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Frontiers in Pediatrics 2023Although SARS-CoV-2 infection can lead to severe COVID-19 in children, the role of biomarkers for assessing the risk of progression to severe disease is not well...
INTRODUCTION
Although SARS-CoV-2 infection can lead to severe COVID-19 in children, the role of biomarkers for assessing the risk of progression to severe disease is not well established in the pediatric population. Given the differences in monocyte signatures associated with worsening COVID-19 in adults, we aimed to determine whether monocyte anisocytosis early in the infectious course would correspond with increasing severity of COVID-19 in children.
METHODS
We performed a multicenter retrospective study of 215 children with SARS-CoV-2 infection, Multisystem Inflammatory Syndrome in Children (MIS-C), convalescent COVID-19, and healthy age-matched controls to determine whether monocyte anisocytosis, quantified by monocyte distribution width (MDW) on complete blood count, was associated with increasing severity of COVID-19. We performed exploratory analyses to identify other hematologic parameters in the inflammatory signature of pediatric SARS-CoV-2 infection and determine the most effective combination of markers for assessing COVID-19 severity in children.
RESULTS
Monocyte anisocytosis increases with COVID-19 severity and need for hospitalization. Although other inflammatory markers such as lymphocyte count, neutrophil/lymphocyte ratio, C-reactive protein, and cytokines correlate with disease severity, these parameters were not as sensitive as MDW for identifying severe disease in children. An MDW threshold of 23 offers a sensitive marker for severe pediatric COVID-19, with improved accuracy when assessed in combination with other hematologic parameters.
CONCLUSION
Monocyte anisocytosis corresponds with shifting hematologic profiles and inflammatory markers in children with COVID-19, and MDW serves as a clinically accessible biomarker for severe COVID-19 in children.
PubMed: 37425266
DOI: 10.3389/fped.2023.1177048 -
Pathogens & Immunity 2020Red cell distribution width (RDW), a measure of anisocytosis, is observed in chronic inflammation and is a prognostic marker in critically ill patients without COVID-19,...
BACKGROUND
Red cell distribution width (RDW), a measure of anisocytosis, is observed in chronic inflammation and is a prognostic marker in critically ill patients without COVID-19, but data in COVID-19 are limited.
METHODS
Between March 12 and April 19, 2020, 282 individuals with confirmed COVID-19 and RDW available within 7 days prior to COVID-19 confirmation were evaluated. Individuals were grouped by quartiles of RDW. Association between quartiles of RDW and mortality was assessed using the Kaplan-Meier method and statistical significance was assessed using the log-rank test. The association between RDW and all-cause mortality was further assessed using a Cox proportional hazards model. Plasma cytokine levels in uninfected ambulatory adults without cardiovascular disease (n=38) were measured and bivariate Spearman correlations and principle components analysis were used to identify relationships between cytokine concentrations with RDW.
RESULTS
After adjusting for age, sex, race, cardiovascular disease, and hemoglobin, there was an association between RDW and mortality (Quartile 4 vs Quartile 1: HR 4.04 [1.08-15.07]), with each 1% increment in RDW associated with a 39% increased rate of mortality (HR 1.39 [1.21-1.59]). Remote RDW was also associated with mortality after COVID-19 infection. Among uninfected ambulatory adults without cardiovascular disease, RDW was associated with elevated pro-inflammatory cytokines (TNF-α, IL8, IL6, IL1b), but not regulatory cytokines (TGFb).
CONCLUSIONS
Anisocytosis predicts short-term mortality in COVID-19 patients, often predates viral exposure, and may be related to a pro-inflammatory phenotype. Additional study of whether the RDW can assist in the early identification of pending cytokine storm is warranted.
PubMed: 33089037
DOI: 10.20411/pai.v5i1.391 -
Antioxidants (Basel, Switzerland) Jan 2023Viral infections activate the innate immune response and the secretion of inflammatory cytokines. They also alter oxidative stress markers, which potentially can have an...
