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2.
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
3.
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
4.
Int J Lab Hematol ; 43 Suppl 1: 137-141, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1526369

ABSTRACT

INTRODUCTION: Eosinopenia has been observed during infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19. This study evaluated the role of eosinopenia as a diagnostic and prognostic indicator in COVID-19 infection. METHODS: Information on 429 patients with confirmed COVID-19, admitted to Apollo Hospitals, Chennai, India between 04 June 2020 to 15 August 2020, was retrospectively collected through electronic records and analysed. RESULTS: 79.25% of the patients included in the study had eosinopenia on admission. The median eosinophil count in COVID-19-positive patients was 0.015 × 109 /L, and in negative patients, it was 0.249 × 109 /L. Eighteen per cent of the positive patients presented with 0 eosinophil count. Eosinopenia for early diagnosis of COVID-19 had a sensitivity of 80.68% and specificity of 100% with an accuracy of 85.24. Role of eosinopenia in prognostication of COVID-19 was found to be insignificant. There was no statistically significant difference between the median eosinophil counts in survivors and nonsurvivors. Eosinophil trends during the course of disease were found to be similar between survivors and nonsurvivors. CONCLUSIONS: Eosinopenia on admission is a reliable and convenient early diagnostic marker for COVID-19 infection, helping in early identification, triaging and isolation of the patients till nucleic acid test results are available. Role of eosinopenia as a prognostic indicator is insignificant.


Subject(s)
COVID-19 Testing/methods , COVID-19/blood , Eosinophils , Leukocyte Count , Leukopenia/etiology , Area Under Curve , Biomarkers , COVID-19/diagnosis , COVID-19/mortality , Eosinophilia/blood , Eosinophilia/etiology , Humans , India , Leukopenia/blood , Prognosis , ROC Curve , Retrospective Studies , Selection Bias , Sensitivity and Specificity , Survival Analysis
5.
Front Immunol ; 12: 769059, 2021.
Article in English | MEDLINE | ID: covidwho-1505989

ABSTRACT

The prognosis of severe COVID-19 patients has motivated research communities to uncover mechanisms of SARS-CoV-2 pathogenesis also on a regional level. In this work, we aimed to understand the immunological dynamics of severe COVID-19 patients with different degrees of illness, and upon long-term recovery. We analyzed immune cellular subsets and SARS-CoV-2-specific antibody isotypes of 66 COVID-19 patients admitted to the Hospital Clínico Universidad de Chile, which were categorized according to the WHO ten-point clinical progression score. These included 29 moderate patients (score 4-5) and 37 severe patients under either high flow oxygen nasal cannula (18 patients, score 6), or invasive mechanical ventilation (19 patients, score 7-9), plus 28 convalescent patients and 28 healthy controls. Furthermore, six severe patients that recovered from the disease were longitudinally followed over 300 days. Our data indicate that severe COVID-19 patients display increased frequencies of plasmablasts, activated T cells and SARS-CoV-2-specific antibodies compared to moderate and convalescent patients. Remarkably, within the severe COVID-19 group, patients rapidly progressing into invasive mechanical ventilation show higher frequencies of plasmablasts, monocytes, eosinophils, Th1 cells and SARS-CoV-2-specific IgG than patients under high flow oxygen nasal cannula. These findings demonstrate that severe COVID-19 patients progressing into invasive mechanical ventilation show a distinctive type of immunity. In addition, patients that recover from severe COVID-19 begin to regain normal proportions of immune cells 100 days after hospital discharge and maintain high levels of SARS-CoV-2-specific IgG throughout the study, which is an indicative sign of immunological memory. Thus, this work can provide useful information to better understand the diverse outcomes of severe COVID-19 pathogenesis.


