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1.
Front Endocrinol (Lausanne) ; 12: 774346, 2021.
Article in English | MEDLINE | ID: covidwho-1662575

ABSTRACT

Background: Both lymphopenia and thyroid dysfunction are commonly observed among COVID-19 patients. Whether thyroid function independently correlates with lymphocyte counts (LYM) remains to be elucidated. Methods: We included consecutive adults without known thyroid disorder admitted to Queen Mary Hospital for COVID-19 from July 2020 to April 2021 who had thyroid-stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3) and LYM measured on admission. Results: A total of 541 patients were included. Median LYM was 1.22 x 109/L, with 36.0% of the cohort lymphopenic. 83 patients (15.4%) had abnormal thyroid function tests (TFTs), mostly non-thyroidal illness syndrome (NTIS). Patients with lymphopenia had lower TSH, fT4 and fT3 levels than those without. Multivariable stepwise linear regression analysis revealed that both TSH (standardized beta 0.160, p<0.001) and fT3 (standardized beta 0.094, p=0.023), but not fT4, remained independently correlated with LYM, in addition to age, SARS-CoV-2 viral load, C-reactive protein levels, coagulation profile, sodium levels and more severe clinical presentations. Among the 40 patients who had reassessment of TFTs and LYM after discharge, at a median of 9 days from admission, there were significant increases in TSH (p=0.031), fT3 (p<0.001) and LYM (p<0.001). Furthermore, patients who had both lymphopenia and NTIS were more likely to deteriorate compared to those who only had either one alone, and those without lymphopenia or NTIS (p for trend <0.001). Conclusion: TSH and fT3 levels showed independent positive correlations with LYM among COVID-19 patients, supporting the interaction between the hypothalamic-pituitary-thyroid axis and immune system in COVID-19.


Subject(s)
COVID-19/complications , Lymphocytes/pathology , Lymphopenia/epidemiology , SARS-CoV-2/isolation & purification , Thyroid Diseases/epidemiology , Thyrotropin/blood , Triiodothyronine/blood , Adult , Aged , COVID-19/virology , China/epidemiology , Female , Hospitalization , Humans , Lymphocyte Count , Lymphopenia/blood , Lymphopenia/immunology , Lymphopenia/virology , Male , Middle Aged , Thyroid Diseases/blood , Thyroid Diseases/immunology , Thyroid Diseases/virology , Thyroid Function Tests , Thyroid Hormones/blood
2.
J Clin Lab Anal ; 36(1): e24064, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1525450

ABSTRACT

BACKGROUND: The unresolved COVID-19 pandemic considerably impacts the health services in Iraq and worldwide. Consecutive waves of mutated virus increased virus spread and further constrained health systems. Although molecular identification of the virus by polymerase chain reaction is the only recommended method in diagnosing COVID-19 infection, radiological, biochemical, and hematological studies are substantially important in risk stratification, patient follow-up, and outcome prediction. AIM: This narrative review summarized the hematological changes including the blood indices, coagulative indicators, and other associated biochemical laboratory markers in different stages of COVID-19 infection, highlighting the diagnostic and prognostic significance. METHODS: Literature search was conducted for multiple combinations of different hematological tests and manifestations with novel COVID-19 using the following key words: "hematological," "complete blood count," "lymphopenia," "blood indices," "markers" "platelet" OR "thrombocytopenia" AND "COVID-19," "coronavirus2019," "2019-nCoV," OR "SARS-CoV-2." Articles written in the English language and conducted on human samples between December 2019 and January 2021 were included. RESULTS: Hematological changes are not reported in asymptomatic or presymptomatic COVID-19 patients. In nonsevere cases, hematological changes are subtle, included mainly lymphocytopenia (80.4%). In severe, critically ill patients and those with cytokine storm, neutrophilia, lymphocytopenia, elevated D-dimer, prolonged PT, and reduced fibrinogen are predictors of disease progression and adverse outcome. CONCLUSION: Monitoring hematological changes in patients with COVID-19 can predict patients needing additional care and stratify the risk for severe course of the disease. More studies are required in Iraq to reflect the hematological changes in COVID-19 as compared to global data.


Subject(s)
COVID-19/blood , COVID-19/etiology , Cytokine Release Syndrome/blood , Pregnancy Complications, Infectious/blood , Biomarkers/blood , Blood Coagulation , Cytokine Release Syndrome/virology , Female , Hematologic Tests , Humans , Leukocyte Count , Lymphopenia/blood , Lymphopenia/virology , Pregnancy , Pregnancy Complications, Infectious/virology , Severity of Illness Index
3.
J Infect Dis ; 224(8): 1333-1344, 2021 10 28.
Article in English | MEDLINE | ID: covidwho-1493827

ABSTRACT

BACKGROUND: Lymphopenia is a key feature for adult patients with coronavirus disease 2019 (COVID-19), although it is rarely observed in children. The underlying mechanism remains unclear. METHODS: Immunohistochemical and flow cytometric analyses were used to compare the apoptotic rate of T cells from COVID-19 adults and children and apoptotic responses of adult and child T cells to COVID-19 pooled plasma. Biological properties of caspases and reactive oxygen species were assessed in T cells treated by COVID-19 pooled plasma. RESULTS: Mitochondria apoptosis of peripheral T cells were identified in COVID-19 adult patient samples but not in the children. Furthermore, increased tumor necrosis factor-α and interleukin-6 in COVID-19 plasma induced mitochondria apoptosis and caused deoxyribonucleic acid damage by elevating reactive oxygen species levels of the adult T cells. However, the child T cells showed tolerance to mitochondrial apoptosis due to mitochondria autophagy. Activation of autophagy could decrease apoptotic sensitivity of the adult T cells to plasma from COVID-19 patients. CONCLUSIONS: Our results indicated that the mitochondrial apoptosis pathway was activated in T cells of COVID-19 adult patients specifically, which may shed light on the pathophysiological difference between adults and children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 ).


