bronchiolitis were more commonly positive for RSV compared to URTI and pneumonia. RSV was almost equally distributed among boys (42.5%) and girls (48.7%). More children were RSV positive when the mean age lesser (8.4 mo) was compared to RSV negative (9.93 mo). Well nourished children and children with normal birth weight had more RSV positives, though not statistically significant. In a sub sample analysis of cytokines done (n=25), Interleukin-2 and Interleukin-8 levels were higher in the RSV positive children and these levels declined after 5 days of illness.. RSV is more commonly associated with bronchiolitis in younger infants with normal birth weight or more weight for age (WFA). Proinflammatory cytokine IL-8 was secreted at high concentrations in the nasopharyngeal aspirate in all the children. Topics: Bronchiolitis, Viral; Child, Preschool; Female; Humans; India; Infant; Interleukin-2; Interleukin-8; Male; Nutritional Status; Pneumonia, Viral; Prevalence; Respiratory Syncytial Virus Infections; Respiratory Tract Infections; Risk Factors | 2010 |
Herpesvirus chemokine-binding glycoprotein G (gG) efficiently inhibits neutrophil chemotaxis in vitro and in vivo.
Glycoprotein G (gG) of alphaherpesviruses has been described to function as a viral chemokine-binding protein (vCKBP). More recently, mutant viruses devoid of gG have been shown to result in increased virulence, but it remained unclear whether the potential of gG to serve as a vCKBP is responsible for this observation. In this study, we used equine herpesvirus type 1 (EHV-1) as a model to study the pathophysiological importance of vCKBP activity. First, in vitro chemotaxis assays studying migration of immune cells, an important function of chemokines, were established. In such assays, supernatants of EHV-1-infected cells significantly inhibited IL-8-induced chemotaxis of equine neutrophils. Identification of gG as the responsible vCKBP was achieved by repeating similar experiments with supernatants from cells infected with a gG-negative mutant, which were unable to alter IL-8-induced equine neutrophil migration. Furthermore, rEHV-1 gG was able to significantly reduce neutrophil migration, establishing gG as a bona fide vCKBP. Second, and importantly, in vivo analyses in a murine model of EHV-1 infection showed that neutrophil migration in the target organ lung was significantly reduced in the presence of gG. In summary, we demonstrate for the first time that EHV-1 gG not only binds to chemokines but is also capable of inhibiting their chemotactic function both in vitro and in vivo, thereby contributing to viral pathogenesis and virulence. Topics: Animals; Binding, Competitive; Cell Line; Cell Migration Inhibition; Cell-Free System; Chemokine CCL2; Chemokines; Chemotaxis, Leukocyte; Female; Herpesviridae Infections; Herpesvirus 1, Equid; Horses; Interleukin-8; Mice; Neutrophils; Pneumonia, Viral; Protein Binding; Rabbits; Viral Envelope Proteins; Virulence | 2007 |
Adenovirus type 7 induces interleukin-8 in a lung slice model and requires activation of Erk.
Adenovirus (Ad), particularly Ad type 7 (Ad7), causes severe lung infection and pneumonia. Initially, Ad causes neutrophilic inflammation of the distal airways and alveoli. Interleukin-8 (IL-8) is the major lung neutrophil chemotaxin, and we have shown that Ad7 induces IL-8 release from the A549 alveolar epithelial cell line. We sought to determine whether ex vivo human and bovine lung tissue containing primary pneumocytes could be used as a more accurate and relevant model to study Ad acute inflammation. We found that cultured lung tissue preserved normal lung architecture for more than 10 days. IL-8 was generated upon exposure of the lung organ culture to Ad7. IL-8 production required activation of the Ras/Erk pathway, since a pharmacological inhibitor blocked the appearance of IL-8 in the medium. Both human and bovine lung explants supported replication of Ad7, and immunohistochemistry experiments demonstrated the presence of the Ad hexon antigen within alveolar epithelial cells. These findings show that our novel human lung organ culture accurately reproduces the in vivo infectious disease process. Thus, this organ culture model represents a valuable tool for studying the acute innate immune response to respiratory infections. Topics: Adenovirus Infections, Human; Adenoviruses, Human; Animals; Cattle; Cell Line; Culture Techniques; Enzyme Activation; Enzyme Inhibitors; Epithelial Cells; Humans; Interleukin-8; Lung; Mitogen-Activated Protein Kinase Kinases; Mitogen-Activated Protein Kinases; Models, Biological; Phosphorylation; Pneumonia, Viral; Pulmonary Alveoli | 2004 |
Respiratory syncytial virus infection and virus-induced inflammation are modified by contaminants of indoor air.