Subject(s)
COVID-19/immunology , Eosinophils/immunology , Plasma Cells/immunology , SARS-CoV-2/physiology , Th1 Cells/immunology , Aged , Antibodies, Viral/blood , Convalescence , Disease Progression , Female , Humans , Immunity, Cellular , Immunoglobulin G/blood , Immunologic Memory , Male , Middle Aged , Severity of Illness Index
6.
Infection ; 49(6): 1325-1329, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1460517

ABSTRACT

PURPOSE: Eosinopenia has been described in COVID-19. With this study, we aim to study the peripheral blood eosinophil counts in COVID-19 patients and to investigate whether there is an association between the peripheral blood eosinophil counts and disease severity of COVID-19. METHODS: We revised the electronical medical records of confirmed COVID-19 patients with polymerase chain reaction (PCR) assays in the Groene Hart Ziekenhuis, Gouda, The Netherlands. We divided patients in mild, moderate and severe groups based on clinical severity of COVID-19. Clinical severity was based on the therapy needed and the outcome of patients. We compared clinical characteristics, laboratory results and outcome between the three groups. RESULTS: Of the 230 patients included in this study, the mild, moderate and severe groups consisted of 16.5%, 45.7% and 37.8% of the included patients, respectively. The mean age was 68 years (IQR 57-78). 63% of patients were male. A significant decrease in the peripheral eosinophil counts was found corresponding to the increase of COVID-19 severity. In the mild, moderate and severe groups, the percentage of patients with eosinopenia was 73.7%, 86.7% and 94.3%, respectively (p value 0.002). CONCLUSION: Eosinopenia is significantly more frequent present in patients with a severe COVID-19.


Subject(s)
COVID-19 , Aged , Eosinophils , Humans , Leukocyte Count , Male , Retrospective Studies , SARS-CoV-2
7.
Cell Rep ; 37(1): 109798, 2021 10 05.
Article in English | MEDLINE | ID: covidwho-1415262

ABSTRACT

Despite the worldwide effect of the coronavirus disease 2019 (COVID-19) pandemic, the underlying mechanisms of fatal viral pneumonia remain elusive. Here, we show that critical COVID-19 is associated with enhanced eosinophil-mediated inflammation when compared to non-critical cases. In addition, we confirm increased T helper (Th)2-biased adaptive immune responses, accompanying overt complement activation, in the critical group. Moreover, enhanced antibody responses and complement activation are associated with disease pathogenesis as evidenced by formation of immune complexes and membrane attack complexes in airways and vasculature of lung biopsies from six fatal cases, as well as by enhanced hallmark gene set signatures of Fcγ receptor (FcγR) signaling and complement activation in myeloid cells of respiratory specimens from critical COVID-19 patients. These results suggest that SARS-CoV-2 infection may drive specific innate immune responses, including eosinophil-mediated inflammation, and subsequent pulmonary pathogenesis via enhanced Th2-biased immune responses, which might be crucial drivers of critical disease in COVID-19 patients.


Subject(s)
Antibodies, Viral/immunology , COVID-19/immunology , Complement System Proteins/immunology , Eosinophils/immunology , Inflammation/immunology , Pneumonia, Viral/immunology , SARS-CoV-2/immunology , Adaptive Immunity , Adult , Aged , Aged, 80 and over , Antigen-Antibody Complex/metabolism , COVID-19/metabolism , COVID-19/virology , Complement Activation , Complement Membrane Attack Complex/metabolism , Eosinophils/virology , Female , Humans , Inflammation/metabolism , Inflammation/virology , Lung Injury/immunology , Lung Injury/pathology , Lung Injury/virology , Male , Middle Aged , Pneumonia, Viral/metabolism , Receptors, IgG/immunology , Receptors, IgG/metabolism , Severity of Illness Index , Signal Transduction , Th2 Cells/immunology , Viral Load , Young Adult
8.
Int J Clin Pract ; 75(11): e14781, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1388273

