Prevalence, pattern and clinical implications of transfusion transmissible viral infections among paediatric haemophiliacs in northern Nigeria

Abstract Background: Scarcity of FVIII concentrate compels caregivers in poor countries to use multiple transfusions of fresh whole blood (FWB), fresh frozen plasma and cryoprecipitate for managing haemophilia A. FWB is the most frequently transfused blood product due to ease of production and its ability to simultaneously stop active bleeding and treat anaemia. Iron deficiency anaemia is common among haemophiliacs in poor tropical countries such as Nigeria, due to the combined effects of bleeding, malnutrition, and haemorrhagic parasitic diseases. Multiple FWB transfusion is usually initiated at local sub-tertiary hospitals before eventual referral to tertiary hospitals. The Nigerian blood transfusion service is underdeveloped, donor screening is rudimentary and transfusion safety is poor. The prevalence of transfusion transmissible viral infections (TTVIs), including HIV, and hepatitis B and C viruses (HBV and HCV), is therefore predicted to be high among Nigerian haemophiliacs. Aims: To determine prevalence and pattern of TTVIs (HIV, HBV, HCV infections) among paediatric haemophiliacs who have received multiple FWB transfusions in Nigeria. Materials and methods: Retrospective analyses of demographic and clinical data, disease severity, number of previous transfusions of FWB, and prevalence and pattern of TTVIs (HIV, HBV and HCV infections) of newly referred haemophiliacs as seen in five tertiary hospitals in northern Nigeria. Prevalence rates of TTVIs were expressed as percentages. Comparisons of parameters (age, disease severity and number of previous transfusions) between patients with and without TTVIs were performed using Students t-test for mean values and Fisher’s exact test for percentages, with p-values of less than 0.05 taken as significant. Results: Of 97 haemophiliacs studied, 24 (24.7%) were infected with TTVIs. The pattern and frequencies of TTVIs among the infected patients revealed HBV infection in 10 (41.7%), HIV-1 infection in five (20.8%), HCV infection in four (16.7%), HBV and HIV co-infection in three (12.5%), and HBV and HCV co-infection in two (8.3%). In comparison with haemophiliacs without TTVIs, haemophiliacs with TTVIs had a significantly lower mean age (4.9 vs. 7.8; p=0.007); a higher proportion of severe disease (62.5% vs. 26%; p=0.009), and a higher mean number of transfusions per patient (27.5 vs. 15.3; p=0.006). Conclusions: The prevalence of TTVIs among haemophiliacs in Nigeria is high, and the risk is correlated with disease severity and number of previous transfusions. There is need for the national transfusion service to be upgraded and for standard haemophilia care centres with an adequate supply of FVIII concentrates for optimal care to be set up. Haemophilia healthcare providers in Nigeria can minimise multiple transfusions by incorporating regular screening and treatment of haemorrhagic parasitic diseases, iron supplementation, and the use of pharmacological agents in the standard of care for haemophilia.

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CD169/SIGLEC1 is expressed on circulating monocytes in COVID-19 and expression levels are associated with disease severity

Infection ◽

10.1007/s15010-021-01606-9 ◽

2021 ◽

Author(s):

Jan-Moritz Doehn ◽

Christoph Tabeling ◽

Robert Biesen ◽

Jacopo Saccomanno ◽

Elena Madlung ◽

...

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Disease Severity ◽

Clinical Studies ◽

Viral Infections ◽

Severe Disease ◽

Type I Interferons ◽

Type I ◽

Interferon Signaling ◽

Expression Levels

AbstractCoronavirus disease 2019 (COVID-19) is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Type I interferons are important in the defense of viral infections. Recently, neutralizing IgG auto-antibodies against type I interferons were found in patients with severe COVID-19 infection. Here, we analyzed expression of CD169/SIGLEC1, a well described downstream molecule in interferon signaling, and found increased monocytic CD169/SIGLEC1 expression levels in patients with mild, acute COVID-19, compared to patients with severe disease. We recommend further clinical studies to evaluate the value of CD169/SIGLEC1 expression in patients with COVID-19 with or without auto-antibodies against type I interferons.