Subject(s)
COVID-19/complications , Lymphopenia/blood , SARS-CoV-2/immunology , T-Lymphocytes/pathology , Adolescent , Adult , Age Factors , Aged , Apoptosis/immunology , Autophagy , COVID-19/blood , COVID-19/immunology , COVID-19/virology , Child , Child, Preschool , Humans , Infant , Lymphopenia/immunology , Lymphopenia/pathology , Lymphopenia/virology , Male , Middle Aged , Mitochondria/immunology , Mitochondria/pathology , Reactive Oxygen Species/metabolism , T-Lymphocytes/cytology , T-Lymphocytes/immunology
4.
J Immunol Res ; 2021: 9822706, 2021.
Article in English | MEDLINE | ID: covidwho-1476890

ABSTRACT

BACKGROUND: Neutralizing antibody (nAb) response is generated following infection or immunization and plays an important role in the protection against a broad of viral infections. The role of nAb during clinical progression of coronavirus disease 2019 (COVID-19) remains little known. METHODS: 123 COVID-19 patients during hospitalization in Tongji Hospital were involved in this retrospective study. The patients were grouped based on the severity and outcome. The nAb responses of 194 serum samples were collected from these patients within an investigation period of 60 days after the onset of symptoms and detected by a pseudotyped virus neutralization assay. The detail data about onset time, disease severity and laboratory biomarkers, treatment, and clinical outcome of these participants were obtained from electronic medical records. The relationship of longitudinal nAb changes with each clinical data was further assessed. RESULTS: The nAb response in COVID-19 patients evidently experienced three consecutive stages, namely, rising, stationary, and declining periods. Patients with different severity and outcome showed differential dynamics of the nAb response over the course of disease. During the stationary phase (from 20 to 40 days after symptoms onset), all patients evolved nAb responses. In particular, high levels of nAb were elicited in severe and critical patients and older patients (≥60 years old). More importantly, critical but deceased COVID-19 patients showed high levels of several proinflammation cytokines, such as IL-2R, IL-8, and IL-6, and anti-inflammatory cytokine IL-10 in vivo, which resulted in lymphopenia, multiple organ failure, and the rapidly decreased nAb response. CONCLUSION: Our results indicate that nAb plays a crucial role in preventing the progression and deterioration of COVID-19, which has important implications for improving clinical management and developing effective interventions.


Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19/immunology , SARS-CoV-2/immunology , Adult , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Biomarkers/blood , COVID-19/pathology , Cytokines/blood , Female , Humans , Lymphopenia/blood , Lymphopenia/immunology , Male , Middle Aged , Neutralization Tests , Retrospective Studies , Severity of Illness Index
5.
J Immunol Res ; 2021: 8669098, 2021.
Article in English | MEDLINE | ID: covidwho-1476888

ABSTRACT

OBJECTIVE: This study explored the consistency and differences in the immune cells and cytokines between patients with COVID-19 or cancer. We further analyzed the correlations between the acute inflammation and cancer-related immune disorder. METHODS: This retrospective study involved 167 COVID-19 patients and 218 cancer patients. COVID-19 and cancer were each further divided into two subgroups. Quantitative and qualitative variables were measured by one-way ANOVA and chi-square test, respectively. Herein, we carried out a correlation analysis between immune cells and cytokines and used receiver operating characteristic (ROC) curves to discover the optimal diagnostic index. RESULTS: COVID-19 and cancers were associated with lymphopenia and high levels of monocytes, neutrophils, IL-6, and IL-10. IL-2 was the optimal indicator to differentiate the two diseases. Compared with respiratory cancer patients, COVID-19 patients had lower levels of IL-2 and higher levels of CD3+CD4+ T cells and CD19+ B cells. In the subgroup analysis, IL-6 was the optimal differential diagnostic parameter that had the ability to identify if COVID-19 patients would be severely affected, and severe COVID-19 patients had lower levels of lymphocyte subsets (CD3+ T cells, CD3+CD4+ T cells, CD3+CD8+T cells, and CD19+ B cells) and CD16+CD56+ NK cells and higher level of neutrophils. There were significant differences in the levels of CD3+CD4+ T cells and CD19+ B cells between T1-2 and T3-4 stages as well as IL-2 and CD19+ B cells between N0-1 and N2-3 stages while no significant differences between the metastatic and nonmetastatic cancer patients. Additionally, there were higher correlations between IL-2 and IL-4, TNF-α and IL-2, TNF-α and IL-4, TNF-α and IFN-γ, and CD16+CD56+NK cells and various subsets of T cells in COVID-19 patients. There was a higher correlation between CD3+CD4+ T cells and CD19+ B cells in cancer patients. CONCLUSION: Inflammation associated with COVID-19 or cancer had effects on patients' outcomes. Accompanied by changes in immune cells and cytokines, there were consistencies, differences, and satisfactory correlations between patients with COVID-19 and those with cancers.


Subject(s)
COVID-19/immunology , Cytokines/blood , Lymphopenia/blood , Monocytes/immunology , Neoplasms/immunology , Neutrophils/immunology , Adolescent , Adult , Aged , Aged, 80 and over , B-Lymphocytes/immunology , CD4 Lymphocyte Count , CD4-Positive T-Lymphocytes/immunology , COVID-19/diagnosis , COVID-19/pathology , Female , Humans , Inflammation/blood , Inflammation/pathology , Killer Cells, Natural/immunology , Lymphocyte Subsets/immunology , Male , Middle Aged , Neoplasms/diagnosis , Neoplasms/pathology , Retrospective Studies , SARS-CoV-2/immunology , Young Adult
6.
Int J Lab Hematol ; 43(6): 1309-1318, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1409690

