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1.
Clin Lab ; 68(8)2022 Aug 01.
Article in English | MEDLINE | ID: covidwho-1994479

ABSTRACT

BACKGROUND: Serum ferritin is an acute-phase protein whose level is increased in several inflammatory diseases. This review describes the structure and function of ferritin as well as its association with the prognosis of patients with COVID-19. METHODS: We searched MEDLINE/PubMed databases, Scopus, and Web of Science for prospective and review articles that examined ferritin and its association with COVID-19 severity. Based on all these articles and clinical experience, a review was constructed and full texts of the articles that were retrieved were accessed. RESULTS: All COVID-19 related studies conducted in 2020, which performed serum ferritin testing, clearly showed ferritin as a biomarker of COVID-19 severity in hospitalized patients. Ferritin levels in severe patients were significantly increased relative to those in non-severe patients (p < 0.001). Non-survivors had significantly higher ferritin levels than the survivors (p < 0.001). CONCLUSIONS: Determination of ferritin levels was specific and sensitive for early disease severity prediction in patients with COVID-19. Serum ferritin can also be used for predicting the response to COVID-19 vaccines.


Subject(s)
COVID-19 , Ferritins , COVID-19/diagnosis , COVID-19 Vaccines , Ferritins/blood , Humans , Prospective Studies , SARS-CoV-2
2.
Sao Paulo Med J ; 140(5): 627-635, 2022.
Article in English | MEDLINE | ID: covidwho-1951677

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) can cause cytokine release syndrome (CRS), which leads to high mortality rates. Tocilizumab suppresses CRS by blocking the signal transduction of interleukin-6 (IL-6). OBJECTIVE: To evaluate the clinical and laboratory parameters associated with mortality among patients receiving tocilizumab treatment. DESIGN AND SETTING: Retrospective observational study conducted in the chest disease departments of two different training and research hospitals in the center of Ankara, Turkey. METHODS: Patients who were hospitalized and treated with tocilizumab in September 2020 were retrospectively analyzed. Their laboratory parameters and clinical characteristics were obtained from the hospital information system database. Comparative analyses were performed between the patients who died and the ones who survived. RESULTS: A total of 58 patients who received tocilizumab treatment were included in this study, among whom 35 (60.3%) died. There was no difference between the mortality and survival groups in terms of white blood cell (WBC), neutrophil, lymphocyte, ferritin or C-reactive protein (CRP) levels detected on admission. WBC, lymphocyte, neutrophil and CRP levels measured on the third and fifth days after tocilizumab administration were found to be significantly lower in the survival group (P < 0.05). In multiple logistic regression analysis, age and oxygen saturation were determined to be independent risk factors for mortality. CONCLUSION: Persistently high WBC, CRP and neutrophil levels and low lymphocyte levels could be considered to be valuable indicators of mortality among COVID-19 patients treated with tocilizumab. Age and low oxygen saturation are independent risk factors for mortality among patients receiving tocilizumab treatment.


Subject(s)
Antibodies, Monoclonal, Humanized , COVID-19 , Antibodies, Monoclonal, Humanized/therapeutic use , C-Reactive Protein/analysis , COVID-19/blood , COVID-19/complications , COVID-19/drug therapy , Cytokine Release Syndrome/prevention & control , Cytokine Release Syndrome/virology , Ferritins/blood , Humans , Interleukin-6/blood , Leukocyte Count , Retrospective Studies , Treatment Outcome
3.
J Chromatogr B Analyt Technol Biomed Life Sci ; 1194: 123184, 2022 Apr 01.
Article in English | MEDLINE | ID: covidwho-1701949

ABSTRACT

INTRODUCTION: Ferritin is the major iron-storage glycoprotein found in all tissues. Ferritin glycosylation can be assessed by the differential affinities of ferritin glycoforms for Concanavalin A (ConA), a lectin. The fraction of serum ferritin bound to ConA is called "glycosylated ferritin" (GF). Low GF reflects macrophagic activation and is an essential biomarker used in adult-onset Still's disease (AOSD), macrophage activation syndrome (MAS) and Gaucher disease diagnosis and therapeutic management. To date, no complete assay description and method validation according to the ISO 15189 standard has been published. This study aimed to describe and validate our method used for GF measurement and describe GF values observed in patients. MATERIALS AND METHODS: Ferritin glycoforms were separated based on their affinities for ConA using commercially available TRIS-barbital buffer, Sepharose and ConA/Sepharose 4B gels. Ferritin concentrations were measured on the Siemens Dimension Vista 1500®. We analysed 16,843 GF values obtained between 2000 and 2021 from our database of patients. RESULTS: Optimal separation of ferritin glycoforms was obtained by 15-min incubation of serum with ConA/Sepharose at pH 8. The optimized volume were 0.4 mL for total serum ferritin (TSF) 30-1000 µg/L and 0.5 mL for TSF 1000-2500 µg/L. Serum with higher TSF should be pre-diluted in the TRIS-barbital buffer. Reproducibility of ferritin measurement in the TRIS-barbital buffer matrix was excellent (intra-assay CV < 1%; inter-assay CV < 4%). Reproducibility of GF assay was good (intra-assay CV < 10% for low and high ferritin samples, respectively; and inter-assay CV < 10%). Inter-operator variability was 21.6% for GF < 20%. Ferritin was stable for up to 3 days in the TRIS-barbital buffer. An inter-laboratory exchange program conducted with another French hospital showed good agreement between results. In our database, <20% GF levels were scarce, compatible with the low prevalence of Still's disease, MAS, and Gaucher disease. The 95% confidence interval for GF was [26-58]%, lower than values described in the literature for healthy individuals. CONCLUSION: Thanks to good performances, this technique can become readily available for laboratories servicing patients with AOSD, MAS (including severe COVID-19 patients) and Gaucher disease patients.