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Effect of the SARS-CoV-2 pandemic on the control and severity of pediatric asthma

Allergologia et Immunopathologia ◽

10.15586/aei.v50i1.492 ◽

2022 ◽

Vol 50 (1) ◽

pp. 99-103

Author(s):

Silvia Sanchez-Garcia ◽

Javier Ruiz-Hornillos ◽

Marta Bernaola-Abraira ◽

Alicia Habernau-Mena ◽

Eva Maria Lasa ◽

...

Keyword(s):

Viral Infections ◽

Healthcare Providers ◽

Pediatric Asthma ◽

Care Providers ◽

Asthmatic Children ◽

Global Pandemic ◽

Oral Corticosteroids ◽

Tertiary Hospitals ◽

Animal Dander ◽

Age Range

Background: The novel disease caused by the new coronavirus SARS-CoV-2 has caused an unprecedented global pandemic. Care providers of asthmatic children are increasingly con-cerned; as viral infections are one of the primary triggers of asthma flare-up. However, the effect of SARS-CoV-2 as well as the generated worldwide lockdown on asthmatic children is unknown.Objective: The aim of this study was to analyze the effects of pandemic SARS-CoV-2 in pediat-ric asthma control.Material and Methods: A retrospective, open, transversal study was performed at five tertiary hospitals. Recruited patients were aged <18 years and had physician-diagnosed asthma. Information regarding the 2019 and 2020 seasons were provided.Results: Data were collected from 107 children (age range: 3–18 years, mean age: 12 years). Well-controlled asthma was observed in 58 (54.2%) patients in 2020 versus 30 (28%) in 2019, and 15 (14%) patients had poorly controlled asthma in 2020 versus 28 (26.2%) in 2019. In 2020, a decrease in exacerbations caused by allergies to pollen, dust mites, molds, and through other causes not related to SARS-CoV-2 infection was observed. An increase in exacerbations was observed due to animal dander, stress, physical exercise, and SARS-CoV-2 infection. Children had a reduced need for asthma-controlling medication, made fewer visits to healthcare pro-viders and had lesser need of treatment with oral corticosteroids if compared with the same season of 2019.Conclusion: Pediatric asthma control improved, the need for controller medication declined, and fewer visits to healthcare providers were made during the pandemic if compared with the 2019 season.

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Serum β2-microglobulin levels in Coronavirus disease 2019 (Covid-19): Another prognosticator of disease severity?

PLoS ONE ◽

10.1371/journal.pone.0247758 ◽

2021 ◽

Vol 16 (3) ◽

pp. e0247758

Author(s):

Walter Conca ◽

Mayyadah Alabdely ◽

Faisal Albaiz ◽

Michael Warren Foster ◽

Maha Alamri ◽

...

Keyword(s):

Disease Severity ◽

Viral Infections ◽

Linear Trend ◽

Severe Disease ◽

Tertiary Care ◽

Care Hospital ◽

Mhc I ◽

Mild Disease ◽

Moderate Disease ◽

Single Center Study

β2-microglobulin (β2-m), a 11.8 kDa protein, pairs non-covalently with the α3 domain of the major histocompatibility class (MHC) I α-chain and is essential for the conformation of the MHC class I protein complex. Shed β2-m is measurable in circulation, and various disorders are accompanied by increases in β2-m levels, including several viral infections. Therefore, we explored whether β2-m levels could also be elevated in Coronavirus disease 2019 (Covid-19) and whether they predict disease severity. Serum β2-m levels were measured in a cohort of 34 patients infected with SARS-CoV-2 on admission to a tertiary care hospital in Riyadh, Saudi Arabia, as well as in an approximately age-sex matched group of 34 uninfected controls. Mean β2-m level was 3.25±1.68 mg/l (reference range 0.8–2.2 mg/l) in patients (mean age 48.2±21.6) and 1.98±0.61 mg/l in controls (mean age 48.2±21.6). 17 patients (mean age 36.9± 18.0) with mean β2-m levels of 2.27±0.64 mg/l had mild disease by WHO severity categorization, 12 patients (mean age 53.3±18.1) with mean β2-m levels of 3.57±1.39 mg/l had moderate disease, and five patients (of whom 2 died; mean age 74.4±13.8) with mean β2-m levels of 5.85±1.85 mg/l had severe disease (P < = 0.001, by ANOVA test for linear trend). In multivariate ordinal regression β2-m levels were the only significant predictor of disease severity. Our findings suggest that higher β2-m levels could be an early indicator of severity of disease and predict outcome of Covid-19. As the main limitations of the study are a single-center study, sample size and ethnicity, these results need confirmation in larger cohorts outside the Arabian Peninsula in order to delineate the value of β2-m measurements. The role of β2-m in the etiology and pathogenesis of severe Covid-19 remains to be elucidated.