ABSTRACT

INTRODUCTION: Developing prognostic markers can be useful for clinical decision-making. Peripheral blood (PB) examination is simple and basic that can be performed in any facility. We aimed to investigate whether PB examination can predict prognosis in coronavirus disease (COVID-19). METHODS: Complete blood count (CBC) and PB cell morphology were examined in 38 healthy controls (HCs) and 40 patients with COVID-19. Patients with COVID-19, including 26 mild and 14 severe cases, were hospitalized in Juntendo University Hospital (Tokyo, Japan) between April 1 and August 6, 2020. PB examinations were performed using Sysmex XN-3000 automated hematology analyzer and Sysmex DI-60 employing the convolutional neural network-based automatic image-recognition system. RESULTS: Compared with mild cases, severe cases showed a significantly higher incidence of anemia, lymphopenia, and leukocytosis (P < .001). Granular lymphocyte counts were normal or higher in mild cases and persistently decreased in fatal cases. Temporary increase in granular lymphocytes was associated with survival of patients with severe infection. Red cell distribution width was significantly higher in severe cases than in mild cases (P < .001). Neutrophil dysplasia was consistently observed in COVID-19 cases, but not in HCs. Levels of giant neutrophils and toxic granulation/Döhle bodies were increased in severe cases. CONCLUSION: Basic PB examination can be useful to predict the prognosis of COVID-19, by detecting SARS-CoV-2 infection-induced multi-lineage changes in blood cell counts and morphological anomalies. These changes were dynamically correlated with disease severity and may be associated with disruption of hematopoiesis and the immunological system due to bone marrow stress in severe infection.


Subject(s)
Blood Cell Count , COVID-19/blood , Leukocytosis/etiology , Lymphocytes/ultrastructure , Lymphopenia/etiology , Neutrophils/ultrastructure , SARS-CoV-2 , Aged , Anemia/blood , Anemia/etiology , Blood Cell Count/instrumentation , Blood Cell Count/methods , COVID-19/mortality , Cell Shape , Cytoplasmic Granules/ultrastructure , Erythrocyte Indices , Female , Humans , Image Processing, Computer-Assisted , Leukocytosis/blood , Lymphocyte Count , Lymphopenia/blood , Male , Middle Aged , Neural Networks, Computer , Prognosis , Severity of Illness Index
7.
PLoS Pathog ; 17(9): e1009850, 2021 09.
Article in English | MEDLINE | ID: covidwho-1394562

ABSTRACT

The Coronavirus Disease 2019 (COVID-19) is caused by the betacoronavirus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus that can mediate asymptomatic or fatal infections characterized by pneumonia, acute respiratory distress syndrome (ARDS), and multi-organ failure. Several studies have highlighted the importance of B and T lymphocytes, given that neutralizing antibodies and T cell responses are required for an effective immunity. In addition, other reports have described myeloid cells such as macrophages and monocytes play a major role in the immunity against SARS-CoV-2 as well as dysregulated pro-inflammatory signature that characterizes severe COVID-19. During COVID-19, neutrophils have been defined as a heterogeneous group of cells, functionally linked to severe inflammation and thrombosis triggered by degranulation and NETosis, but also to suppressive phenotypes. The physiological role of suppressive neutrophils during COVID-19 and their implications in severe disease have been poorly studied and is not well understood. Here, we discuss the current evidence regarding the role of neutrophils with suppressive properties such as granulocytic myeloid-derived suppressor cells (G-MDSCs) and their possible role in suppressing CD4+ and CD8+ T lymphocytes expansion and giving rise to lymphopenia in severe COVID-19 infection.


Subject(s)
COVID-19/immunology , Lymphopenia/complications , Neutrophils/immunology , SARS-CoV-2/physiology , Animals , COVID-19/blood , COVID-19/complications , Humans , Lymphopenia/blood , Lymphopenia/immunology , Neutrophils/virology , SARS-CoV-2/immunology , Severity of Illness Index
8.
J Infect Dis ; 224(8): 1333-1344, 2021 10 28.
Article in English | MEDLINE | ID: covidwho-1349787

ABSTRACT

BACKGROUND: Lymphopenia is a key feature for adult patients with coronavirus disease 2019 (COVID-19), although it is rarely observed in children. The underlying mechanism remains unclear. METHODS: Immunohistochemical and flow cytometric analyses were used to compare the apoptotic rate of T cells from COVID-19 adults and children and apoptotic responses of adult and child T cells to COVID-19 pooled plasma. Biological properties of caspases and reactive oxygen species were assessed in T cells treated by COVID-19 pooled plasma. RESULTS: Mitochondria apoptosis of peripheral T cells were identified in COVID-19 adult patient samples but not in the children. Furthermore, increased tumor necrosis factor-α and interleukin-6 in COVID-19 plasma induced mitochondria apoptosis and caused deoxyribonucleic acid damage by elevating reactive oxygen species levels of the adult T cells. However, the child T cells showed tolerance to mitochondrial apoptosis due to mitochondria autophagy. Activation of autophagy could decrease apoptotic sensitivity of the adult T cells to plasma from COVID-19 patients. CONCLUSIONS: Our results indicated that the mitochondrial apoptosis pathway was activated in T cells of COVID-19 adult patients specifically, which may shed light on the pathophysiological difference between adults and children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 ).