Subject(s)
Chemistry Techniques, Analytical/methods , Concanavalin A/metabolism , Ferritins/blood , Macrophage Activation Syndrome/blood , Still's Disease, Adult-Onset/blood , Biomarkers/blood , Biomarkers/metabolism , Ferritins/metabolism , Gaucher Disease/blood , Gaucher Disease/metabolism , Humans , Macrophage Activation Syndrome/metabolism , Protein Binding , Still's Disease, Adult-Onset/metabolism
4.
Acta Haematol ; 145(4): 440-447, 2022.
Article in English | MEDLINE | ID: covidwho-1662364

ABSTRACT

BACKGROUND: Tocilizumab has been proposed as an effective treatment for severe COVID-19. We aimed to investigate whether tocilizumab administration is associated with increased availability of serum iron which may possibly be associated with adverse effects on clinical outcomes. METHODS: We performed an observational, retrospective cohort study. We included adults, who were hospitalized in ICU with the diagnosis of severe COVID-19 infection eligible for tocilizumab treatment. Laboratory data including serum iron, ferritin, transferrin saturation, hemoglobin, and C-reactive protein levels of all patients were collected shortly before and 24 h, 48 h, and 72 h after tocilizumab administration. RESULTS: During the study period, 15 patients fulfilled the inclusion criteria and were eligible to receive tocilizumab treatment. Tocilizumab therapy was associated with a prominent increase in serum iron and transferrin saturation levels (26 ± 13 µg/dL and 15 ± 8% before treatment and 79 ± 32 µg/dL and 41 ± 15% 72 h after treatment, respectively, p < 0.001) and decrease in serum ferritin levels (1,921 ± 2,071 ng/mL before and 1,258 ± 1,140 ng/mL 72 h after treatment, p = 0.027). CONCLUSION: Treatment of severe COVID-19 patients with tocilizumab is associated with a profound increase in serum iron and ferritin saturation levels along with a decrease in ferritin levels. This may represent an undesirable side effect that may potentiate viral replication.


Subject(s)
Antibodies, Monoclonal, Humanized , COVID-19 , Iron , Adult , Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/drug therapy , Ferritins/blood , Homeostasis , Humans , Iron/blood , Retrospective Studies , Transferrins/blood
5.
J Coll Physicians Surg Pak ; 32(1): 37-41, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1599461

ABSTRACT

OBJECTIVE: To determine the efficacy and cut-off values of C-reactive protein (CRP), lactate dehydrogenase (LDH), serum ferritin, and D-dimer for predicting mortality of COVID-19 infection. STUDY DESIGN: Observational study. PLACE AND DURATION OF STUDY: Department of Medicine, Jinnah Hospital, Lahore from January to May 2021. METHODOLOGY: Serum CRP, LDH, ferritin, and D-dimer were measured in patients with moderate to severe COVID-19 infection at admission. Patients were followed for in-hospital disease outcome. ROC curve was used to determine area under curve (AUC) and cut-off values of biomarkers, followed by multi-variate analysis by logistic regression. RESULTS: In 386 patients, male to female ratio was 1.47/1 (230/156); and mean age was 54.03 ± 16.2 years. Disease was fatal in 135 (35%) patients. AUC for mortality was 0.730 for LDH, 0.737 for CRP, 0.747 for ferritin and 0.758 for D-dimer. Mortality was higher with LDH ≥400 U/ml, Odds Ratio (OR) 5.37 (95% CI 3.01-9.57: p = 0.001), CRP ≥30 ng/L, OR 4.30 (95% CI 2.11-8.74: p = <0.001), serum ferritin ≥200 ng/ml, OR 4.13 (95% CI 1.05-16.2: p = 0.02), and D-dimer ≥400 ng/ml, OR 2.72 (95% CI 1.06-7.01: p = 0.03) with 2 log likelihood of 131.54 for predicting disease outcome with 71.7% accuracy in multi-variate analysis. CONCLUSION: Elevated serum CRP, LDH, ferritin and D-dimer are associated with higher mortality in patients of COVID-19 infection. Serum CRP ≥30ng/ml, LDH ≥400 U/L, ferritin ≥200 ng/ml and D-dimer ≥400 ng/ml can predict fatal outcome in COVID-19 patients. Key Words: C-reactive protein (CRP), COVID-19 infection, D-dimer, Ferritin, Lactate dehydrogenase (LDH), Mortality.


Subject(s)
Biomarkers/blood , COVID-19 , Adult , Aged , C-Reactive Protein/analysis , COVID-19/mortality , Female , Ferritins/blood , Fibrin Fibrinogen Degradation Products/analysis , Humans , L-Lactate Dehydrogenase/blood , Male , Middle Aged , Prognosis , ROC Curve , Retrospective Studies
6.
Cytokine ; 150: 155790, 2022 02.
Article in English | MEDLINE | ID: covidwho-1587975

ABSTRACT

BACKGROUND: Several immune mediators (IM) including cytokines, chemokines, and their receptors have been suggested to play a role in COVID-19 pathophysiology and severity. AIM: To determine if early IM profiles are predictive of clinical outcome and which of the IMs tested possess the most clinical utility. METHODS: A custom bead-based multiplex assay was used to measure IM concentrations in a cohort of SARS-CoV-2 PCR positive patients (n = 326) with varying disease severities as determined by hospitalization status, length of hospital stay, and survival. Patient groups were compared, and clinical utility was assessed. Correlation plots were constructed to determine if significant relationships exist between the IMs in the setting of COVID-19. RESULTS: In PCR positive SARS-CoV-2 patients, IL-6 was the best predictor of the need for hospitalization and length of stay. Additionally, MCP-1 and sIL-2Rα were moderate predictors of the need for hospitalization. Hospitalized PCR positive SARS-CoV-2 patients displayed a notable correlation between sIL-2Rα and IL-18 (Spearman's ρ = 0.48, P=<0.0001). CONCLUSIONS: IM profiles between non-hospitalized and hospitalized patients were distinct. IL-6 was the best predictor of COVID-19 severity among all the IMs tested.


