Utility of neutrophil CD64 in distinguishing bacterial infection from inflammation in severe alcoholic hepatitis fulfilling SIRS criteria

To assess utility of neutrophilCD64 (nCD64) expression in differentiating bacterial infection from inflammation in patients with severe alcoholic hepatitis (SAH) fulfilling systemic inflammatory response syndrome criteria. Patients with SAH and infection (n = 58), SAH without infection (n = 70), and healthy controls (n = 20) were included. Neutrophil CD64 expression by flowcytometry, serum Procalcitonin (ELISA) and C-reactive protein (Nephelometry) and neutrophil–lymphocyte ratio (NLR) were studied. Percentage of neutrophils with CD64 expression (nCD64%) was significantly higher in patients with SAH and infection than in those without infection and controls [76.2% (56.9–86.5) vs. 16% (12.6–23.1) vs. 7.05% (1.4–9.5), p < 0.05], as was their mean fluorescence intensity [MFI; 1431 (229–1828) vs. 853 (20–968) vs. 99.5 (54.7–140.7), p < 0.05]. Using a cut-off of 27%, the sensitivity and specificity of nCD64% to diagnose bacterial infection was 94% and 81%, respectively, with area under curve (AUC) of 0.95. At a cut-off value of 0.261 ng/ml, the sensitivity and specificity of serum procalcitonin was 83% and 72%, respectively, with AUC of 0.86. Serum CRP, total leukocyte count, NLR had AUCs of 0.78, 0.63 and 0.64, respectively. Quantitative measurement of nCD64 can better distinguish systemic bacterial infection and inflammation in SAH as compared to traditional biomarkers.

Effect of Neutrophil CD64 Index in Elderly Patient with Community-acquired Pneumonia

Background: Elderly patient with community-acquired pneumonia is the leading infectious cause of death. During the clinical diagnosis and treatment, some elderly patients do not have typical clinical symptoms .Therefore establishment of safe and effective diagnosis, prognostic assessment systems is important for clinicians. Objective: To evaluate the diagnostic and prognostic value of the neutrophil CD64(nCD64) in elderly patients with community-acquired pneumonia. Methods: One hundred and twenty-eight elderly patients(≥65year) diagnosed with community-acquired pneumonia from December 2018 to December 2020. All patients were further subdivided into two groups: Non severe community-acquired pneumonia(N-SCAP) group and severe community-acquired pneumonia (SCAP)group. nCD64 index, procalcitonin (PCT) level, C-reactive protein (CRP) level, White blood cell (WBC) counts and Neutrophil (NEUT) absolute counts were obtained and CURB-65 scores were calculated for each patient. Results: The nCD64, CRP ,PCT, WBC,NEUT levels,CURB-65 score were higher in severe community-acquired pneumonia group patients. The nCD64, CRP, PCT levels ,CURB-65 score were higher in non-survivors. The receiver operating characteristic (ROC) curve of nCD64 was higher than those of CRP, PCT, WBC, NEUT levels for diagnosing infection. The AUC of nCD64 for predicting 28-day mortality in community-acquired pneumonia was significantly higher than those of CRP ,PCT, WBC and NEUT. The AUC of nCD64 combined with CURB-65 score was significantly higher than that of CRP, PCT, WBC and NEUT parameter combined with CURB-65 score for predicting 28-day mortality. Conclusions: The neutrophil CD64 index is a valuable biomarker for diagnosis of infection and prognostic evaluation in elderly patients (≥65 year) with community-acquired pneumonia.

Diagnostic value of neutrophil CD64, procalcitonin, and interleukin-6 in sepsis: a meta-analysis