ABSTRACT

OBJECTIVES: Neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), monocyte/lymphocyte ratio (MLR), eosinophil/lymphocyte ratio (ELR), and C-reactive protein (CRP)/lymphocyte ratio (CLR) are well-established inflammatory indices. This study aimed to examine whether NLR, PLR, MLR, ELR and CLR could differentiate coronavirus disease 2019 (COVID-19) patients with pneumonia from those of without. METHODS: We retrospectively examined the laboratory parameters including CRP, D-dimer, procalcitonin and complete blood count of 306 COVID-19 patients (pneumonic = 152 and non-pneumonic = 154). NLR, PLR, MLR, ELR and CLR values of each patient were calculated. The ability of these indices to distinguish COVID-19 patients with and without pneumonia was determined by receiver operating characteristic (ROC) analysis. RESULTS: NLR, PLR and CLR values were higher while ELR value was lower in pneumonic COVID-19 patients compared with patients with non-pneumonic COVID-19 infection. MLR value was similar in the two groups. NLR, PLR and CLR were positively correlated with CRP and procalcitonin. ELR was negatively correlated with CRP. The ROC analysis revealed that the optimal cut-off value of CLR for discriminating COVID-19 patients with pneumonia from those without pneumonia was 1.14 and the area under curve (AUC) for CLR was 0.731 (sensitivity = 81.5% and specificity = 55.6%), which was markedly higher than the AUCs of NLR (0.622), PLR (0.585) and ELR (0.613). However, no statistical differences were observed between AUC values of NLR, PLR and ELR (P > .05). CONCLUSION: Our findings showed that NLR, PLR, ELR and CLR indices can be used in differentiating COVID-19 patients with or without pneumonia. Among them, the CLR index was the best predictor of pneumonia in COVID-19 patients.


Subject(s)
COVID-19 , Pneumonia , Eosinophils , Humans , Lymphocytes , Neutrophils , Pneumonia/diagnosis , Prognosis , Retrospective Studies , SARS-CoV-2
9.
Viruses ; 13(9)2021 08 24.
Article in English | MEDLINE | ID: covidwho-1374531

ABSTRACT

Knowledge about the immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, particularly regarding the function of eosinophils, has been steadily emerging recently. There exists controversy regarding the implications of eosinophils in the coronavirus disease 2019 (COVID-19)'s pathology. We report a retrospective cohort study including the comparison of leukocyte counts in COVID-19 patients, considering the outcomes of recovery (n = 59) and death (n = 60). Among the different types of leukocytes, the eosinophil counts were those that showed the greatest difference between recovered and deceased patients. Eosinopenia (eosinophil count < 0.01 × 109/L) was more frequently observed in deceased than recovered patients (p = 0.0012). The eosinophil counts more rapidly increased and showed a greater proportion over the course of the disease in the recovered than deceased patients. Furthermore, the estimated survival rate was greater in patients without eosinopenia than in patients with eosinopenia (p = 0.0070) during hospitalization. Importantly, recovered but not deceased patients showed high negative correlations of the eosinophils with the neutrophil-to-lymphocyte ratio (NLR) and neutrophil counts at Day 9 of the onset of clinical symptoms (p ≤ 0.0220). Our analysis suggests that eosinopenia may be associated with unfavorable disease outcomes and that the eosinophils have a beneficial function in COVID-19 patients, probably contributing by controlling the exacerbated inflammation induced by neutrophils.


Subject(s)
COVID-19/blood , COVID-19/virology , Eosinophils , Host-Pathogen Interactions , Leukocyte Count , SARS-CoV-2 , Adult , Aged , Aged, 80 and over , Biomarkers , COVID-19/diagnosis , COVID-19/immunology , Comorbidity , Disease Progression , Eosinophils/immunology , Female , Host-Pathogen Interactions/immunology , Humans , Kaplan-Meier Estimate , Length of Stay , Leukocytes , Lymphocyte Count , Lymphocytes , Male , Middle Aged , Neutrophils , Prognosis , Retrospective Studies , SARS-CoV-2/immunology , Severity of Illness Index , Young Adult
10.
BMC Pulm Med ; 21(1): 268, 2021 Aug 17.
Article in English | MEDLINE | ID: covidwho-1362052