Subject(s)
COVID-19/immunology , Cytokines/physiology , Hospitalization , Receptors, Cytokine/physiology , SARS-CoV-2 , Adult , Area Under Curve , Biomarkers , C-Reactive Protein/analysis , COVID-19/physiopathology , COVID-19/therapy , Chemokines/blood , Chemokines/physiology , Cytokines/blood , Female , Ferritins/blood , Fibrin Fibrinogen Degradation Products/analysis , Hospital Mortality , Humans , Interleukin-6/blood , Length of Stay/statistics & numerical data , Male , Middle Aged , Prognosis , ROC Curve , Receptors, Chemokine/physiology , Respiration, Artificial/statistics & numerical data , Severity of Illness Index , Treatment Outcome
7.
Front Immunol ; 12: 627844, 2021.
Article in English | MEDLINE | ID: covidwho-1573949

ABSTRACT

BACKGROUND: The effective treatment of coronavirus disease 2019 (COVID-19) remains unclear. We reported successful use of high-dose intravenous immunoglobulin (IVIg) in cases of severe COVID-19, but evidence from larger case series is still lacking. METHODS: A multi-center retrospective study was conducted to evaluate the effectiveness of IVIg administered within two weeks of disease onset at a total dose of 2 g/kg body weight, in addition to standard care. The primary endpoint was 28-day mortality. Efficacy of high-dose IVIg was assessed by using the Cox proportional hazards regression model and the Kaplan-Meier curve adjusted by inverse probability of treatment weighting (IPTW) analysis, and IPTW after multiple imputation (MI) analysis. RESULTS: Overall, 26 patients who received high-dose IVIg with standard therapy and 89 patients who received standard therapy only were enrolled in this study. The IVIg group was associated with a lower 28-day mortality rate and less time to normalization of inflammatory markers including IL-6, IL-10, and ferritin compared with the control. The adjusted HR of 28-day mortality in high-dose IVIg group was 0.24 (95% CI 0.06-0.99, p<0.001) in IPTW model, and 0.27 (95% CI 0.10-0.57, p=0.031) in IPTW-MI model. In subgroup analysis, patients with no comorbidities or treated in the first week of disease were associated with more benefit from high-dose IVIg. CONCLUSIONS: High-dose IVIg administered in severe COVID-19 patients within 14 days of onset was linked to reduced 28-day mortality, more prominent with those having no comorbidities or treated at earlier stage.


Subject(s)
COVID-19/drug therapy , COVID-19/mortality , Immunoglobulins, Intravenous/administration & dosage , SARS-CoV-2/metabolism , Adult , Aged , COVID-19/blood , China/epidemiology , Disease-Free Survival , Female , Ferritins/blood , Humans , Interleukin-10/blood , Interleukin-6/blood , Male , Middle Aged , Retrospective Studies , Survival Rate
8.
J Autoimmun ; 126: 102778, 2022 01.
Article in English | MEDLINE | ID: covidwho-1556992

ABSTRACT

While it took decades to arrive to a conclusion that ferritin is more than an indicator of iron storage level, it took a short period of time through the COVID-19 pandemic to wonder what the reason behind high levels of ferritin in patients with severe COVID-19 might be. Unsurprisingly, acute phase reactant was not a satisfactory explanation. Moreover, the behavior of ferritin in patients with severe COVID-19 and the subsequent high mortality rates in patients with high ferritin levels necessitated further investigations to understand the role of ferritin in the diseases. Ferritin was initially described to accompany various acute infections, both viral and bacterial, indicating an acute response to inflammation. However, with the introduction of the hyperferritinemic syndrome connecting four severe pathological conditions such as adult-onset Still's disease, macrophage activation syndrome, catastrophic antiphospholipid syndrome, and septic shock added another aspect of ferritin where it could have a pathogenetic role rather than an extremely elevated protein only. In fact, suggesting that COVID-19 is a new member in the spectrum of hyperferritinemic syndrome besides the four mentioned conditions could hopefully direct further search on the pathogenetic role of ferritin. Doubtlessly, improving our understanding of those aspects of ferritin would enormously contribute to better coping with severe diseases in terms of treatment and prevention of complications. The origin, history, importance, and the advances of searching the role of ferritin in various pathological and clinical processes are presented hereby in our article. In addition, the implications of ferritin in COVID-19 are addressed.