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Do Blood Eosinophils Predict in-Hospital Mortality or Severity of Disease in SARS-CoV-2 Infection? A Retrospective Multicenter Study

Microorganisms ◽

10.3390/microorganisms9020334 ◽

2021 ◽

Vol 9 (2) ◽

pp. 334

Author(s):

Pierrick Le Borgne ◽

Laure Abensur Vuillaume ◽

Karine Alamé ◽

François Lefebvre ◽

Sylvie Chabrier ◽

...

Keyword(s):

Disease Severity ◽

Viral Infections ◽

Severe Disease ◽

Healthcare Systems ◽

Severe Form ◽

Operating Characteristics ◽

Severity Of Disease ◽

Inflammatory Processes ◽

Blood Eosinophils ◽

Retrospective Multicenter Study

Introduction: Healthcare systems worldwide have been battling the ongoing COVID-19 pandemic. Eosinophils are multifunctional leukocytes implicated in the pathogenesis of several inflammatory processes including viral infections. We focus our study on the prognostic value of eosinopenia as a marker of disease severity and mortality in COVID-19 patients. Methods: Between 1 March and 30 April 2020, we conducted a multicenter and retrospective study on a cohort of COVID-19 patients (moderate or severe disease) who were hospitalized after presenting to the emergency department (ED). We led our study in six major hospitals of northeast France, one of the outbreak’s epicenters in Europe. Results: We have collected data from 1035 patients, with a confirmed diagnosis of COVID-19. More than three quarters of them (76.2%) presented a moderate form of the disease, while the remaining quarter (23.8%) presented a severe form requiring admission to the intensive care unit (ICU). Mean circulating eosinophils rate, at admission, varied according to disease severity (p < 0.001), yet it did not differ between survivors and non-survivors (p = 0.306). Extreme eosinopenia (=0/mm3) was predictive of severity (aOR = 1.77, p = 0.009); however, it was not predictive of mortality (aOR = 0.892, p = 0.696). The areas under the Receiver operating characteristics (ROC) curve were, respectively, 58.5% (CI95%: 55.3–61.7%) and 51.4% (CI95%: 46.8–56.1%) for the ability of circulating eosinophil rates to predict disease severity and mortality. Conclusion: Eosinopenia is very common and often profound in cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Eosinopenia was not a useful predictor of mortality; however, undetectable eosinophils (=0/mm3) were predictive of disease severity during the initial ED management.

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Serum C-Reactive Protein and Interleukin-6 Levels as Biomarkers for Disease Severity and Clinical Outcomes in Patients with Idiopathic Granulomatous Mastitis

Journal of Clinical Medicine ◽

10.3390/jcm10102077 ◽

2021 ◽

Vol 10 (10) ◽

pp. 2077

Author(s):

Yi-Min Huang ◽

Chiao Lo ◽

Chiao-Feng Cheng ◽

Cheng-Hsun Lu ◽

Song-Chou Hsieh ◽

...

Keyword(s):