Viral infections activate the innate immune response and the secretion of inflammatory cytokines. They also alter oxidative stress markers, which potentially can have an involvement in the pathogenesis of the disease. The aim of this research was to study the role of the oxidative stress process assessed through lactate dehydrogenase (LDH) on the severity of COVID-19 measured by oxygen saturation (SaO) and the putative interaction with inflammation. The investigation enrolled 1808 patients (mean age of 68 and 60% male) with COVID-19 from the HM Hospitals database. To explore interactions, a regression model and mediation analyses were performed. The patients with lower SaO presented lymphopenia and higher values of neutrophils-to-lymphocytes ratio and on the anisocytosis coefficient. The regression model showed an interaction between LDH and anisocytosis, suggesting that high levels of LDH (>544 U/L) and an anisocytosis coefficient higher than 10% can impact SaO in COVID-19 patients. Moreover, analysis revealed that LDH mediated 41% ( value = 0.001) of the effect of anisocytosis on SaO in this cohort. This investigation revealed that the oxidative stress marker LDH and the interaction with anisocytosis have an important role in the severity of COVID-19 infection and should be considered for the management and treatment of the oxidative phenomena concerning this within a precision medicine strategy.
PubMed: 36829793
DOI: 10.3390/antiox12020234 -
Kardiologia Polska May 2020
Relationship among the leptin-to-adiponectin ratio, systemic inflammation, and anisocytosis: a plausible pathophysiological mechanism of a novel cardiovascular risk marker.
Topics: Adiponectin; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Humans; Inflammation; Leptin; Risk Factors
PubMed: 32458664
DOI: 10.33963/KP.15381 -
Tropical Medicine and Health Oct 2022Anaemia, anisocytosis, malnutrition (especially stunting) are common health problems in developing countries with children being the most vulnerable. These conditions...
Malnutrition, anaemia and anisocytosis as public health problems among children ≤ 5 years living in malaria perennial transmission areas of Mount Cameroon: a cross sectional study.
BACKGROUND
Anaemia, anisocytosis, malnutrition (especially stunting) are common health problems in developing countries with children being the most vulnerable. These conditions have negative impacts on human performance, growth and development, and can further be complicated if comorbidity exists within a holoendemic stratum with strong and perennial malaria parasite transmission such as the Mount Cameroon area. The study aimed at determining the prevalence and severity malnutrition, anaemia and anisocytosis in children ≤ 5 years, living in the conflict hit malaria perennial transmission zone of the Mount Cameroon area.
METHOD
A cross-sectional community-based survey involving 628 children ≤ 5 years was conducted. Malaria parasitaemia was confirmed by Giemsa-stained microscopy and the density was log transformed. Haemoglobin (Hb), mean cell volume and red blood cell distribution width were estimated using an auto-haematology analyser and defined according to WHO standards. Anthropometric indices were analysed and compared with WHO growth reference standards using WHO Anthro software.
RESULTS
Plasmodium infection, anaemia, microcytic anaemia, anisocytosis and stunting were prevalent in 36.0, 72.8, 30.1, 54.1 and 29.0% of the children, respectively. The ≤ 24 months children were more moderately stunted (14.7%), with higher prevalence of microcytic anaemia (38.8%) and anisocytosis (68.8%) (P < 0.002 and P < 0.001, respectively) when compared with the older children. The mean Hb level in the study population was 10.04 g/dL with children ≤ 24 months having the least mean haemoglobin level (9.69 g/dL) when compared with their older counterparts at P < 0.001. The odds of having anisocytosis were highest among children who were malnourished (OR = 4.66, P = 0.005), those infected with malaria parasites (OR = 1.85, P = 0.007), and whose parents had a primary (OR = 3.51, P = 0.002) and secondary levels of education (OR = 2.69, P = 0.017).
CONCLUSION
Malaria, anaemia, anisocytosis and undernutrition still remain severe public health concerns among children ≤ 60 months in the Mount Cameroon area. This therefore emphasizes the need for the implementation of consistent policies, programmes and activities to avoid malaria, anaemia, anisocytosis and stunting in the paediatric age group.
PubMed: 36280882
DOI: 10.1186/s41182-022-00469-6 -
World Journal of Cardiology Dec 2019The incorporation of biomarkers in the actually used risk scores seem to be helpful for early identifying atrial fibrillation (AF) patients at higher risk. The aim of... (Review)
Review
The incorporation of biomarkers in the actually used risk scores seem to be helpful for early identifying atrial fibrillation (AF) patients at higher risk. The aim of this critical review of the scientific literature is to investigate the potential clinical significance of red blood cell distribution width (RDW) in AF. A systematic electronic search was carried out to identify all articles describing an epidemiological association between RDW and AF in adult human populations. Data abstraction was conducted on a final number of 35 articles (13 cross-sectional, 12 prospective and 10 retrospective studies). The results of these epidemiological investigations were all virtually concordant to emphasize that an enhanced RDW value is not only a predictive factor and a marker of AF but its measurement may also be helpful for predicting the risk of developing many adverse complications in patients with AF, such as recurrence and duration of AF, hospitalization for heart failure, bleeding, left atrial thrombosis and stasis, thromboembolic events and mortality. AF patients with RDW values exceeding the local reference range may be more aggressively investigated and managed, in order to identify and attenuate the impact of possible underlying disorders causing both anisocytosis and AF.