Subject(s)
COVID-19/blood , Ferritins/blood , Acute-Phase Proteins , Autoimmune Diseases/blood , Communicable Diseases/blood , Humans , Hyperferritinemia , Inflammation , Iron
9.
Front Immunol ; 12: 745515, 2021.
Article in English | MEDLINE | ID: covidwho-1551502

ABSTRACT

Objective: A critical role in coronavirus disease 2019 (COVID-19) pathogenesis is played by immune dysregulation that leads to a generalized uncontrolled multisystem inflammatory response, caused by overproduction of proinflammatory cytokines, known as "a cytokine storm" (CS), strongly associated with a severe course of disease. The aim of this study is to identify prognostic biomarkers for CS development in COVID-19 patients and integrate them into a prognostic score for CS-associated risk applicable to routine clinical practice. Materials and Methods: The authors performed a review of 458 medical records from COVID-19 patients (241 men and 217 women aged 60.0 ± 10.0) who received treatment in the St. Petersburg State Budgetary Institution of Healthcare City Hospital 40 (City Hospital 40, St. Petersburg), from Apr. 18, 2020 to Nov. 21, 2020. The patients were split in two groups: one group included 100 patients with moderate disease symptoms; the other group included 358 patients with progressive moderately severe, severe, and extremely severe disease. The National Early Warning Score (NEWS) score was used alongside with clinical assessment, chest computed tomographic (CT) scans, electrocardiography (ECG), and lab tests, like ferritin, C-reactive protein (CRP), interleukin (IL)-6, lactate dehydrogenase (LDH), and D-dimer. Results: The basic risk factors for cytokine storms in COVID-19 patients are male gender, age over 40 years, positive test result for replicative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA, absolute lymphocyte count, dynamics in the NEWS score, as well as LDH, D-dimer, ferritin, and IL-6 levels. These clinical and instrumental findings can be also used as laboratory biomarkers for diagnosis and dynamic monitoring of cytokine storms. The suggested prognostic scale (including the NEWS score dynamics; serum IL-6 greater than 23 pg/ml; serum CRP 50 mg/L or greater; absolute lymphocyte count less than 0.72 × 109/L; positive test result for replicative coronavirus (SARS-CoV-2) RNA; age 40 years and over) is a useful tool to identify patients at a high risk for cytokine storm, requiring an early onset of anti-inflammatory therapy.


Subject(s)
COVID-19/pathology , Cytokine Release Syndrome/diagnosis , Cytokine Release Syndrome/pathology , Cytokines/blood , Severity of Illness Index , Adult , Age Factors , Aged , Biomarkers/analysis , C-Reactive Protein/analysis , COVID-19/drug therapy , Cytokines/metabolism , Female , Ferritins/blood , Fibrin Fibrinogen Degradation Products/analysis , Humans , Interleukin-6/blood , L-Lactate Dehydrogenase/blood , Lymphocyte Count , Male , Middle Aged , Prognosis , Risk Factors , SARS-CoV-2/immunology
10.
PLoS One ; 16(12): e0260537, 2021.
Article in English | MEDLINE | ID: covidwho-1546957

ABSTRACT

Several reports highlighted the central role of inflammation in the pathogenesis of corona virus disease-19 (COVID-19) disease. Also, the hyper-inflammatory response that is triggered by severe acute respiratory syndrom-Covid-2 (SARS-CoV-2) infection was believed to play an essential role in disease severity and adverse clinical course. For that reason, the classical inflammatory markers were proposed as a possible indicator for COVID-19 severity. However, an extensive analysis of the predictive value of inflammatory biomarkers in large patients' cohorts is still limited and critically needed. In this study we investigated the predictive value of the classical inflammatory biomarkers in a patient cohort consists of 541 COVID-19 patients admitted to Al Kuwait Hospital, Dubai, UAE. A detailed analysis of the association between the essential inflammatory markers and clinical characteristics as well as clinical outcome of the patients were made. In addition, the correlation between those markers and a wide range of laboratory biomarkers and incidence of acute organs injury were investigated. Our results showed a significant elevation of many inflammatory markers including white cell count (WBC) count, neutrophils count, C-reactive protein (CRP), D-Dimer, ferritin, procalcitonin (PCT), and lactate dehydrogenase (LDH) levels in patients with more severe illness. Also, our results highlighted that higher levels of those markers can predict worse patient outcome including the need of ventilation, intensive care unit (ICU) admission, multiple organs dysfunction as well as death. In addition, Our results showed that the presence of lymphopenia and lower absolute lymphocyte count (ALC) at the time of admission were associated with severe to critical COVID-19 illness (P<0.0001), presence of acute respiratory distress syndrome (ARDS) (P<0.0001) and the need for ventilation and ICU admission., Moreover, our results showed a strong association between lower ALC count and multiple organs dysfunction and patient's death (P<0.0001). In conclusion, our results highlighted the possible use of classical inflammatory biomarkers at time of admission as a potential predictive marker for more severe clinical course in COVID-19 patients that might need more aggressive therapeutic approach including the need of ventilators and ICU admission. The presence of such predictive markers might improve patient's stratification and help in the direction of the available resources to patients in need, which in turn help in improving our response to the disease pandemic.


Subject(s)
COVID-19/blood , Inflammation/blood , Biomarkers/blood , C-Reactive Protein/analysis , COVID-19/complications , COVID-19/pathology , Calcitonin/blood , Female , Ferritins/blood , Fibrin Fibrinogen Degradation Products/analysis , Hospitalization/statistics & numerical data , Humans , Inflammation/etiology , Intensive Care Units/statistics & numerical data , L-Lactate Dehydrogenase/blood , Leukocyte Count , Male , Middle Aged , Multiple Organ Failure/etiology , Patient Acuity , Respiration, Artificial/statistics & numerical data , Treatment Outcome
11.
Viruses ; 13(11)2021 11 15.
Article in English | MEDLINE | ID: covidwho-1524170