Disease Severity ◽

Severe Disease ◽

Linear Regression Analysis ◽

Multiple Linear Regression Analysis ◽

Serum Biomarkers ◽

Healthy Controls ◽

Granulomatous Mastitis ◽

C Reactive Protein ◽

Idiopathic Granulomatous Mastitis ◽

Reactive Protein

Idiopathic granulomatous mastitis (IGM) is a rare inflammatory breast disease mimicking breast cancer. Limited research has been conducted on the application of serum biomarkers. This study aims to investigate the association of serum biomarkers with disease severity in patients with IGM. From November 2011 to March 2020, medical records of patients with IGM were reviewed. Serum cytokine levels were measured in patients and healthy controls between July 2018 and March 2020. A total of 41 patients with histologically proven IGM were found. Serum interleukin (IL)-6 level was significantly higher in patients with IGM (n = 11) than healthy controls (n = 7). Serum IL-6 and C-reactive protein (CRP) levels were significantly higher in patients with severe disease than mild and moderate disease. Serum IL-6 (Spearman’s ρ = 0.855; p < 0.001) and CRP (Spearman’s ρ = 0.838; p = 0.001) levels were associated with time to resolution. A higher serum CRP level was associated with a longer time to resolution (B = 0.322; p < 0.001) in multiple linear regression analysis. Serum IL-6 and CRP levels can be used as biomarkers for the evaluation of disease severity in IGM. IL-6 may play a crucial role in the immunopathology of IGM.

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Disease severity-specific neutrophil signatures in blood transcriptomes stratify COVID-19 patients

Genome Medicine ◽

10.1186/s13073-020-00823-5 ◽

2021 ◽

Vol 13 (1) ◽

Cited By ~ 1

Author(s):

Anna C. Aschenbrenner ◽

◽

Maria Mouktaroudi ◽

Benjamin Krämer ◽

Marie Oestreich ◽

...

Keyword(s):

Immune System ◽

Disease Severity ◽

Whole Blood ◽

Viral Infections ◽

Inflammatory Diseases ◽

Target Prediction ◽

Data Driven ◽

Host Responses ◽

Drug Candidates ◽

Drug Target Prediction

Abstract Background The SARS-CoV-2 pandemic is currently leading to increasing numbers of COVID-19 patients all over the world. Clinical presentations range from asymptomatic, mild respiratory tract infection, to severe cases with acute respiratory distress syndrome, respiratory failure, and death. Reports on a dysregulated immune system in the severe cases call for a better characterization and understanding of the changes in the immune system. Methods In order to dissect COVID-19-driven immune host responses, we performed RNA-seq of whole blood cell transcriptomes and granulocyte preparations from mild and severe COVID-19 patients and analyzed the data using a combination of conventional and data-driven co-expression analysis. Additionally, publicly available data was used to show the distinction from COVID-19 to other diseases. Reverse drug target prediction was used to identify known or novel drug candidates based on finding from data-driven findings. Results Here, we profiled whole blood transcriptomes of 39 COVID-19 patients and 10 control donors enabling a data-driven stratification based on molecular phenotype. Neutrophil activation-associated signatures were prominently enriched in severe patient groups, which was corroborated in whole blood transcriptomes from an independent second cohort of 30 as well as in granulocyte samples from a third cohort of 16 COVID-19 patients (44 samples). Comparison of COVID-19 blood transcriptomes with those of a collection of over 3100 samples derived from 12 different viral infections, inflammatory diseases, and independent control samples revealed highly specific transcriptome signatures for COVID-19. Further, stratified transcriptomes predicted patient subgroup-specific drug candidates targeting the dysregulated systemic immune response of the host. Conclusions Our study provides novel insights in the distinct molecular subgroups or phenotypes that are not simply explained by clinical parameters. We show that whole blood transcriptomes are extremely informative for COVID-19 since they capture granulocytes which are major drivers of disease severity.

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The Initial Course of IL1β, IL-6, IL-8, IL-10, IL-12, IFN-γ and TNF-α with Regard to Severity Grade in Acute Pancreatitis

Biomolecules ◽

10.3390/biom11040591 ◽

2021 ◽

Vol 11 (4) ◽

pp. 591

Author(s):

Hanna Sternby ◽

Hannes Hartman ◽

Henrik Thorlacius ◽

Sara Regnér

Keyword(s):

