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1.
Cells ; 10(12)2021 11 30.
Article in English | MEDLINE | ID: covidwho-1613627

ABSTRACT

The COVID-19 pandemic drastically highlighted the vulnerability of the elderly population towards viral and other infectious threats, illustrating that aging is accompanied by dysregulated immune responses currently summarized in terms like inflammaging and immunoparalysis. To gain a better understanding on the underlying mechanisms of the age-associated risk of adverse outcome in individuals experiencing a SARS-CoV-2 infection, we analyzed the impact of age on circulating monocyte phenotypes, activation markers and inflammatory cytokines including interleukin 6 (IL-6), IL-8 and tumor necrosis factor (TNF) in the context of COVID-19 disease progression and outcome in 110 patients. Our data indicate no age-associated differences in peripheral monocyte counts or subset composition. However, age and outcome are associated with differences in monocyte activation status. Moreover, a distinct cytokine pattern of IL-6, IL-8 and TNF in elderly survivors versus non-survivors, which consolidates over the time of hospitalization, suggests that older patients with adverse outcomes experience an inappropriate immune response, reminiscent of an inflammaging driven immunoparalysis. Our study underscores the value, necessity and importance of longitudinal monitoring in elderly COVID-19 patients, as dynamic changes after symptom onset can be observed, which allow for a differentiated insight into confounding factors that impact the complex pathogenesis following an infection with SARS-CoV-2.


Subject(s)
Aging/pathology , COVID-19/blood , COVID-19/pathology , Cytokines/blood , Monocytes/pathology , Acute Disease , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Biomarkers/metabolism , Humans , Longitudinal Studies , Middle Aged , Neutrophils/metabolism , Prospective Studies , SARS-CoV-2 , Young Adult
2.
Biophys J ; 120(14): 2838-2847, 2021 07 20.
Article in English | MEDLINE | ID: covidwho-1605922

ABSTRACT

Clinical syndrome coronavirus disease 2019 (COVID-19) induced by severe acute respiratory syndrome coronavirus 2 is characterized by rapid spreading and high mortality worldwide. Although the pathology is not yet fully understood, hyperinflammatory response and coagulation disorders leading to congestions of microvessels are considered to be key drivers of the still-increasing death toll. Until now, physical changes of blood cells have not been considered to play a role in COVID-19 related vascular occlusion and organ damage. Here, we report an evaluation of multiple physical parameters including the mechanical features of five frequent blood cell types, namely erythrocytes, lymphocytes, monocytes, neutrophils, and eosinophils. More than four million blood cells of 17 COVID-19 patients at different levels of severity, 24 volunteers free from infectious or inflammatory diseases, and 14 recovered COVID-19 patients were analyzed. We found significant changes in lymphocyte stiffness, monocyte size, neutrophil size and deformability, and heterogeneity of erythrocyte deformation and size. Although some of these changes recovered to normal values after hospitalization, others persisted for months after hospital discharge, evidencing the long-term imprint of COVID-19 on the body.


Subject(s)
COVID-19 , Hospitalization , Humans , Neutrophils , Phenotype , SARS-CoV-2
3.
BMC Pulm Med ; 22(1): 1, 2022 Jan 03.
Article in English | MEDLINE | ID: covidwho-1608729

ABSTRACT

BACKGROUND: Quantitative evaluation of radiographic images has been developed and suggested for the diagnosis of coronavirus disease 2019 (COVID-19). However, there are limited opportunities to use these image-based diagnostic indices in clinical practice. Our aim in this study was to evaluate the utility of a novel visually-based classification of pulmonary findings from computed tomography (CT) images of COVID-19 patients with the following three patterns defined: peripheral, multifocal, and diffuse findings of pneumonia. We also evaluated the prognostic value of this classification to predict the severity of COVID-19. METHODS: This was a single-center retrospective cohort study of patients hospitalized with COVID-19 between January 1st and September 30th, 2020, who presented with suspicious findings on CT lung images at admission (n = 69). We compared the association between the three predefined patterns (peripheral, multifocal, and diffuse), admission to the intensive care unit, tracheal intubation, and death. We tested quantitative CT analysis as an outcome predictor for COVID-19. Quantitative CT analysis was performed using a semi-automated method (Thoracic Volume Computer-Assisted Reading software, GE Health care, United States). Lungs were divided by Hounsfield unit intervals. Compromised lung (%CL) volume was the sum of poorly and non-aerated volumes (- 500, 100 HU). We collected patient clinical data, including demographic and clinical variables at the time of admission. RESULTS: Patients with a diffuse pattern were intubated more frequently and for a longer duration than patients with a peripheral or multifocal pattern. The following clinical variables were significantly different between the diffuse pattern and peripheral and multifocal groups: body temperature (p = 0.04), lymphocyte count (p = 0.01), neutrophil count (p = 0.02), c-reactive protein (p < 0.01), lactate dehydrogenase (p < 0.01), Krebs von den Lungen-6 antigen (p < 0.01), D-dimer (p < 0.01), and steroid (p = 0.01) and favipiravir (p = 0.03) administration. CONCLUSIONS: Our simple visual assessment of CT images can predict the severity of illness, a resulting decrease in respiratory function, and the need for supplemental respiratory ventilation among patients with COVID-19.