ABSTRACT

BACKGROUND: Curcumin, a derivative of the spice turmeric, has been adopted by Eastern medicine for centuries as an adjunct to treat several medical conditions (e.g., anorexia and arthritis) because of its well-established anti-inflammatory properties. Studies have shown that the use of curcumin in mice models has led to reduction in several inflammatory markers as well as key inflammatory pathway enzymes. As a result, studies in Western medicine have developed to determine if this recognized benefit can be utilized for patients with inflammatory lung diseases, such as asthma. This study will seek to better understand if curcumin can be used as an adjunctive therapy for improving asthma control of patients with moderate to severe asthma; a finding we hope will allow for a more affordable treatment. METHODS: This study will utilize a randomized, placebo controlled, double blinded pilot superiority phase 2 trial at an outpatient pulmonary clinic in Southern California, USA. Subjects will be receiving Curcumin 1500 mg or matching placebo by mouth twice daily for the study period of 12 weeks. Subjects will be randomized to either a placebo or intervention Curcumin. Subjects will have 6 clinic visits: screening visit, a baseline visit, monthly clinic visits (weeks 4, 8, and 12), at weeks 4, 8, and a follow-up clinic visit or phone-call (week 16). Changes in asthma control test scores, number of days missed from school/work, FEV1 (% predicted), FEV1/FVC ratio, FVC (% predicted), blood eosinophil count, blood total IgE, and FeNO levels will be compared by group over time. DISCUSSION: The therapeutic effects of curcumin have been studied on a limited basis in asthmatics and has shown mixed results thus far. Our study hopes to further establish the benefits of curcumin, however, there are potential issues that may arise from our study design that we will address within this paper. Moreover, the onset of the COVID-19 pandemic has resulted in safety concerns that have delayed initiation of our study. This study will contribute to existing literature on curcumin's role in reducing lung inflammation as it presents in asthmatics as well as patients suffering from COVID-19. TRIAL REGISTRATION: This study protocol has been approved by the Institutional Review Board at Loma Linda University Health, (NCT04353310). IND# 145101 Registered April 20th, 2020. https://clinicaltrials.gov/ct2/show/NCT04353310 .


Subject(s)
Asthma , COVID-19 , Curcumin , Eosinophils , Immunoglobulin E/blood , Administration, Oral , Adult , Ambulatory Care/methods , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Antioxidants/administration & dosage , Antioxidants/adverse effects , Asthma/blood , Asthma/diagnosis , Asthma/drug therapy , Asthma/physiopathology , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19/physiopathology , Clinical Trials, Phase II as Topic , Curcumin/administration & dosage , Curcumin/adverse effects , Double-Blind Method , Drug Monitoring/methods , Female , Humans , Leukocyte Count/methods , Male , Randomized Controlled Trials as Topic , SARS-CoV-2/isolation & purification , Severity of Illness Index
11.
Front Immunol ; 12: 690653, 2021.
Article in English | MEDLINE | ID: covidwho-1359187

ABSTRACT

Although vaccine resources are being distributed worldwide, insufficient vaccine production remains a major obstacle to herd immunity. In such an environment, the cases of re-positive occurred frequently, and there is a big controversy regarding the cause of re-positive episodes and the infectivity of re-positive cases. In this case-control study, we tracked 39 patients diagnosed with COVID-19 from the Jiaodong Peninsula area of China, of which 7 patients tested re-positive. We compared the sex distribution, age, comorbidities, and clinical laboratory results between normal patients and re-positive patients, and analysed the correlation between the significantly different indicators and the re-positive. Re-positive patients displayed a lower level of serum creatinine (63.38 ± 4.94 U/L vs. 86.82 ± 16.98 U/L; P =0.014) and lower albumin (34.70 ± 5.46 g/L vs. 41.24 ± 5.44 g/L, P =0.039) at the time of initial diagnosis. In addition, two positive phases and the middle negative phase in re-positive patients with significantly different eosinophil counts (0.005 ± 0.005 × 109/L; 0.103 ± 0.033 × 109/L; 0.007 ± 0.115 × 109/L; Normal range: 0.02-0.52 × 109/L). The level of eosinophils in peripheral blood can be used as a marker to predict re-positive in patients who once had COVID-19.