Acute Pancreatitis ◽

Roc Analysis ◽

Paired Comparison ◽

Severe Disease ◽

Temporal Development ◽

Predictive Capacity ◽

Mean Values ◽

Tnf Α ◽

Significant Difference ◽

Ifn Γ

Clinical reports on early immune dysregulation in acute pancreatitis (AP) are scarce. Herein we investigate the initial temporal development of selected biomarkers. Blood samples were taken at 0–24 and 25–48 h after onsets of AP were acquired. Mean values and temporal intermediate difference (delta-values) of IL-1β, IL-6, IL-8, IL-10, IL-12, IFN-γ and TNF-α were calculated. Differences between severity groups, predictive capacity of the biomarkers and association with severe disease were analyzed. Paired comparison of samples (n = 115) taken at 0–24 and 25–48 h after onsets of AP showed a change over time for IL-1β, IL-6, IL-8 and IL-10 (p < 0.05) and a significant difference between severity groups after 24 h. In ROC-analysis an IL-6 cut-off level of 196.6 pg/mL could differentiate severe AP (sensitivity 81.9, specificity 91.3). The delta-values of IL-1β and IL-6 were significantly associated with severe outcomes (odds ratios 1.085 and 1.002, respectively). Data of this work demonstrate a distinct change in IL-1β, IL-8, IL-10 and IL-6 over the first 48 h after onset of AP. The temporal development of biomarkers can assist in the early stratification of the disease. Herein IL-1β and IL-6 were associated with severe disease, however the prognostic capacity of investigated biomarkers is low.

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What is stopping us? An implementation science study of kangaroo care in British Columbia’s neonatal intensive care units

BMC Pregnancy and Childbirth ◽

10.1186/s12884-020-03488-5 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Sarah Coutts ◽

Alix Woldring ◽

Ann Pederson ◽

Julie De Salaberry ◽

Horacio Osiovich ◽

...

Keyword(s):

Intensive Care ◽

Healthcare Provider ◽

Preterm Infants ◽

Neonatal Intensive Care ◽

Healthcare Providers ◽

Neurodevelopmental Outcomes ◽

Kangaroo Care ◽

Optimal Care ◽

Barriers And Enablers ◽

Provider Beliefs

Abstract Background The goal of the Neonatal Intensive Care Unit (NICU) is to provide optimal care for preterm and sick infants while supporting their growth and development. The NICU environment can be stressful for preterm infants and often cannot adequately support their neurodevelopmental needs. Kangaroo Care (KC) is an evidence-based developmental care strategy that has been shown to be associated with improved short and long term neurodevelopmental outcomes for preterm infants. Despite evidence for best practice, uptake of the practice of KC in resource supported settings remains low. The aim of this study was to identify and describe healthcare providers’ perspectives on the barriers and enablers of implementing KC. Methods This qualitative study was set in 11 NICUs in British Columbia, Canada, ranging in size from 6 to 70 beds, with mixed levels of care from the less acute up to the most complex acute neonatal care. A total of 35 semi-structured healthcare provider interviews were conducted to understand their experiences providing KC in the NICU. Data were coded and emerging themes were identified. The Consolidated Framework for Implementation Research (CFIR) guided our research methods. Results Four overarching themes were identified as barriers and enablers to KC by healthcare providers in their particular setting: 1) the NICU physical environment; 2) healthcare provider beliefs about KC; 3) clinical practice variation; and 4) parent presence. Depending on the specific features of a given site these factors functioned as an enabler or barrier to practicing KC. Conclusions A ‘one size fits all’ approach cannot be identified to guide Kangaroo Care implementation as it is a complex intervention and each NICU presents unique barriers and enablers to its uptake. Support for improving parental presence, shifting healthcare provider beliefs, identifying creative solutions to NICU design and space constraints, and the development of a provincial guideline for KC in NICUs may together provide the impetus to change practice and reduce barriers to KC for healthcare providers, families, and administrators at local and system levels.

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Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio and Their Role as Predictors of Disease Severity of Coronavirus Disease 2019 (COVID-19)

Journal of Laboratory Physicians ◽

10.1055/s-0041-1723057 ◽

2021 ◽

Author(s):

Rohit Jain ◽

Arun Gopal ◽

Basant Kumar Pathak ◽

Sourya Sourabh Mohakuda ◽

TVSVGK Tilak ◽

...