Subject(s)
COVID-19/classification , COVID-19/diagnostic imaging , Tomography, X-Ray Computed , Adult , Aged , Amides/therapeutic use , Antiviral Agents/therapeutic use , Body Temperature , C-Reactive Protein/metabolism , COVID-19/drug therapy , COVID-19/physiopathology , Female , Fibrin Fibrinogen Degradation Products/metabolism , Humans , L-Lactate Dehydrogenase/blood , Lung/diagnostic imaging , Lymphocyte Count , Male , Middle Aged , Mucin-1/blood , Neutrophils , Predictive Value of Tests , Prognosis , Pyrazines/therapeutic use , Radiographic Image Interpretation, Computer-Assisted , Retrospective Studies , SARS-CoV-2 , Steroids/therapeutic use
4.
Nat Immunol ; 23(1): 23-32, 2022 01.
Article in English | MEDLINE | ID: covidwho-1585822

ABSTRACT

Systemic immune cell dynamics during coronavirus disease 2019 (COVID-19) are extensively documented, but these are less well studied in the (upper) respiratory tract, where severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replicates1-6. Here, we characterized nasal and systemic immune cells in individuals with COVID-19 who were hospitalized or convalescent and compared the immune cells to those seen in healthy donors. We observed increased nasal granulocytes, monocytes, CD11c+ natural killer (NK) cells and CD4+ T effector cells during acute COVID-19. The mucosal proinflammatory populations positively associated with peripheral blood human leukocyte antigen (HLA)-DRlow monocytes, CD38+PD1+CD4+ T effector (Teff) cells and plasmablasts. However, there was no general lymphopenia in nasal mucosa, unlike in peripheral blood. Moreover, nasal neutrophils negatively associated with oxygen saturation levels in blood. Following convalescence, nasal immune cells mostly normalized, except for CD127+ granulocytes and CD38+CD8+ tissue-resident memory T cells (TRM). SARS-CoV-2-specific CD8+ T cells persisted at least 2 months after viral clearance in the nasal mucosa, indicating that COVID-19 has both transient and long-term effects on upper respiratory tract immune responses.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Nasopharynx/immunology , Nose/cytology , Respiratory Mucosa/immunology , SARS-CoV-2/immunology , Antibodies, Viral/blood , COVID-19/immunology , COVID-19/pathology , Granulocytes/immunology , HLA-DR Antigens/metabolism , Humans , Killer Cells, Natural/immunology , Monocytes/immunology , Nasopharynx/cytology , Nasopharynx/virology , Neutrophils/immunology , Nose/immunology , Nose/virology , Prospective Studies , Respiratory Mucosa/cytology , Respiratory Mucosa/virology
5.
Eur J Med Res ; 26(1): 146, 2021 Dec 17.
Article in English | MEDLINE | ID: covidwho-1582003

ABSTRACT

BACKGROUND: At the end of 2019, the world witnessed the emergence and ravages of a viral infection induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Also known as the coronavirus disease 2019 (COVID-19), it has been identified as a public health emergency of international concern (PHEIC) by the World Health Organization (WHO) because of its severity. METHODS: The gene data of 51 samples were extracted from the GSE150316 and GSE147507 data set and then processed by means of the programming language R, through which the differentially expressed genes (DEGs) that meet the standards were screened. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed on the selected DEGs to understand the functions and approaches of DEGs. The online tool STRING was employed to construct a protein-protein interaction (PPI) network of DEGs and, in turn, to identify hub genes. RESULTS: A total of 52 intersection genes were obtained through DEG identification. Through the GO analysis, we realized that the biological processes (BPs) that have the deepest impact on the human body after SARS-CoV-2 infection are various immune responses. By using STRING to construct a PPI network, 10 hub genes were identified, including IFIH1, DDX58, ISG15, EGR1, OASL, SAMD9, SAMD9L, XAF1, IFITM1, and TNFSF10. CONCLUSION: The results of this study will hopefully provide guidance for future studies on the pathophysiological mechanism of SARS-CoV-2 infection.