PubMed: 31908729
DOI: 10.4330/wjc.v11.i12.292 -
BMC Infectious Diseases Jun 2022Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening complication that can develop weeks to months after an initial SARS-CoV-2 infection. A...
BACKGROUND
Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening complication that can develop weeks to months after an initial SARS-CoV-2 infection. A complex, time-consuming laboratory evaluation is currently required to distinguish MIS-C from other illnesses. New assays are urgently needed early in the evaluation process to expedite MIS-C workup and initiate treatment when appropriate. This study aimed to measure the performance of a monocyte anisocytosis index, obtained on routine complete blood count (CBC), to rapidly identify subjects with MIS-C at risk for cardiac complications.
METHODS
We measured monocyte anisocytosis, quantified by monocyte distribution width (MDW), in blood samples collected from children who sought medical care in a single medical center from April 2020 to October 2020 (discovery cohort). After identifying an effective MDW threshold associated with MIS-C, we tested the utility of MDW as a tier 1 assay for MIS-C at multiple institutions from October 2020 to October 2021 (validation cohort). The main outcome was the early screening of MIS-C, with a focus on children with MIS-C who displayed cardiac complications. The screening accuracy of MDW was compared to tier 1 routine laboratory tests recommended for evaluating a child for MIS-C.
RESULTS
We enrolled 765 children and collected 846 blood samples for analysis. In the discovery cohort, monocyte anisocytosis, quantified as an MDW threshold of 24.0, had 100% sensitivity (95% CI 78-100%) and 80% specificity (95% CI 69-88%) for identifying MIS-C. In the validation cohort, an initial MDW greater than 24.0 maintained a 100% sensitivity (95% CI 80-100%) and monocyte anisocytosis displayed a diagnostic accuracy greater that other clinically available hematologic parameters. Monocyte anisocytosis decreased with disease resolution to values equivalent to those of healthy controls.
CONCLUSIONS
Monocyte anisocytosis detected by CBC early in the clinical workup improves the identification of children with MIS-C with cardiac complications, thereby creating opportunities for improving current practice guidelines.
Topics: COVID-19; Child; Humans; Monocytes; SARS-CoV-2; Systemic Inflammatory Response Syndrome
PubMed: 35725405
DOI: 10.1186/s12879-022-07526-9 -
Infection and Drug Resistance 2023Information about dynamic changes occurring in the parameters and morphology of erythrocytes and platelets during the coronavirus disease 2019 (COVID-19) infection and...
PURPOSE
Information about dynamic changes occurring in the parameters and morphology of erythrocytes and platelets during the coronavirus disease 2019 (COVID-19) infection and convalescence is scarce. To explore potential associations between dynamic erythrocyte and platelet parameters, morphological changes, and the course or severity of the disease is essential.
PATIENTS AND METHODS
From January 17th, 2020, to February 20th, 2022, we followed up on 35 patients with non-severe and 11 patients with severe COVID-19 following their discharge. We collected clinical features, dynamic complete blood count (CBC), and peripheral blood smears (PBS) and analyzed parameter and morphological changes of erythrocytes and platelets depending on the course or severity of the disease. The course of the disease included four periods, namely onset (T1), discharge (T2), 1-year follow-up (T3), and 2-year follow-up (T4).
RESULTS
Red blood cell (RBC) counts and hemoglobin were the lowest in T2, followed by T1, and lower in T1 and T2 than in T3 and T4. Inversely, the red blood cell distribution width (RDW) was the highest in T2, followed by T1, and higher than in T3 and T4. Compared to non-severe patients, the platelet of severe patients was lower in T1 and T2. In contrast, the mean platelet volume (MPV) and platelet distribution width (PDW) tended to be higher in severe patients. Similarly, anisocytosis was more common in peripheral blood smears at early stages and in severe patients. Finally, large platelets were more common in severe patients.
CONCLUSION
Anisocytosis of erythrocytes and large platelets are found in patients with severe COVID-19, these changes may help primary hospitals to identify patients with a high risk of severe COVID-19 at an early stage.