The airway epithelium is the first cellular component of the lung to be encountered by the particles and pathogens present in inhaled air. In addition to its role as a physical barrier, the immunological activity of the airway epithelium is an essential part of the pulmonary immune system. This means that the symptoms of lung diseases that involve immunological mechanisms are frequently exacerbated by infection of the airway epithelium with respiratory viruses. The virus-induced enhancement of immunological activity in infected epithelial cells is well characterized. However, the effects that contaminants of inhaled air have upon the infectivity and replication of respiratory viruses and the inflammation they cause, are comparatively unknown. In this study, we have shown that pre-exposure of airway epithelial cells to bacterial lipopolysaccharides or a proteolytically active house dust mite allergen, is able to, respectively, inhibit or enhance the level of cellular infection with respiratory syncytial virus and similarly alter virus-induced expression of the inflammatory chemokine interleukin-8. These results suggest that respiratory syncytial virus infection and the inflammation caused by respiratory syncytial virus may be modified by the biologically active contaminants of indoor air. Topics: Air Pollutants; Air Pollution, Indoor; Antigens, Dermatophagoides; Arthropod Proteins; Cell Culture Techniques; Cell Line; Cysteine Endopeptidases; Disease Susceptibility; Epithelial Cells; Humans; Interleukin-8; Lipopolysaccharides; Pneumonia, Viral; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Virus Replication | 2003 |
Type-specific induction of interleukin-8 by adenovirus.
Infection with adenovirus (Ad) causes acute pneumonia in a type-specific fashion because type 7 but not type 5 Ad has been isolated as a causative agent. We postulated that the type specificity of induction of pneumonia may be related to type-specific cytokine induction in lung cells. To test this hypothesis, we infected human fetal lung fibroblasts and the lung epithelial cell line A549 with live type 5 and type 7 Ad. Virus inactivated by irradiation was used as a control. Type 7 but not type 5 Ad induced interleukin (IL)-8 protein production in both cell types in a dose- and time-dependent manner. Inactivated virus had no effect on the production of IL-8 protein. Type 7 but not type 5 virus also stimulated IL-8-specific messenger RNA (mRNA) production in these cells. Because half-life of IL-8 mRNA was prolonged in both type 5- and type 7-infected A549 cells, induction likely involves enhancement of message stability as well as other effects. Virus early gene expression did not consistently correlate with IL-8 message induction and followed induction in fibroblasts. These results suggest that there is type-specific induction of IL-8 production during infection of lung cells with Ad. Induction involves message stabilization and may not require viral gene expression. Because IL-8 is one of the important mediators of lung inflammation, type-specific induction of this and other cytokines may account for the different consequences of lung infection with different types of Ad. Topics: Adenoviruses, Human; Cell Line; Gene Expression; Humans; Interleukin-8; Pneumonia, Viral; RNA Stability; RNA, Messenger; Virus Replication | 1999 |
Lower airway inflammation in infants and young children with cystic fibrosis.