Subject(s)
COVID-19/genetics , Computational Biology/methods , Gene Expression Regulation/genetics , Lung/pathology , Protein Interaction Maps/genetics , COVID-19/pathology , Databases, Genetic , Gene Expression Profiling , Gene Ontology , Humans , Immunity, Humoral/genetics , Immunity, Humoral/immunology , Lung/virology , Neutrophil Activation/genetics , Neutrophil Activation/immunology , Neutrophils/immunology , SARS-CoV-2 , Transcriptome/genetics
6.
Viruses ; 13(12)2021 12 15.
Article in English | MEDLINE | ID: covidwho-1572672

ABSTRACT

Uncontrolled inflammatory responses play a critical role in coronavirus disease (COVID-19). In this context, because the triggering-receptor expressed on myeloid cells-1 (TREM-1) is considered an intrinsic amplifier of inflammatory signals, this study investigated the role of soluble TREM-1 (sTREM-1) as a biomarker of the severity and mortality of COVID-19. Based on their clinical scores, we enrolled COVID-19 positive patients (n = 237) classified into mild, moderate, severe, and critical groups. Clinical data and patient characteristics were obtained from medical records, and their plasma inflammatory mediator profiles were evaluated with immunoassays. Plasma levels of sTREM-1 were significantly higher among patients with severe disease compared to all other groups. Additionally, levels of sTREM-1 showed a significant positive correlation with other inflammatory parameters, such as IL-6, IL-10, IL-8, and neutrophil counts, and a significant negative correlation was observed with lymphocyte counts. Most interestingly, sTREM-1 was found to be a strong predictive biomarker of the severity of COVID-19 and was related to the worst outcome and death. Systemic levels of sTREM-1 were significantly correlated with the expression of matrix metalloproteinases (MMP)-8, which can release TREM-1 from the surface of peripheral blood cells. Our findings indicated that quantification of sTREM-1 could be used as a predictive tool for disease outcome, thus improving the timing of clinical and pharmacological interventions in patients with COVID-19.


Subject(s)
Biomarkers/blood , COVID-19/diagnosis , COVID-19/mortality , Leukocytes/metabolism , Matrix Metalloproteinase 8/metabolism , Severity of Illness Index , Triggering Receptor Expressed on Myeloid Cells-1/blood , Adolescent , Adult , Aged , Aged, 80 and over , Brazil , Female , Humans , Inflammation , Interleukin-10/blood , Interleukin-6/blood , Interleukin-8/blood , Leukocyte Count , Male , Middle Aged , Neutrophils/metabolism , Prospective Studies , SARS-CoV-2 , Triggering Receptor Expressed on Myeloid Cells-1/metabolism , Young Adult
7.
Dis Markers ; 2021: 6304189, 2021.
Article in English | MEDLINE | ID: covidwho-1553755

ABSTRACT

Background: Early identification of patients with severe coronavirus disease (COVID-19) at an increased risk of progression may promote more individualized treatment schemes and optimize the use of medical resources. This study is aimed at investigating the utility of the C-reactive protein to albumin (CRP/Alb) ratio for early risk stratification of patients. Methods: We retrospectively reviewed 557 patients with COVID-19 with confirmed outcomes (discharged or deceased) admitted to the West Court of Union Hospital, Wuhan, China, between January 29, 2020 and April 8, 2020. Patients with severe COVID-19 (n = 465) were divided into stable (n = 409) and progressive (n = 56) groups according to whether they progressed to critical illness or death during hospitalization. To predict disease progression, the CRP/Alb ratio was evaluated on admission. Results: The levels of new biomarkers, including neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, CRP/Alb ratio, and systemic immune-inflammation index, were higher in patients with progressive disease than in those with stable disease. Correlation analysis showed that the CRP/Alb ratio had the strongest positive correlation with the sequential organ failure assessment score and length of hospital stay in survivors. Multivariate logistic regression analysis showed that percutaneous oxygen saturation (SpO2), D-dimer levels, and the CRP/Alb ratio were risk factors for disease progression. To predict clinical progression, the areas under the receiver operating characteristic curves of Alb, CRP, CRP/Alb ratio, SpO2, and D-dimer were 0.769, 0.838, 0.866, 0.107, and 0.748, respectively. Moreover, patients with a high CRP/Alb ratio (≥1.843) had a markedly higher rate of clinical deterioration (log - rank p < 0.001). A higher CRP/Alb ratio (≥1.843) was also closely associated with higher rates of hospital mortality, ICU admission, invasive mechanical ventilation, and a longer hospital stay. Conclusion: The CRP/Alb ratio can predict the risk of progression to critical disease or death early, providing a promising prognostic biomarker for risk stratification and clinical management of patients with severe COVID-19.


