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Nedel W, Henrique LR, Portela LV. Why should lymphocytes immune profile matter in sepsis? World J Crit Care Med 2025; 14:98791. [DOI: 10.5492/wjccm.v14.i2.98791] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2024] [Revised: 12/11/2024] [Accepted: 12/19/2024] [Indexed: 02/27/2025] Open
Abstract
The global incidence of critical illness has been steadily increasing, resulting in higher mortality rates thereby presenting substantial challenges for clinical management. Among these conditions, sepsis stands out as the leading cause of critical illness, underscoring the urgent need for continued research to enhance patient care and deepen our understanding of its complex pathophysiology. Lymphocytes play a pivotal role in both innate and adaptive immune responses, acting as key regulators of the balance between pro-inflammatory and anti-inflammatory processes to preserve immune homeostasis. In the context of sepsis, an impaired immunity has been associated with disrupted lymphocytic metabolic activity, persistent pro-inflammatory state, and subsequent immunosuppression. These disruptions not only impair pathogen clearance but also predispose patients to secondary infections and hinder recovery, highlighting the importance of targeting lymphocyte dysfunction in sepsis management. Moreover, studies have identified absolute lymphocyte counts and derived parameters as promising clinical biomarkers for prognostic assessment and therapeutic decision-making. In particular, neutrophil-to-lymphocyte ratio, and lymphopenia have gained recognition in the literature as a critical prognostic markers and therapeutic target in the management of sepsis. This review aims to elucidate the multifaceted role of lymphocytes in pathophysiology, with a focus on recent advancements in their use as biomarkers and key findings in this evolving field.
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Affiliation(s)
- Wagner Nedel
- Department of Intensive Care Unit, Conceição Hospital Group, Porto Alegre 91350200, Brazil
| | - Lílian R Henrique
- Department of Intensive Care Unit, Conceição Hospital Group, Porto Alegre 91350200, Brazil
| | - Luis Valmor Portela
- Department of Biochemistry, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Porto Alegre 90035-003, Brazil
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Osa-Andrews B, van Wijk XMR, Herrera Rivera N, Seifert RP, Harris NS, Marin MJ. An Introduction to the Complete Blood Count for Clinical Chemists: White Blood Cells. J Appl Lab Med 2025; 10:459-475. [PMID: 39873240 DOI: 10.1093/jalm/jfaf004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2024] [Accepted: 12/26/2024] [Indexed: 01/30/2025]
Abstract
BACKGROUND The most frequently ordered laboratory test worldwide is the complete blood count (CBC). As clinical chemists are increasingly assigned to assist or direct laboratories outside of the traditional clinical chemistry sections, such as the automated hematology section, expertise must be established. This review article is a dedication to that ongoing effort. CONTENT In this primer, the white blood cell (WBC) test components of the CBC are introduced, followed by a discussion of the laboratory evaluation of leukopenia and leukocytosis. SUMMARY The laboratorian's approach to consult cases should be guided by the patient's clinical history and presentation while being able to provide key laboratory-based insights to assist in resolving result discrepancies that may otherwise go unnoticed.
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Affiliation(s)
- Bremansu Osa-Andrews
- Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL, United States
| | - Xander M R van Wijk
- Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA, United States
| | | | - Robert P Seifert
- Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL, United States
| | - Neil S Harris
- Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL, United States
| | - Maximo J Marin
- Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL, United States
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Kealy DJ, Wilson JC, Jaconelli T, Hogg K, Coop R, Forshaw G, Todd N, Yates D, Signoret N. Blood immune profiles reveal a CXCR3/CCR5 axis of dysregulation in early sepsis. J Leukoc Biol 2025; 117:qiae204. [PMID: 39312202 DOI: 10.1093/jleuko/qiae204] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2024] [Accepted: 09/20/2024] [Indexed: 03/06/2025] Open
Abstract
We report on a pilot study exploring whether blood immune signatures can reveal early specific indicator profiles for patients meeting sepsis criteria upon hospital admission. We analyzed samples of sepsis-suspected patients (n = 20) and age-spanning healthy controls (n = 12) using flow cytometry-based assays. We measured inflammatory markers from plasma fractions and immunophenotyped freshly isolated unfixed peripheral blood mononucleated cells for leukocyte subset representation and expression of activation markers, including chemokine receptors. We found that besides IL-6 and sCD14, CXCR3 ligands (CXCL9 and CXCL10) separated sepsis-suspected patients from healthy controls. The abundance of CD4+ T cells was significantly reduced in patients, while they displayed substantial losses of CCR5-expressing monocytes and CXCR3/CCR5 double-positive T cells. Post hoc subgrouping of patients according to their sepsis diagnosis on discharge identified CXCR3/CCR5 double expression on T cells as a separating characteristic for confirmed cases. This work suggests a potential novel axis of dysregulation affecting CXCR3 and CCR5 in early sepsis.
