interleukin-8 and Lymphopenia

The systemic processes involved in the manifestation of life-threatening COVID-19 and in disease recovery are still incompletely understood, despite investigations focusing on the dysregulation of immune responses after SARS-CoV-2 infection. To define hallmarks of severe COVID-19 in acute disease (n = 58) and in disease recovery in convalescent patients (n = 28) from Hannover Medical School, we used flow cytometry and proteomics data with unsupervised clustering analyses. In our observational study, we combined analyses of immune cells and cytokine/chemokine networks with endothelial activation and injury. ICU patients displayed an altered immune signature with prolonged lymphopenia but the expansion of granulocytes and plasmablasts along with activated and terminally differentiated T and NK cells and high levels of SARS-CoV-2-specific antibodies. The core signature of seven plasma proteins revealed a highly inflammatory microenvironment in addition to endothelial injury in severe COVID-19. Changes within this signature were associated with either disease progression or recovery. In summary, our data suggest that besides a strong inflammatory response, severe COVID-19 is driven by endothelial activation and barrier disruption, whereby recovery depends on the regeneration of the endothelial integrity.

Topics: Antibodies, Viral; Biomarkers; Blood Proteins; C-Reactive Protein; Chemokine CXCL10; Chemokine CXCL9; Cluster Analysis; Convalescence; COVID-19; Cytokine Release Syndrome; Disease Progression; Endothelium, Vascular; Granulocytes; Hematopoietic Cell Growth Factors; Hepatocyte Growth Factor; Humans; Intensive Care Units; Interleukin-12 Subunit p40; Interleukin-6; Interleukin-8; Killer Cells, Natural; Lectins, C-Type; Lymphopenia; Plasma Cells; SARS-CoV-2; Survival Analysis; T-Lymphocytes

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

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

Study of immunological features of immune response in 14 children (aged from 12 days up to 15 years) and of 10 adults who developed COVID-19 show increased number of activated CD4 and CD8 cells expressing DR and higher plasmatic levels of IL-12 and IL-1β in adults with COVID-19, but not in children. In addition, plasmatic levels of CCL5/RANTES are higher in children and adults with COVID-19, while CXCL9/MIG was only increased in adults. Higher number of activated T cells and expression of IL-12 and CXCL9 suggest prominent Th1 polarization of immune response against SARS-CoV2 in infected adults as compared with children.

Topics: Adolescent; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Chemokine CCL2; Chemokine CCL5; Chemokine CXCL10; Chemokine CXCL9; Chemokines; Child; Child, Preschool; COVID-19; Female; Humans; Infant; Infant, Newborn; Interleukin-8; Lymphocyte Activation; Lymphocyte Count; Lymphopenia; Male; SARS-CoV-2; T-Lymphocyte Subsets

Sepsis-related mortality has been found increased in RAG-1 knockout mice. However, in patients admitted to medical intensive care units, it is unknown whether severe lymphocyte depletion at admission is associated with increased interleukin (IL)-7 and IL-15 levels in circulation, and increased mortality. We prospectively enrolled 92 patients who were admitted to medical intensive care units for severe sepsis or septic shock. At admission, 24 patients (26.1%) had severe lymphopenia, defined as lymphocyte counts of less than 0.5 × 10(3)/μL. Severe lymphopenia was associated with significantly higher plasma levels of tumor necrosis factor α, IL-6, IL-8, and IL-10 and was also independently associated with 28-day mortality (adjusted hazard ratio, 3.532; 95% confidence interval, 1.482-8.416; P = 0.004). The levels of plasma IL-15, but not IL-7, were increased modestly in patients with severe lymphopenia compared with those without (median, 12.2 vs. 6.4 pg/mL; P = 0.005). The elevated plasma IL-15 levels were contrarily associated with significantly decreased B-cell lymphoma 2 mRNA expression in peripheral blood mononuclear cells. In conclusion, severe lymphopenia was associated with increased mortality in patients with severe sepsis. We found that patients with sepsis with severe lymphopenia had down-regulated B-cell lymphoma 2 mRNA expression in peripheral blood mononuclear cells, despite increased plasma IL-15 concentrations. Whether IL-7 and IL-15 are insufficient in patients with severe lymphopenia during severe sepsis warrants further investigations.

Topics: Aged; Aged, 80 and over; Animals; Female; Genes, RAG-1; Humans; Interleukin-10; Interleukin-15; Interleukin-6; Interleukin-7; Interleukin-8; Lymphopenia; Male; Mice; Mice, Knockout; Middle Aged; Prospective Studies; Sepsis

Dengue virus (DENV) infection could lead to dengue fever (DF), dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). The disease outcome is controlled by both viral and host factors. Inflammation mediators from DENV-infected cells could contribute to increased vascular permeability, leading to severe DHF/DSS. Therefore, suppression of inflammation could be a potential therapeutic approach for treatment of dengue patients. In this context, p38 MAPK (mitogen-activated protein kinase) is a key enzyme that modulates the initiation of stress and inflammatory responses. Here we show that SB203580, a p38 MAPK inhibitor, suppressed the over production of DENV-induced pro-inflammatory mediators such as TNF-α, IL-8, and RANTES from human PBMCs, monocytic THP-1, and granulocyte KU812 cell lines. Oral administration of SB203580 in DENV-infected AG129 mice prevented hematocrit rise and lymphopenia, limited the development of inflammation and pathology (including intestine leakage), and significantly improved survival. These results, for the first time, have provided experimental evidence to imply that a short term inhibition of p38 MAPK may be beneficial to reduce disease symptoms in dengue patients.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Capillary Permeability; Cell Line; Chemokine CCL5; Cricetinae; Culicidae; Dengue; Dengue Virus; Enzyme Inhibitors; Hematocrit; Humans; Imidazoles; Inflammation; Interleukin-8; Lymphopenia; Mice; p38 Mitogen-Activated Protein Kinases; Pyridines; Tumor Necrosis Factor-alpha

This study investigated whether the lymphocyte count is a useful indicator to assess surgical damage following extracorporeal bypass. In Study 1, to investigate the correlation between extracorporeal circulating time (ECCT) and lymphocyte counts, 40 elective CABG patients were studied retrospectively. The lymphocyte recovery ratio (LRR), which represented the actual lymphocyte count divided by the preoperative lymphocyte count, was determined preoperatively, and on postoperative day (POD) 1, POD 3, and POD 5. In Study 2, the correlation between the interleukin-8 (IL-8) level and LRR was examined prospectively in elective CABG patients (n = 20). We measured the LRR and serum IL-8 levels preoperatively and during extracorporeal circulation (ECC) at 5 min, at the end of ECC, and 1, 3, and 12 h following ECC termination. Study 1 showed that the LRR decreased until POD 1 and gradually increased thereafter. The LRR had a negative correlation with the ECCT. In Study 2, the IL-8 level demonstrated a time course opposite to that of the LRR; it increased until 3 h after ECC termination and declined thereafter. There was a significant negative correlation between the LRR on POD 3 and the IL-8 level at 3 h after ECC termination. In summary, long-term ECC induced significant and prolonged lymphocytopenia. The LRR had a negative correlation with IL-8. These results indicated that the LRR may represent the degree of surgical stress following ECC; therefore, the counting of lymphocytes can be a quite useful bedside monitor to assess surgical damage and prognosis.

Topics: Coronary Artery Bypass; Extracorporeal Circulation; Humans; Interleukin-8; Lymphocyte Count; Lymphopenia; Prospective Studies; Retrospective Studies; Stress, Physiological; Time Factors