Subject(s)
COVID-19/pathology , Creatinine/blood , Eosinophils/cytology , Reinfection/blood , Serum Albumin/analysis , Biomarkers/blood , Case-Control Studies , China , Eosinophils/immunology , Female , Humans , Leukocyte Count , Male , Middle Aged , Reinfection/immunology , Reinfection/virology , SARS-CoV-2/immunology , Severity of Illness Index
12.
Int J Mol Sci ; 22(15)2021 Jul 27.
Article in English | MEDLINE | ID: covidwho-1346498

ABSTRACT

Eosinophils are granulocytes primarily associated with TH2 responses to parasites or immune hyper-reactive states, such as asthma, allergies, or eosinophilic esophagitis. However, it does not make sense from an evolutionary standpoint to maintain a cell type that is only specific for parasitic infections and that otherwise is somehow harmful to the host. In recent years, there has been a shift in the perception of these cells. Eosinophils have recently been recognized as regulators of immune homeostasis and suppressors of over-reactive pro-inflammatory responses by secreting specific molecules that dampen the immune response. Their role during parasitic infections has been well investigated, and their versatility during immune responses to helminths includes antigen presentation as well as modulation of T cell responses. Although it is known that eosinophils can present antigens during viral infections, there are still many mechanistic aspects of the involvement of eosinophils during viral infections that remain to be elucidated. However, are eosinophils able to respond to bacterial infections? Recent literature indicates that Helicobacter pylori triggers TH2 responses mediated by eosinophils; this promotes anti-inflammatory responses that might be involved in the long-term persistent infection caused by this pathogen. Apparently and on the contrary, in the respiratory tract, eosinophils promote TH17 pro-inflammatory responses during Bordetella bronchiseptica infection, and they are, in fact, critical for early clearance of bacteria from the respiratory tract. However, eosinophils are also intertwined with microbiota, and up to now, it is not clear if microbiota regulates eosinophils or vice versa, or how this connection influences immune responses. In this review, we highlight the current knowledge of eosinophils as regulators of pro and anti-inflammatory responses in the context of both infection and naïve conditions. We propose questions and future directions that might open novel research avenues in the future.


Subject(s)
Bordetella Infections/immunology , Bordetella bronchiseptica/immunology , Eosinophils/immunology , Helicobacter Infections/immunology , Helicobacter pylori/immunology , Microbiota/immunology , Animals , Humans , Th17 Cells/immunology , Th2 Cells/immunology
13.
Cells ; 10(8)2021 07 26.
Article in English | MEDLINE | ID: covidwho-1335011

ABSTRACT

The first formal description of the microbicidal activity of extracellular traps (ETs) containing DNA occurred in neutrophils in 2004. Since then, ETs have been identified in different populations of cells involved in both innate and adaptive immune responses. Much of the knowledge has been obtained from in vitro or ex vivo studies; however, in vivo evaluations in experimental models and human biological materials have corroborated some of the results obtained. Two types of ETs have been described-suicidal and vital ETs, with or without the death of the producer cell. The studies showed that the same cell type may have more than one ETs formation mechanism and that different cells may have similar ETs formation mechanisms. ETs can act by controlling or promoting the mechanisms involved in the development and evolution of various infectious and non-infectious diseases, such as autoimmune, cardiovascular, thrombotic, and neoplastic diseases, among others. This review discusses the presence of ETs in neutrophils, macrophages, mast cells, eosinophils, basophils, plasmacytoid dendritic cells, and recent evidence of the presence of ETs in B lymphocytes, CD4+ T lymphocytes, and CD8+ T lymphocytes. Moreover, due to recently collected information, the effect of ETs on COVID-19 is also discussed.


Subject(s)
Extracellular Traps/immunology , Animals , Basophils/immunology , COVID-19 , Eosinophils/immunology , Humans , Lymphocytes/immunology , Macrophages/immunology , Mast Cells/immunology , Neutrophils/immunology
14.
J Cutan Pathol ; 49(1): 34-41, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1320386