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Affiliation(s)
- David J Kealy
- Hull York Medical School, Department of Biology, University of York, Wentworth Way, York YO10 5DD, UK
| | - Julie C Wilson
- Department of Mathematics, James College, University of York, York YO10 5DD, UK
| | - Tom Jaconelli
- York & Scarborough Teaching Hospital NHS Foundation Trust, Wigginton Rd, Clifton, York YO31 8HE, UK
| | - Karen Hogg
- Bioscience Technology Facility, Departement of Biology, University of York, York YO10 5DD, UK
| | - Rebecca Coop
- York & Scarborough Teaching Hospital NHS Foundation Trust, Wigginton Rd, Clifton, York YO31 8HE, UK
| | - Greg Forshaw
- York & Scarborough Teaching Hospital NHS Foundation Trust, Wigginton Rd, Clifton, York YO31 8HE, UK
| | - Neil Todd
- York & Scarborough Teaching Hospital NHS Foundation Trust, Wigginton Rd, Clifton, York YO31 8HE, UK
| | - David Yates
- York & Scarborough Teaching Hospital NHS Foundation Trust, Wigginton Rd, Clifton, York YO31 8HE, UK
| | - Nathalie Signoret
- Hull York Medical School, Department of Biology, University of York, Wentworth Way, York YO10 5DD, UK
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Du C, Tan SC, Bu HF, Subramanian S, Geng H, Wang X, Xie H, Wu X, Zhou T, Liu R, Xu Z, Liu B, Tan XD. Predicting patients with septic shock and sepsis through analyzing whole-blood expression of NK cell-related hub genes using an advanced machine learning framework. Front Immunol 2024; 15:1493895. [PMID: 39669564 PMCID: PMC11634752 DOI: 10.3389/fimmu.2024.1493895] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2024] [Accepted: 10/29/2024] [Indexed: 12/14/2024] Open
Abstract
Background Sepsis is a life-threatening condition that causes millions of deaths globally each year. The need for biomarkers to predict the progression of sepsis to septic shock remains critical, with rapid, reliable methods still lacking. Transcriptomics data has recently emerged as a valuable resource for disease phenotyping and endotyping, making it a promising tool for predicting disease stages. Therefore, we aimed to establish an advanced machine learning framework to predict sepsis and septic shock using transcriptomics datasets with rapid turnaround methods. Methods We retrieved four NCBI GEO transcriptomics datasets previously generated from peripheral blood samples of healthy individuals and patients with sepsis and septic shock. The datasets were processed for bioinformatic analysis and supplemented with a series of bench experiments, leading to the identification of a hub gene panel relevant to sepsis and septic shock. The hub gene panel was used to establish a novel prediction model to distinguish sepsis from septic shock through a multistage machine learning pipeline, incorporating linear discriminant analysis, risk score analysis, and ensemble method combined with Least Absolute Shrinkage and Selection Operator analysis. Finally, we validated the prediction model with the hub gene dataset generated by RT-qPCR using peripheral blood samples from newly recruited patients. Results Our analysis led to identify six hub genes (GZMB, PRF1, KLRD1, SH2D1A, LCK, and CD247) which are related to NK cell cytotoxicity and septic shock, collectively termed 6-HubGss. Using this panel, we created SepxFindeR, a machine learning model that demonstrated high accuracy in predicting sepsis and septic shock and distinguishing septic shock from sepsis in a cross-database context. Remarkably, the SepxFindeR model proved compatible with RT-qPCR datasets based on the 6-HubGss panel, facilitating the identification of newly recruited patients with sepsis and septic shock. Conclusions Our bioinformatic approach led to the discovery of the 6-HubGss biomarker panel and the development of the SepxFindeR machine learning model, enabling accurate prediction of septic shock and distinction from sepsis with rapid processing capabilities.
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Affiliation(s)
- Chao Du
- Department of Gastroenterology, Weihai Municipal Hospital of Shandong University, Weihai, Shandong, China
- Department of Pediatrics, Feinberg School of Medicine, Northwestern
University, Chicago, IL, United States
- Department of Gastroenterology, Linyi People’s Hospital, Weifang Medical University, Linyi, Shandong, China
| | - Stephanie C. Tan
- Department of Pediatrics, Feinberg School of Medicine, Northwestern
University, Chicago, IL, United States
- Loyola University Chicago Stritch School of Medicine, Maywood, IL, United States
| | - Heng-Fu Bu
- Department of Pediatrics, Feinberg School of Medicine, Northwestern
University, Chicago, IL, United States
- Center for Pediatric Translational Research and Education, Department of Pediatrics, College of Medicine, University of Illinois at Chicago, Chicago, IL, United States
| | - Saravanan Subramanian
- Department of Pediatrics, Feinberg School of Medicine, Northwestern
University, Chicago, IL, United States
- Center for Pediatric Translational Research and Education, Department of Pediatrics, College of Medicine, University of Illinois at Chicago, Chicago, IL, United States
| | - Hua Geng
- Department of Pediatrics, Feinberg School of Medicine, Northwestern
University, Chicago, IL, United States
- Center for Pediatric Translational Research and Education, Department of Pediatrics, College of Medicine, University of Illinois at Chicago, Chicago, IL, United States
| | - Xiao Wang
- Department of Pediatrics, Feinberg School of Medicine, Northwestern
University, Chicago, IL, United States
- Center for Pediatric Translational Research and Education, Department of Pediatrics, College of Medicine, University of Illinois at Chicago, Chicago, IL, United States
| | - Hehuang Xie
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Blacksburg, VA, United States
| | - Xiaowei Wu
- Department of Statistics, Virginia Tech, Blacksburg, VA, United States
| | - Tingfa Zhou
- Department of Critical Care Medicine, Linyi People’s Hospital, Weifang Medical University, Linyi, Shandong, China
| | - Ruijin Liu
- Department of Critical Care Medicine, Linyi People’s Hospital, Weifang Medical University, Linyi, Shandong, China
| | - Zhen Xu
- Department of Gastroenterology, Linyi People’s Hospital, Weifang Medical University, Linyi, Shandong, China
| | - Bing Liu
- Department of Gastroenterology, Linyi People’s Hospital, Weifang Medical University, Linyi, Shandong, China
| | - Xiao-Di Tan
- Department of Pediatrics, Feinberg School of Medicine, Northwestern
University, Chicago, IL, United States
- Center for Pediatric Translational Research and Education, Department of Pediatrics, College of Medicine, University of Illinois at Chicago, Chicago, IL, United States
- Department of Research & Development, Jesse Brown Veterans Affairs Medical Center, Chicago, IL, United States
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Coman O, Grigorescu BL, Huțanu A, Bacârea A, Văsieșiu AM, Fodor RȘ, Petrișor M, Azamfirei L. The Role of PD-1/PD-L1 and IL-7 in Lymphocyte Dynamics and Sepsis Progression: A Biomarker Study in Critically Ill Patients. Int J Mol Sci 2024; 25:12612. [PMID: 39684323 PMCID: PMC11641135 DOI: 10.3390/ijms252312612] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2024] [Revised: 11/19/2024] [Accepted: 11/21/2024] [Indexed: 12/18/2024] Open
Abstract
Sepsis pathophysiology involves a dysregulated immune response to infection, excessive inflammation, and immune paralysis. This study explores the relationships between cell death biomarkers (serum-soluble levels of programmed cell death protein 1 (PD-1), programmed death ligand 1 (PD-L1), and interleukin-7 (IL-7)) and the percentages of various lymphocyte subsets in relation to the severity and progression of sepsis. This prospective, observational study included 87 critically ill patients. We monitored parameters on days 1 (sepsis was diagnosed according to the Sepsis-3 Consensus) and 5. We established an IL-7 cutoff value of 1.94 pg/mL by comparing levels between a healthy control group and patients with sepsis (p < 0.0001). Lymphopenia was observed in all patients, with negative correlations between helper T lymphocytes and cytotoxic and B lymphocytes, and positive correlations involving cytotoxic lymphocytes across all groups. We found correlations between PD-1/PD-L1 and lymphocyte subsets. IL-7 showed a statistical correlation with PD-1 in non-survivors. Assessing lymphocyte levels shows potential as a biomarker for evaluating the progression of sepsis. Monitoring IL-7 levels could help assess survival, as low levels are associated with higher mortality risk. Monitoring IL-7 levels could help assess survival, as low levels are associated with higher mortality risk. Elevated PD-1/PD-L1 expression impairs costimulatory signalling, reducing T cell responses and lymphopenia, which increases the risk of nosocomial infections.