Subject(s)
COVID-19/complications , Lymphopenia/blood , SARS-CoV-2/immunology , T-Lymphocytes/pathology , Adolescent , Adult , Age Factors , Aged , Apoptosis/immunology , Autophagy , COVID-19/blood , COVID-19/immunology , COVID-19/virology , Child , Child, Preschool , Humans , Infant , Lymphopenia/immunology , Lymphopenia/pathology , Lymphopenia/virology , Male , Middle Aged , Mitochondria/immunology , Mitochondria/pathology , Reactive Oxygen Species/metabolism , T-Lymphocytes/cytology , T-Lymphocytes/immunology
9.
Mol Immunol ; 138: 121-127, 2021 10.
Article in English | MEDLINE | ID: covidwho-1347762

ABSTRACT

AIMS: Coronavirus disease 2019 (COVID-19) is a novel viral infection threatening worldwide health as currently there exists no effective treatment strategy and vaccination programs are not publicly available yet. T lymphocytes play an important role in antiviral defenses. However, T cell frequency and functionality may be affected during the disease. MATERIAL AND METHODS: Total blood samples were collected from patients with mild and severe COVID-19, and the total lymphocyte number, as well as CD4+ and CD8 + T cells were assessed using flowcytometry. Besides, the expression of exhausted T cell markers was evaluated. The levels of proinflammatory cytokines were also investigated in the serum of all patients using enzyme-linked immunesorbent assay (ELISA). Finally, the obtained results were analyzed along with laboratory serological reports. RESULTS: COVID-19 patients showed lymphopenia and reduced CD4+ and CD8 + T cells, as well as high percentage of PD-1 expression by T cells, especially in severe cases. Serum secretion of TNF-α, IL-1ß, and IL-2 receptor (IL-2R) were remarkably increased in patients with severe symptoms, as compared with healthy controls. Moreover, high levels of triglyceride (TG) and low density lipoprotein cholesterol (LDL-C), were correlated with the severity of the disease. CONCLUSION: Reduced number and function of T cells were observed in COVID-19 patients, especially in severe patients. Meanwhile, the secretion of proinflammatory cytokines was increased as the disease developed. High level of serum IL-2R was also considered as a sign of lymphopenia. Additionally, hypercholesterolemia and hyperlipidemia could be important prognostic factors in determining the severity of the infection.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , Lymphopenia/immunology , SARS-CoV-2/immunology , Adult , Aged , CD4-Positive T-Lymphocytes/metabolism , CD4-Positive T-Lymphocytes/virology , CD8-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/virology , COVID-19/metabolism , COVID-19/virology , Cholesterol, LDL/blood , Cytokines/blood , Cytokines/immunology , Cytokines/metabolism , Disease Progression , Female , Humans , Lymphocyte Count , Lymphopenia/blood , Lymphopenia/virology , Male , Middle Aged , Prognosis , SARS-CoV-2/physiology , Severity of Illness Index , Triglycerides/blood
10.
J Immunol Res ; 2021: 6657894, 2021.
Article in English | MEDLINE | ID: covidwho-1314178

ABSTRACT

BACKGROUND: The 2019 novel coronavirus SARS-CoV-2 caused large outbreaks of COVID-19 worldwide. COVID-19 resembles community-acquired pneumonia (CAP). Our aim was to identify lymphocyte subpopulations to distinguish between COVID-19 and CAP. METHODS: We compared the peripheral blood lymphocytes and their subsets in 296 patients with COVID-19 and 130 patients with CAP. Parameters for independent prediction of COVID-19 were calculated by logistic regression. RESULTS: The main lymphocyte subpopulations (CD3+CD4+, CD16+CD56+, and CD4+/CD8+ ratio) and cytokines (TNF-α and IFN-γ) of COVID-19 patients were significantly different from that of CAP patients. CD16+CD56+%, CD4+/CD8+ratio, CD19+, and CD3+CD4+ were identified as predictors of COVID-19 diagnosis by logistic regression. In addition, the CD3+CD4+counts, CD3+CD8+ counts, andTNF-α are independent predictors of disease severity in patients. CONCLUSIONS: Lymphopenia is an important part of SARS-CoV-2 infection, and lymphocyte subsets and cytokines may be useful to predict the severity and clinical outcomes of the disease.


Subject(s)
CD4-CD8 Ratio , COVID-19/blood , Interferon-gamma/blood , Lymphocyte Subsets/cytology , Pneumonia/blood , Tumor Necrosis Factor-alpha/blood , Adult , Aged , COVID-19/immunology , COVID-19/pathology , COVID-19 Testing , Community-Acquired Infections/microbiology , Female , Humans , Lymphocyte Subsets/immunology , Lymphopenia/blood , Lymphopenia/pathology , Male , Middle Aged , Pneumonia/immunology , Pneumonia/pathology , Prognosis , SARS-CoV-2/immunology , Severity of Illness Index
11.
Int J Lab Hematol ; 43(6): 1302-1308, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1288297

ABSTRACT

INTRODUCTION: We aimed to identify the associations between the lymphocytes (LYM) absolute count on admission and clinical outcomes in COVID-19 patients. METHODS: In this retrospective study, 224 COVID-19 patients who were admitted to General Hospital of Central Theater Command of the PLA from January 22 to April 4, 2020, were consecutively included. These patients were divided into the lymphopenia group and the nonlymphopenia group according to whether the LYM count on admission was below the normal range. RESULTS: During hospitalization, patients in the lymphopenia group have a much higher all-cause mortality (14.5% vs 0.0%; P < .001) and an evidently longer length of hospital stay (24.0 vs 17.5 days; P < .001) than patients in the nonlymphopenia group. The correlation analysis results indicated that the LYM count was negatively correlated with the values of NEU (R = -.2886, P < .001), PT (R = -.2312, P < .001), FIB (R = -.2954, P < .001), D-D (R = -.3554, P < .001), CRP (R = -.4899, P < .001), IL-6 (R = -.5459, P < .001), AST (R = -.2044, P < .01), Cr (R = -.1350, P < .05), CPK (R = -.2119, P < .01), CK-Mb (R = -.1760, P < .01), and LDH (R = -.4330, P < .001), and was positively correlated with the count of PLT (R = .2679, P < .001). In addition, LYM as a continuous variable was associated with 97% decreased risk of in-hospital mortality in the fully adjusted models (OR = 0.03, 95%CI, 0.00-0.37, P < .001). DISCUSSION: LYM screening on admission is a critical predictor for assessment of disease severity and clinical outcomes in patients with COVID-19, and lymphopenia substantially correlates with poor clinical outcomes.


