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1.
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
2.
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
3.
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
4.
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 , Asian Continental Ancestry Group , COVID-19/blood , COVID-19/mortality , COVID-19/therapy , European Continental Ancestry Group , Female , Hospitalization , Humans , Male , Middle Aged , New York , Oxygen Inhalation Therapy , Pneumonia , Respiration, Artificial , Retrospective Studies , SARS-CoV-2 , Treatment Outcome
5.
Trop Biomed ; 38(3): 366-370, 2021 Sep 01.
Article in English | MEDLINE | ID: covidwho-1404406

ABSTRACT

Many biomarkers are used in addition to radiologic examinations to determine the severity of COVID-19. This study aims to determine WBC, neutrophil, lymphocyte, platelet, D-dimer, CRP, AST, ALT, LDH, PT, APTT, INR, urea, creatinine, lactate, and ferritin levels in COVID-19 patients and the effect of their changes on mortality rate. The study was conducted between 11 March 2020 and 31 August 2020 (during the COVID-19 pandemic). A total of 502 patients older than 18 years who presented with suspected COVID-19 were included in the study. Of these 502 patients who applied to the hospital, 229(45.6%) were male and 273(54%) were female. 301(60%) patients were diagnosed with COVID-19 through computed tomography and PCR tests. 201(40%) patients with negative test results constituted the control group. Patients with positive test results 48.2% (n=145) were men, and 51.8% (n=156) were women. The median age of the patients was 51±25 years. The patients tested positive for COVID-19 were divided into three groups as outpatients (26.9%), inpatients (68.8%), and intensive care unit patients (4.3%). The mortality rate of the patients followed via the patient follow-up system after 30 days was determined as 2.7%. The biomarker values of patients examined in this study tested negative and positive for COVID-19 were compared. In the study, D-dimer, ferritin, Lactate, AST, ALT, LDH, Urea, Creatinine, APTT, and INR levels were found to be higher in the positive tested patients than the negative ones. In the study, it was concluded that neutrophil, lymphocyte, CRP, and ferritin ratios should also be followed in the follow-up phase of the disease. It is important that additional measures should be taken in cases when these biomarkers increase by following the values of the patients who started taking treatment. Also, the ratio of biomarkers is crucial in determining whether the treatment has been effective or not.


Subject(s)
COVID-19/mortality , SARS-CoV-2 , Adult , Aged , Biomarkers/blood , C-Reactive Protein/analysis , COVID-19/blood , Female , Ferritins/blood , Humans , Male , Middle Aged
7.
Metallomics ; 13(6)2021 06 11.
Article in English | MEDLINE | ID: covidwho-1387958

ABSTRACT

This report provides perspectives concerning dual roles of serum ferritin as a measure of both iron status and inflammation. We suggest benefits of a lower range of serum ferritin as has occurred for total serum cholesterol and fasting blood glucose levels. Observations during a prospective randomized study using phlebotomy in patients with peripheral arterial disease offered unique insights into dual roles of serum ferritin both as an iron status marker and acute phase reactant. Robust positive associations between serum ferritin, interleukin 6 [IL-6], tissue necrosis factor-alpha, and high sensitivity C-reactive protein were discovered. Elevated serum ferritin and IL-6 levels associated with increased mortality and with reduced mortality at ferritin levels <100 ng mL-1. Epidemiologic studies demonstrate similar outcomes. Extremely elevated ferritin and IL-6 levels also occur in individuals with high mortality due to SARS-CoV-2 infection. Disordered iron metabolism reflected by a high range of serum ferritin level signals disease severity and outcomes. Based upon experimental and epidemiologic data, we suggest testing the hypotheses that optimal ferritin levels for cardiovascular mortality reduction range from 20 to 100 ng mL-1 with % transferrin levels from 20 to 50%, to ensure adequate iron status and that ferritin levels above 194 ng mL-1 associate with all-cause mortality in population cohorts.