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Affiliation(s)
- Oana Coman
- Department of Simulation Applied in Medicine, University of Medicine, Pharmacy, Science and Technology “George Emil Palade”, 540142 Targu Mures, Romania; (O.C.); (M.P.)
| | - Bianca-Liana Grigorescu
- Department of Anaesthesiology and Intensive Care, University of Medicine, Pharmacy, Science and Technology “George Emil Palade”, 540142 Targu Mures, Romania; (R.Ș.F.); (L.A.)
| | - Adina Huțanu
- Department of Laboratory Medicine, University of Medicine, Pharmacy, Science and Technology “George Emil Palade”, 540142 Targu Mures, Romania;
- Centre for Advanced Medical and Pharmaceutical Research, Immunology, University of Medicine, Pharmacy, Science and Technology “George Emil Palade”, 540142 Targu Mures, Romania
| | - Anca Bacârea
- Department of Pathophysiology, University of Medicine, Pharmacy, Science and Technology “George Emil Palade”, 540142 Targu Mures, Romania;
| | - Anca Meda Văsieșiu
- Department of Infectious Disease, University of Medicine, Pharmacy, Science and Technology “George Emil Palade”, 540142 Targu Mures, Romania;
| | - Raluca Ștefania Fodor
- Department of Anaesthesiology and Intensive Care, University of Medicine, Pharmacy, Science and Technology “George Emil Palade”, 540142 Targu Mures, Romania; (R.Ș.F.); (L.A.)
| | - Marius Petrișor
- Department of Simulation Applied in Medicine, University of Medicine, Pharmacy, Science and Technology “George Emil Palade”, 540142 Targu Mures, Romania; (O.C.); (M.P.)
| | - Leonard Azamfirei
- Department of Anaesthesiology and Intensive Care, University of Medicine, Pharmacy, Science and Technology “George Emil Palade”, 540142 Targu Mures, Romania; (R.Ș.F.); (L.A.)
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Li L, Yang L, Yuan Z, Wu Q, Lyu X. The Combination of Systemic Immune-Inflammation Index and Serum Procalcitonin has High Auxiliary Predictive Value for Short-Term Adverse Prognosis in Septic Shock Patients. J Emerg Med 2024; 67:e357-e367. [PMID: 39183119 DOI: 10.1016/j.jemermed.2024.05.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Revised: 04/25/2024] [Accepted: 05/03/2024] [Indexed: 08/27/2024]
Abstract
BACKGROUND Septic shock is the most serious complication of sepsis, with more secure and efficient biomarkers urgently needed. Systemic immune-inflammation index (SII) and serum procalcitonin (PCT) show involvement in predicting septic shock prognosis. OBJECTIVE Herein, we explored the clinical value of the SII-PCT combination in the short-term prognosis of septic shock patients. METHODS Totally 200 septic shock patients were analyzed retrospectively and allocated into the survival and death groups upon 28-day in-hospital outcomes. Correlations of SII, PCT, acute physiology and chronic health evaluation II (APACHE II)/sepsis-related organ failure assessment (SOFA) scores, C-reactive protein (CRP), and serum creatinine (Scr) were analyzed using Spearman. The influencing factors of SII and serum PCT for short-term poor prognosis were analyzed using logistic multivariate regression model. The auxiliary predictive value of SII, PCT, and their combination for short-term adverse septic shock prognosis was evaluated by the receiver operating characteristic curve. Differences in the area under the curve (AUC) were compared using MedCalc. RESULTS The death group had higher APACHE II/SOFA scores, LYM, CRP, Scr, SII, and PCT levels than the survival group. SII and PCT were positively correlated with APACHE II and SOFA scores, LYM, CRP, and Scr, and were independent risk factors influencing the adverse septic shock prognosis. The AUC of the SII-PCT combination in predicting short-term adverse septic shock prognosis was 0.893 (0.841-0.932), with 76.12% sensitivity and 87.97% specificity, with the combination showing a higher AUC than SII/PCT alone. CONCLUSIONS The SII-PCT combination helps predict the adverse prognosis of septic shock patients.
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Affiliation(s)
- Liang Li
- Department of Emergency Department Longhua Branch, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, Guangdong, China
| | - Le Yang
- Emergency Department of Shenzhen University General Hospital, Shenzhen, China
| | - Zhenmin Yuan
- Emergency Department of The Second People's Hospital of Shenzhen (The First Affiliated Hospital of Shenzhen University) 518035, China
| | - Quanli Wu
- Department of Emergency Department Longhua Branch, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, Guangdong, China
| | - Xia Lyu
- Department of Nursing Department Longhua Branch, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, Guangdong, China.