Subject(s)
COVID-19/blood , Lymphocyte Count , SARS-CoV-2 , Adult , Aged , Biomarkers/blood , Blood Cell Count , Blood Coagulation Tests , Blood Proteins/analysis , COVID-19/mortality , China/epidemiology , Creatinine/blood , Female , Hospital Mortality , Hospitals, General/statistics & numerical data , Humans , Lymphopenia/blood , Lymphopenia/etiology , Male , Mass Screening , Middle Aged , Patient Admission , Prognosis , Retrospective Studies , Severity of Illness Index , Treatment Outcome
12.
J Med Virol ; 93(9): 5474-5480, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1219314

ABSTRACT

In this study, laboratorial parameters of hospitalized novel coronavirus (COVID-19) patients, who were complicated with severe pneumonia, were compared with the findings of cytokine storm developing in macrophage activation syndrome (MAS)/secondary hemophagocytic lymphohistiocytosis (sHLH). Severe pneumonia occurred as a result of cytokine storm in some patients who needed intensive care unit (ICU), and it is aimed to determine the precursive parameters in this situation. Also in this study, the aim is to identify laboratory criteria that predict worsening disease and ICU intensification, as well as the development of cytokine storm. This article comprises a retrospective cohort study of patients admitted to a single institution with COVID-19 pneumonia. This study includes 150 confirmed COVID-19 patients with severe pneumonia. When they were considered as severe pneumonia patients, the clinic and laboratory parameters of this group are compared with H-score criteria. Patients are divided into two subgroups; patients with worsened symptoms who were transferred into tertiary ICU, and patients with stable symptoms followed in the clinic. For the patients with confirmed COVID-19 infection, after they become complicated with severe pneumonia, lymphocytopenia (55.3%), anemia (12.0%), thrombocytopenia (19.3%), hyperferritinemia (72.5%), hyperfibrinogenemia (63.7%) and elevated lactate dehydrogenase (LDH) (90.8%), aspartate aminotransaminase (AST) (31.3%), alanine aminotransaminase (ALT) (20.7%) are detected. There were no significant changes in other parameters. Blood parameters between the pre-ICU period and the ICU period (in which their situation had been worsened and acute respiratory distress syndrome [ARDS] was developed) were also compared. In the latter group lymphocyte levels were found significantly reduced (p = 0.01), and LDH, highly sensitive troponin (hs-troponin), procalcitonin, and triglyceride levels were significantly increased (p < 0.05). In addition, there was no change in hemoglobin, leukocyte, platelet, ferritin, and liver function test levels, including patients who developed ARDS, similar to the cytokine storm developed in MAS/sHLH. COVID-19 pneumonia has similar findings as hyperinflammatory syndromes but does not seem to have typical features as in cytokine storm developed in MAS/sHLH. In the severe patient group who has started to develop ARDS signs, a decrease in lymphocyte level in addition to the elevated LDH, hs-troponin, procalcitonin, and triglyceride levels can be a predictor in progression to ICU admission and could help in the planning of anti-cytokine therapy.


Subject(s)
COVID-19/pathology , Cytokine Release Syndrome/pathology , Lymphohistiocytosis, Hemophagocytic/pathology , Macrophage Activation Syndrome/pathology , SARS-CoV-2/pathogenicity , Aged , Alanine Transaminase/blood , Anemia/blood , Anemia/diagnosis , Anemia/immunology , Anemia/pathology , Aspartate Aminotransferases/blood , Biomarkers/blood , COVID-19/blood , COVID-19/diagnosis , COVID-19/immunology , Cytokine Release Syndrome/blood , Cytokine Release Syndrome/diagnosis , Cytokine Release Syndrome/immunology , Diagnosis, Differential , Disease Progression , Female , Fibrinogen/metabolism , Humans , Hyperferritinemia/blood , Hyperferritinemia/diagnosis , Hyperferritinemia/immunology , Hyperferritinemia/pathology , Intensive Care Units , L-Lactate Dehydrogenase/blood , Lymphohistiocytosis, Hemophagocytic/blood , Lymphohistiocytosis, Hemophagocytic/diagnosis , Lymphohistiocytosis, Hemophagocytic/immunology , Lymphopenia/blood , Lymphopenia/diagnosis , Lymphopenia/immunology , Lymphopenia/pathology , Macrophage Activation Syndrome/blood , Macrophage Activation Syndrome/diagnosis , Macrophage Activation Syndrome/immunology , Male , Middle Aged , Procalcitonin/blood , Retrospective Studies , Thrombocytopenia/blood , Thrombocytopenia/diagnosis , Thrombocytopenia/immunology , Thrombocytopenia/pathology , Triglycerides/blood , Troponin/blood
13.
Turk J Med Sci ; 51(2): 440-447, 2021 04 30.
Article in English | MEDLINE | ID: covidwho-1211943

ABSTRACT

Background/aim: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Turkey on March 10, 2020 and the number of the patients are increasing day by day. Coronavirus disease 2019 (Covid-19) has high mortality rates in intensive care units (ICUs). We aimed to describe the demographic characteristics, comorbidities, treatment protocols, and clinical outcomes among the critically ill patients admitted to the ICU of our hospital. Materials and methods: This cohort study included 103 consecutive patients who had laboratory confirmed Covid-19 and admitted to ICU of Sakarya University Training and Research Hospital between March 19 and April 13, 2020. The final date of the follow-up was April 18. Results: The mean age of the patients was 69.6 ± 14.1 years. Most of the patients had increased CRP (99%), serum ferritin (73.8%), d-dimer (82.5%), and hs-troponin levels (38.8%). 34 patients (33%) had lymphocytopenia, 24 patients (23.3%) had thrombocytopenia. 63 patients (61.2%) developed acute respiratory distress syndrome (ARDS), 31 patients (30.1%) had acute kidney injury, and 52 patients (50.5%) had multiple organ dysfunction syndrome (MODS) during follow-up. Sixty-two patients (60.2%) received mechanical ventilation. As of April 18, of the 103 patients, 52 (50.5%) had died, 30 (29.1%) had been discharged from the ICU, 21 (20.4%) were still in the ICU. Conclusions: Covid-19 has high mortality rates in ICU. Patients with elevated procalcitonin, hs-troponin, d-dimer, and CRP levels and lower platelet count at admission have higher mortality.


