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1.
J Med Life ; 15(2): 180-187, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1789887

ABSTRACT

COVID-19 is an emerging infectious disease caused by the novel enveloped single-stranded RNA virus quickly declared a pandemic. This study aimed to investigate the severity of COVID-19 infection in patients with blood group type A. A cross-sectional study was conducted at Al-Amal specialized hospital, Al-Najaf (March 8 to March 20/2021). The study included 123 hospitalized patients (63 females and 60 males), aged between 15-95 years, diagnosed with COVID-19, tested for blood group, blood sugar, blood urea, D-dimer, and serum ferritin. Results indicated significant differences in blood sugar and D-dimer in patients with type A blood group at P>0.05. At the same time, no significant difference was found in blood urea and ferritin at P>0.05. The majority of patients showed elevated levels of blood sugar, blood urea, serum D-dimer and ferritin. COVID-19 can infect people of all ages and causes severe infection in all blood groups.


Subject(s)
Blood Group Antigens , COVID-19 , Adolescent , Adult , Aged , Aged, 80 and over , Biomarkers , Blood Glucose , Cross-Sectional Studies , Female , Ferritins , Fibrin Fibrinogen Degradation Products , Hematologic Tests , Humans , Male , Middle Aged , SARS-CoV-2 , Urea , Young Adult
2.
J Infect Dev Ctries ; 16(3): 409-417, 2022 Mar 31.
Article in English | MEDLINE | ID: covidwho-1786138

ABSTRACT

INTRODUCTION: Determining prognostic factors in patients with coronavirus disease (COVID-19) can have great impact on treatment planning and follow-up strategies. Herein, we aimed to evaluate prognostic factors and clinical scores for confirmed COVID-19 patients in a tertiary-care hospital in the Bursa region of Turkey. METHODOLOGY: Patients who had been diagnosed with COVID-19 microbiologically and/or radiologically between March and October 2020 in a tertiary-care university hospital were enrolled retrospectively. Adult patients (≥ 18 years) with a clinical spectrum of moderate, severe, or critical illness were included. The dependent variable was 30-day mortality and logistic regression analysis was used to evaluate any variables with a significant p value (< 0.05) in univariate analysis. RESULTS: A total of 257 patients were included in the study. The mortality rate (30-day) was 14.4%. In logistic regression analysis, higher scores on sequential organ failure assessment (SOFA) (p < 0.001, odds ratio (OR) = 1.86, 95% CI = 1.42-2.45) and CURB-65 pneumonia severity criteria (p = 0.001, OR = 2.60, 95% CI = 1.47-4.57) were found to be significant in predicting mortality at admission. In deceased patients, there were also significant differences between the baseline, day-3, day-7, and day-14 results of D-dimer (p = 0.01), ferritin (p = 0.042), leukocyte (p = 0.019), and neutrophil (p = 0.007) counts. CONCLUSIONS: In our study of COVID-19 patients, we found that high SOFA and CURB-65 scores on admission were associated with increased mortality. In addition, D-dimer, ferritin, leukocyte and neutrophil counts significantly increased after admission in patients who died.


Subject(s)
COVID-19 , Adult , Ferritins , Humans , Prognosis , ROC Curve , Retrospective Studies
3.
CMAJ ; 194(14): E513-E523, 2022 Apr 11.
Article in English | MEDLINE | ID: covidwho-1785217