ABSTRACT

BACKGROUND: As more people become vaccinated against the SARS-CoV-2 virus, reports of delayed cutaneous hypersensitivity reactions are beginning to emerge. METHODS: In this IRB-approved retrospective case series, biopsy specimens of potential cutaneous adverse reactions from the Pfizer-BioNTech or Moderna mRNA vaccine were identified and reviewed. Clinical information was obtained through the requisition form, referring clinician, or medical chart review. RESULTS: Twelve cases were included. Histopathological features from two injection-site reactions showed a mixed-cell infiltrate with eosinophils and a spongiotic dermatitis with eosinophils. Three biopsy specimens came from generalized eruptions that showed interface changes consistent with an exanthematous drug reaction. Three biopsy specimens revealed a predominantly spongiotic pattern, consistent with eczematous dermatitis. Small-vessel vascular injury was seen in two specimens, which were diagnosed as urticarial vasculitis and leukocytoclastic vasculitis, respectively. There were two cases of new-onset bullous pemphigoid supported by histopathological examination and direct immunofluorescence studies. Eosinophils were seen in 10 cases. CONCLUSIONS: Dermatopathologists should be aware of potential cutaneous adverse reactions to mRNA-based COVID-19 vaccines. Histopathological patterns include mixed-cell infiltrates, epidermal spongiosis, and interface changes. Eosinophils are a common finding but are not always present. Direct immunofluorescence studies may be helpful for immune-mediated cutaneous presentations such as vasculitis or bullous pemphigoid.


Subject(s)
COVID-19 Vaccines/adverse effects , COVID-19/prevention & control , Drug-Related Side Effects and Adverse Reactions/pathology , Hypersensitivity, Delayed/pathology , /adverse effects , Adult , Aged , Aged, 80 and over , Biopsy/methods , COVID-19/diagnosis , COVID-19/immunology , COVID-19/virology , Dermatitis/etiology , Dermatitis/pathology , Drug-Related Side Effects and Adverse Reactions/etiology , Eosinophils/pathology , Female , Fluorescent Antibody Technique, Direct/methods , Humans , Hypersensitivity, Delayed/etiology , Male , Middle Aged , Pemphigoid, Bullous/diagnosis , Pemphigoid, Bullous/pathology , Retrospective Studies , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Skin/pathology , Vasculitis/chemically induced , Vasculitis/pathology
15.
Int J Mol Sci ; 22(13)2021 Jun 30.
Article in English | MEDLINE | ID: covidwho-1288907

ABSTRACT

Eosinophils are complex granulocytes with the capacity to react upon diverse stimuli due to their numerous and variable surface receptors, which allows them to respond in very different manners. Traditionally believed to be only part of parasitic and allergic/asthmatic immune responses, as scientific studies arise, the paradigm about these cells is continuously changing, adding layers of complexity to their roles in homeostasis and disease. Developing principally in the bone marrow by the action of IL-5 and granulocyte macrophage colony-stimulating factor GM-CSF, eosinophils migrate from the blood to very different organs, performing multiple functions in tissue homeostasis as in the gastrointestinal tract, thymus, uterus, mammary glands, liver, and skeletal muscle. In organs such as the lungs and gastrointestinal tract, eosinophils are able to act as immune regulatory cells and also to perform direct actions against parasites, and bacteria, where novel mechanisms of immune defense as extracellular DNA traps are key factors. Besides, eosinophils, are of importance in an effective response against viral pathogens by their nuclease enzymatic activity and have been lately described as involved in severe acute respiratory syndrome coronavirus SARS-CoV-2 immunity. The pleiotropic role of eosinophils is sustained because eosinophils can be also detrimental to human physiology, for example, in diseases like allergies, asthma, and eosinophilic esophagitis, where exosomes can be significant pathophysiologic units. These eosinophilic pathologies, require specific treatments by eosinophils control, such as new monoclonal antibodies like mepolizumab, reslizumab, and benralizumab. In this review, we describe the roles of eosinophils as effectors and regulatory cells and their involvement in pathological disorders and treatment.