ABSTRACT

INTRODUCTION: Hospitalized patients with COVID-19 are at increased risk for venous thromboembolism (VTE), but also for bleeding. We previously derived a prognostic score including four variables (elevated D-dimer, elevated ferritin, critical illness, and therapeutic-dose anticoagulation) that identified those at increased risk for major bleeding. METHODS: We aimed to validate the score in a subsequent cohort of hospitalized patients with COVID-19 receiving standard-, intermediate- or therapeutic doses of VTE prophylaxis. We evaluated its capacity to predict major bleeding, non-major bleeding, and bleeding-related death. RESULTS: The cohort included 972 patients from 29 hospitals, of whom 280 (29%) received standard-; 412 (42%) intermediate-, 157 (16%) therapeutic doses of VTE prophylaxis and 123 (13%) other drugs. Median duration of prophylaxis was 14.7 ± 10.3 days. Major bleeding occurred in 65 patients (6.7%) and non-major bleeding in 67 (6.9%). Thirty patients with major bleeding (46%) died within the first 30 days after bleeding. The prognostic score identified 203 patients (21%) at very low risk, 285 (29%) at low risk, 263 (27%) intermediate-risk and 221 (23%) at high risk for bleeding. Major bleeding occurred in 1.0%, 2.1%, 8.7% and 15.4% of the patients, respectively. Non-major bleeding occurred in 0.5%, 3.5%, 9.5% and 14.2%, respectively. The c-statistics was: 0.74 (95% confidence intervals [CI]: 0.68-0.79) for major bleeding, 0.73 (95% CI: 0.67-0.78) for non-major bleeding and 0.82 (95% CI: 0.76-0.87) for bleeding-related death. CONCLUSIONS: In hospitalized patients with COVID-19, we validated that a prognostic score including 4 easily available items may identify those at increased risk for bleeding.


Subject(s)
Anticoagulants/therapeutic use , COVID-19/complications , Ferritins/blood , Fibrin Fibrinogen Degradation Products/analysis , Hemorrhage/etiology , Cohort Studies , Critical Illness , Female , Hemorrhage/epidemiology , Hospitalization , Humans , Male , Prognosis , Risk Factors , Venous Thromboembolism/complications , Venous Thromboembolism/prevention & control
12.
J Crit Care ; 67: 172-181, 2022 02.
Article in English | MEDLINE | ID: covidwho-1521256

ABSTRACT

Ferritin is a known inflammatory biomarker in COVID-19. However, many factors and co-morbidities can confound the level of serum ferritin. This current metaanalysis evaluates serum ferritin level in different severity levels in COVID-19. Studies evaluating serum ferritin level in different clinical contexts (COVID-19 vs. control, mild to moderate vs. severe to critical, non-survivor vs. survivor, organ involvement, ICU and mechanical ventilation requirement) were included (total 9 literature databases searched). Metaanalysis and metaregression was carried out using metaphor "R" package. Compared to control (COVID-19 negative), higher ferritin levels were found among the COVID-19 patients [SMD -0.889 (95% C.I. -1.201, -0.577), I2 = 85%]. Severe to critical COVID-19 patients showed higher ferritin levels compared to mild to moderate COVID-19 patients [SMD 0.882 (0.738, 1.026), I2 = 85%]. In meta-regression, high heterogeneity was observed could be attributed to difference in "mean age", and "percentage of population with concomitant co-morbidities". Non-survivors had higher serum ferritin level compared to survivors [SMD 0.992 (0.672, 1.172), I2 = 92.33%]. In meta-regression, high heterogeneity observed could be attributed to difference in "mean age" and "percentage of male sex". Patients requiring ICU [SMD 0.674 (0.515 to 0.833), I2 = 80%] and mechanical ventilation [SMD 0.430 (0.258, 0.602), I2 = 32%] had higher serum ferritin levels compared to those who didn't. To conclude, serum ferritin level may serve as an important biomarker which can aid in COVID-19 management. However, presence of other co-morbid conditions/confounders warrants cautious interpretation.


Subject(s)
Biomarkers/blood , COVID-19 , Ferritins/blood , COVID-19/diagnosis , Humans , Regression Analysis
13.
Mycoses ; 65(1): 120-127, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1501485

ABSTRACT

BACKGROUND: Whether dysregulated iron metabolism is associated with COVID-19-associated mucormycosis (CAM) remains unknown. Herein, we compare the serum iron indices in COVID-19 subjects with and without mucormycosis. METHODS: We conducted a case-control study enrolling COVID-19 participants with and without mucormycosis. We compared the baseline serum iron indices (iron, ferritin, total iron-binding capacity [TIBC], unsaturated iron-binding capacity and percentage transferrin saturation) between CAM cases and COVID-19 controls. Additionally, we performed a multivariate logistic regression analysis to assess whether any iron indices are associated with CAM. RESULTS: We enrolled 28 CAM cases (mean age 53.6 years old; 78.6% men) and 26 controls (mean age 57.2 years old; 73.1% men). Rhino-orbital (±cerebral) mucormycosis (85.7%) was the most clinical presentation. Diabetes mellitus was more frequent in the cases than controls (75% vs. 42.3%; p = .015). Hypoxaemia during COVID-19 illness was more common in controls than cases. The mean serum iron values (33 vs. 45 µg/dl, p = .03) and TIBC (166.6 vs. 201.6 µg/dl, p = .003) were significantly lower in CAM cases than controls. On multivariate analysis, we found a lower TIBC (odds ratio [OR] 0.97; 95% confidence interval [CI], 0.95-0.99) and diabetes mellitus (OR 5.23; 95% CI, 1.21-22.68) to be independently associated with CAM after adjusting for serum iron, ferritin and glucocorticoid therapy. The case fatality rate of CAM was 73.9%. The iron indices were not significantly different between CAM survivors and non-survivors. CONCLUSIONS: The CAM is associated with lower TIBC levels than COVID-19 subjects without mucormycosis, suggesting dysregulated iron metabolism in its pathogenesis. Further studies are required to confirm our preliminary observations.