ABSTRACT

BACKGROUND: SARS-CoV-2 infection can lead to multisystem inflammatory syndrome in children (MIS-C). We sought to investigate risk factors for admission to the intensive care unit (ICU) and explored changes in disease severity over time. METHODS: We obtained data from chart reviews of children younger than 18 years with confirmed or probable MIS-C who were admitted to 15 hospitals in Canada, Iran and Costa Rica between Mar. 1, 2020, and Mar. 7, 2021. Using multivariable analyses, we evaluated whether admission date and other characteristics were associated with ICU admission or cardiac involvement. RESULTS: Of 232 children with MIS-C (median age 5.8 yr), 130 (56.0%) were male and 50 (21.6%) had comorbidities. Seventy-three (31.5%) patients were admitted to the ICU but none died. We observed an increased risk of ICU admission among children aged 13-17 years (adjusted risk difference 27.7%, 95% confidence interval [CI] 8.3% to 47.2%), those aged 6-12 years (adjusted risk difference 25.2%, 95% CI 13.6% to 36.9%) or those with initial ferritin levels greater than 500 µg/L (adjusted risk difference 18.4%, 95% CI 5.6% to 31.3%). Children admitted to hospital after Oct. 31, 2020, had numerically higher rates of ICU admission (adjusted risk difference 12.3%, 95% CI -0.3% to 25.0%) and significantly higher rates of cardiac involvement (adjusted risk difference 30.9%, 95% CI 17.3% to 44.4%). At Canadian sites, the risk of ICU admission was significantly higher for children admitted to hospital between December 2020 and March 2021 than those admitted between March and May 2020 (adjusted risk difference 25.3%, 95% CI 6.5% to 44.0%). INTERPRETATION: We observed that age and higher ferritin levels were associated with more severe MIS-C. We observed greater severity of MIS-C later in the study period. Whether emerging SARS-CoV-2 variants pose different risks of severe MIS-C needs to be determined.


Subject(s)
COVID-19 , Connective Tissue Diseases , COVID-19/complications , COVID-19/epidemiology , Canada/epidemiology , Child , Child, Preschool , Cohort Studies , Ferritins , Humans , Male , SARS-CoV-2 , Systemic Inflammatory Response Syndrome
4.
Cell Rep ; 38(11): 110514, 2022 03 15.
Article in English | MEDLINE | ID: covidwho-1739598

ABSTRACT

The success of nucleoside-modified mRNAs in lipid nanoparticles (mRNA-LNP) as COVID-19 vaccines heralded a new era of vaccine development. For HIV-1, multivalent envelope (Env) trimer protein nanoparticles are superior immunogens compared with trimers alone for priming of broadly neutralizing antibody (bnAb) B cell lineages. The successful expression of complex multivalent nanoparticle immunogens with mRNAs has not been demonstrated. Here, we show that mRNAs can encode antigenic Env trimers on ferritin nanoparticles that initiate bnAb precursor B cell expansion and induce serum autologous tier 2 neutralizing activity in bnAb precursor VH + VL knock-in mice. Next-generation sequencing demonstrates acquisition of critical mutations, and monoclonal antibodies that neutralize heterologous HIV-1 isolates are isolated. Thus, mRNA-LNP can encode complex immunogens and may be of use in design of germline-targeting and sequential boosting immunogens for HIV-1 vaccine development.


Subject(s)
AIDS Vaccines , COVID-19 , HIV-1 , Nanoparticles , Animals , Antibodies, Monoclonal , Antibodies, Neutralizing , COVID-19 Vaccines , Epitopes , Ferritins/genetics , HIV Antibodies , Humans , Liposomes , Mice , RNA, Messenger , env Gene Products, Human Immunodeficiency Virus/genetics
6.
PLoS One ; 17(3): e0265089, 2022.
Article in English | MEDLINE | ID: covidwho-1731605

ABSTRACT

BACKGROUND: Peru is the country with the world's highest COVID-19 death rate per capita. Characteristics associated with increased mortality among adult patients with COVID-19 pneumonia in this setting are not well described. METHODS: Retrospective, single-center cohort study including 1537 adult patients hospitalized with a diagnosis of SARS-CoV-2 pneumonia between May 2020 and August 2020 at a national hospital in Lima, Peru. The primary outcome measure was in-hospital mortality. RESULTS: In-hospital mortality was 49.71%. The mean age was 60 ± 14.25 years, and 68.38% were males. We found an association between mortality and inflammatory markers, mainly leukocytes, D-dimer, lactate dehydrogenase, C-reactive protein and ferritin. A multivariate model adjusted for age, hypertension, diabetes mellitus, and corticosteroid use demonstrated that in-hospital mortality was associated with greater age (RR: 2.01, 95%CI: 1.59-2.52) and a higher level of oxygen requirement (RR: 2.77, 95%CI: 2.13-3.62). Conclusions: In-hospital mortality among COVID-19 patients in Peru is high and is associated with greater age and higher oxygen requirements.