Subject(s)
Eosinophils/physiology , Antibodies, Monoclonal/therapeutic use , Asthma/drug therapy , Asthma/immunology , Asthma/pathology , COVID-19/immunology , COVID-19/pathology , COVID-19/virology , Eosinophilic Esophagitis/drug therapy , Eosinophilic Esophagitis/immunology , Eosinophilic Esophagitis/pathology , Eosinophils/cytology , Eosinophils/immunology , Exosomes/metabolism , Extracellular Traps/metabolism , Humans , Plasma Cells/cytology , Plasma Cells/metabolism , SARS-CoV-2/isolation & purification
16.
PLoS One ; 16(6): e0252599, 2021.
Article in English | MEDLINE | ID: covidwho-1285199

ABSTRACT

Inflammation has an important role in the progression of various viral pneumonia, including COVID-19. Circulating biomarkers that can evaluate inflammation and immune status are potentially useful in diagnosing and prognosis of COVID-19 patients. Even more so when they are a part of the routine evaluation, chest CT could have even higher diagnostic accuracy than RT-PCT alone in a suggestive clinical context. This study aims to evaluate the correlation between inflammatory markers such as neutrophil-to-lymphocyte ratio (NLR), platelets-to-lymphocytes ratio (PLR), and eosinophils with the severity of CT lesions in patients with COVID-19. The second objective was to seek a statically significant cut-off value for NLR and PLR that could suggest COVID-19. Correlation of both NLR and PLR with already established inflammatory markers such as CRP, ESR, and those specific for COVID-19 (ferritin, D-dimers, and eosinophils) were also evaluated. One hundred forty-nine patients with confirmed COVID-19 disease and 149 age-matched control were evaluated through blood tests, and COVID-19 patients had thorax CT performed. Both NLR and PLR correlated positive chest CT scan severity. Both NLR and PLR correlated positive chest CT scan severity. When NLR value is below 5.04, CT score is lower than 3 with a probability of 94%, while when NLR is higher than 5.04, the probability of severe CT changes is only 50%. For eosinophils, a value of 0.35% corresponds to chest CT severity of 2 (Se = 0.88, Sp = 0.43, AUC = 0.661, 95% CI (0.544; 0.779), p = 0.021. NLR and PLR had significantly higher values in COVID-19 patients. In our study a NLR = 2.90 and PLR = 186 have a good specificity (0.89, p = 0.001, respectively 0.92, p<0.001). Higher levels in NLR, PLR should prompt the clinician to prescribe a thorax CT as it could reveal important lesions that could influence the patient's future management.


Subject(s)
Blood Platelets/cytology , COVID-19/diagnostic imaging , COVID-19/immunology , Eosinophils/cytology , Neutrophils/cytology , Signal-To-Noise Ratio , Tomography, X-Ray Computed , Adult , COVID-19/pathology , Female , Humans , Lymphocyte Count , Male , Middle Aged
17.
Front Immunol ; 12: 668074, 2021.
Article in English | MEDLINE | ID: covidwho-1278394

ABSTRACT

Background: Studies on the role of eosinophils in coronavirus disease 2019 (COVID-19) are scarce, though available findings suggest a possible association with disease severity. Our study analyzes the relationship between eosinophils and COVID-19, with a focus on disease severity and patients with underlying chronic respiratory diseases. Methods: We performed a retrospective analysis of 3018 subjects attended at two public hospitals in Madrid (Spain) with PCR-confirmed SARS-CoV-2 infection from January 31 to April 17, 2020. Patients with eosinophil counts less than 0.02×109/L were considered to have eosinopenia. Individuals with chronic respiratory diseases (n=384) were classified according to their particular underlying condition, i.e., asthma, chronic pulmonary obstructive disease, or obstructive sleep apnea. Results: Of the 3018 patients enrolled, 479 were excluded because of lack of information at the time of admission. Of 2539 subjects assessed, 1396 patients presented an eosinophil count performed on admission, revealing eosinopenia in 376 cases (26.93%). Eosinopenia on admission was associated with a higher risk of intensive care unit (ICU) or respiratory intensive care unit (RICU) admission (OR:2.21; 95%CI:1.42-3.45; p<0.001) but no increased risk of mortality (p>0.05). Conclusions: Eosinopenia on admission conferred a higher risk of severe disease (requiring ICU/RICU care), but was not associated with increased mortality. In patients with chronic respiratory diseases who develop COVID-19, age seems to be the main risk factor for progression to severe disease or death.