Background The aim of the study was to conduct a meta-analysis to evaluate the accuracy of neutrophil CD64, procalcitonin (PCT), and interleukin-6 (IL-6) as markers for the diagnosis of sepsis in adult patients. Methods Various databases were searched to collect published studies on the diagnosis of sepsis in adult patients using neutrophil CD64, PCT, and IL-6 levels. Utilizing the Stata SE 15.0 software, forest plots and the area under the summary receiver operating characteristic curves were drawn. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the curve (AUC) were calculated. Results Fifty-four articles were included in the study. The pooled sensitivity, specificity, and AUC of neutrophil CD64 for the diagnosis of sepsis were 0.88 (95% confidence interval [CI], 0.81–0.92), 0.88 (95% CI, 0.83–0.91), and 0.94 (95% CI, 0.91–0.96), respectively. The pooled sensitivity, specificity, and AUC of PCT for the diagnosis of sepsis were 0.82 (95% CI, 0.78–0.85), 0.78 (95% CI, 0.74–0.82), and 0.87 (95% CI, 0.83–0.89), respectively. Subgroup analysis showed that the AUC for PCT diagnosis of intensive care unit (ICU) sepsis was 0.86 (95% CI, 0.83–0.89) and the AUC for PCT diagnosis of non-ICU sepsis was 0.82 (95% CI, 0.78–0.85). The pooled sensitivity, specificity, and AUC of IL-6 for the diagnosis of sepsis were 0.72 (95% CI, 0.65–0.78), 0.70 (95% CI, 0.62–0.76), and 0.77 (95% CI, 0.73–0.80), respectively. Conclusions Of the three biomarkers studied, neutrophil CD64 showed the highest diagnostic value for sepsis, followed by PCT, and IL-6. On the other hand, PCT showed a better diagnostic potential for the diagnosis of sepsis in patients with severe conditions compared with that in patients with non-severe conditions.

Diagnostic Value of Neutrophil CD64 in Burn Patients with Infection in Chinese Population：A Systematic Review and Meta-analysis

Background Infection is one of the leading causes of death in burn patients. Many researches regard neutrophil CD64 (nCD64) as a biomarker in the early diagnosis of burn patients with infection. Nevertheless, the conclusions are controversial. Methods A comprehensive analysis of the diagnostic value of nCD64 for burn infection was performed in China using a meta-analysis method. Pubmed, Cochrane library, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), and China Wanfang databases were searched for studies on nCD64 as a diagnostic biomarker of burn patients with infection from the establishment of the databases to September 29, 2020. The data was analyzed by Stata 15.0 software. Results Six studies were identified. The results showed that the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and DOR were 0.92 (95%CI:0.88~0.95), 0.82 (95%CI:0.76~0.87), 5.10 (95%CI:3.90~6.80), 0.10 (95%CI:0.06~0.15) and 52 (95%CI:29~94), respectively. The area under curve (AUC) was 0.94 (95%CI:0.92~0.94). According to the analysis of the sepsis subgroup, it showed that nCD64 had good diagnostic value in the patients with burn sepsis in Chinese population. Conclusion nCD64 is highly efficient to diagnose burn infection in Chinese population. Therefore, nCD64 could be regarded as a valuable biomarker for early diagnosis of burn infection in China, especially in patients with burn sepsis. Combined with other diagnostic indexes, nCD64 can be clinically used in the early diagnosis of burn infection to improve the sensitivity and specificity.

The Potential Prognostic Performance of Neutrophil CD64 and Monocyte HLA-DR in Patients with Complicated Intra-abdominal Infections

Background: Complicated intra-abdominal infections are still associated with a high risk of an unfavorable outcome. Despite the equal treatment, the mortality rates in some patients’ populations remain significant, especially when the impaired immune response is present. Aim: The object of this research is to analyze the impact of pro-inflammatory neutrophil CD64 and anti-inflammatory monocyte HLA-DR on the final outcome. Methods: We have searched in the PubMed database, the literature relating the prognostic value of two biomarkers - nCD64 and mHLA-DR in patients with complicated intra-abdominal infections and/or sepsis. Results: Eighteen original studies with 2960 patients fulfilled our inclusion criteria. The data about nCD64 that we found was contradictory, whereas low mHLA-DR expression showed good prognostic value. Conclusion : Our review showed heterogeneous data about nCD64 survival prediction. Further investigations with surgical patients exclusively are needed to evaluate its prognostic value in cIAIs. However, we observed a good prognostic performance of low mHLA-DR expression. After a validation in larger multicentre studies, mHLA-DR could be used as promising prognostic biomarker in cIAIs.

