scholarly journals Validation of a Quick Flow Cytometry-Based Assay for Acute Infection Based on CD64 and CD169 Expression. New Tools for Early Diagnosis in COVID-19 Pandemic

2021 ◽  
Vol 8 ◽  
Author(s):  
Alejandra Comins-Boo ◽  
Maria Gutiérrez-Larrañaga ◽  
Adriel Roa-Bautista ◽  
Sandra Guiral Foz ◽  
Mónica Renuncio García ◽  
...  

Objectives: Several parameters aid in deciphering between viral and bacterial infections; however, new tools should be investigated in order to reduce the time to results and proceed with an early target-therapy. Validation of a biomarker study, including CD64 and CD169 expression, was conducted.Material and Methods: Patients with active SARS-CoV-2 infection (ACov-2), bacterial infection (ABI), healthy controls, and antiretroviral-controlled chronic HIV infection were assessed. Whole blood was stained and, after lysing no-wash protocol, acquired by flow cytometry. The median fluorescence intensity (MFI) of CD64 and CD169 was measured in granulocytes, monocytes, and lymphocytes. The CD64 MFI ratio granulocytes to lymphocytes (CD64N) and CD169 MFI ratio monocytes to lymphocytes (CD169Mo) were evaluated as biomarkers of acute bacterial and viral infection, respectively.Results: A CD64N ratio higher than 3.3 identified patients with ABI with 83.3 and 85.9% sensitivity and specificity, with an area under the curve (AUC) of 83.5%. In contrast, other analytic or hematological parameters used in the clinic had lower AUC compared with the CD64N ratio. Moreover, a CD169Mo ratio higher than 3.3 was able to identify ACov-2 with 91.7 and 89.8 sensitivity and specificity, with the highest AUC (92.0%).Conclusion: This work confirms the previous data of CD64N and CD169Mo ratios in an independent cohort, including controlled chronic viral HIV infection patients as biomarkers of acute bacterial and viral infections, respectively. Such an approach would benefit from quick pathogen identification for a direct-therapy with a clear application in different Health Care Units, especially during this COVID pandemic.

2019 ◽  
Vol 13 (16) ◽  
pp. 1373-1386 ◽  
Author(s):  
Pénélope Bourgoin ◽  
Thomas Soliveres ◽  
Dalia Ahriz ◽  
Isabelle Arnoux ◽  
Christian Meisel ◽  
...  

Aim: Management of patients with infections within the Emergency Department (ED) is challenging for practitioners, as the identification of infectious causes remains difficult with current techniques. A new combination of two biomarkers was tested with a new rapid flow cytometry technique. Materials & methods: Subjects from the ED were tested for their CD64 on neutrophils (nCD64) and CD169 on monocytes (mCD169) levels and results were compared to their clinical records. Results: Among 139 patients, 29% had confirmed bacterial infections and 5% viral infections. nCD64 and mCD169 respectively showed 88 and 86% sensitivity and 90 and 100% specificity for identifying subjects in bacterial or viral conditions. Conclusion: This point-of-care technique could allow better management of patients in the ED.


2020 ◽  
Author(s):  
Pénélope Bourgoin ◽  
Thomas Soliveres ◽  
Alexandra Barbaresi ◽  
Anderson Loundou ◽  
Isabelle Arnoux ◽  
...  