Subject(s)
Ferritins/blood , Inflammation/blood , Iron/blood , Peripheral Arterial Disease/blood , Adult , Aged , Aged, 80 and over , Biomarkers/blood , C-Reactive Protein/analysis , COVID-19/blood , COVID-19/prevention & control , COVID-19/virology , Female , Humans , Interleukin-6/blood , Male , Middle Aged , Phlebotomy/methods , SARS-CoV-2/isolation & purification , SARS-CoV-2/physiology , Transferrin/analysis
9.
PLoS One ; 16(8): e0256226, 2021.
Article in English | MEDLINE | ID: covidwho-1374147

ABSTRACT

Coronavirus disease (COVID)-19, as a result of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, has been the direct cause of over 2.2 million deaths worldwide. A timely coordinated host-immune response represents the leading driver for restraining SARS-CoV-2 infection. Indeed, several studies have described dysregulated immunity as the crucial determinant for critical illness and the failure of viral control. Improved understanding and management of COVID-19 could greatly reduce the mortality and morbidity caused by SARS-CoV-2. One aspect of the immune response that has to date been understudied is whether lipid mediator production is dysregulated in critically ill patients. In the present study, plasma from COVID-19 patients with either severe disease and those that were critically ill was collected and lipid mediator profiles were determined using liquid chromatography tandem mass spectrometry. Results from these studies indicated that plasma concentrations of both pro-inflammatory and pro-resolving lipid mediator were reduced in critically ill patients when compared with those with severe disease. Furthermore, plasma concentrations of a select group of mediators that included the specialized pro-resolving mediators (SPM) Resolvin (Rv) D1 and RvE4 were diagnostic of disease severity. Interestingly, peripheral blood SPM concentrations were also linked with outcome in critically ill patients, where we observed reduced overall concentrations of these mediators in those patients that did not survive. Together the present findings establish a link between plasma lipid mediators and disease severity in patients with COVID-19 and indicate that plasma SPM concentrations may be linked with survival in these patients.


Subject(s)
COVID-19/diagnosis , Docosahexaenoic Acids/blood , SARS-CoV-2/isolation & purification , Adult , Aged , COVID-19/virology , Chromatography, High Pressure Liquid , Critical Illness , Female , Ferritins/blood , Fibrin Fibrinogen Degradation Products/analysis , Humans , Male , Middle Aged , Severity of Illness Index , Tandem Mass Spectrometry , Up-Regulation
10.
Int J Mol Sci ; 21(21)2020 Nov 03.
Article in English | MEDLINE | ID: covidwho-1344351

ABSTRACT

Progressive respiratory failure is seen as a major cause of death in severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2)-induced infection. Relatively little is known about the associated morphologic and molecular changes in the circulation of these patients. In particular, platelet and erythrocyte pathology might result in severe vascular issues, and the manifestations may include thrombotic complications. These thrombotic pathologies may be both extrapulmonary and intrapulmonary and may be central to respiratory failure. Previously, we reported the presence of amyloid microclots in the circulation of patients with coronavirus disease 2019 (COVID-19). Here, we investigate the presence of related circulating biomarkers, including C-reactive protein (CRP), serum ferritin, and P-selectin. These biomarkers are well-known to interact with, and cause pathology to, platelets and erythrocytes. We also study the structure of platelets and erythrocytes using fluorescence microscopy (using the markers PAC-1 and CD62PE) and scanning electron microscopy. Thromboelastography and viscometry were also used to study coagulation parameters and plasma viscosity. We conclude that structural pathologies found in platelets and erythrocytes, together with spontaneously formed amyloid microclots, may be central to vascular changes observed during COVID-19 progression, including thrombotic microangiopathy, diffuse intravascular coagulation, and large-vessel thrombosis, as well as ground-glass opacities in the lungs. Consequently, this clinical snapshot of COVID-19 strongly suggests that it is also a true vascular disease and considering it as such should form an essential part of a clinical treatment regime.