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Wang Z, Zhang W, Chen L, Lu X, Tu Y. Lymphopenia in sepsis: a narrative review. Crit Care 2024; 28:315. [PMID: 39304908 PMCID: PMC11414153 DOI: 10.1186/s13054-024-05099-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2024] [Accepted: 09/14/2024] [Indexed: 09/22/2024] Open
Abstract
This narrative review provides an overview of the evolving significance of lymphopenia in sepsis, emphasizing its critical function in this complex and heterogeneous disease. We describe the causal relationship of lymphopenia with clinical outcomes, sustained immunosuppression, and its correlation with sepsis prediction markers and therapeutic targets. The primary mechanisms of septic lymphopenia are highlighted. In addition, the paper summarizes various attempts to treat lymphopenia and highlights the practical significance of promoting lymphocyte proliferation as the next research direction.
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Affiliation(s)
- Zhibin Wang
- Department of Critical Care Medicine, School of Anesthesiology, Naval Medical University, Shanghai, 200433, China.
| | - Wenzhao Zhang
- Department of Critical Care Medicine, School of Anesthesiology, Naval Medical University, Shanghai, 200433, China
| | - Linlin Chen
- Department of Critical Care Medicine, School of Anesthesiology, Naval Medical University, Shanghai, 200433, China
| | - Xin Lu
- Department of Critical Care Medicine, School of Anesthesiology, Naval Medical University, Shanghai, 200433, China
| | - Ye Tu
- Department of Pharmacy, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China.
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Zhang J, Zhao Q, Liu S, Yuan N, Hu Z. Clinical predictive value of the CRP-albumin-lymphocyte index for prognosis of critically ill patients with sepsis in intensive care unit: a retrospective single-center observational study. Front Public Health 2024; 12:1395134. [PMID: 38841671 PMCID: PMC11150768 DOI: 10.3389/fpubh.2024.1395134] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2024] [Accepted: 05/06/2024] [Indexed: 06/07/2024] Open
Abstract
Background Sepsis is a complex syndrome characterized by physiological, pathological, and biochemical abnormalities caused by infection. Its development is influenced by factors such as inflammation, nutrition, and immune status. Therefore, we combined C-reactive protein (CRP), albumin, and lymphocyte, which could reflect above status, to be the CRP-albumin-lymphocyte (CALLY) index, and investigated its association with clinical prognosis of critically ill patients with sepsis. Methods This retrospective observational study enrolled critically ill patients with sepsis who had an initial CRP, albumin, and lymphocyte data on the first day of ICU admission. All data were obtained from the Affiliated Hospital of Jiangsu University. The patients were divided into quartiles (Q1-Q4) based on their CALLY index. The outcomes included 30-/60-day mortality and acute kidney injury (AKI) occurrence. The association between the CALLY index and these clinical outcomes in critically ill patients with sepsis was evaluated using Cox proportional hazards and logistic regression analysis. Results A total of 1,123 patients (63.0% male) were included in the study. The 30-day and 60-day mortality rates were found to be 28.1 and 33.4%, respectively, while the incidence of AKI was 45.6%. Kaplan-Meier analysis revealed a significant association between higher CALLY index and lower risk of 30-day and 60-day mortality (log-rank p < 0.001). Multivariate Cox proportional hazards analysis indicated that the CALLY index was independently associated with 30-day mortality [HR (95%CI): 0.965 (0.935-0.997); p = 0.030] and 60-day mortality [HR (95%CI): 0.969 (0.941-0.997); p = 0.032]. Additionally, the multivariate logistic regression model showed that the CALLY index served as an independent risk predictor for AKI occurrence [OR (95%CI): 0.982 (0.962-0.998); p = 0.033]. Conclusion The findings of this study indicated a significant association between the CALLY index and both 30-day and 60-day mortality, as well as the occurrence of AKI, in critically ill patients with sepsis. These findings suggested that the CALLY index may be a valuable tool in identifying sepsis patients who were at high risk for unfavorable outcomes.
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Affiliation(s)
- Jinhui Zhang
- Department of Critical Care Medicine, The Affiliated Hospital, Jiangsu University, Zhenjiang, Jiangsu, China
| | | | | | | | - Zhenkui Hu
- Department of Critical Care Medicine, The Affiliated Hospital, Jiangsu University, Zhenjiang, Jiangsu, China
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Hastak P, Cromer D, Malycha J, Andersen CR, Raith E, Davenport MP, Plummer M, Sasson SC. Defining the correlates of lymphopenia and independent predictors of poor clinical outcome in adults hospitalized with COVID-19 in Australia. Sci Rep 2024; 14:11102. [PMID: 38750134 PMCID: PMC11096393 DOI: 10.1038/s41598-024-61729-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2024] [Accepted: 05/08/2024] [Indexed: 05/18/2024] Open
Abstract
Lymphopenia is a common feature of acute COVID-19 and is associated with increased disease severity and 30-day mortality. Here we aim to define the demographic and clinical characteristics that correlate with lymphopenia in COVID-19 and determine if lymphopenia is an independent predictor of poor clinical outcome. We analysed the ENTER-COVID (Epidemiology of hospitalized in-patient admissions following planned introduction of Epidemic SARS-CoV-2 to highly vaccinated COVID-19 naïve population) dataset of adults (N = 811) admitted for COVID-19 treatment in South Australia in a retrospective registry study, categorizing them as (a) lymphopenic (lymphocyte count < 1 × 109/L) or (b) non-lymphopenic at hospital admission. Comorbidities and laboratory parameters were compared between groups. Multiple regression analysis was performed using a linear or logistic model. Intensive care unit (ICU) patients and non-survivors exhibited lower median lymphocyte counts than non-ICU patients and survivors respectively. Univariate analysis revealed that low lymphocyte counts associated with hypertension and correlated with haemoglobin, platelet count and negatively correlated with urea, creatinine, bilirubin, and aspartate aminotransferase (AST). Multivariate analysis identified age, male, haemoglobin, platelet count, diabetes, creatinine, bilirubin, alanine transaminase, c-reactive protein (CRP) and lactate dehydrogenase (LDH) as independent predictors of poor clinical outcome in COVID-19, while lymphopenia did not emerge as a significant predictor.