Subject(s)
COVID-19/mortality , Hospitalization/statistics & numerical data , Age Factors , Aged , C-Reactive Protein/analysis , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/virology , Comorbidity , Female , Ferritins/analysis , Fibrin Fibrinogen Degradation Products/analysis , Hospital Mortality , Humans , Male , Middle Aged , Peru/epidemiology , Respiration, Artificial , Retrospective Studies , Risk Factors , SARS-CoV-2/isolation & purification
7.
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
8.
Sci Transl Med ; 14(632): eabi5735, 2022 Feb 16.
Article in English | MEDLINE | ID: covidwho-1691438

ABSTRACT

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants stresses the continued need for next-generation vaccines that confer broad protection against coronavirus disease 2019 (COVID-19). We developed and evaluated an adjuvanted SARS-CoV-2 spike ferritin nanoparticle (SpFN) vaccine in nonhuman primates. High-dose (50 µg) SpFN vaccine, given twice 28 days apart, induced a Th1-biased CD4 T cell helper response and elicited neutralizing antibodies against SARS-CoV-2 wild-type and variants of concern, as well as against SARS-CoV-1. These potent humoral and cell-mediated immune responses translated into rapid elimination of replicating virus in the upper and lower airways and lung parenchyma of nonhuman primates following high-dose SARS-CoV-2 respiratory challenge. The immune response elicited by SpFN vaccination and resulting efficacy in nonhuman primates supports the utility of SpFN as a vaccine candidate for SARS-causing betacoronaviruses.


Subject(s)
COVID-19 , Nanoparticles , Animals , Antibodies, Neutralizing , Antibodies, Viral , COVID-19 Vaccines , Ferritins , Humans , Immunity , Macaca mulatta , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
10.
Int Immunopharmacol ; 105: 108542, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1638183

ABSTRACT

It remains important to investigate the changing and impact of routine blood values (RBVs) in order to predict mortality and follow an appropriate treatment in COVID-19 patients. In the study, the importance of RBVs in the mortality of patients with COVID-19 was investigated. The changes in the biochemical, hematological, and immunological parameters of patients who recovered (n = 4364) and died (n = 233) from COVID-19 over time and their relationship with the mortality of the disease were evaluated retrospectively. Odds ratios of the parameters affecting one-month mortality were calculated by running multiple-logistic-regression analysis. The cut off values and diagnostic efficiencies of the parameters that posed a risk for mortality were obtained via receiver operating curve analysis. It was determined that the C-reactive protein (CRP), D-dimer, procalcitonin, erythrocyte-sedimentation-rate (ESR), troponin values were at abnormal levels until death occurred in the patients who died. In addition, the procalcitonin levels were consistently high in patients who died. The patients who died generally had a sustained increase in their leukocyte and neutrophil levels and biochemical variables, and an ongoing decrease in lymphopenia and eosinopenia levels. Although significant changes were observed in liver function tests, cardiac troponin, hemogram values, kidney function tests and parameters related to inflammation in deceased patients, high ESR, international-normalized-ratio (INR), prothrombin-time (PT), CRP, D-dimer, ferritin and red-cell-distribution width (RDW) values, respectively, were the most effective predictive mortality risk biomarkers of COVID-19. In addition, neutrophilia, leukocytosis, thrombocytopenia, erythrocytopenia were other risk predictors of mortality. Indicators was found in this study can be successfully used to predict mortality from COVID-19.