Subject(s)
Blood Platelets/pathology , Cardiovascular Diseases/virology , Coronavirus Infections/blood , Coronavirus Infections/pathology , Erythrocytes/pathology , Ferritins/blood , P-Selectin/blood , Pneumonia, Viral/blood , Pneumonia, Viral/pathology , Betacoronavirus/isolation & purification , Blood Coagulation/physiology , Blood Platelets/virology , COVID-19 , Cardiovascular Diseases/blood , Cardiovascular Diseases/pathology , Coronavirus Infections/virology , Erythrocytes/virology , Female , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/virology , SARS-CoV-2 , Thrombosis/pathology , Thrombosis/virology
11.
JAMA ; 326(3): 230-239, 2021 07 20.
Article in English | MEDLINE | ID: covidwho-1338164

ABSTRACT

Importance: Effective treatments for patients with severe COVID-19 are needed. Objective: To evaluate the efficacy of canakinumab, an anti-interleukin-1ß antibody, in patients hospitalized with severe COVID-19. Design, Setting, and Participants: This randomized, double-blind, placebo-controlled phase 3 trial was conducted at 39 hospitals in Europe and the United States. A total of 454 hospitalized patients with COVID-19 pneumonia, hypoxia (not requiring invasive mechanical ventilation [IMV]), and systemic hyperinflammation defined by increased blood concentrations of C-reactive protein or ferritin were enrolled between April 30 and August 17, 2020, with the last assessment of the primary end point on September 22, 2020. Intervention: Patients were randomly assigned 1:1 to receive a single intravenous infusion of canakinumab (450 mg for body weight of 40-<60 kg, 600 mg for 60-80 kg, and 750 mg for >80 kg; n = 227) or placebo (n = 227). Main Outcomes and Measures: The primary outcome was survival without IMV from day 3 to day 29. Secondary outcomes were COVID-19-related mortality, measurements of biomarkers of systemic hyperinflammation, and safety evaluations. Results: Among 454 patients who were randomized (median age, 59 years; 187 women [41.2%]), 417 (91.9%) completed day 29 of the trial. Between days 3 and 29, 198 of 223 patients (88.8%) survived without requiring IMV in the canakinumab group and 191 of 223 (85.7%) in the placebo group, with a rate difference of 3.1% (95% CI, -3.1% to 9.3%) and an odds ratio of 1.39 (95% CI, 0.76 to 2.54; P = .29). COVID-19-related mortality occurred in 11 of 223 patients (4.9%) in the canakinumab group vs 16 of 222 (7.2%) in the placebo group, with a rate difference of -2.3% (95% CI, -6.7% to 2.2%) and an odds ratio of 0.67 (95% CI, 0.30 to 1.50). Serious adverse events were observed in 36 of 225 patients (16%) treated with canakinumab vs 46 of 223 (20.6%) who received placebo. Conclusions and Relevance: Among patients hospitalized with severe COVID-19, treatment with canakinumab, compared with placebo, did not significantly increase the likelihood of survival without IMV at day 29. Trial Registration: ClinicalTrials.gov Identifier: NCT04362813.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/drug therapy , Interleukin-1beta/antagonists & inhibitors , Respiration, Artificial/statistics & numerical data , Aged , Antibodies, Monoclonal, Humanized/adverse effects , C-Reactive Protein/analysis , COVID-19/mortality , COVID-19/therapy , Combined Modality Therapy , Double-Blind Method , Female , Ferritins/blood , Fibrin Fibrinogen Degradation Products/analysis , Hospitalization , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Survival Rate , Treatment Outcome
12.
Biomolecules ; 11(8)2021 08 01.
Article in English | MEDLINE | ID: covidwho-1334994