Subject(s)
COVID-19/blood , Eosinophils , Lung Diseases/epidemiology , Adult , Aged , Aged, 80 and over , COVID-19/immunology , Chronic Disease , Eosinophils/immunology , Female , Hospitalization , Humans , Leukocyte Count , Male , Middle Aged , Prevalence , Retrospective Studies , Risk Factors , SARS-CoV-2 , Spain
19.
J Microbiol Immunol Infect ; 54(1): 61-68, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-1272575

ABSTRACT

OBJECTIVES: To analyse the diagnostic performance of eosinopenia, alone or combined with polymorphonuclear neutrophils (PMN) and/or lymphocytes, as a marker of active COVID-19 in patients hospitalized for suspicion of SARS-CoV-2 infection. METHODS: A prospective observational study including patients hospitalized for suspicion of COVID-19 in a COVID unit was performed from 20th March to 5th April 2020, in Perpignan, France. Patients for which there was a doubt upon diagnosis, who were recently under oral corticosteroids, had myeloid malignancy or human immunodeficient virus infection were excluded. SARS-CoV-2 detection was performed using an RT-PCR assay, from nasopharyngeal swab specimens. Complete blood count were performed for all patients. RESULTS: One-hundred and twenty-one patient were included: 57 patients were diagnosed with COVID-19, 64 patients were not. Eosinophil count was lower in the COVID-19 group (median: 0/µL versus 70/µL, p < 0.0001). To diagnose COVID-19, eosinopenia had a sensitivity of 89.5% and a specificity of 78.1% while lymphopenia's were 73.7% and 62.5% respectively. Using area under curve (AUC) of receiving operating characteristics (ROC) curves, eosinophil's optimal cut-off level was 10/µL, sensitivity and specificity were 86%, and 79.7% respectively. Regarding the eosinophil/PMN ratio, the optimal cut-off level was 3.344, sensitivity and specificity were 87.7% and 73.4% respectively. The AUC of lymphocyte/PMN ratio was significantly lower than eosinophil/PMN ratio's (0.621 versus 0.846, p = 0.0003). CONCLUSION: Eosinopenia - <10/µL - and eosinophil/PMN ratio are useful, low-cost, reproducible tools to help diagnose COVID-19, during an epidemic period, in a population of hospitalized patients admitted for suspicion of COVID-19.


Subject(s)
COVID-19/blood , COVID-19/diagnosis , Eosinophils/pathology , Aged , Aged, 80 and over , Biomarkers/blood , Blood Cell Count , COVID-19 Testing/methods , Female , Humans , Leukocyte Count , Leukocytes/pathology , Male , Middle Aged , Prospective Studies , ROC Curve , SARS-CoV-2 , Sensitivity and Specificity
20.
Medicine (Baltimore) ; 100(23): e26047, 2021 Jun 11.
Article in English | MEDLINE | ID: covidwho-1266220

ABSTRACT

BACKGROUND: The conclusions about the relationship between eosinophil counts and the severity of coronavirus disease 2019 (COVID-19) were controversial, so we updated the evidences and reassessed it. METHODS: We searched the PubMed, Cochrane library, Excerpta Medica Database, and Web of Science to compare the eosinophil counts about non-severe disease group (mild pneumonia, moderate pneumonia, non-critical disease and recovery group) and severe disease group (severe pneumonia, critical pneumonia, critical disease and death group) in COVID-19. RESULTS: A total of 1228 patients from 10 studies were included. Compared with non-severe group, severe group had strikingly lower average eosinophil counts (SMD 0.65, 95% confidence intervals [CI] 0.29-1.01; P < .001). The result of subgroup analysis of different countries showed SMD 0.66, 95% CI 0.26-1.06; P < .001. Another subgroup analysis between mild-moderate pneumonia versus severe-critical pneumonia showed SMD 0.69, 95% CI 0.25-1.13; P < .001, and no significant risk of publication bias (Begg test 0.063 and Egger test 0.057) in this subgroup. The heterogeneity was substantial, but the sensitivity analyses showed no significant change when individual study was excluded, which suggested the crediblity and stablity of our results. CONCLUSIONS: The eosinophil counts had important value as an indicator of severity in patients with COVID-19. PROSPERO REGISTRATION NUMBER: CRD42020205497.


Subject(s)
COVID-19/blood , Eosinophils , Humans , Leukocyte Count , Severity of Illness Index
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