Subject(s)
C-Reactive Protein/metabolism , COVID-19/diagnosis , Coronary Disease/diagnosis , Hypertension/diagnosis , Pulmonary Disease, Chronic Obstructive/diagnosis , SARS-CoV-2/pathogenicity , Serum Albumin, Human/metabolism , Aged , Area Under Curve , Biomarkers/blood , Blood Platelets/pathology , Blood Platelets/virology , COVID-19/epidemiology , COVID-19/mortality , COVID-19/virology , China/epidemiology , Comorbidity , Coronary Disease/epidemiology , Coronary Disease/mortality , Coronary Disease/virology , Disease Progression , Early Diagnosis , Female , Fibrin Fibrinogen Degradation Products/metabolism , Humans , Hypertension/epidemiology , Hypertension/mortality , Hypertension/virology , Length of Stay/statistics & numerical data , Lymphocytes/pathology , Lymphocytes/virology , Male , Middle Aged , Neutrophils/pathology , Neutrophils/virology , Prognosis , Pulmonary Disease, Chronic Obstructive/epidemiology , Pulmonary Disease, Chronic Obstructive/mortality , Pulmonary Disease, Chronic Obstructive/virology , ROC Curve , Retrospective Studies , SARS-CoV-2/growth & development , Severity of Illness Index , Survival Analysis
8.
Clin Lab ; 67(12)2021 Dec 01.
Article in English | MEDLINE | ID: covidwho-1538781

ABSTRACT

BACKGROUND: Neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR), and platelet-lymphocyte ratio (PLR) are inflammation markers in inflammatory, cardiovascular, and malignant diseases and are important to assess prognosis. The aim of the study is to show the correlation between the inflammation markers of NLR, LMR, and PLR identified in total blood count of patients with Coronavirus disease 2019 (COVID-19) with the disease severity. METHODS: A total of 409 patients attending hospital with clinical symptoms of COVID-19 and with positive quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) test were divided into two groups as 61 severe patients and 348 non-severe patients. The levels of inflammation markers NLR, LMR, PLR, and c-reactive protein (CRP) were assessed. RESULTS: The mean age of 409 patients was 49.9 ± 18.3 years and 48.7% of all patients were female. In the severe patient group, NLR 8.94 ± 13.24, LMR 2.24 ± 1.46, and PLR 248 ± 254 were identified. NLR exhibited the largest area under the curve at 0.698, with the highest specificity (67%) and sensitivity (67.3%) among the other inflammation markers such as LMR and PLR. Consistent with the severity of disease in severe COVID-19 patients, NLR, PLR, CRP and other inflammation markers increase, while LMR is observed to reduce. CONCLUSIONS: NLR and PLR, calculated with the simple, cheap, and easily accessible hemogram test requested for diagnosis and follow-up of COVID-19 disease, were correlated with the total score for radiological findings and duration of hospitalization, and we observed NLR and LMR may predict disease severity.


Subject(s)
COVID-19 , Female , Humans , Lymphocytes , Neutrophils , Retrospective Studies , SARS-CoV-2 , Severity of Illness Index
9.
Biochem Med (Zagreb) ; 31(3): 030501, 2021 Oct 15.
Article in English | MEDLINE | ID: covidwho-1534569

ABSTRACT

Coronavirus disease 2019 (COVID-19) pandemic represents a scientific and social crisis. One of the main unmet needs for coronavirus disease 2019 is its unpredictable clinical course, which can rapidly change in an irreversible outcome. COVID-19 patients can be classified into mild, moderate, and severe. Several haematological parameters, such as platelets, white blood cell total count, lymphocytes, neutrophils, (together with neutrophil-lymphocyte and platelet-lymphocyte ratio), and haemoglobin were described to be associated with COVID-19 infection and severity. The purpose of these review is to describe the current state of the art about complete blood count alterations during COVID-19 infection, and to summarize the crucial role of some haematological parameters during the course of the disease. Decreased platelet, lymphocyte, haemoglobin, eosinophil, and basophil count, increased neutrophil count and neutrophil-lymphocyte and platelet-lymphocyte ratio have been associated with COVID-19 infection and a worse clinical outcome. Our study adds some novelty about the identification of effective biomarkers of progressive disease, and might be helpful for diagnosis, prevention of complications, and effective therapy.