The Utility of Neutrophil CD64 and Presepsin as Diagnostic, Prognostic, and Monitoring Biomarkers in Neonatal Sepsis

Background. Neonatal septicemia is a critical medical situation; current conventional laboratory methods still have many limitations and diagnostic obstacles. For this purpose, last decades have witnessed a challenge between the battery of sepsis biomarkers including many leukocyte surface antigens, not only for early diagnostic purposes but also for better follow-up and good management of sepsis patients. Aim. To evaluate the diagnostic, prognostic, and monitoring performance of both neutrophil CD64 (nCD64) and presepsin as sepsis biomarkers compared to each other and to the conventional laboratory sepsis parameters aiming to decide which is the best fitting for routine daily use in neonatal intensive care units (NICUs). Methods. 235 neonates were enrolled from three Egyptian neonatal ICUs, during the period from November 2015 till March 2018; they were classified into two main groups: the control group (n = 102) and the sepsis group (n = 133). Laboratory sepsis evaluation included highly sensitive CRP (hs-CRP), CBC, in addition to nCD64 (flow cytometry technique), and presepsin measurement (CLEIA technique combined with Magtration® technology); the diagnosis was confirmed thereafter by positive blood culture results (BacT/Alert system). Sixty-two of the enrolled sepsis neonates were subjected to follow-up assessment; they were reclassified according to their clinical improvement at the second time assessment into (group 1: sepsis group without improvement) (n = 20) and (group 2: improved sepsis group) (n = 42). Results. Significant increase in nCD64 and presepsin values was found in sepsis groups compared to the controls. At cutoff 41.6%, nCD64% could discriminate the presence of septicemia with sensitivity 94.7%, specificity 93.6 %, and AUC 0.925, while presepsin at cutoff 686 pg/ml achieves sensitivity 82.7%, specificity 95.5%, and AUC 0.887, respectively. Significant increase in nCD64 ( P < 0.001 ) and hs-CRP ( P = 0.018 ) values was observed in severe sepsis/septic shock patients compared to nonsevere sepsis patients. Delta change percentage (dC%) between initial and follow-up evaluations for both improved and nonimproved sepsis patients was dC Z value −5.904 for nCD64% followed by dC Z value −4.494 for presepsin. Conclusion. nCD64 and presepsin are valuable early diagnostic and monitoring sepsis biomarkers; the highest sensitivity could be achieved by a univariant sepsis marker in this study was recorded by the nCD64% biomarker, while the highest specificity was documented by presepsin. Combined measurement of both achieves the highest diagnostic performance in sepsis neonates. Either of CD64 or presepsin combined with hs-CRP associated with better performance than any of them alone. nCD64 carries an additional promising role in reflecting sepsis prognosis.

An ultra-sensitive, ultra-fast whole blood monocyte CD169 assay for COVID-19 screening

CoVID-19 is an unprecedented epidemic, globally challenging health systems, societies, and economy. Its diagnosis relies on molecular methods, with drawbacks revealed by current use as mass screening. Monocyte CD169 upregulation has been reported as a marker of viral infections, we evaluated a flow cytometry three-color rapid assay of whole blood monocyte CD169 for CoVID-19 screening.Outpatients (n=177) with confirmed CoVID-19 infection, comprising 80 early-stage (≤14 days after symptom onset), 71 late-stage (≥15 days), and 26 asymptomatic patients received whole blood CD169 testing in parallel with SARS-CoV-2 RT-PCR. Upregulation of monocyte CD169 without polymorphonuclear neutrophil CD64 changes was the primary endpoint. Sensitivity was 98% and 100% in early-stage and asymptomatic patients respectively, specificity was 50% and 84%. Rapid whole blood monocyte CD169 evaluation was highly sensitive when compared with RT-PCR, especially in early-stage, asymptomatic patients whose RT-PCR tests were not yet positive.Diagnostic accuracy, easy finger prick sampling and minimal time-to-result (15-30 minutes) rank whole blood monocyte CD169 upregulation as a potential screening and diagnostic support for CoVID-19. Secondary endpoints were neutrophil CD64 upregulation as a marker of bacterial infections and monocyte HLA-DR downregulation as a surrogate of immune fitness, both assisting with adequate and rapid management of non-CoVID cases.