ABSTRACTBackgroundThe identification of a bacterial, viral or even non-infectious cause is essential in the management of febrile syndrome in the emergency department (ED) setting, especially in epidemic contexts such as flu or CoVID-19.ObjectivesThe aim of this study was to assess discriminative performances of two biomarkers, CD64 on neutrophils (nCD64) and CD169 on monocytes (mCD169), using a new flow cytometry procedure, in patients presenting with fever to the ED. Human leucocyte antigen-DR on monocytes (mHLA-DR), HLA-ABC ratio (rHLA-ABC), and CD64 on monocytes (mCD64) were also assessed.Methods85 adult patients presenting with potential infection were included during the 2019 flu season in the ED of La Timone Hospital. They were divided into four diagnostic outcomes according to their clinical records: no-infection, bacterial infection, viral infection and co-infection.ResultsmCD169 was elevated in patients suffering from Flu A virus or Respiratory Syncytial Virus, while nCD64 was mainly found elevated in subjects with Streptococcus pneumoniae. In total, 38 (45%) patients were diagnosed with bacterial infections, 11 (13%) with viral infections and 29 (34%) with co-infections. nCD64 and mCD169 showed 90% and 80% sensitivity, and 78% and 91% specificity, respectively, for identifying patients with bacterial or viral infections. Other biomarkers had lower discriminative performances.ConclusionsnCD64 and mCD169 have potential for accurately distinguishing bacterial and acute viral infections. Combined in an easy and rapid flow cytometry procedure, they constitute a potential improvement for infection management in the ED setting, and could even help for the triage of patients during emerging epidemics.


2020 ◽  
Vol 66 (6) ◽  
pp. 802-808 ◽  
Author(s):  
Sophie Trouillet-Assant ◽  
Sébastien Viel ◽  
Antoine Ouziel ◽  
Lucille Boisselier ◽  
Philippe Rebaud ◽  
...  

Abstract Background Fever is one of the leading causes of consultation in the pediatric emergency department for patients under the age of 3 years. Distinguishing between bacterial and viral infections etiologies in febrile patients remains challenging. We hypothesized that specific host biomarkers for viral infections, such as type I-interferon (IFN), could help clinicians’ decisions and limit antibiotic overuse. Methods Paxgene tubes and serum were collected from febrile children (n = 101), age from 7 days to 36 months, with proven viral or bacterial infections, being treated at pediatric emergency departments in France. We assessed the performance of an IFN signature, which was based on quantification of expression of IFN-stimulated genes using the Nanostring® technology and plasma IFN-α quantified by digital ELISA technology. Results Serum concentrations of IFN-α were below the quantification threshold (30 fg/mL) for 2% (1/46) of children with proven viral infections and for 71% (39/55) of children with bacterial infections (P < 0.001). IFN-α concentrations and IFN score were significantly higher in viral compared to bacterial infection (P < 0.001). There was a strong correlation between serum IFN-α concentrations and IFN score (p-pearson = 0.83). Both serum IFN-α concentration and IFN score robustly discriminated (Area Under the Curve >0.91 for both) between viral and bacterial infection in febrile children, compared to C-reactive protein (0.83). Conclusions IFN-α is increased in blood of febrile infants with viral infections. The discriminative performance of IFN-α femtomolar concentrations as well as blood transcriptional signatures could show a diagnostic benefit and potentially limit antibiotic overuse. Clinical Trials Registration clinicaltrials.gov (NCT03163628).


2021 ◽  
Vol 12 (5) ◽  
pp. 107-113
Author(s):  
I. V. Babachenko ◽  
E. V. Sharipova ◽  
L. A. Alekseeva ◽  
S. N. Chuprova ◽  
T. V. Bessonova ◽  
...  