Subject(s)
COVID-19 , Blood Cell Count , Humans , Leukocyte Count , Lymphocytes , Neutrophils , Retrospective Studies , SARS-CoV-2
10.
Front Immunol ; 12: 758588, 2021.
Article in English | MEDLINE | ID: covidwho-1528821

ABSTRACT

Reactive oxygen species (ROS) are a group of oxygen-containing highly-reactive molecules produced from oxidative metabolic processes or in response to intracellular signals like cytokines and external stimuli like pathogen attack. They regulate a range of physiological processes and are involved in innate immune responses against infectious agents. Deregulation of ROS contributes to a plethora of disease conditions. Sialic acids are carbohydrates, present on cell surfaces or soluble proteins. Sialic acid-binding immunoglobulin-like lectins (Siglecs) recognize and bind to sialic acids. These are widely expressed on various types of immune cells. Siglecs modulate immune activation and can promote or inhibit ROS generation under different contexts. Siglecs promote ROS-dependent cell death in neutrophils and eosinophils while limiting oxidative stress associated with chronic obstructive pulmonary disease (COPD), sickle cell disease (SCD), coronavirus disease-2019 (COVID-19), etc. This review distinguishes itself in summarizing the current understanding of the role of Siglecs in moderating ROS production and their distinct effect on different immune cells; that ultimately determine the cellular response and the disease outcome. This is an important field of investigation having scope for both expansion and medical importance.


Subject(s)
Reactive Oxygen Species/immunology , Sialic Acid Binding Immunoglobulin-like Lectins/immunology , Animals , Eosinophils/immunology , Humans , Neutrophils/immunology
11.
Am J Perinatol ; 38(12): 1236-1243, 2021 10.
Article in English | MEDLINE | ID: covidwho-1521902

ABSTRACT

OBJECTIVE: This study aimed to determine if laboratory inflammatory markers can predict critical disease in symptomatic COVID-19 pregnant women. STUDY DESIGN: Multicenter, retrospective cohort study of all pregnant women presenting to New York City Health + Hospitals emergency departments from March 1 to May 30, 2020. We assessed all symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive pregnant women with room air oxygen saturation <95% on presentation. Logistic regression modeled the relationship of inflammatory markers to outcomes. Area under receiver operating characteristic (ROC) curve and maximum Youden index determined prognostic ability and optimal predictive cut-off values. RESULTS: A total of 498 of 5,002 pregnant women were SARS-CoV-2 RT-PCR positive of which 77 presented with hypoxemia. The absolute lymphocyte count (ALC) and neutrophil to lymphocyte ratio (NLR) were highly sensitive for progression to severe illness. ROC curve analysis identified predictive cutoffs: ALC < 1.49 × 109/L (96% sensitivity, 52% specificity, area under the receiver operating characteristic curve [AUC] = 0.80 (95% confidence interval [CI]: 0.70-0.90) and NLR >8.1 (100% sensitivity, 70% specificity, AUC = 0.86 (95% CI: [0.76-0.96]). CONCLUSION: ALC and NLR on presentation are sensitive markers of progression to critical COVID-19 disease in symptomatic pregnant women. This finding provides a practical, rapid method for assessment and can assist clinicians with decision-making regarding triage, level of care, and patient management. KEY POINTS: · Few tools exist to gauge risk of severe COVID-19 disease in pregnancy.. · ALC and NLR are sensitive predictive markers of disease progression in symptomatic women.. · Cut-off values for ALC and NLR will help direct patient triage and management..


Subject(s)
COVID-19/complications , Lymphocyte Count , Lymphopenia/virology , Neutrophils/metabolism , Pregnancy Complications, Infectious/virology , Severity of Illness Index , Adult , Cohort Studies , Disease Progression , Female , Humans , Pregnancy , Retrospective Studies , Sensitivity and Specificity
12.
mSphere ; 6(5): e0075221, 2021 10 27.
Article in English | MEDLINE | ID: covidwho-1526451