ABSTRACT

Severe coronavirus disease 2019 (COVID-19) is associated with hyperinflammation leading to organ injury, including respiratory failure. Galectin-3 was implicated in innate immunological response to infections and in chronic fibrosis. The aim of our preliminary study was the assessment of the diagnostic utility of serum galectin-3 in patients with COVID-19. The prospective observational study included adult patients admitted with active COVID-19 and treated in tertiary hospital between June and July 2020. The diagnosis was confirmed by the quantitative detection of nucleic acid of severe acute respiratory syndrome coronavirus 2 in nasopharyngeal swabs. Galectin-3 was measured by enzyme immunoassay in serum samples obtained during the first five days of hospital stay. We included 70 patients aged 25 to 73 years; 90% had at least one comorbidity. During the hospital stay, 32.9% were diagnosed with COVID-19 pneumonia and 12.9% required treatment in the intensive care unit (ICU). Serum galectin-3 was significantly increased in patients who developed pneumonia, particularly those who required ICU admission. Positive correlations were found between galectin-3 and inflammatory markers (interleukin-6, C-reactive protein, ferritin, pentraxin-3), a marker of endothelial injury (soluble fms-like tyrosine kinase-1), and a range of tissue injury markers. Serum galectin-3 enabled the diagnosis of pneumonia with moderate diagnostic accuracy and the need for ICU treatment with high diagnostic accuracy. Our findings strengthen the hypothesis that galectin-3 may be involved in severe COVID-19. Further studies are planned to confirm the preliminary results and to verify possible associations of galectin-3 with long-term consequences of COVID-19, including pulmonary fibrosis.


Subject(s)
COVID-19/blood , Galectin 3/blood , Adult , Biomarkers/blood , C-Reactive Protein/analysis , COVID-19/epidemiology , COVID-19/pathology , COVID-19/therapy , Comorbidity , Critical Care/statistics & numerical data , Female , Ferritins/blood , Humans , Interleukin-6/blood , Male , Middle Aged , Serum Amyloid P-Component/analysis , Vascular Endothelial Growth Factor Receptor-1/blood
13.
BMC Infect Dis ; 21(1): 398, 2021 Apr 29.
Article in English | MEDLINE | ID: covidwho-1327867

ABSTRACT

BACKGROUND: Secondary hemophagocytic lymphohistiocytosis (sHLH) is a life-threatening hyperinflammatory event and a fatal complication of viral infections. Whether sHLH may also be observed in patients with a cytokine storm induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is still uncertain. We aimed to determine the incidence of sHLH in severe COVID-19 patients and evaluate the underlying risk factors. METHOD: Four hundred fifteen severe COVID-19 adult patients were retrospectively assessed for hemophagocytosis score (HScore). A subset of 7 patients were unable to be conclusively scored due to insufficient patient data. RESULTS: In 408 patients, 41 (10.04%) had an HScore ≥169 and were characterized as "suspected sHLH positive". Compared with patients below a HScore threshold of 98, the suspected sHLH positive group had higher D-dimer, total bilirubin, alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, serum creatinine, triglycerides, ferritin, interleukin-6, C-reactive protein, procalcitonin, lactate dehydrogenase, creatine kinase isoenzyme, troponin, Sequential Organ Failure Assessment (SOFA) score, while leukocyte, hemoglobin, platelets, lymphocyte, fibrinogen, pre-albumin, albumin levels were significantly lower (all P < 0.05). Multivariable logistic regression revealed that high ferritin (>1922.58 ng/mL), low platelets (<101 × 109/L) and high triglycerides (>2.28 mmol/L) were independent risk factors for suspected sHLH in COVID-19 patients. Importantly, COVID-19 patients that were suspected sHLH positive had significantly more multi-organ failure. Additionally, a high HScore (>98) was an independent predictor for mortality in COVID-19. CONCLUSIONS: HScore should be measured as a prognostic biomarker in COVID-19 patients. In particular, it is important that HScore is assessed in patients with high ferritin, triglycerides and low platelets to improve the detection of suspected sHLH.


Subject(s)
COVID-19/complications , Lymphohistiocytosis, Hemophagocytic/etiology , Adult , Aged , Aspartate Aminotransferases/blood , COVID-19/epidemiology , COVID-19/therapy , China/epidemiology , Comorbidity , Cytokine Release Syndrome/complications , Cytokine Release Syndrome/virology , Female , Ferritins/blood , Humans , Incidence , Lymphocyte Count , Lymphohistiocytosis, Hemophagocytic/epidemiology , Lymphohistiocytosis, Hemophagocytic/mortality , Male , Middle Aged , Mortality , Retrospective Studies , Risk Factors
14.
Emerg Med J ; 38(9): 685-691, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1320447