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Affiliation(s)
- Priyanka Hastak
- The Kirby Institute, University of New South Wales, Sydney, Wallace Wurth Building (C27), Cnr High St & Botany St, Kensington, NSW, 2052, Australia.
| | - Deborah Cromer
- The Kirby Institute, University of New South Wales, Sydney, Wallace Wurth Building (C27), Cnr High St & Botany St, Kensington, NSW, 2052, Australia
| | - James Malycha
- Royal Adelaide Hospital, Adelaide, SA, Australia
- University of Adelaide, Adelaide, SA, Australia
| | - Christopher R Andersen
- The Kirby Institute, University of New South Wales, Sydney, Wallace Wurth Building (C27), Cnr High St & Botany St, Kensington, NSW, 2052, Australia
- The George Institute for Global Health, Sydney, Australia
- Royal North Shore Hospital, Sydney, Australia
| | - Eamon Raith
- Royal Adelaide Hospital, Adelaide, SA, Australia
- University of Adelaide, Adelaide, SA, Australia
| | - Miles P Davenport
- The Kirby Institute, University of New South Wales, Sydney, Wallace Wurth Building (C27), Cnr High St & Botany St, Kensington, NSW, 2052, Australia
| | - Mark Plummer
- Royal Adelaide Hospital, Adelaide, SA, Australia
- University of Adelaide, Adelaide, SA, Australia
| | - Sarah C Sasson
- The Kirby Institute, University of New South Wales, Sydney, Wallace Wurth Building (C27), Cnr High St & Botany St, Kensington, NSW, 2052, Australia
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10
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Yang J, Zhu X, Feng J. The Changes in the Quantity of Lymphocyte Subpopulations during the Process of Sepsis. Int J Mol Sci 2024; 25:1902. [PMID: 38339179 PMCID: PMC10855580 DOI: 10.3390/ijms25031902] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Revised: 01/18/2024] [Accepted: 01/27/2024] [Indexed: 02/12/2024] Open
Abstract
Sepsis remains a global challenge, especially in low- and middle-income countries, where there is an urgent need for easily accessible and cost-effective biomarkers to predict the occurrence and prognosis of sepsis. Lymphocyte counts are easy to measure clinically, and a large body of animal and clinical research has shown that lymphocyte counts are closely related to the incidence and prognosis of sepsis. This review extensively collected experimental articles related to lymphocyte counts since the unification of the definition of sepsis. The article categorizes and discusses the relationship between absolute lymphocyte counts, intrinsic lymphocyte subsets, effector T-lymphocytes, B-lymphocytes, dendritic cells, and the incidence and prognosis of sepsis. The results indicate that comparisons of absolute lymphocyte counts alone are meaningless. However, in addition to absolute lymphocyte counts, innate lymphocyte subsets, effector T-cells, B-lymphocytes, and dendritic cells have shown certain research value in related studies.
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Affiliation(s)
- Jiale Yang
- Department of Emergency Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430074, China;
- Department of Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430074, China
| | - Xiaojian Zhu
- Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430074, China;
| | - Jun Feng
- Department of Emergency Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430074, China;
- Department of Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430074, China
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11
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Tao X, Wang J, Liu B, Cheng P, Mu D, Du H, Niu B. Plasticity and crosstalk of mesenchymal stem cells and macrophages in immunomodulation in sepsis. Front Immunol 2024; 15:1338744. [PMID: 38352879 PMCID: PMC10861706 DOI: 10.3389/fimmu.2024.1338744] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2023] [Accepted: 01/10/2024] [Indexed: 02/16/2024] Open
Abstract
Sepsis is a multisystem disease characterized by dysregulation of the host immune response to infection. Immune response kinetics play a crucial role in the pathogenesis and progression of sepsis. Macrophages, which are known for their heterogeneity and plasticity, actively participate in the immune response during sepsis. These cells are influenced by the ever-changing immune microenvironment and exhibit two-sided immune regulation. Recently, the immunomodulatory function of mesenchymal stem cells (MSCs) in sepsis has garnered significant attention. The immune microenvironment can profoundly impact MSCs, prompting them to exhibit dual immunomodulatory functions akin to a double-edged sword. This discovery holds great importance for understanding sepsis progression and devising effective treatment strategies. Importantly, there is a close interrelationship between macrophages and MSCs, characterized by the fact that during sepsis, these two cell types interact and cooperate to regulate inflammatory processes. This review summarizes the plasticity of macrophages and MSCs within the immune microenvironment during sepsis, as well as the intricate crosstalk between them. This remains an important concern for the future use of these cells for immunomodulatory treatments in the clinic.