Keyword(s):

Disease Severity ◽

Complete Blood Count ◽

Wide Spectrum ◽

Statistical Significance ◽

Severe Disease ◽

Neutrophil To Lymphocyte Ratio ◽

Screening Tools ◽

Platelet To Lymphocyte Ratio ◽

Lymphocyte Ratio ◽

Time Of Admission

Abstract Context Due to the wide spectrum of clinical illness in coronavirus disease 2019 (COVID-19) patients, it is important to stratify patients into severe and nonsevere categories. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been evaluated rapidly by a few studies worldwide for its association with severe disease, but practically none have been conducted in the Indian population. This study was undertaken to examine the role of NLR and PLR in predicting severe disease in Indian patients. Objectives The objective was to study the association of NLR and PLR observed at the time of admission with maximum disease severity during hospitalization and to study their role in predicting disease severity. Material and Methods A total of 229 COVID-19 patients were admitted at the center during the study period. After applying inclusion and exclusion criteria, 191 patients were included in the study. The demographic, clinical, and laboratory (complete blood count, NLR, and PLR) data of all patients were obtained at the time of admission. Maximum disease severity of all patients was assessed during hospitalization. Statistical Analysis Chi-square and Mann–Whitney U tests were used to assess statistical significance. Receiver operating characteristic curve (ROC) was plotted for NLR and PLR to estimate the cutoff values and sensitivity and specificity using Youden’s index for predicting severe disease. Logistic regression analysis was used to estimate the odds ratios (OR) and 95% confidence intervals. Results Mean NLR and PLR were significantly higher in severe patients (NLR = 7.41; PLR = 204) compared with nonsevere patients (NLR = 3.30; PLR = 121). ROC analysis showed that NLR, in comparison to PLR, had a higher area under the curve (AUC) of 0.779, with a larger OR of 1.237 and cutoff of 4.1, and showed 69% sensitivity and 78% specificity in predicting severe disease. Cut off for PLR was 115.3, which showed 79% sensitivity and 62% specificity in predicting severe disease. Conclusion NLR and PLR, both showing acceptable AUCs, can be used as screening tools to predict disease severity. However, NLR was a better predictor of disease severity.

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Informing the public health response to COVID-19: a systematic review of risk factors for disease, severity, and mortality

BMC Infectious Diseases ◽

10.1186/s12879-021-05992-1 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

M. Flook ◽

C. Jackson ◽

E. Vasileiou ◽

C. R. Simpson ◽

M. D. Muckian ◽

...

Keyword(s):

Public Health ◽

Risk Factors ◽

Systematic Review ◽

At Risk ◽

Risk Factor ◽

Disease Severity ◽

Severe Disease ◽

Public Health Response ◽

Wide Range ◽

Multivariable Analyses

Abstract Background Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2) has challenged public health agencies globally. In order to effectively target government responses, it is critical to identify the individuals most at risk of coronavirus disease-19 (COVID-19), developing severe clinical signs, and mortality. We undertook a systematic review of the literature to present the current status of scientific knowledge in these areas and describe the need for unified global approaches, moving forwards, as well as lessons learnt for future pandemics. Methods Medline, Embase and Global Health were searched to the end of April 2020, as well as the Web of Science. Search terms were specific to the SARS-CoV-2 virus and COVID-19. Comparative studies of risk factors from any setting, population group and in any language were included. Titles, abstracts and full texts were screened by two reviewers and extracted in duplicate into a standardised form. Data were extracted on risk factors for COVID-19 disease, severe disease, or death and were narratively and descriptively synthesised. Results One thousand two hundred and thirty-eight papers were identified post-deduplication. Thirty-three met our inclusion criteria, of which 26 were from China. Six assessed the risk of contracting the disease, 20 the risk of having severe disease and ten the risk of dying. Age, gender and co-morbidities were commonly assessed as risk factors. The weight of evidence showed increasing age to be associated with severe disease and mortality, and general comorbidities with mortality. Only seven studies presented multivariable analyses and power was generally limited. A wide range of definitions were used for disease severity. Conclusions The volume of literature generated in the short time since the appearance of SARS-CoV-2 has been considerable. Many studies have sought to document the risk factors for COVID-19 disease, disease severity and mortality; age was the only risk factor based on robust studies and with a consistent body of evidence. Mechanistic studies are required to understand why age is such an important risk factor. At the start of pandemics, large, standardised, studies that use multivariable analyses are urgently needed so that the populations most at risk can be rapidly protected. Registration This review was registered on PROSPERO as CRD42020177714.

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