Subject(s)
COVID-19/blood , COVID-19/mortality , SARS-CoV-2 , Adult , Aged , Aged, 80 and over , Biomarkers/blood , Blood Sedimentation , C-Reactive Protein , COVID-19/immunology , Erythrocyte Indices , Female , Ferritins , Fibrin Fibrinogen Degradation Products , Humans , International Normalized Ratio , Leukocyte Count , Male , Middle Aged , Odds Ratio , Procalcitonin , Retrospective Studies , Troponin
11.
Lancet Respir Med ; 9(12): 1427-1438, 2021 12.
Article in English | MEDLINE | ID: covidwho-1621131

ABSTRACT

BACKGROUND: Infections with SARS-CoV-2 continue to cause significant morbidity and mortality. Interleukin (IL)-1 and IL-6 blockade have been proposed as therapeutic strategies in COVID-19, but study outcomes have been conflicting. We sought to study whether blockade of the IL-6 or IL-1 pathway shortened the time to clinical improvement in patients with COVID-19, hypoxic respiratory failure, and signs of systemic cytokine release syndrome. METHODS: We did a prospective, multicentre, open-label, randomised, controlled trial, in hospitalised patients with COVID-19, hypoxia, and signs of a cytokine release syndrome across 16 hospitals in Belgium. Eligible patients had a proven diagnosis of COVID-19 with symptoms between 6 and 16 days, a ratio of the partial pressure of oxygen to the fraction of inspired oxygen (PaO2:FiO2) of less than 350 mm Hg on room air or less than 280 mm Hg on supplemental oxygen, and signs of a cytokine release syndrome in their serum (either a single ferritin measurement of more than 2000 µg/L and immediately requiring high flow oxygen or mechanical ventilation, or a ferritin concentration of more than 1000 µg/L, which had been increasing over the previous 24 h, or lymphopenia below 800/mL with two of the following criteria: an increasing ferritin concentration of more than 700 µg/L, an increasing lactate dehydrogenase concentration of more than 300 international units per L, an increasing C-reactive protein concentration of more than 70 mg/L, or an increasing D-dimers concentration of more than 1000 ng/mL). The COV-AID trial has a 2 × 2 factorial design to evaluate IL-1 blockade versus no IL-1 blockade and IL-6 blockade versus no IL-6 blockade. Patients were randomly assigned by means of permuted block randomisation with varying block size and stratification by centre. In a first randomisation, patients were assigned to receive subcutaneous anakinra once daily (100 mg) for 28 days or until discharge, or to receive no IL-1 blockade (1:2). In a second randomisation step, patients were allocated to receive a single dose of siltuximab (11 mg/kg) intravenously, or a single dose of tocilizumab (8 mg/kg) intravenously, or to receive no IL-6 blockade (1:1:1). The primary outcome was the time to clinical improvement, defined as time from randomisation to an increase of at least two points on a 6-category ordinal scale or to discharge from hospital alive. The primary and supportive efficacy endpoints were assessed in the intention-to-treat population. Safety was assessed in the safety population. This study is registered online with ClinicalTrials.gov (NCT04330638) and EudraCT (2020-001500-41) and is complete. FINDINGS: Between April 4, and Dec 6, 2020, 342 patients were randomly assigned to IL-1 blockade (n=112) or no IL-1 blockade (n=230) and simultaneously randomly assigned to IL-6 blockade (n=227; 114 for tocilizumab and 113 for siltuximab) or no IL-6 blockade (n=115). Most patients were male (265 [77%] of 342), median age was 65 years (IQR 54-73), and median Systematic Organ Failure Assessment (SOFA) score at randomisation was 3 (2-4). All 342 patients were included in the primary intention-to-treat analysis. The estimated median time to clinical improvement was 12 days (95% CI 10-16) in the IL-1 blockade group versus 12 days (10-15) in the no IL-1 blockade group (hazard ratio [HR] 0·94 [95% CI 0·73-1·21]). For the IL-6 blockade group, the estimated median time to clinical improvement was 11 days (95% CI 10-16) versus 12 days (11-16) in the no IL-6 blockade group (HR 1·00 [0·78-1·29]). 55 patients died during the study, but no evidence for differences in mortality between treatment groups was found. The incidence of serious adverse events and serious infections was similar across study groups. INTERPRETATION: Drugs targeting IL-1 or IL-6 did not shorten the time to clinical improvement in this sample of patients with COVID-19, hypoxic respiratory failure, low SOFA score, and low baseline mortality risk. FUNDING: Belgian Health Care Knowledge Center and VIB Grand Challenges program.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal/therapeutic use , COVID-19 , Cytokine Release Syndrome , Respiratory Insufficiency , Aged , Belgium , COVID-19/drug therapy , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/virology , Female , Ferritins , Humans , Hypoxia , Interleukin-1/antagonists & inhibitors , Interleukin-6/antagonists & inhibitors , Male , Middle Aged , Oxygen , Prospective Studies , Respiratory Insufficiency/drug therapy , Respiratory Insufficiency/virology , SARS-CoV-2 , Treatment Outcome
12.
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
13.
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
14.
Int J Environ Res Public Health ; 19(1)2021 12 21.
Article in English | MEDLINE | ID: covidwho-1580859