Airway inflammation is an important component of cystic fibrosis (CF) lung disease. To determine whether this begins early in the illness, before the onset of infection, we examined bronchoalveolar lavage (BAL) fluid from 46 newly diagnosed infants with CF under the age of 6 mo identified by a neonatal screening program. These infants were divided into three groups: 10 had not experienced respiratory symptoms or received antibiotics and pathogens were absent in their BAL fluid; 18 had clear evidence of lower respiratory viral or bacterial (> or = 10(5) CFU/ml) infection; and the remaining 18 had either respiratory symptoms, taken antibiotics, or had < 10(5) CFU/ml of respiratory pathogens. Their BAL cytology, interleukin-8, and elastolytic activity were compared with those from 13 control subjects. In a longitudinal study to assess if inflammation develops or persists in the absence of infection, the results of 56 paired annual BAL specimens from 44 CF infants were grouped according to whether they showed absence, development, clearance, or persistence of infection. In newly diagnosed infants with CF, those without infection had BAL profiles comparable with control subjects while those with a lower respiratory infection had evidence of airway inflammation. In older children, the development and persistence of infection was accompanied by increased inflammatory markers, whereas these were decreased in the absence, or with the clearance, of infection. We conclude that airway inflammation follows respiratory infection and, in young children, improves when pathogens are eradicated from the airways. Topics: Anti-Bacterial Agents; Bacterial Infections; Biomarkers; Bronchoalveolar Lavage Fluid; Child, Preschool; Cross-Sectional Studies; Cystic Fibrosis; Drug Therapy, Combination; Female; Humans; Infant; Inflammation; Interleukin-8; Leukocyte Count; Leukocyte Elastase; Longitudinal Studies; Male; Neutrophils; Pneumonia, Bacterial; Pneumonia, Viral; Respiratory Tract Infections; Virus Diseases | 1997 |
Safety of adenovirus-mediated transfer of the human cystic fibrosis transmembrane conductance regulator cDNA to the lungs of nonhuman primates.
To define the toxicity of cystic fibrosis transmembrane conductance regulator gene (CFTR) gene therapy with a replication-deficient recombinant adenovirus (Av1Cf2) in a nonhuman primate model, 10(10) plaque forming units (pfu) were instilled directly through a bronchoscope into the right lung of 5 macaques, and a lower dose of 4 x 10(6) pfu was administered to the right lung of 1 macaque. One sham-treated control received phosphate-buffered saline (PBS). The macaques were evaluated sequentially by clinical examination, vital signs, weight, hematology, blood chemistry, chest radiography, pulse oximetry, and bronchoalveolar lavage (BAL) at baseline and 3-28 days post-treatment. After the period of observation, macaques were sacrificed for autopsy and histological examination. The macaques tolerated the experimental therapy clinically with no changes in body temperature, oxygen saturation, heart rate, body weight, or blood pressure. However, 1 macaque with visible evidence of aspiration at the time of initial bronchoscopy developed tachypnea with right lower lobe (RLL) pneumonia on chest radiograph and by histology. There were no changes in Hgb, Wbc, BUN, plasma electrolytes, bilirubin, or hepatic transaminases. In the macaques that received 10(10) pfu, there was a progressive increase in the number of CD8+ lymphocytes in BAL that was maximal at 28 days. Histological examination of the treated lungs of the high-dose macaques at 3 days showed marked peribronchial and perivascular cuffing by inflammatory cells and alveolar accumulation of neutrophils and macrophages. The alveolitis appeared to be resolving at 28 days, although the perivascular and peribronchial aggregates of mononuclear cells were still present. In the high-dose macaques, BAL interleukin-8 (IL-8) was increased at all time points (256-388 pg/ml versus 1-84 pg/ml at baseline and in control), whereas IL-1 beta was increased only at days 21 and 28 (341-852 pg/ml versus 30-92 pg/ml at baseline and in control). There were no increases in BAL cell counts, IL-1 beta or IL-8, and histological changes were mild in the macaque that received 4 x 10(6) pfu. Evaluation for Av1Cf2-derived human CFTR expression using RS-PCR demonstrated expression at 3, 10, and 21, but not 28 days in macaques treated with 10(10) pfu of Av1Cf2. In situ hybridization analysis demonstrated human CFTR mRNA in the alveolar regions of the lobes that received the vector at 10 and 21 days. There was no evidence of expression after tr Topics: Adenoviridae; Animals; Base Sequence; Bronchoalveolar Lavage Fluid; Cystic Fibrosis Transmembrane Conductance Regulator; Defective Viruses; DNA, Complementary; Female; Genetic Therapy; Genetic Vectors; Hemodynamics; Humans; In Situ Hybridization; Interleukin-1; Interleukin-8; Kidney Function Tests; Liver Function Tests; Lung; Macaca fascicularis; Molecular Sequence Data; Pneumonia, Aspiration; Pneumonia, Viral; Recombinant Fusion Proteins; Respiratory Function Tests; Single-Blind Method; Tissue Distribution; Transfection | 1996 |