Subject(s)
Acute Kidney Injury/physiopathology , COVID-19/physiopathology , Multiple Organ Failure/physiopathology , Respiratory Distress Syndrome/physiopathology , Respiratory Insufficiency/physiopathology , Age Factors , Aged , Aged, 80 and over , Antiviral Agents/therapeutic use , C-Reactive Protein/metabolism , COVID-19/metabolism , COVID-19/mortality , COVID-19/therapy , Cohort Studies , Continuous Renal Replacement Therapy , Critical Illness , Female , Ferritins/metabolism , Fibrin Fibrinogen Degradation Products/metabolism , Glucocorticoids/therapeutic use , Hospital Mortality , Humans , Intensive Care Units , Length of Stay , Lymphopenia/blood , Male , Middle Aged , Oxygen Inhalation Therapy , Platelet Count , Procalcitonin/metabolism , Prognosis , Respiration, Artificial , Respiratory Insufficiency/therapy , SARS-CoV-2 , Severity of Illness Index , Thrombocytopenia/blood , Troponin/metabolism , Turkey
14.
Front Endocrinol (Lausanne) ; 12: 640529, 2021.
Article in English | MEDLINE | ID: covidwho-1190303

ABSTRACT

This retrospective study examined changes in fasting blood glucose (FBG) levels during hospitalization and their effect on risk of death for Coronavirus disease 2019 (COVID-19) patients without previously diagnosed diabetes. A model with low- and high-stable pattern trajectories was established based on a longitudinal change in FBG levels. We analyzed FBG trajectory-associated clinical features and risk factors for death due to COVID-19. Of the 230 enrolled patients, 44 died and 87.83% had a low-stable pattern (average FBG range: 6.63-7.54 mmol/L), and 12.17% had a high-stable pattern (average FBG range: 12.59-14.02 mmol/L). There were statistical differences in laboratory findings and case fatality between the two FBG patterns. Multivariable logistic regression analysis showed that increased neutrophil count (odds ratio [OR], 25.43; 95% confidence interval [CI]: 2.07, 313.03), elevated direct bilirubin (OR, 5.80; 95%CI: 1.72, 19.58), elevated creatinine (OR, 26.69; 95% CI: 5.82, 122.29), lymphopenia (OR, 8.07; 95% CI: 2.70, 24.14), and high-stable FBG pattern (OR, 8.79; 95% CI: 2.39, 32.29) were independent risk factors for higher case fatality in patients with COVID-19 and hyperglycemia but no history of diabetes. FBG trajectories were significantly associated with death risk in patients with COVID-19 and no diabetes.


Subject(s)
Blood Glucose/analysis , COVID-19/blood , COVID-19/mortality , Aged , Bilirubin/blood , COVID-19/therapy , Creatinine/blood , Diabetes Mellitus , Fasting , Female , Glycemic Control , Hospital Mortality , Humans , Hyperglycemia/blood , Hyperglycemia/mortality , Leukocyte Count , Lymphopenia/blood , Male , Middle Aged , Retrospective Studies , Risk Factors , Treatment Outcome
15.
PLoS One ; 16(4): e0249346, 2021.
Article in English | MEDLINE | ID: covidwho-1190165

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a serious illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and in severe cases associated with acute respiratory distress syndrome (ARDS). OBJECTIVE: To describe the clinical characteristics of patients with ARDS-COVID-19. MATERIALS AND METHODS: This study involved 197 male Egyptian participants, among them111 COVID-19 patients presented with ARDS, 60 COVID-19 patients presented with non-ARDS, and 26 Non-COVID-19 patients. We reported the analysis results of clinical and laboratory information, including blood routine tests, blood biochemistry parameters [aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine and C-reactive protein (CRP)], thrombotic activity (D-dimer) and serum ferritin and lactate dehydrogenase (LDH). RESULTS: The levels of hemoglobin, AST, creatinine, monocyte count, monocyte %, RBC count, TLC, and platelet count were not significantly different among the groups. The lymphopenia and increased CRP, ALT, D-dimer, ferritin, and LDH were observed in patients with ARDS-COVID-19. CONCLUSION: COVID-19 patients with ARDS presented with lymphopenia, increased thrombotic activity, increased CRP, LDH, and ferritin levels. The results revealed that CRP, D-dimer, LDH levels, and lymphopenia have a significant association with the COVID-19 severity and can be used as biomarkers to predict the disease severity.


Subject(s)
COVID-19/diagnosis , COVID-19/epidemiology , Respiratory Distress Syndrome/virology , Adult , Aged , Alanine Transaminase/blood , Alanine Transaminase/metabolism , Aspartate Aminotransferases/blood , Aspartate Aminotransferases/metabolism , Biomarkers/blood , C-Reactive Protein/metabolism , COVID-19/blood , COVID-19/virology , Creatinine/blood , Creatinine/metabolism , Egypt/epidemiology , Fibrin Fibrinogen Degradation Products/metabolism , Hospitalization , Humans , L-Lactate Dehydrogenase/blood , L-Lactate Dehydrogenase/metabolism , Leukocyte Count , Lymphocyte Count , Lymphopenia/blood , Male , Middle Aged , Platelet Count , Respiratory Distress Syndrome/blood , Respiratory Distress Syndrome/diagnosis , Respiratory Distress Syndrome/epidemiology , SARS-CoV-2/isolation & purification , Severity of Illness Index
16.
Int J Lab Hematol ; 43(5): 1237-1242, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1175057