ABSTRACT

During the progression of coronavirus disease 2019 (COVID-19), immune response and inflammation reactions are dynamic events that develop rapidly and are associated with the severity of disease. Here, we aimed to develop a predictive model based on the immune and inflammatory response to discriminate patients with severe COVID-19. COVID-19 patients were enrolled, and their demographic and immune inflammatory reaction indicators were collected and analyzed. Logistic regression analysis was performed to identify the independent predictors, which were further used to construct a predictive model. The predictive performance of the model was evaluated by receiver operating characteristic curve, and optimal diagnostic threshold was calculated; these were further validated by 5-fold cross-validation and external validation. We screened three key indicators, including neutrophils, eosinophils, and IgA, for predicting severe COVID-19 and obtained a combined neutrophil, eosinophil, and IgA ratio (NEAR) model (NEU [109/liter] - 150×EOS [109/liter] + 3×IgA [g/liter]). NEAR achieved an area under the curve (AUC) of 0.961, and when a threshold of 9 was applied, the sensitivity and specificity of the predicting model were 100% and 88.89%, respectively. Thus, NEAR is an effective index for predicting the severity of COVID-19 and can be used as a powerful tool for clinicians to make better clinical decisions. IMPORTANCE The immune inflammatory response changes rapidly with the progression of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and is responsible for clearance of the virus and further recovery from the infection. However, the intensified immune and inflammatory response in the development of the disease may lead to more serious and fatal consequences, which indicates that immune indicators have the potential to predict serious cases. Here, we identified both eosinophils and serum IgA as prognostic markers of COVID-19, which sheds light on new research directions and is worthy of further research in the scientific research field as well as clinical application. In this study, the combination of NEU count, EOS count, and IgA level was included in a new predictive model of the severity of COVID-19, which can be used as a powerful tool for better clinical decision-making.


Subject(s)
COVID-19 Testing/methods , COVID-19/diagnosis , COVID-19/immunology , Clinical Decision Rules , Severity of Illness Index , Adult , Aged , Biomarkers/blood , COVID-19/blood , Clinical Decision-Making/methods , Disease Progression , Eosinophils/metabolism , Female , Humans , Immunoglobulin A/blood , Inflammation/blood , Inflammation/diagnosis , Inflammation/virology , Logistic Models , Male , Middle Aged , Neutrophils/metabolism , Predictive Value of Tests , Prognosis , Sensitivity and Specificity
15.
BMJ Case Rep ; 14(11)2021 Nov 11.
Article in English | MEDLINE | ID: covidwho-1515267

ABSTRACT

Idiosyncratic drug-induced agranulocytosis is a rare life-threatening adverse reaction characterised by an absolute neutrophil count <500 cells/µL of blood. Nitrofurantoin has been associated with haematological adverse events, but few agranulocytosis cases worldwide have been reported. We present a case of a 68-year-old woman who presented with fever and agranulocytosis following treatment with nitrofurantoin. Extensive workup for agranulocytosis, including a bone marrow aspirate, was unremarkable. Treatment with nitrofurantoin was discontinued, which led to a complete recovery of the complete blood count. This case stresses the importance of monitoring treatments, given that widely used drugs are not free from severe adverse reactions.


Subject(s)
Neutropenia , Nitrofurantoin , Aged , Blood Cell Count , Female , Humans , Leukocyte Count , Neutrophils , Nitrofurantoin/adverse effects
16.
Saudi Med J ; 42(4): 370-376, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1513257

ABSTRACT

OBJECTIVES: To assess the neutrophil-to-lymphocyte ratio (NLR) diagnostic and prognostic value in the context of Coronavirus disease-2019 (COVID-19) infection in Saudi Arabia. METHODS: A case-control study in which 701 confirmed COVID-19 patients (of which 41 were intensive care unit [ICU]-admitted) and 250 control subjects were enrolled. The study was conducted retrospectively in October on patients admitted to 3 separate hospitals in Saudi Arabia namely: King Abdullah Bin Abdulaziz University Hospital (Riyadh), Ohud Hospital (Madinah), and Nojood Medical Center (Madinah) between May and September 2020. Neutrophil-to-lymphocyte ratio was calculated based on absolute neutrophil and lymphocyte count. Institutional ethical approval was obtained prior to the study. RESULTS: Patients (median age 35 years), of which 54.8% were females, were younger than the control cohort (median age 48 years). Patients had significantly higher NLR compared to the control group. Intensive care unit admitted patients had significantly higher platelet, WBC and neutrophil counts. The ICU patients' NLR was almost twice as of the non-intensive patients. The NLR value of 5.5 was found to be of high specificity (96.4%) and positive predictive value (91.4%) in diagnosing COVID-19. Furthermore, it had a very good sensitivity (86.4%) in predicting severe forms of disease, such as, ICU admission. CONCLUSION: Neutrophil-to-lymphocyte ratio is an important tool in determining the COVID-19 clinical status. This study further confirms the prognostic value of NLR in detecting severe infection, and those patients with high NLR should be closely monitored and managed.