ABSTRACT

High ferritin serum levels can be found in patients with macrophage activation syndrome, and increased serum ferritin due to cytokine storm have been reported in severe COVID-19 patients. Saliva is being increasingly used in COVID-19 tests as a diagnostic sample for virus detection and quantification. This study aimed to evaluate the possible changes in ferritin in saliva in COVID-19 patients. In addition, the effects of different inactivation SARS-CoV-2 treatments in ferritin measurements in saliva, the correlation between ferritin in saliva and serum, and the possible effects of correction of ferritin values by total protein were assessed. Ferritin was measured in saliva from healthy (n = 30) and COVID-19 (n = 65) patients with severe, (n = 18) or mild (n = 47) disease, depending on the need for nasal flow oxygen or assisted respiration. Ferritin was also measured in paired serum and saliva samples (n = 32) from healthy and COVID-19 patients. The evaluated inactivation protocols did not affect the assay's results except the addition of 0.5% SDS. Significantly higher ferritin was found in the saliva of COVID-19 patients (median; 25-75th percentile) (27.75; 9.77-52.2 µg/L), compared with healthy controls (4.21; 2.6-8.08 µg/L). Individuals with severe COVID-19 showed higher ferritin values in saliva (48.7; 18.7-53.9) than mild ones (15.5; 5.28-41.3 µg/L). Significant correlation (r = 0.425; p < 0.001) was found between serum and saliva in ferritin. Ferritin levels were higher in COVID-19 patients in serum and saliva, and the highest values were found in those patients presenting severe symptomatology. In conclusion, ferritin in saliva has the potential to be a biomarker to evaluate severity in patients with COVID-19.


Subject(s)
COVID-19 , Ferritins/analysis , Saliva/chemistry , Biomarkers , COVID-19/diagnosis , Humans
15.
Sci Rep ; 11(1): 24224, 2021 12 20.
Article in English | MEDLINE | ID: covidwho-1585790

ABSTRACT

Since 2019, a large number of people worldwide have been infected with severe acute respiratory syndrome coronavirus 2. Among those infected, a limited number develop severe coronavirus disease 2019 (COVID-19), which generally has an acute onset. The treatment of patients with severe COVID-19 is challenging. To optimize disease prognosis and effectively utilize medical resources, proactive measures must be adopted for patients at risk of developing severe COVID-19. We analyzed the data of COVID-19 patients from seven medical institutions in Tokyo and used mathematical modeling of patient blood test results to quantify and compare the predictive ability of multiple prognostic indicators for the development of severe COVID-19. A machine learning logistic regression model was used to analyze the blood test results of 300 patients. Due to the limited data set, the size of the training group was constantly adjusted to ensure that the results of machine learning were effective (e.g., recognition rate of disease severity > 80%). Lymphocyte count, hemoglobin, and ferritin levels were the best prognostic indicators of severe COVID-19. The mathematical model developed in this study enables prediction and classification of COVID-19 severity.