ABSTRACT

INTRODUCTION: Outbreak of corona virus disease in 2019 (COVID-19) has resulted in significant morbidity and mortality worldwide. Our aim is to document hematological parameters of patients with COVID-19 during initial stage of diagnosis and to identify early hematological indicators of severe infection. MATERIALS AND METHODS: This retrospective study was conducted at Shifa International Hospital, Pakistan from April to November 2020. Patients hospitalized with COVID-19, diagnosed on RT-PCR and had a complete blood count (CBC) done within 48 hours of diagnosis were included. Data was analyzed using IBM® SPSS Statistics. RESULTS: A total of 425 patients were included in this study out of whom 272(64%) were males. The mean age was 55.61 ± 17.84 years. 95 patients (22.4%) had normal blood counts within 48 hours of COVID-19 diagnosis. Cytopenias were seen in 193(45.4%) patients. There were 75(17.6%) mortalities during the study period. Chi-square test showed that thrombocytopenia, lymphopenia and neutrophilic leucocytosis were significantly associated with mortality (P = .037, P < .001, P < .001 respectively) and need for ventilator (P = .009, P < .001, P < .001, respectively). Neutrophilia was also associated with development of Acute Respiratory Distress Syndrome (P < .001). On ROC analysis, Neutrophil-to-Lymphocyte Ratio yielded an area under the curve (AUC) of 0.693 and 0.660 for the outcomes mortality and need for ventilator, respectively. For a subset of 288 patients who had D-dimer levels checked within 48 hours of COVID-19 diagnosis, the AUC for mortality and ventilator need was 0.708 and 0.671, respectively. CONCLUSION: Hematological indices are vital indicators in the prognosis and risk stratification of COVID-19 during initial stages of disease.


Subject(s)
COVID-19/blood , Adult , Aged , Blood Cell Count , COVID-19/complications , COVID-19/diagnosis , Female , Fibrin Fibrinogen Degradation Products/analysis , Hospitalization , Humans , Leukocyte Count , Lymphopenia/blood , Lymphopenia/diagnosis , Lymphopenia/etiology , Male , Middle Aged , Pakistan/epidemiology , Prognosis , Retrospective Studies , SARS-CoV-2/isolation & purification , Severity of Illness Index , Thrombocytopenia/blood , Thrombocytopenia/diagnosis , Thrombocytopenia/etiology
17.
Front Endocrinol (Lausanne) ; 12: 596518, 2021.
Article in English | MEDLINE | ID: covidwho-1156116

ABSTRACT

Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT04365634. Context: Diabetes mellitus was associated with increased severity and mortality of disease in COVID-19 pneumonia. So far the effect of type 2 diabetes (T2DM) or hyperglycemia on the immune system among COVID-19 disease has remained unclear. Objective: We aim to explore the clinical and immunological features of type 2 diabetes mellitus (T2DM) among COVID-19 patients. Design and Methods: In this retrospective study, the clinical and immunological characteristics of 306 hospitalized confirmed COVID-19 patients (including 129 diabetic and 177 non-diabetic patients) were analyzed. The serum concentrations of laboratory parameters including cytokines and numbers of immune cells were measured and compared between diabetic and non-diabetic groups. Results: Compared with non-diabetic group, diabetic cases more frequently had lymphopenia and hyperglycemia, with higher levels of urea nitrogen, myoglobin, D-dimer and ferritin. Diabetic cases indicated the obviously elevated mortality and the higher levels of cytokines IL-2R, IL-6, IL-8, IL-10, and TNF-α, as well as the distinctly reduced Th1/Th2 cytokines ratios compared with non-diabetic cases. The longitudinal assays showed that compared to that at week 1, the levels of IL-6 and IL-8 were significantly elevated at week 2 after admission in non-survivors of diabetic cases, whereas there were greatly reductions from week 1 to week 2 in survivors of diabetic cases. Compared with survival diabetic patients, non-survival diabetic cases displayed distinct higher serum concentrations of IL-2R, IL-6, IL-8, IL-10, TNF-α, and lower Th1/Th2 cytokines ratios at week 2. Samples from a subset of participants were evaluated by flow cytometry for the immune cells. The counts of peripheral total T lymphocytes, CD4+ T cells, CD8+ T cells and NK cells were markedly lower in diabetic cases than in non-diabetic cases. The non-survivors showed the markedly declined counts of CD8+ T cells and NK cells than survivors. Conclusion: The elevated cytokines, imbalance of Th1/Th2 cytokines ratios and reduced of peripheral numbers of CD8+ T cells and NK cells might contribute to the pathogenic mechanisms of high mortality of COVID-19 patients with T2DM.


Subject(s)
COVID-19/immunology , Diabetes Mellitus, Type 2/immunology , Adult , Aged , CD4-Positive T-Lymphocytes/pathology , CD8-Positive T-Lymphocytes/pathology , COVID-19/blood , COVID-19/complications , COVID-19/mortality , China/epidemiology , Cytokines/analysis , Cytokines/blood , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/mortality , Female , Humans , Hyperglycemia/blood , Hyperglycemia/complications , Hyperglycemia/immunology , Hyperglycemia/mortality , Immune System/metabolism , Immune System/pathology , Killer Cells, Natural/pathology , Lymphocyte Count , Lymphopenia/blood , Lymphopenia/complications , Lymphopenia/immunology , Lymphopenia/mortality , Male , Middle Aged , Retrospective Studies , SARS-CoV-2/immunology , SARS-CoV-2/physiology , Th1 Cells/pathology , Th2 Cells/pathology
18.
J Clin Endocrinol Metab ; 106(7): 1994-2009, 2021 06 16.
Article in English | MEDLINE | ID: covidwho-1133638