Subject(s)
COVID-19/diagnosis , Lymphocyte Count , Neutrophils , Adult , Blood Cell Count , COVID-19/blood , Case-Control Studies , Female , Hospitalization , Humans , Intensive Care Units , Leukocyte Count , Male , Middle Aged , Platelet Count , Predictive Value of Tests , Prognosis , Retrospective Studies , SARS-CoV-2 , Saudi Arabia , Sensitivity and Specificity , Severity of Illness Index
17.
Elife ; 102021 07 22.
Article in English | MEDLINE | ID: covidwho-1513065

ABSTRACT

Immature neutrophils and HLA-DRneg/low monocytes expand in cancer, autoimmune diseases and viral infections, but their appearance and immunoregulatory effects on T-cells after acute myocardial infarction (AMI) remain underexplored. We found an expansion of circulating immature CD16+CD66b+CD10neg neutrophils and CD14+HLA-DRneg/low monocytes in AMI patients, correlating with cardiac damage, function and levels of immune-inflammation markers. Immature CD10neg neutrophils expressed high amounts of MMP-9 and S100A9, and displayed resistance to apoptosis. Moreover, we found that increased frequency of CD10neg neutrophils and elevated circulating IFN-γ levels were linked, mainly in patients with expanded CD4+CD28null T-cells. Notably, the expansion of circulating CD4+CD28null T-cells was associated with cytomegalovirus (CMV) seropositivity. Using bioinformatic tools, we identified a tight relationship among the peripheral expansion of immature CD10neg neutrophils, CMV IgG titers, and circulating levels of IFN-γ and IL-12 in patients with AMI. At a mechanistic level, CD10neg neutrophils enhanced IFN-γ production by CD4+ T-cells through a contact-independent mechanism involving IL-12. In vitro experiments also highlighted that HLA-DRneg/low monocytes do not suppress T-cell proliferation but secrete high levels of pro-inflammatory cytokines after differentiation to macrophages and IFN-γ stimulation. Lastly, using a mouse model of AMI, we showed that immature neutrophils (CD11bposLy6GposCD101neg cells) are recruited to the injured myocardium and migrate to mediastinal lymph nodes shortly after reperfusion. In conclusion, immunoregulatory functions of CD10neg neutrophils play a dynamic role in mechanisms linking myeloid cell compartment dysregulation, Th1-type immune responses and inflammation after AMI.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , HLA-DR Antigens/immunology , Monocytes/immunology , Myocardial Infarction/immunology , Neprilysin/immunology , Neutrophils/immunology , Aged , Animals , Biomarkers , Cell Differentiation , Cell Proliferation , Cytokines , Female , Humans , Inflammation , Lymphocyte Activation , Male , Mice , Middle Aged , Myocardial Infarction/pathology , T-Lymphocytes/immunology
18.
Viruses ; 12(8)2020 07 27.
Article in English | MEDLINE | ID: covidwho-1512665

ABSTRACT

Acute viral bronchiolitis causes significant mortality in the developing world, is the number one cause of infant hospitalisation in the developed world, and is associated with the later development of chronic lung diseases such as asthma. A vaccine against respiratory syncytial virus (RSV), the leading cause of viral bronchiolitis in infancy, remains elusive, and hence new therapeutic modalities are needed to limit disease severity. However, much remains unknown about the underlying pathogenic mechanisms. Neutrophilic inflammation is the predominant phenotype observed in infants with both mild and severe disease, however, a clear understanding of the beneficial and deleterious effects of neutrophils is lacking. In this review, we describe the multifaceted roles of neutrophils in host defence and antiviral immunity, consider their contribution to bronchiolitis pathogenesis, and discuss whether new approaches that target neutrophil effector functions will be suitable for treating severe RSV bronchiolitis.