ABSTRACT

BACKGROUND: Guidelines recommend maximal efforts to obtain blood and sputum cultures in patients with COVID-19, as bacterial coinfection is associated with worse outcomes. The aim of this study was to evaluate the yield of bacteriological tests, including blood and sputum cultures, and the association of multiple biomarkers and the Pneumonia Severity Index (PSI) with clinical and microbiological outcomes in patients with COVID-19 presenting to the emergency department (ED). METHODS: This is a substudy of a large observational cohort study (PredictED study). The PredictED included adult patients from whom a blood culture was drawn at the ED of Haga Teaching Hospital, The Netherlands. For this substudy, all patients who tested positive for SARS-CoV-2 by PCR in March and April 2020 were included. The primary outcome was the incidence of bacterial coinfection. We used logistic regression analysis for associations of procalcitonin, C reactive protein (CRP), ferritin, lymphocyte count and PSI score with a severe disease course, defined as intensive care unit admission and/or 30-day mortality. The area under the receiver operating characteristics curve (AUC) quantified the discriminatory performance. RESULTS: We included 142 SARS-CoV-2 positive patients. On presentation, the median duration of symptoms was 8 days. 41 (29%) patients had a severe disease course and 24 (17%) died within 30 days. The incidence of bacterial coinfection was 2/142 (1.4%). None of the blood cultures showed pathogen growth while 6.3% was contaminated. The AUCs for predicting severe disease were 0.76 (95% CI 0.68 to 0.84), 0.70 (0.61 to 0.79), 0.62 (0.51 to 0.74), 0.62 (0.51 to 0.72) and 0.72 (0.63 to 0.81) for procalcitonin, CRP, ferritin, lymphocyte count and PSI score, respectively. CONCLUSION: Blood cultures appear to have limited value while procalcitonin and the PSI appear to be promising tools in helping physicians identify patients at risk for severe disease course in COVID-19 at presentation to the ED.


Subject(s)
Bacterial Infections/diagnosis , Bacteriological Techniques/methods , COVID-19/diagnosis , Coinfection/diagnosis , Adult , Aged , Aged, 80 and over , Bacterial Infections/blood , Bacterial Infections/complications , Bacterial Infections/microbiology , Bacteriological Techniques/statistics & numerical data , C-Reactive Protein/analysis , COVID-19/blood , COVID-19/complications , COVID-19/virology , COVID-19 Nucleic Acid Testing , Coinfection/blood , Coinfection/epidemiology , Coinfection/microbiology , Emergency Service, Hospital , Female , Ferritins/blood , Humans , Incidence , Lymphocyte Count , Male , Middle Aged , Netherlands/epidemiology , Procalcitonin/blood , Prognosis , ROC Curve , Retrospective Studies , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Severity of Illness Index
15.
Sci Rep ; 11(1): 14471, 2021 07 14.
Article in English | MEDLINE | ID: covidwho-1310815

ABSTRACT

Early detection of severe forms of COVID-19 is absolutely essential for timely triage of patients. We longitudinally followed-up two well-characterized patient groups, hospitalized moderate to severe (n = 26), and ambulatory mild COVID-19 patients (n = 16) at home quarantine. Human D-dimer, C-reactive protein (CRP), ferritin, cardiac troponin I, interleukin-6 (IL-6) levels were measured on day 1, day 7, day 14 and day 28. All hospitalized patients were SARS-CoV-2 positive on admission, while all ambulatory patients were SARS-CoV-2 positive at recruitment. Hospitalized patients had higher D-dimer, CRP and ferritin, cardiac troponin I and IL-6 levels than ambulatory patients (p < 0.001, p < 0.001, p = 0.016, p = 0.035, p = 0.002 respectively). Hospitalized patients experienced significant decreases in CRP, ferritin and IL-6 levels from admission to recovery (p < 0.001, p = 0.025, and p = 0.001 respectively). Cardiac troponin I levels were high during the acute phase in both hospitalized and ambulatory patients, indicating a potential myocardial injury. In summary, D-dimer, CRP, ferritin, cardiac troponin I, IL-6 are predictive laboratory markers and can largely determine the clinical course of COVID-19, in particular the prognosis of critically ill COVID-19 patients.