Subject(s)
COVID-19 , Ferritins/blood , Iron/blood , Mucormycosis , COVID-19/complications , Case-Control Studies , Diabetes Mellitus/epidemiology , Female , Humans , Male , Middle Aged , Mucormycosis/epidemiology
14.
Sci Rep ; 11(1): 21124, 2021 10 26.
Article in English | MEDLINE | ID: covidwho-1493211

ABSTRACT

Patients with coronavirus disease 2019 (COVID-19) can have increased risk of mortality shortly after intubation. The aim of this study is to develop a model using predictors of early mortality after intubation from COVID-19. A retrospective study of 1945 intubated patients with COVID-19 admitted to 12 Northwell hospitals in the greater New York City area was performed. Logistic regression model using backward selection was applied. This study evaluated predictors of 14-day mortality after intubation for COVID-19 patients. The predictors of mortality within 14 days after intubation included older age, history of chronic kidney disease, lower mean arterial pressure or increased dose of required vasopressors, higher urea nitrogen level, higher ferritin, higher oxygen index, and abnormal pH levels. We developed and externally validated an intubated COVID-19 predictive score (ICOP). The area under the receiver operating characteristic curve was 0.75 (95% CI 0.73-0.78) in the derivation cohort and 0.71 (95% CI 0.67-0.75) in the validation cohort; both were significantly greater than corresponding values for sequential organ failure assessment (SOFA) or CURB-65 scores. The externally validated predictive score may help clinicians estimate early mortality risk after intubation and provide guidance for deciding the most effective patient therapies.


Subject(s)
COVID-19/diagnosis , COVID-19/mortality , Intubation, Intratracheal/methods , Severity of Illness Index , Adolescent , Adult , Age Factors , Aged , Arterial Pressure , COVID-19/therapy , Female , Ferritins/blood , Humans , Hydrogen-Ion Concentration , Male , Middle Aged , New York , Nitrogen/metabolism , Oxygen/metabolism , Predictive Value of Tests , ROC Curve , Regression Analysis , Reproducibility of Results , Retrospective Studies , Sensitivity and Specificity , Vasoconstrictor Agents/pharmacology , Young Adult
15.
Medicine (Baltimore) ; 100(30): e26719, 2021 Jul 30.
Article in English | MEDLINE | ID: covidwho-1475908

ABSTRACT

ABSTRACT: Liver dysfunction in patients with COVID-19 (coronavirus disease 2019) has been described. However, it is not clear if the presence of abnormal liver function tests at presentation was related to underlying undiagnosed liver disease, or a result of the viral infection.We retrospectively examined the first 554 consecutive polymerase chain reaction positive SARS-CoV-2 patients admitted from February 2020 to April 2020 to our academic medical centre. We reviewed their clinical data, chest radiography and laboratory studies obtained within 24 hour of admission.Despite similar hemodynamic parameters, we found significant aspartate transaminase elevation (64 ±â€Š141 vs 35 ±â€Š23 U/L, P < .001) in those with pneumonia compared to those without. Elevated liver enzymes were seen in 102 patients (18.4%). They presented with higher temperatures (38.5 ±â€Š0.9 vs 37.5 ±â€Š0.8 degC, P = .011), higher total white cell counts (6.95 ±â€Š2.29 vs 6.39 ±â€Š2.19 x109/L, P = .021), serum ferritin (240 ±â€Š274 vs 165 ±â€Š198 ng/ml, P = .002) and lactate dehydrogenase (632 ±â€Š912 vs 389 ±â€Š107 U/L, P < .001). These patients were more likely to require intensive care (6.9% vs 2.7% P = .036) and mechanical ventilation (5.9% vs 2.2%, P = .046). Migrant workers from dormitories had a higher rate of baseline liver function test abnormalities (88/425 vs 14/129, P = .01), which were more likely to persist at the time of discharge.Despite relatively mild COVID-19 disease, there was a significant prevalence of liver dysfunction, particularly amongst migrant workers. Elevated liver enzymes were associated with more severe disease, despite similar haemodynamic characteristics. Future studies should explore whether pre-existing liver disease may predispose to more severe COVID-19 disease.


Subject(s)
Aspartate Aminotransferases/blood , COVID-19/complications , L-Lactate Dehydrogenase/blood , Liver Diseases/etiology , Adult , COVID-19/blood , Female , Ferritins/blood , Humans , Leukocyte Count , Liver Diseases/blood , Liver Function Tests , Male , Middle Aged , Retrospective Studies , Risk Factors , Singapore
16.
Scand J Immunol ; 95(1): e13108, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1462877