Purpose: to evaluate the importance of increasing cardioenzymes in the diagnosis of infectious heart lesions.Object and methods: Under observation were 71 children aged 3 to 17 years (average age – 6.6 ± 0.4 years) who received treatment at the clinic of Pediatric Research and Clinical Center for Infectious Diseases. All children in the acute period of illness and 49 patients with follow-up history were identified with levels of creatine phosphokinase (CPK), MВ fractions of creatine phosphokinase (CPK-MВ), lactate dehydrogenase (LDH), C-reactive protein (CRP), aspartate aminotransferase (AST). Follow-up observation and examination of patients was performed after 1 month and after 1 year. All children were examined for a wide range of pathogens of acute respiratory viral infections, active herpes virus infections (EBV, CMV, HHV-6 type), B19 parvovirus, Chlamydophila pneumoniae, Mycoplasma pneumonia, enteroviruses and bacterial respiratory pathogens. All examined patients underwent electrocardiography and echocardiography.The results of the study. In the examined patients with an increased level of “cardioenzymes” (CPK-MВ, LDH, AST) against the background of acute respiratory infection (ARI), a wide range of diseases was established with damage to both the upper respiratory tract and lower (bronchitis, bronchiolitis, pneumonia), and also other infectious nosologies, including respiratory syndrome (infectious mononucleosis, enterovirus and parvovirus infection). The etiological structure was dominated by a group of herpesvirus (53%) and bacterial infections (25%), as well as their combinations. An analysis of the dynamics of the main biochemical and hematological parameters characterizing the severity of the systemic inflammation syndrome (leukocytes, SRE, CRP, CPK), as well as reflecting myocardial injuries and used in cardiology practice (CPK- MВ, LDH, AST), revealed a long-term (within 1 year observations) the preservation of a moderately elevated level of CPK-MВ, unlike other indicators that returned to normal within 1 month. An increase in CPK-MВ was recorded in 79% of patients with drip infections, while the average level of CPK-MВ in the total sample exceeded the normal values by 1.8-2.4 times.Conclusion. It was found that elevated levels of CPK-MВ and LDH can be used as criteria for the formation of dynamic observation groups and early rehabilitation.


2020 ◽  
Vol 15 (3) ◽  
pp. 189-201 ◽  
Author(s):  
Pénélope Bourgoin ◽  
Guillaume Lediagon ◽  
Isabelle Arnoux ◽  
Denis Bernot ◽  
Pierre-Emmanuel Morange ◽  
...  

Aim: In an Emergency Department (ED), the etiological identification of infected subjects is essential. 13 infection-related biomarkers were assessed using a new flow cytometry procedure. Materials & methods: If subjects presented with febrile symptoms at the ED, 13 biomarkers’ levels, including CD64 on neutrophils (nCD64) and CD169 on monocytes (mCD169), were tested and compared with clinical records. Results: Among 50 subjects, 78% had bacterial infections and 8% had viral infections. nCD64 showed 82% sensitivity and 91% specificity for identifying subjects with bacterial infections. mCD169, HLA-ABC ratio and HLA-DR on monocytes had high values in subjects with viral infections. Conclusion: Biomarkers showed promising performances to improve the ED's infectious stratification.


Medicina ◽  
2019 ◽  
Vol 55 (8) ◽  
pp. 503
Author(s):  
Linda Rautiainen ◽  
Anna Cirko ◽  
Jana Pavare ◽  
Reinis Balmaks ◽  
Ilze Grope ◽  
...  

Background and objectives: In children, acute infection is the most common cause of visits in the primary care or emergency department. In 2002, criteria for diagnostics of pediatric sepsis were published, and then revised in 2016 as “life-threatening organ dysfunction due to a dysregulated host response to infection”. In the pathophysiology of sepsis endothelial dysfunction plays a very important role. Deficient proteolysis of von Willebrand factor, due to reduced ADAMTS-13 activity, results in disseminated platelet-rich thrombi in the microcirculation. ADAMTS-13 deficiency has been detected in systemic inflammation. The clinical relevance of ADAMTS-13 during sepsis is still unclear. We aimed to investigate the possible use of ADAMTS-13 as a prognostic marker in children with serious bacterial infection (SBI). Materials and Methods: Inclusion criteria were hospitalized children with SBI, aged from 1 month to 17 years. SBI was defined based on available clinical, imaging, and later also on microbiological data. Sepsis was diagnosed using criteria by The International Consensus Conference. In all the patients, the levels of ADAMTS-13 were measured at the time of inclusion. Results: Data from 71 patients were analyzed. A total of 47.9% (34) had sepsis, 21.1% (15) were admitted to the ICU, 8.5% (6) had mechanical ventilator support, and 4.2% (3) patients had a positive blood culture. The median level of ADAMTS-13 in this study population was 689.43 ng/mL. Patients with sepsis, patients admitted to the Intensive Care Unit, and patients in need of mechanical ventilator support had significantly lower levels of ADAMTS-13. None of the patients had ADAMTS-13 deficiency. In patients with SBI, the area under the curve (AUC) to predict sepsis was 0.67. A cut-off ADAMTS-13 level of ≤730.49 had 82% sensitivity and 60% specificity for sepsis in patients with SBI. Conclusions: ADATMS-13 levels were lower in patients with SBI and sepsis, but AUC and sensitivity were too low to accept it as a prognostic marker.