Subject(s)
COVID-19/blood , COVID-19/diagnosis , Ambulatory Care , Biomarkers/blood , C-Reactive Protein/analysis , Early Diagnosis , Ferritins/blood , Fibrin Fibrinogen Degradation Products/analysis , Follow-Up Studies , Hospitalization , Humans , Interleukin-6/blood , Longitudinal Studies , Pneumonia, Viral/blood , Pneumonia, Viral/diagnosis , Precision Medicine , Prognosis , Quarantine , SARS-CoV-2 , Severity of Illness Index , Troponin I/blood
16.
Strahlenther Onkol ; 197(11): 1010-1020, 2021 11.
Article in English | MEDLINE | ID: covidwho-1298545

ABSTRACT

PURPOSE: To evaluate the efficacy and safety of lung low-dose radiation therapy (LD-RT) for pneumonia in patients with coronavirus disease 2019 (COVID-19). MATERIALS AND METHODS: Inclusion criteria comprised patients with COVID-19-related moderate-severe pneumonia warranting hospitalization with supplemental O2 and not candidates for admission to the intensive care unit because of comorbidities or general status. All patients received single lung dose of 0.5 Gy. Respiratory and systemic inflammatory parameters were evaluated before irradiation, at 24 h and 1 week after LD-RT. Primary endpoint was increased in the ratio of arterial oxygen partial pressure (PaO2) or the pulse oximetry saturation (SpO2) to fractional inspired oxygen (FiO2) ratio of at least 20% at 24 h with respect to the preirradiation value. RESULTS: Between June and November 2020, 36 patients with COVID-19 pneumonia and a mean age of 84 years were enrolled. Seventeen were women and 19 were men and all of them had comorbidities. All patients had bilateral pulmonary infiltrates on chest X­ray. All patients received dexamethasone treatment. Mean SpO2 pretreatment value was 94.28% and the SpO2/FiO2 ratio varied from 255 mm Hg to 283 mm Hg at 24 h and to 381 mm Hg at 1 week, respectively. In those who survived (23/36, 64%), a significant improvement was observed in the percentage of lung involvement in the CT scan at 1 week after LD-RT. No adverse effects related to radiation treatment have been reported. CONCLUSIONS: LD-RT appears to be a feasible and safe option in a population with COVID-19 bilateral interstitial pneumonia in the presence of significant comorbidities.


Subject(s)
COVID-19/radiotherapy , Radiotherapy, Conformal/methods , SARS-CoV-2 , Aged , Aged, 80 and over , Anti-Inflammatory Agents/therapeutic use , C-Reactive Protein/analysis , COVID-19/diagnostic imaging , COVID-19/mortality , COVID-19/therapy , Cause of Death , Combined Modality Therapy , Comorbidity , Dexamethasone/therapeutic use , Female , Ferritins/blood , Fibrin Fibrinogen Degradation Products/analysis , Hospital Mortality , Humans , Interleukin-6/blood , L-Lactate Dehydrogenase/blood , Lung/diagnostic imaging , Lung/radiation effects , Lung Diseases, Interstitial/diagnostic imaging , Lung Diseases, Interstitial/drug therapy , Lung Diseases, Interstitial/radiotherapy , Lung Diseases, Interstitial/therapy , Male , Oxygen/blood , Oxygen/therapeutic use , Oxygen Inhalation Therapy , Partial Pressure , Prospective Studies , Radiotherapy Dosage , Severity of Illness Index , Tomography, X-Ray Computed , Treatment Outcome
17.
PLoS One ; 16(6): e0253894, 2021.
Article in English | MEDLINE | ID: covidwho-1286873