ABSTRACT

The novel coronavirus disease 2019 (COVID-19) remains a global health emergency, and understanding the interactions between the virus and host immune responses is crucial to preventing its lethal effects. The expansion of myeloid-derived suppressor cells (MDSCs) in COVID-19, thereby suppressing immune responses, has been described as responsible for the severity of the disease, but the correlation between MDSC subsets and COVID-19 severity remains elusive. Therefore, we classified patients according to clinical and laboratory findings-aiming to investigate the relationship between MDSC subsets and laboratory findings such as high C-reactive protein, ferritin and lactate dehydrogenase levels, which indicate the severity of the disease. Forty-one patients with COVID-19 (26 mild and 15 severe; mean age of 49.7 ± 15 years) and 26 healthy controls were included in this study. MDSCs were grouped into two major subsets-polymorphonuclear MDSCs (PMN-MDSCs) and monocytic MDSCs-by flow cytometric immunophenotyping, and PMN-MDSCs were defined as mature and immature, according to CD16 expressions, for the first time in COVID-19. Total MDSCs, PMN-MDSCs, mature PMN-MDSCs and monocytic MDSCs were significantly higher in patients with COVID-19 compared with the healthy controls (P < .05). Only PMN-MDSCs and their immature PMN-MDSC subsets were higher in the severe subgroup than in the mild subgroup. In addition, a significant correlation was found between C-reactive protein, ferritin and lactate dehydrogenase levels and MDSCs in patients with COVID-19. These findings suggest that MDSCs play a role in the pathogenesis of COVID-19, while PMN-MDSCs, especially immature PMN-MDSCs, are associated with the severity of the disease.


Subject(s)
Acute-Phase Proteins/metabolism , C-Reactive Protein/metabolism , COVID-19/metabolism , Ferritins/blood , L-Lactate Dehydrogenase/blood , Myeloid-Derived Suppressor Cells/immunology , SARS-CoV-2/physiology , Adult , Aged , COVID-19/immunology , Case-Control Studies , Disease Progression , Female , Humans , Male , Middle Aged , Prospective Studies , Severity of Illness Index , Young Adult
17.
Postgrad Med ; 134(1): 58-63, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1454909

ABSTRACT

BACKGROUND: In COVID-19 patients the progressive clinical deterioration seems secondary to the activation of a cytokine storm. Ferritin is considered a direct mediator of the immune system and some evidences suggested a shared physio-pathogenic basis between COVID-19 and 'Hyperferritinemic Syndromes.' The aim of our study was to evaluate the prognostic role of ferritin in COVID-19 patients. METHODS: We retrospectively studied consecutive COVID-19 patients admitted to four Italian Internal Medicine Units. Role of potential prognostic markers was evaluated with binary logistic regression analysis and results were expressed as odds ratios (ORs) with the corresponding 95% confidence intervals (CIs). Poor outcome was defined as death or need to transfer in the intensive care unit. RESULTS: Two hundred patients were included (mean age 68.75 ± 13.22 years). Ferritin value was highly elevated (>3000 ng/mL) in 8% of our population; 13% of patients were transferred to intensive care units and 12% of patients died. At multivariate analysis, highly elevated ferritin levels (OR 16.67 C.I. 4.89-57.57 p < 0.001) and hemoglobin < 10 g/dL (OR 8.88 C.I. 2.02-39.09 p = 0.004) were independently associated with a bad outcome.Patients with ferritin values > 3000 ng/ml appeared to have an inflammatory activation with elevated values of CRP and D-dimer and low values of lymphocyte count. CONCLUSION: Our results confirm the prognostic role of ferritin in hospitalized COVID-19 patients. Patients with high ferritin levels should be considered critically ill and treated in an adequate setting. Furthermore, COVID-19 seems to share some characteristics with hyperferritinemic syndromes with potential therapeutic implications.


Subject(s)
COVID-19 , Ferritins , Aged , Aged, 80 and over , COVID-19/diagnosis , Ferritins/blood , Humans , Middle Aged , Prognosis , Retrospective Studies , SARS-CoV-2
18.
Sci Rep ; 11(1): 19618, 2021 10 04.
Article in English | MEDLINE | ID: covidwho-1450293

ABSTRACT

The pathophysiology and the factors determining disease severity in COVID-19 are not yet clear, with current data indicating a possible role of altered iron metabolism. Previous studies of iron parameters in COVID-19 are cross-sectional and have not studied catalytic iron, the biologically most active form of iron. The study was done to determine the role of catalytic iron in the adverse outcomes in COVID-19. We enrolled adult patients hospitalized with a clinical diagnosis of COVID-19 and measured serum iron, transferrin saturation, ferritin, hepcidin and serum catalytic iron daily. Primary outcome was a composite of in-hospital mortality, need for mechanical ventilation, and kidney replacement therapy. Associations between longitudinal iron parameter measurements and time-to-event outcomes were examined using a joint model. We enrolled 120 patients (70 males) with median age 50 years. The primary composite outcome was observed in 25 (20.8%) patients-mechanical ventilation was needed in 21 (17.5%) patients and in-hospital mortality occurred in 21 (17.5%) patients. Baseline levels of ferritin and hepcidin were significantly associated with the primary composite outcome. The joint model analysis showed that ferritin levels were significantly associated with primary composite outcome [HR (95% CI) = 2.63 (1.62, 4.24) after adjusting for age and gender]. Both ferritin and serum catalytic iron levels were positively associated with in-hospital mortality [HR (95% CI) = 3.22 (2.05, 5.07) and 1.73 (1.21, 2.47), respectively], after adjusting for age and gender. The study shows an association of ferritin and catalytic iron with adverse outcomes in COVID-19. This suggests new pathophysiologic pathways in this disease, also raising the possibility of considering iron chelation therapy.