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Affiliation(s)
- Xingyu Tao
- Department of Critical Care Medicine, Chongqing Key Laboratory of Emergency Medicine, School of Medicine, Chongqing University Central Hospital, Chongqing University, Chongqing, China
| | - Jialian Wang
- Department of Critical Care Medicine, Chongqing Key Laboratory of Emergency Medicine, School of Medicine, Chongqing University Central Hospital, Chongqing University, Chongqing, China
| | - Bin Liu
- Department of Critical Care Medicine, Chongqing Key Laboratory of Emergency Medicine, School of Medicine, Chongqing University Central Hospital, Chongqing University, Chongqing, China
| | - Peifeng Cheng
- Department of Critical Care Medicine, Chongqing Key Laboratory of Emergency Medicine, School of Medicine, Chongqing University Central Hospital, Chongqing University, Chongqing, China
| | - Dan Mu
- Department of Critical Care Medicine, Chongqing Key Laboratory of Emergency Medicine, School of Medicine, Chongqing University Central Hospital, Chongqing University, Chongqing, China
| | - Huimin Du
- Department of Oncology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Bailin Niu
- Department of Critical Care Medicine, Chongqing Key Laboratory of Emergency Medicine, School of Medicine, Chongqing University Central Hospital, Chongqing University, Chongqing, China
- Department of Surgery, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, United States
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12
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Liu X, Mu Y. Lymphocyte to C-Reactive Protein Ratio as an Early Biomarker to Distinguish Sepsis from Pneumonia in Neonates. J Inflamm Res 2023; 16:3509-3517. [PMID: 37608883 PMCID: PMC10441656 DOI: 10.2147/jir.s424897] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Accepted: 08/11/2023] [Indexed: 08/24/2023] Open
Abstract
Background Neonatal sepsis is an acute and severe disease that seriously threatens the life and health of newborns. Neonates with pneumonia may also have unrecognized neonatal sepsis. Early diagnosis of neonatal sepsis is beneficial for early treatment. This study aimed to evaluate the clinical significance of the lymphocyte-to-C-reactive protein ratio (LCR) as an early biomarker to distinguish sepsis from pneumonia. Methods This retrospective study enrolled 1635 neonates with pneumonia from February 2016 to March 2022. Among them, 182 cases were diagnosed with sepsis based on the positive blood culture results. Clinical and laboratory data were extracted from the electronic medical records. LCR was calculated as the ratio of the total lymphocyte count (×109 cells/L) to the C-reactive protein level (mg/L). Binary logistic regression analysis was conducted to evaluate the clinical significance of LCR as an early biomarker in distinguishing sepsis from pneumonia. Receiver operating characteristic (ROC) analysis was performed to assess the diagnostic value of LPCR in sepsis cases. All statistical analyses were conducted using Statistical Product and Service Solutions, version 24.0. Results The neonates with pneumonia combined with sepsis had a lower LCR than that of the neonates with pneumonia. Further analysis showed that the prevalence of neonatal pneumonia combined with sepsis was significantly higher in the low-LCR group than in the high-LCR group (20.7% vs 5.5%, P < 001). Binary logistic regression revealed that LCR was an independent risk factor for identifying pneumonia combined with sepsis. The ROC curve analysis revealed that LCR had better power than the lymphocyte count and CRP level individually in diagnosing neonatal pneumonia combined with sepsis (0.72 vs 0.65 vs 0.66, P < 0.001), with 62% sensitivity and 72% specificity. Conclusion LCR can be a potential early biomarker in distinguishing neonates with sepsis from those with pneumonia.
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Affiliation(s)
- Xinrui Liu
- Zhengzhou Key Laboratory of Children’s Infection and Immunity, Children’s Hospital Affiliated to Zhengzhou University, Henan Children’s Hospital, Zhengzhou Children’s Hospital, Zhengzhou, People’s Republic of China
| | - Yuan Mu
- Institute of Thermology, Henan Institute of Metrology and Testing Sciences, Zhengzhou, People’s Republic of China
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Developing a new sepsis screening tool based on lymphocyte count, international normalized ratio and procalcitonin (LIP score). Sci Rep 2022; 12:20002. [PMID: 36411279 PMCID: PMC9678875 DOI: 10.1038/s41598-022-16744-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2022] [Accepted: 07/14/2022] [Indexed: 11/22/2022] Open
Abstract
Exploring an effective sepsis screening tool that can be widely implemented is important for improving the prognosis of sepsis worldwide. This study aimed to develop a new simple screening tool for sepsis (LIP scoring system) that includes the peripheral blood lymphocyte count, international normalized ratio, and procalcitonin level. In a single-center, prospective, observational study, 444 acute sepsis inpatients and 444 nonsepsis inpatients were ultimately included based on the Sepsis-3 and exclusion criteria. The differences in the Lym, INR, PCT level and other clinical biomarkers were compared between the two groups. Univariable and multivariable logistic regression analyses and receiver operating characteristic analysis were used to establish a LIP screening tool for sepsis with a combination of biomarkers. The Kappa and McNemar tests were used to evaluate the differences between the LIP screening results (LIP score ≥ 3) and Sepsis-3 criteria (SOFA score ≥ 2). Logistic regression analysis showed that the lymphocyte count, INR, PCT level, platelets, neutrophil/lymphocyte ratio (NLR) and prothrombin time (PT) were independent risk factors for the development of sepsis. The ROC analysis showed that the lymphocyte count, INR, and PCT level had high area under the ROC curve values (AUROC (95% CI): Lym 0.84 (0.810-0.860), INR 0.921 (0.902-0.938), PCT level 0.928 (0.909-0.944)). The LIP tool had satisfactory screening efficacy for sepsis (sensitivity, 92.8%; specificity, 94.1%), and a LIP score equal to or greater than 3 points had good agreement with Sepsis-3 criteria in the diagnosis of sepsis (Kappa = 0862 in the Kappa test and P = 0.512 in the McNemar test). The LIP tool has satisfactory sensitivity and specificity for sepsis screening, and it can be used for rapid screening of patients with sepsis in outpatient and emergency departments or in economically underdeveloped areas with limited resources.
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14
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Xia B, Song B, Zhang J, Zhu T, Hu H. Prognostic value of blood urea nitrogen-to-serum albumin ratio for mortality of pneumonia in patients receiving glucocorticoids: Secondary analysis based on a retrospective cohort study. J Infect Chemother 2022; 28:767-773. [PMID: 35272941 DOI: 10.1016/j.jiac.2022.02.015] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Revised: 02/06/2022] [Accepted: 02/18/2022] [Indexed: 01/17/2023]
Abstract
INTRODUCTION Previous studies have revealed that blood urea nitrogen-to-serum albumin ratio (BUN/ALB) is one of major risk factors of mortality in pneumonia. However, there are fewer scientific research about the correlation between BUN/ALB ratio and outcome of pneumonia in patients receiving glucocorticoids. This study was undertaken to explore the prognostic value of BUN/ALB ratio for mortality of pneumonia in patients receiving glucocorticoids. METHODS The present study was a retrospective cohort study. 1397 subjects receiving glucocorticoids alone or glucocorticoids and other immunosuppressants from six secondary and tertiary academic hospitals in China were analyzed. The endpoint of the study was 30-day mortality. It was noted that the entire study was completed by Li et al. and uploaded the data to the DATADRYAD website. The author only used this data for secondary analysis. RESULTS After adjusting potential confounders (age, sex, WBC, persistent lymphocytopenia, PLT, ALT, AST, Cr, high-dose steroid use, and COPD), non-linear relationship was detected between BUN/ALB ratio and 30-day mortality, whose point was 0.753. The effect sizes and the confidence intervals on the left and right sides of inflection point were 23.110 (7.157, 74.623) and 0.410 (0.074, 2.283), respectively. Subgroup analysis revealed the positive association was stronger among subjects with connective tissue disease. CONCLUSIONS The relationship between BUN/ALB ratio and 30-day mortality of pneumonia in patients receiving glucocorticoids is non-linear. BUN/ALB ratio is positively related with 30-day mortality when BUN/ALB ratio is less than 0.753.