ABSTRACT

CONTEXT: Lymphopenia is a key feature of immune dysfunction in patients with bacterial sepsis and coronavirus disease 2019 (COVID-19) and is associated with poor clinical outcomes, but the cause is largely unknown. Severely ill patients may present with thyroid function abnormalities, so-called nonthyroidal illness syndrome, and several studies have linked thyrotropin (thyroid stimulating hormone, TSH) and the thyroid hormones thyroxine (T4) and 3,5,3'-triiodothyronine (T3) to homeostatic regulation and function of lymphocyte populations. OBJECTIVE: This work aimed to test the hypothesis that abnormal thyroid function correlates with lymphopenia in patients with severe infections. METHODS: A retrospective analysis of absolute lymphocyte counts, circulating TSH, T4, free T4 (FT4), T3, albumin, and inflammatory biomarkers was performed in 2 independent hospitalized study populations: bacterial sepsis (n = 224) and COVID-19 patients (n = 161). A subgroup analysis was performed in patients with severe lymphopenia and normal lymphocyte counts. RESULTS: Only T3 significantly correlated (ρ = 0.252) with lymphocyte counts in patients with bacterial sepsis, and lower concentrations were found in severe lymphopenic compared to nonlymphopenic patients (n = 56 per group). Severe lymphopenic COVID-19 patients (n = 17) showed significantly lower plasma concentrations of TSH, T4, FT4, and T3 compared to patients without lymphopenia (n = 18), and demonstrated significantly increased values of the inflammatory markers interleukin-6, C-reactive protein, and ferritin. Remarkably, after 1 week of follow-up, the majority (12 of 15) of COVID-19 patients showed quantitative recovery of their lymphocyte numbers, whereas TSH and thyroid hormones remained mainly disturbed. CONCLUSION: Abnormal thyroid function correlates with lymphopenia in patients with severe infections, like bacterial sepsis and COVID-19, but future studies need to establish whether a causal relationship is involved.


Subject(s)
COVID-19/complications , Euthyroid Sick Syndromes/diagnosis , Lymphopenia/immunology , Sepsis/complications , Aged , Aged, 80 and over , COVID-19/blood , COVID-19/immunology , Euthyroid Sick Syndromes/blood , Euthyroid Sick Syndromes/immunology , Female , Greece , Humans , Lymphocyte Count , Lymphopenia/blood , Lymphopenia/diagnosis , Male , Netherlands , Retrospective Studies , SARS-CoV-2/immunology , Sepsis/blood , Sepsis/immunology , Thyroid Hormones/blood , Thyroid Hormones/immunology , Thyrotropin/blood , Thyrotropin/immunology
19.
Diabetes Metab Syndr ; 15(2): 535-541, 2021.
Article in English | MEDLINE | ID: covidwho-1091860

ABSTRACT

BACKGROUND AND AIMS: Corona virus disease 2019 (COVID-19) has been an extremely difficult pandemic to contain and it has affected more than 148 countries worldwide. The main aim of this systematic review is to provide a comprehensive summary of clinical and laboratory parameters that are associated with and indicative of increased severity among COVID-19 patients. MATERIAL AND METHODS: All the available data from high-quality research articles relevant to the epidemiology, demographics, trends in hospitalization and outcomes, clinical signs and symptoms, diagnostic methods and treatment methods of COVID-19 were retrieved and evaluated for inclusion. RESULTS: As per our review, the mean age of patients in the severe group was 59.3 years compared to 46.5 years in non severe group. COVID-19 was more severe among men than women. Clinical presentation was variable among different studies. and dyspnea was the factor indicating severe disease. Laboratory parameters associated with increased severity were lymphopenia <0.8 × 109/L, thrombocytopenia 100 × 109/L, leucocytosis TC > 11 × 109/L, procalcitonin >0.5 ng/mL, d dimer >2 mcg/mL, aspartate transaminase elevation >150U/L, LDH >250U/L. CONCLUSION: This systematic review suggests that COVID-19 is a disease with varied clinical presentation and laboratory parameters. The commonest clinical symptoms were fever, cough and dyspnea. The laboratory parameters associated with severe disease were lymphopenia, elevated LDH, D dimer and Procalcitonin.


Subject(s)
Aspartate Aminotransferases/blood , COVID-19/blood , Fibrin Fibrinogen Degradation Products/metabolism , L-Lactate Dehydrogenase/blood , Leukocytosis/blood , Lymphopenia/blood , Procalcitonin/blood , Thrombocytopenia/blood , COVID-19/epidemiology , COVID-19/physiopathology , Comorbidity , Cough/physiopathology , Dyspnea/physiopathology , Fever/physiopathology , Humans , Respiration, Artificial , Risk Factors , SARS-CoV-2 , Severity of Illness Index
20.
Am J Trop Med Hyg ; 104(4): 1188-1201, 2021 02 19.
Article in English | MEDLINE | ID: covidwho-1090244

ABSTRACT

COVID-19 is caused by SARS-CoV-2. Although pulmonary manifestations have been identified as the major symptoms, several hematological abnormalities have also been identified. This review summarizes the reported hematological abnormalities (changes in platelet, white blood cell, and hemoglobin, and coagulation/fibrinolytic alterations), explores their patho-mechanisms, and discusses its management. Common hematological abnormalities in COVID-19 are lymphopenia, thrombocytopenia, and elevated D-dimer levels. These alterations are significantly more common/prominent in patients with severe COVID-19 disease, and thus may serve as a possible biomarker for those needing hospitalization and intensive care unit care. Close attention needs to be paid to coagulation abnormalities, and steps should be taken to prevent these occurring or to mitigate their harmful effects. The effect of COVID-19 in patients with hematological abnormalities and recognized hematological drug toxicities of therapies for COVID-19 are also outlined.


Subject(s)
Blood Coagulation , Blood Platelets/pathology , COVID-19/blood , COVID-19/complications , Hematologic Diseases/complications , Lymphopenia/blood , Thrombocytopenia/blood , Biomarkers/blood , COVID-19/therapy , Erythrocytes/pathology , Hematologic Diseases/therapy , Humans , Leukocytes/pathology , Lymphopenia/etiology , SARS-CoV-2 , Thrombocytopenia/etiology
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