Subject(s)
COVID-19/pathology , Models, Theoretical , Adolescent , Adult , Aged , C-Reactive Protein/analysis , COVID-19/virology , Female , Ferritins/analysis , Hemoglobins/analysis , Humans , Lymphocyte Count , Machine Learning , Male , Middle Aged , Prognosis , Retrospective Studies , Risk Factors , SARS-CoV-2/isolation & purification , Severity of Illness Index , Young Adult
16.
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
17.
Ann Med ; 53(1): 257-266, 2021 12.
Article in English | MEDLINE | ID: covidwho-1574445

ABSTRACT

OBJECTIVES: To appraise effective predictors for COVID-19 mortality in a retrospective cohort study. METHODS: A total of 1270 COVID-19 patients, including 984 admitted in Sino French New City Branch (training and internal validation sets randomly split at 7:3 ratio) and 286 admitted in Optical Valley Branch (external validation set) of Wuhan Tongji hospital, were included in this study. Forty-eight clinical and laboratory features were screened with LASSO method. Further multi-tree extreme gradient boosting (XGBoost) machine learning-based model was used to rank importance of features selected from LASSO and subsequently constructed death risk prediction model with simple-tree XGBoost model. Performances of models were evaluated by AUC, prediction accuracy, precision, and F1 scores. RESULTS: Six features, including disease severity, age, levels of high-sensitivity C-reactive protein (hs-CRP), lactate dehydrogenase (LDH), ferritin, and interleukin-10 (IL-10), were selected as predictors for COVID-19 mortality. Simple-tree XGBoost model conducted by these features can predict death risk accurately with >90% precision and >85% sensitivity, as well as F1 scores >0.90 in training and validation sets. CONCLUSION: We proposed the disease severity, age, serum levels of hs-CRP, LDH, ferritin, and IL-10 as significant predictors for death risk of COVID-19, which may help to identify the high-risk COVID-19 cases. KEY MESSAGES A machine learning method is used to build death risk model for COVID-19 patients. Disease severity, age, hs-CRP, LDH, ferritin, and IL-10 are death risk factors. These findings may help to identify the high-risk COVID-19 cases.


Subject(s)
COVID-19/mortality , Clinical Decision Rules , Hospitalization , Machine Learning , Adult , Aged , Aged, 80 and over , C-Reactive Protein/metabolism , COVID-19/epidemiology , COVID-19/metabolism , COVID-19/physiopathology , Cardiovascular Diseases/epidemiology , China/epidemiology , Cohort Studies , Comorbidity , Diabetes Mellitus/epidemiology , Female , Ferritins/metabolism , Humans , Hypertension/epidemiology , Interleukin-10/metabolism , L-Lactate Dehydrogenase/metabolism , Male , Middle Aged , Prognosis , Reproducibility of Results , Retrospective Studies , SARS-CoV-2 , Severity of Illness Index
18.
Viruses ; 13(12)2021 12 10.
Article in English | MEDLINE | ID: covidwho-1572659

ABSTRACT

Large variability in COVID-19 clinical progression urges the need to find the most relevant biomarkers to predict patients' outcomes. We evaluated iron metabolism and immune response in 303 patients admitted to the main hospital of the northern region of Portugal with variable clinical pictures, from September to November 2020. One hundred and twenty-seven tested positive for SARS-CoV-2 and 176 tested negative. Iron-related laboratory parameters and cytokines were determined in blood samples collected soon after admission. Demographic data, comorbidities and clinical outcomes were recorded. Patients were assigned into five groups according to severity. Serum iron and transferrin levels at admission were lower in COVID-19-positive than in COVID-19-negative patients. The levels of interleukin (IL)-6 and monocyte chemoattractant protein 1 (MCP-1) were increased in COVID-19-positive patients. The lowest serum iron and transferrin levels at diagnosis were associated with the worst outcomes. Iron levels negatively correlated with IL-6 and higher levels of this cytokine were associated with a worse prognosis. Serum ferritin levels at diagnosis were higher in COVID-19-positive than in COVID-19-negative patients. Serum iron is the simplest laboratory test to be implemented as a predictor of disease progression in COVID-19-positive patients.


Subject(s)
Biomarkers/blood , COVID-19 , Iron/blood , Severity of Illness Index , Adult , Aged , Aged, 80 and over , Chemokine CCL2/blood , Cohort Studies , Cytokines/blood , Female , Ferritins , Hepcidins , Humans , Inflammation , Interleukin-6/blood , Male , Middle Aged , Portugal , SARS-CoV-2
19.
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
20.
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
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