ABSTRACT

OBJECTIVE: To describe the laboratory parameters and biomarkers of the cytokine storm syndrome associated with severe and fatal COVID-19 cases. METHODS: A search with standardized descriptors and synonyms was performed on November 28th, 2020 of the MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, LILACS, and IBECS to identify studies of interest. Grey literature searches and snowballing techniques were additionally utilized to identify yet-unpublished works and related citations. Two review authors independently screened the retrieved titles and abstracts, selected eligible studies for inclusion, extracted data from the included studies, and then assessed the risk of bias using the Newcastle-Ottawa Scale. Eligible studies were those including laboratory parameters-including serum interleukin-6 levels-from mild, moderate, or severe COVID-19 cases. Laboratory parameters, such as interleukin-6, ferritin, hematology, C-Reactive Protein, procalcitonin, lactate dehydrogenase, aspartate aminotransferase, creatinine, and D-dimer, were extracted from the studies. Meta-analyses were conducted using the laboratory data to estimate mean differences with associated 95% confidence intervals. DATA SYNTHESIS: The database search yielded 9,620 records; 40 studies (containing a total of 9,542 patients) were included in the final analysis. Twenty-one studies (n = 4,313) assessed laboratory data related to severe COVID-19 cases, eighteen studies (n = 4,681) assessed predictors for fatal COVID-19 cases and one study (n = 548) assessed laboratory biomarkers related to severe and fatal COVID-19 cases. Lymphopenia, thrombocytopenia, and elevated levels of interleukin-6, ferritin, D-dimer, aspartate aminotransferase, C-Reactive-Protein, procalcitonin, creatinine, neutrophils and leucocytes were associated with severe and fatal COVID-19 cases. CONCLUSIONS: This review points to interleukin-6, ferritin, leukocytes, neutrophils, lymphocytes, platelets, C-Reactive Protein, procalcitonin, lactate dehydrogenase, aspartate aminotransferase, creatinine, and D-dimer as important biomarkers of cytokine storm syndrome. Elevated levels of interleukin-6 and hyperferritinemia should be considered as red flags of systemic inflammation and poor prognosis in COVID-19.


Subject(s)
Biomarkers/blood , COVID-19/pathology , Cytokine Release Syndrome/diagnosis , C-Reactive Protein/analysis , COVID-19/complications , COVID-19/mortality , COVID-19/virology , Cytokine Release Syndrome/etiology , Ferritins/blood , Humans , Interleukin-6/blood , Leukocytes/cytology , Leukocytes/metabolism , SARS-CoV-2/isolation & purification , Severity of Illness Index
18.
Sci Rep ; 11(1): 13431, 2021 06 28.
Article in English | MEDLINE | ID: covidwho-1286474

ABSTRACT

Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that leads to severe respiratory failure (RF). It is known that host exposure to viral infection triggers an iron-lowering response to mitigate pathogenic load and tissue damage. However, the association between host iron-lowering response and COVID-19 severity is not clear. This two-center observational study of 136 adult hospitalized COVID-19 patients analyzed the association between disease severity and initial serum iron, total iron-binding capacity (TIBC), and transferrin saturation (TSAT) levels. Serum iron levels were significantly lower in patients with mild RF than in the non-RF group; however, there were no significant differences in iron levels between the non-RF and severe RF groups, depicting a U-shaped association between serum iron levels and disease severity. TIBC levels decreased significantly with increasing severity; consequently, TSAT was significantly higher in patients with severe RF than in other patients. Multivariate analysis including only patients with RF adjusted for age and sex demonstrated that higher serum iron and TSAT levels were independently associated with the development of severe RF, indicating that inadequate response to lower serum iron might be an exacerbating factor for COVID-19.


Subject(s)
COVID-19/pathology , Iron/blood , Adult , Aged , COVID-19/complications , COVID-19/virology , Female , Ferritins/blood , Hospitalization , Humans , Iron/metabolism , Logistic Models , Male , Middle Aged , Respiratory Insufficiency/etiology , SARS-CoV-2/isolation & purification , Severity of Illness Index , Transferrin/analysis
19.
J Laryngol Otol ; 135(8): 723-728, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1286411