Subject(s)
Bronchiolitis, Viral/immunology , Bronchiolitis, Viral/pathology , Immunity, Innate , Neutrophils/immunology , Respiratory Syncytial Virus Infections/pathology , Respiratory Syncytial Virus, Human/immunology , Acute Disease , Animals , Clinical Trials as Topic , Humans , Inflammation/virology , Lung/virology , Mice , Respiratory Syncytial Virus Infections/immunology , Respiratory Syncytial Virus, Human/pathogenicity
19.
Front Cell Infect Microbiol ; 11: 751232, 2021.
Article in English | MEDLINE | ID: covidwho-1506821

ABSTRACT

Understanding of the basis for severity and fatal outcome of SARS-CoV-2 infection is of paramount importance for developing therapeutic options and identification of prognostic markers. So far, accumulation of neutrophils and increased levels of pro-inflammatory cytokines are associated with disease severity in COVID-19 patients. In this study, we aimed to compare circulatory levels of neutrophil secretory proteins, alpha-defensins (DEFA1), calprotectin (S100A8/A9), and myeloperoxidase (MPO) in COVID-19 patients with different clinical presentations. We studied 19 healthy subjects, 63 COVID-19 patients with mild (n=32) and severe (n=31) disease, 23 asymptomatic individuals identified through contact tracing programme and 23 recovering patients (1-4 months post-disease). At the time of disease presentation, serum levels of DEFA1 were significantly higher in patients with mild (mean230 ± 17, p<0.0001) and severe (mean452 ± 46, p<0.0001) disease respectively in comparison to healthy subjects (mean113 ± 11). S100A8/A9 proteins were significantly higher in COVID-19 patients (p<0.0001) irrespective of disease severity. The levels of DEFA1, S100A8/A9 and MPO reduced to normal in recovering patients and comparable to healthy subjects. Surprisingly, DEFA1 levels were higher in severe than mild patients in first week of onset of disease (p=0.004). Odds-ratio analysis showed that DEFA1 could act as potential biomarker in predicting disease severity (OR=11.34). In addition, levels of DEFA1 and S100A8/A9 were significantly higher in patients with fatal outcome (p=0.004 and p=0.03) respectively. The rise in DEFA1 levels was independent of secondary infections. In conclusion, our data suggest that induction of elevated levels of alpha-defensins and S100A8/A9 is associated with poor disease outcome in COVID-19 patients.


Subject(s)
COVID-19 , alpha-Defensins , Humans , Leukocyte L1 Antigen Complex , Neutrophils , Peroxidase , SARS-CoV-2 , Severity of Illness Index
20.
Front Immunol ; 12: 656419, 2021.
Article in English | MEDLINE | ID: covidwho-1506563

ABSTRACT

Tuberculosis (TB) is the global health problem with the second highest number of deaths from a communicable disease after COVID-19. Although TB is curable, poor health infrastructure, long and grueling TB treatments have led to the spread of TB pandemic with alarmingly increasing multidrug-resistant (MDR)-TB prevalence. Alternative host modulating therapies can be employed to improve TB drug efficacies or dampen the exaggerated inflammatory responses to improve lung function. Here, we investigated the adjunct therapy of natural immune-modulatory compound berberine in C57BL/6 mouse model of pulmonary TB. Berberine treatment did not affect Mtb growth in axenic cultures; however, it showed increased bacterial killing in primary murine bone marrow-derived macrophages and human monocyte-derived macrophages. Ad libitum berberine administration was beneficial to the host in combination with rifampicin and isoniazid. Berberine adjunctive treatment resulted in decreased lung pathology with no additive or synergistic effects on bacterial burdens in mice. Lung immune cell flow cytometry analysis showed that adjunctive berberine treatment decreased neutrophil, CD11b+ dendritic cell and recruited interstitial macrophage numbers. Late onset of adjunctive berberine treatment resulted in a similar phenotype with consistently reduced numbers of neutrophils both in lungs and the spleen. Together, our results suggest that berberine can be supplemented as an immunomodulatory agent depending on the disease stage and inflammatory status of the host.


Subject(s)
Antitubercular Agents/therapeutic use , Berberine/therapeutic use , Immunologic Factors/therapeutic use , Isoniazid/therapeutic use , Rifampin/therapeutic use , Tuberculosis, Pulmonary/drug therapy , Animals , Antitubercular Agents/pharmacology , Berberine/pharmacology , Cytokines/immunology , Dendritic Cells/drug effects , Drug Therapy, Combination , Female , Humans , Immunologic Factors/pharmacology , Isoniazid/pharmacology , Lung/drug effects , Lung/immunology , Lung/microbiology , Lung/pathology , Macrophages/drug effects , Macrophages/immunology , Male , Mice, Inbred C3H , Mice, Inbred C57BL , Mycobacterium tuberculosis/drug effects , Mycobacterium tuberculosis/growth & development , Neutrophils/drug effects , Neutrophils/immunology , Rifampin/pharmacology , Spleen/drug effects , Spleen/immunology , Spleen/microbiology , Tuberculosis, Pulmonary/immunology , Tuberculosis, Pulmonary/microbiology , Tuberculosis, Pulmonary/pathology
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