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Affiliation(s)
- Bingtian Xia
- School of Medicine, Zhejiang University, Hangzhou, PR China; Department of Hematology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, PR China
| | - Bingxin Song
- School of Medicine, Zhejiang University, Hangzhou, PR China
| | - Jingcheng Zhang
- Department of Hematology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, PR China
| | - Tingjun Zhu
- Department of Hematology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, PR China
| | - Huixian Hu
- School of Medicine, Zhejiang University, Hangzhou, PR China; Department of Hematology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, PR China.
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15
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Baïsse A, Daix T, Hernandez Padilla AC, Jeannet R, Barraud O, Dalmay F, François B, Vignon P, Lafon T. High prevalence of infections in non-COVID-19 patients admitted to the Emergency Department with severe lymphopenia. BMC Infect Dis 2022; 22:295. [PMID: 35346082 PMCID: PMC8960225 DOI: 10.1186/s12879-022-07295-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Accepted: 03/14/2022] [Indexed: 11/23/2022] Open
Abstract
Background In the Emergency Department (ED), early and accurate recognition of infection is crucial to prompt antibiotic therapy but the initial presentation of patients is variable and poorly characterized. Lymphopenia is commonly associated with bacteraemia and poor outcome in intensive care unit patients. The objective of this retrospective study was to assess the prevalence of community-acquired infection in a cohort of unselected patients admitted to the ED with undifferentiated symptoms and severe lymphopenia. Methods This is a retrospective single-center study conducted over a 1 year-period before the COVID-19 pandemic. Consecutive adult patients admitted to the ED with severe lymphopenia (lymphocyte count < 0.5 G/L) were studied. Patients with hematological or oncological diseases, HIV infection, hepato-cellular deficiency, immunosuppression, or patients over 85 years old were excluded. Diagnoses of infection were validated by an independent adjudication committee. The association between various parameters and infection was assessed using a multivariate logistic regression analysis. Results Of 953 patients admitted to the ED with severe lymphopenia, 245 were studied (148 men; mean age: 63 ± 19 years). Infection was confirmed in 159 patients (65%) (bacterial: 60%, viral: 30%, other: 10%). Only 61 patients (25%) were referred to the ED for a suspected infection. In the univariate analysis, SIRS criteria (OR: 5.39; 95%CI: 3.04–9.70; p < 0.001) and temperature ≥ 38.3 °C (OR: 10.95; 95%CI: 5.39–22.26; p < 0.001) were strongly associate with infection. In the multivariate analysis, only SIRS criteria (OR: 2.4; 95%CI: 1.48–3.9; p < 0.01) and fever (OR: 3.35; 95%CI: 1.26–8.93; p = 0.016) were independently associated with infection. Conclusions The prevalence of underlying infection is high in patients admitted to the ED with lymphopenia, irrespective of the reason for admission. Whether lymphopenia could constitute a valuable marker of underlying infection in this clinical setting remains to be confirmed prospectively in larger cohorts. Trial registration: No registration required as this is a retrospective study. Supplementary Information The online version contains supplementary material available at 10.1186/s12879-022-07295-5.
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16
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Wang J, Zhang W, Jin Z, Ding Y, Zhang S, Wu D, Cao Y. A lethal model of Leptospira infection in hamster nasal mucosa. PLoS Negl Trop Dis 2022; 16:e0010191. [PMID: 35192629 PMCID: PMC8863242 DOI: 10.1371/journal.pntd.0010191] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2021] [Accepted: 01/21/2022] [Indexed: 02/07/2023] Open
Abstract
Leptospirosis is a fatal zoonosis caused by contact between skin or a mucosal surface and contaminated soil or water. Hamsters were infected by intraperitoneal injection fto establish experimental leptospirosis, which is not a natural route of infection. There are no reports of nasal mucosal infection in hamsters. In this study, infection of the nasal mucosa was performed to establish a model of natural infection. Both methods of infection can cause lethal models with similar symptoms in the later stages of infection, such as weight loss, blood concentration, increased neutrophils (GRAN), and decreased lymphocytes (LYM) in the blood, severe organ damage and liver function obstruction. The burden of Leptospira in the organs and blood was lower in the mucosal inoculation groups at 1 day after infection. However, mucosal infection induced a higher Leptospira burden in urine than intraperitoneal infection in the late stages of infection. After nasal mucosal infection, antibody levels were higher and lasted longer. These results indicated that the route of nasal mucosal infection is a good choice for studying leptospirosis in hamsters. The establishment of a leptospirosis experimental model is still key to elucidating the pathogenesis of leptospirosis. Hamsters were infected by intraperitoneal injection to establish experimental leptospirosis, although this is not a natural route of infection. The transmission characteristics of Leptospira and the disease progression in hamsters infected by a natural transmission route (e.g. through mucosal surfaces) had not been explored. In this study, we compared the dynamics of Leptospira infection in hamsters inoculated via the nasal mucosa or by intraperitoneal inoculation, and compared the burden of Leptospira and the level of antibodies produced with disease progression, such as body weight, serology, haematological changes and histopathological changes. Our data suggested that there are significant differences in the dynamics of infection between intraperitoneal and mucosal infection pathways. Although the result was the same in the later stage of infection, the course of mucosal infection was slower, which may better recapitulate the natural history of the disease, assist in studying kidney disease caused by Leptospira, and provide an animal model for the study of leptospirosis mucosal immunity.