PubMed: 36992967
DOI: 10.2147/IDR.S400735 -
Clinical Chemistry and Laboratory... May 2023The SARS-CoV-2 infection is characterized by both systemic and organ hyper-thromboinflammation, with a clinical course ranging from mild up-to critical systemic... (Meta-Analysis)
Meta-Analysis Review
The SARS-CoV-2 infection is characterized by both systemic and organ hyper-thromboinflammation, with a clinical course ranging from mild up-to critical systemic dysfunction and death. In patients with coronavirus disease 2019 (COVID-19) the monocyte/macrophage population is deeply involved as both trigger and target, assuming the value of useful diagnostic/prognostic marker of innate cellular immunity. Several studies correlated morphological and immunophenotypic alterations of circulating monocytes with clinical outcomes in COVID-19 patients, concluding that monocyte distribution width (MDW) may retain clinical value in stratifying the risk of disease worsening. Through an electronic search in Medline and Scopus we performed an updated literature review and meta-analysis aimed to explore the association between increased MDW levels and illness severity in COVID-19 patients, deciphering role(s) and function(s) of monocytes in the harmful network underlining SARS-CoV-2 infection. We found that significantly elevated MDW values were frequently present in COVID-19 patients who developed unfavorable clinical outcomes, compounded by a significant association between monocyte anisocytosis and SARS-CoV-2 outcomes. These findings suggest that blood MDW index and its scatter plot could represent useful routine laboratory tools for early identification of patients at higher risk of unfavorable COVID-19 and for monitoring the progression of viral infection, clinical outcomes, and therapeutic efficacy throughout hospitalization. According to this evidence, therapeutic decisions in patients with SARS-CoV-2 infection could benefit from monitoring MDW value, with administration of drugs limiting thrombo-inflammation due to monocyte hyper-activation in patients with severe/critical COVID-19 disease.
Topics: Humans; COVID-19; Monocytes; SARS-CoV-2; Inflammation; Thrombosis
PubMed: 36626568
DOI: 10.1515/cclm-2022-0936 -
Veterinary Medicine and Science May 2022Gross, histopathological, and immunohistochemical characteristics of uveal melanocytic neoplasms in dogs and cats were investigated.
OBJECTIVE
Gross, histopathological, and immunohistochemical characteristics of uveal melanocytic neoplasms in dogs and cats were investigated.
SAMPLES
Thirty-two enucleated globes with uveal melanocytic neoplasms, 27 from dogs and 5 from cats, were examined.
PROCEDURES
Morphological characteristics of uveal melanocytic neoplasms in dogs and cats were evaluated with anti-PNL2, anti-Melan-A, anti-Ki-67, anti-caspase-3, and anti-BAP1 immunomarkers. Statistical analysis was performed to compare canine melanocytomas and melanomas.
RESULTS
The 32 uveal neoplasms were classified as melanocytomas (19/27 in dogs) or melanomas (8/27 in dogs, 5/5 in cats). Most tumours (84%) were located in the anterior uvea. Neoplastic cells were classified as epithelioid, spindle-shaped, mixed, or special type (balloon and signet ring cells). The percentage of cells with melanin, melanin concentration within cells, anisocytosis and anisokaryosis, mitotic count, lymphocytic inflammation, necrosis, vascular invasion, and glaucoma were also characterized. Anisocytosis, percentage of neoplastic cells with melanin, mitotic count, and indices (proliferation and apoptotic) varied significantly between canine uveal melanomas and melanocytomas; in general, melanomas had greater cell variability, were less pigmented, and had a higher mitotic count. The melanocytic origin of the neoplasms was confirmed by positive anti-PNL2 immunolabelling (29/32) and positive anti-Melan-A immunolabelling (3/32). In canine uveal melanomas, anisocytosis and anisokaryosis correlated with less pigmentation and minimal pigmentation correlated with a high percentage of immunolabelling for caspase-3.
CONCLUSIONS
Uveal melanocytomas were more common in dogs, and uveal melanomas were more frequent in cats. Anisocytosis, percentage of neoplastic cells with melanin, and mitotic count are important histologic characteristics of malignancy to evaluate in uveal melanocytic neoplasms. The proliferation and apoptotic indices are relevant when comparing malignant tumours with benign tumours.
Topics: Animals; Cat Diseases; Cats; Dog Diseases; Dogs; Melanins; Melanoma; Uvea
PubMed: 35122675
DOI: 10.1002/vms3.752