Subject(s)
COVID-19/pathology , Iron/blood , Adult , Aged , COVID-19/mortality , COVID-19/virology , Cross-Sectional Studies , Female , Ferritins/blood , Ferritins/metabolism , Hepcidins/blood , Hepcidins/metabolism , Hospital Mortality , Humans , Iron/chemistry , Male , Middle Aged , Proportional Hazards Models , Respiration, Artificial , SARS-CoV-2/isolation & purification , Severity of Illness Index , Transferrin/chemistry , Transferrin/metabolism
19.
JAMA Netw Open ; 4(10): e2127172, 2021 10 01.
Article in English | MEDLINE | ID: covidwho-1449897

ABSTRACT

Importance: Serum ferritin, an acute phase marker of inflammation, has several physiologic functions, including limiting intracellular oxidative stress. Whether the effectiveness of corticosteroids differs according to serum ferritin level in COVID-19 has not been reported. Objective: To examine the association between admission serum ferritin level and methylprednisolone treatment outcomes in nonintubated patients with severe COVID-19. Design, Setting, and Participants: This retrospective cohort study included patients with severe COVID-19 admitted to an academic referral center in Stony Brook, New York, from March 1 to April 15, 2020, receiving high-flow oxygen therapy (fraction of inspired oxygen, ≥50%). The outcomes of treatment with methylprednisolone were estimated using inverse probability of treatment weights, based on a propensity score comprised of clinical and laboratory variables. Patients were followed up for 28 days. Data were analyzed from December 19, 2020, to July 22, 2021. Exposures: Systemic methylprednisolone administered per the discretion of the treating physician. Main Outcomes and Measures: The primary outcome was mortality, and the secondary outcome was a composite of death or mechanical ventilation at 28 days. Results: Among 380 patients with available ferritin data (median [IQR] age, 60 years [49-72] years; 130 [34.2%] women; 250 [65.8%] men; 310 White patients [81.6%]; 47 Black patients [12.4%]; 23 Asian patients [6.1%]), 142 patients (37.4%) received methylprednisolone (median [IQR] daily dose, 160 [120-240] mg). Ferritin levels were similar in patients who received methylprednisolone vs those who did not (median [IQR], 992 [509-1610] ng/mL vs 893 [474-1467] ng/mL; P = .32). In weighted analyses using tertiles of ferritin values (lower: 29-619 ng/mL; middle: 623-1316 ng/mL; upper: 1322-13 418 ng/mL), methylprednisolone was associated with lower mortality in patients with ferritin in the upper tertile (HR, 0.16; 95% CI, 0.06-0.45) and higher mortality in those with ferritin in the middle (HR, 2.46; 95% CI, 1.15-5.28) and lower (HR, 2.43; 95% CI, 1.13-5.22) tertiles (P for interaction < .001). Composite end point rates were lower with methylprednisolone in patients with ferritin in the upper tertile (HR, 0.45; 95% CI, 0.25-0.80) but not in those with ferritin in the middle (HR, 0.83; 95% CI, 0.50-1.39) and lower (HR, 0.89; 95% CI, 0.51-1.55) tertiles (P for interaction = .11). Conclusions and Relevance: In this cohort study of nonintubated patients with severe COVID-19, methylprednisolone was associated with improved clinical outcomes only among patients with admission ferritin in the upper tertile of values.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , COVID-19/drug therapy , Ferritins/blood , Inflammation/blood , Methylprednisolone/therapeutic use , Severity of Illness Index , African Americans , Aged , COVID-19/blood , COVID-19/mortality , COVID-19/therapy , Female , Hospitalization , Humans , Male , Middle Aged , New York , Oxygen Inhalation Therapy , Pneumonia , Respiration, Artificial , Retrospective Studies , SARS-CoV-2 , Treatment Outcome
20.
Exp Biol Med (Maywood) ; 247(2): 145-151, 2022 01.
Article in English | MEDLINE | ID: covidwho-1438228

ABSTRACT

This study sought to evaluate the candidacy of plasma osteopontin (OPN) as a biomarker of COVID-19 severity and multisystem inflammatory condition in children (MIS-C) in children. A retrospective analysis of 26 children (0-21 years of age) admitted to Children's Healthcare of Atlanta with a diagnosis of COVID-19 between March 17 and May 26, 2020 was undertaken. The patients were classified into three categories based on COVID-19 severity levels: asymptomatic or minimally symptomatic (control population, admitted for other non-COVID-19 conditions), mild/moderate, and severe COVID-19. A fourth category of children met the Centers for Disease Control and Prevention's case definition for MIS-C. Residual blood samples were analyzed for OPN, a marker of inflammation using commercial ELISA kits (R&D), and results were correlated with clinical data. This study demonstrates that OPN levels are significantly elevated in children hospitalized with moderate and severe COVID-19 and MIS-C compared to OPN levels in mild/asymptomatic children. Further, OPN differentiated among clinical levels of severity in COVID-19, while other inflammatory markers including maximum erythrocyte sedimentation rate, C-reactive protein and ferritin, minimum lymphocyte and platelet counts, soluble interleukin-2R, and interleukin-6 did not. We conclude OPN is a potential biomarker of COVID-19 severity and MIS-C in children that may have future clinical utility. The specificity and positive predictive value of this marker for COVID-19 and MIS-C are areas for future larger prospective research studies.


Subject(s)
COVID-19/complications , Osteopontin/blood , Severity of Illness Index , Systemic Inflammatory Response Syndrome/blood , Systemic Inflammatory Response Syndrome/diagnosis , Adolescent , Biomarkers/blood , Blood Sedimentation , C-Reactive Protein/analysis , COVID-19/blood , COVID-19/diagnosis , COVID-19/pathology , Child , Child, Preschool , Female , Ferritins/blood , Humans , Infant , Infant, Newborn , Interleukin-2 Receptor alpha Subunit/blood , Interleukin-6/blood , Lymphocyte Count , Male , Platelet Count , Retrospective Studies , SARS-CoV-2 , Systemic Inflammatory Response Syndrome/pathology , Young Adult
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