ABSTRACT

OBJECTIVE: To analyse the correlations between olfactory psychophysical scores and the serum levels of D-dimer, C-reactive protein, ferritin, lactate dehydrogenase, procalcitonin and neutrophil-to-lymphocyte ratio in coronavirus disease 2019 patients. METHODS: Patients underwent psychophysical olfactory assessment with the Connecticut Chemosensory Clinical Research Center test, and determination of blood serum levels of the inflammatory markers D-dimer, C-reactive protein, ferritin, lactate dehydrogenase, procalcitonin and neutrophil-to-lymphocyte ratio within 10 days of the clinical onset of coronavirus disease 2019 and 60 days after. RESULTS: Seventy-seven patients were included in this study. D-dimer, procalcitonin, ferritin and neutrophil-to-lymphocyte ratio correlated significantly with severe coronavirus disease 2019. No significant correlations were found between baseline and 60-day Connecticut Chemosensory Clinical Research Center test scores and the inflammatory markers assessed. CONCLUSION: Olfactory disturbances appear to have little prognostic value in predicting the severity of coronavirus disease 2019 compared to D-dimer, ferritin, procalcitonin and neutrophil-to-lymphocyte ratio. The lack of correlation between the severity and duration of olfactory disturbances and serum levels of inflammatory markers seems to further suggest that the pathogenetic mechanisms underlying the loss of smell in coronavirus disease 2019 patients are related to local rather than systemic inflammatory factors.


Subject(s)
COVID-19/pathology , Olfaction Disorders/etiology , Aged , Biomarkers/blood , C-Reactive Protein/analysis , COVID-19/blood , COVID-19/complications , Female , Ferritins/blood , Fibrin Fibrinogen Degradation Products/analysis , Humans , Inflammation/blood , L-Lactate Dehydrogenase/blood , Lymphocyte Count , Male , Middle Aged , Olfaction Disorders/blood , Olfaction Disorders/pathology , Procalcitonin/blood , Severity of Illness Index
20.
Nutrients ; 13(7)2021 Jun 24.
Article in English | MEDLINE | ID: covidwho-1285399

ABSTRACT

COVID-19 is a pandemic disease that causes severe pulmonary damage and hyperinflammation. Vitamin A is a crucial factor in the development of immune functions and is known to be reduced in cases of acute inflammation. This prospective, multicenter observational cross-sectional study analyzed vitamin A plasma levels in SARS-CoV-2 infected individuals, and 40 hospitalized patients were included. Of these, 22 developed critical disease (Acute Respiratory Distress Syndrome [ARDS]/Extracorporeal membrane oxygenation [ECMO]), 9 developed severe disease (oxygen supplementation), and 9 developed moderate disease (no oxygen supplementation). A total of 47 age-matched convalescent persons that had been earlier infected with SARS-CoV-2 were included as the control group. Vitamin A plasma levels were determined by high-performance liquid chromatography. Reduced vitamin A plasma levels correlated significantly with increased levels of inflammatory markers (CRP, ferritin) and with markers of acute SARS-CoV-2 infection (reduced lymphocyte count, LDH). Vitamin A levels were significantly lower in hospitalized patients than in convalescent persons (p < 0.01). Of the hospitalized patients, those who were critically ill showed significantly lower vitamin A levels than those who were moderately ill (p < 0.05). Vitamin A plasma levels below 0.2 mg/L were significantly associated with the development of ARDS (OR = 5.54 [1.01-30.26]; p = 0.048) and mortality (OR 5.21 [1.06-25.5], p = 0.042). Taken together, we conclude that vitamin A plasma levels in COVID-19 patients are reduced during acute inflammation and that severely reduced plasma levels of vitamin A are significantly associated with ARDS and mortality.


Subject(s)
COVID-19/blood , Vitamin A/blood , Adult , Aged , Biomarkers/blood , C-Reactive Protein/analysis , COVID-19/mortality , Chromatography, Liquid/methods , Critical Illness , Cross-Sectional Studies , Extracorporeal Membrane Oxygenation/statistics & numerical data , Female , Ferritins/blood , Hospitalization , Humans , Inflammation/epidemiology , Lymphocyte Count , Male , Middle Aged , Prospective Studies , Respiratory Distress Syndrome/epidemiology , SARS-CoV-2 , Severity of Illness Index
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