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Affiliation(s)
- Jiaqi Wang
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, People’s Republic of China
| | - Wenlong Zhang
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, People’s Republic of China
- Key Laboratory for Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, People’s Republic of China
| | - Zhao Jin
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, People’s Republic of China
| | - Yue Ding
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, People’s Republic of China
| | - Shilei Zhang
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, People’s Republic of China
| | - Dianjun Wu
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, People’s Republic of China
- * E-mail: (DW); (YC)
| | - Yongguo Cao
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, People’s Republic of China
- Key Laboratory for Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, People’s Republic of China
- * E-mail: (DW); (YC)
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17
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Kos I, Balensiefer B, Lesan V, Kaddu-Mulindwa D, Thurner L, Christofyllakis K, Bittenbring JT, Ahlgrimm M, Seiffert M, Wagenpfeil S, Bewarder Y, Neumann F, Rixecker T, Smola S, Link A, Krawczyk M, Lammert F, Lepper PM, Bals R, Stilgenbauer S, Bewarder M. Increased B-cell activity with consumption of activated monocytes in severe COVID-19 patients. Eur J Immunol 2021; 51:1449-1460. [PMID: 33788264 PMCID: PMC8250224 DOI: 10.1002/eji.202049163] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Revised: 01/30/2021] [Accepted: 03/22/2021] [Indexed: 12/15/2022]
Abstract
The pathogenesis of autoimmune complications triggered by SARS-CoV2 has not been completely elucidated. Here, we performed an analysis of the cellular immune status, cell ratios, and monocyte populations of patients with COVID-19 treated in the intensive care unit (ICU) (cohort 1, N = 23) and normal care unit (NCU) (cohort 2, n = 10) compared with control groups: patients treated in ICU for noninfectious reasons (cohort 3, n = 30) and patients treated in NCU for infections other than COVID-19 (cohort 4, n = 21). Patients in cohort 1 presented significant differences in comparison with the other cohorts, including reduced frequencies of lymphocytes, reduced CD8+T-cell count, reduced percentage of activated and intermediate monocytes and an increased B/T8 cell ratio. Over time, patients in cohort 1 who died presented with lower counts of B, T, CD4+ T, CD8+ T-lymphocytes, NK cells, and activated monocytes. The B/T8 ratio was significantly lower in the group of survivors. In cohort 1, significantly higher levels of IgG1 and IgG3 were found, whereas cohort 3 presented higher levels of IgG3 compared to controls. Among many immune changes, an elevated B/T8-cell ratio and a reduced rate of activated monocytes were mainly observed in patients with severe COVID-19. Both parameters were associated with death in cohort 1.
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Affiliation(s)
- Igor Kos
- Internal Medicine I, Saarland University Medical Center, Homburg, Germany
| | | | - Vadim Lesan
- Internal Medicine I, Saarland University Medical Center, Homburg, Germany
| | | | - Lorenz Thurner
- Internal Medicine I, Saarland University Medical Center, Homburg, Germany
| | | | | | - Manfred Ahlgrimm
- Internal Medicine I, Saarland University Medical Center, Homburg, Germany
| | - Martina Seiffert
- Division of Molecular Genetics, German Cancer Research Center, Heidelberg, Germany
| | - Stefan Wagenpfeil
- Institute for Medical Biometrics, Epidemiology and Medical Informatics, Saarland University, Homburg, Germany
| | - Yvonne Bewarder
- Department of Cardiology, Angiology and Intensive Care Medicine, Saarland University Medical Center, Saarland University, Homburg, Germany
| | - Frank Neumann
- Internal Medicine I, Saarland University Medical Center, Homburg, Germany
| | - Torben Rixecker
- Department of Pulmonology, Allergology and Critical Care Medicine, Saarland University Medical Center, Saarland University, Homburg, Germany
| | - Sigrun Smola
- Institute of Virology, Saarland University Medical Center, Homburg/Saar, Germany
| | - Andreas Link
- Department of Cardiology, Angiology and Intensive Care Medicine, Saarland University Medical Center, Saarland University, Homburg, Germany
| | - Marcin Krawczyk
- Department of Medicine II, Saarland University Medical Center, Saarland University, Homburg, Germany
| | - Frank Lammert
- Department of Medicine II, Saarland University Medical Center, Saarland University, Homburg, Germany
- Hannover Medical School, Hannover, Germany
| | - Philipp M Lepper
- Department of Pulmonology, Allergology and Critical Care Medicine, Saarland University Medical Center, Saarland University, Homburg, Germany
| | - Robert Bals
- Department of Pulmonology, Allergology and Critical Care Medicine, Saarland University Medical Center, Saarland University, Homburg, Germany
| | | | - Moritz Bewarder
- Internal Medicine I, Saarland University Medical Center, Homburg, Germany
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Sadeghi S, Soudi S, Shafiee A, Hashemi SM. Mesenchymal stem cell therapies for COVID-19: Current status and mechanism of action. Life Sci 2020; 262:118493. [PMID: 32979360 PMCID: PMC7510562 DOI: 10.1016/j.lfs.2020.118493] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2020] [Revised: 09/19/2020] [Accepted: 09/20/2020] [Indexed: 12/12/2022]
Abstract
The outbreak of COVID-19 in December 2019, has become an urgent and serious public health emergency. At present, there is no effective treatment or vaccine for COVID-19. Therefore, there is a crucial unmet need to develop a safe and effective treatment for COVID-19 patients. Mesenchymal stem cells (MSCs) are widely used in basic science and in a variety of clinical trials. MSCs are able to engraft to the damaged tissues after transplantation and promote tissue regeneration, besides MSCs able to secrete immunomodulatory factors that suppress the cytokine storms. Moreover, the contribution of MSCs to prevent cell death and inhibit tissue fibrosis is well established. In the current review article, the potential mechanisms by which MSCs contribute to the treatment of COVID-19 patients are highlighted. Also, current trials that evaluated the potential of MSC-based treatments for COVID-19 are briefly reviewed.
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Affiliation(s)
- Somaye Sadeghi
- Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sara Soudi
- Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Abbas Shafiee
- UQ Diamantina Institute, Translational Research Institute, The University of Queensland, Brisbane, Queensland, Australia.
| | - Seyed Mahmoud Hashemi
- Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Urogenital Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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