2021 ◽  
Vol 17 (2) ◽  
pp. 64-71
Author(s):  
T.A. Litovchenko ◽  
A.V. Litovchenko

The role of non-epidemic viral encephalitis and HIV-infection in the development of acute epileptic seizures and epilepsy, analysis of recent epidemiological data and risk factors are discussed. Infections of the central nervous system produce up to 15 % of all types of new-onset symptomatic epileptic seizures. The risk depends on the ethology of infection, localization of lesion and severity. A high risk of development of epilepsy is seen in case of herpetic encephalitis and HIV-infection. The viral infections have been shown to be often accelerated by epileptic seizures in the acute phase of encephalitis and lead to an increased risk of developing epilepsy later. The mechanisms of development of early and late seizures are different. There are many forms of viral encephalitis, and all are associated to varying degrees with subsequent epilepsy. The risk of developing epilepsy following viral encephalitis is increased seven- to tenfold over premorbid levels. This risk increases the premorbid risk by 22 times if a patient experiences early seizures during the acute infection. Timely treatment of viral infections and early seizures reduces the risk of developing epilepsy later. The treatment of epileptic seizures due to viral infection is similar to those of symptomatic epilepsy. It is necessary to take into account possible drug-drug interactions between antiepileptic and antiviral drugs. Levetiracetam is used as an antiepileptic drug of the first choice in the treatment of epilepsy and epileptic seizures in the case of viral encephalitis.


Medicina ◽  
2019 ◽  
Vol 55 (1) ◽  
pp. 4 ◽  
Author(s):  
Linda Rautiainen ◽  
Jana Pavare ◽  
Ilze Grope ◽  
Peteris Tretjakovs ◽  
Dace Gardovska

Background and objectives: In children, acute infection is the most common cause of visits to the emergency department. Although most of them are self-limiting, mortality due to severe bacterial infections (SBI) in developed countries is still high. When the risk of serious bacterial infection is too high to ignore, yet too low to justify admission and hospital observation, clinicians try to improve diagnostic accuracy by performing various laboratory tests. The aim of the study was to investigate whether an early inflammatory cytokine and chemokine panel can add information in diagnostics of SBI and assessment of efficacy of early therapies in hospitalized children with fever. Methods: This study included 51 children with febrile infections that were admitted to the emergency department (ED). Clinical examination and microbiological and radiological tests were used as reference standards for the definition of SBI. Study population was categorized into two groups: (1) patients with SBI (n = 21); (2) patients without SBI (n = 30). Inflammatory cytokine and chemokine panels were analyzed from the first routine blood samples at hospital admission and after 24 h. Results: Out of 12 cytokines and chemokines, only Eotaxin and granulocyte colony-stimulating factor (G-CSF) had statistically significant differences between groups at the time of inclusion. Receiver operator characteristic analysis to predict SBI showed an area under the curve (AUC) of 0.679 for G-CSF. Conclusions: Analysis of inflammatory cytokine profiles may provide additional information in early diagnostics of SBI.


2008 ◽  
Vol 205 (12) ◽  
pp. 2699-2701 ◽  
Author(s):  
David A. Hafler ◽  
Vijay Kuchroo

Exhaustion of T cell responses during chronic viral infections has been observed in both mouse and man and has been attributed to up-regulation of PD-1 on the surface of exhausted T cells. In patients with chronic human HIV infection, T cell exhaustion leads to opportunistic infections associated with AIDS. However, not all the exhausted T cells express PD-1, suggesting that other molecules may be involved in the phenotype. A new study now demonstrates a central role for T cell immunoglobulin and mucin domain–containing protein-3 (TIM-3) in T cell exhaustion during chronic HIV infection and suggests that TIM-3 may be a novel therapeutic target in chronic viral diseases.


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