Clinical Chemistry and Laboratory Medicine (CCLM)

IntroductionRoutine blood tests play an essential role in modern healthcare, but their administration, processing, and reporting under the current centralized testing model is slow, inefficient, and cumbersome for patients and providers especially in outpatient settings. Truvians benchtop blood testing platform, in late-stage development, aims to decentralize and streamline routine blood testing, replacing traditional send-outs to a central laboratory with a compact, easy-to-use benchtop platform at the point-of-action to ensure timely and actionable results between a patient and healthcare provider. Using only a small amount of blood from a single heparinized sample, the Truvian platform can simultaneously provide results for a full panel of routine blood tests spanning clinical chemistry, hematology, and immunoassays. Evaluation of the Truvian platform in independent external studies is important to understand its performance in real world settings and to identify opportunities for improvement to complete development. To assess the performance of a comprehensive wellness panel on the Truvian platform, a multi-site study was completed at Truvians headquarters in San Diego, California, and at an independent clinical trial site in the Pacific Northwest. The study evaluated the panels precision and accuracy against central laboratory analyzers. MethodsPrecision and accuracy studies were performed with a panel of 32 routine blood tests including immunoassay, clinical chemistry and hematology assays on the Truvian platform. Precision studies were run across multiple days and instruments to assess repeatability and reproducibility for each test in the panel. A method comparison study included 237 patients and compared the Truvian platform to best-in-class FDA cleared central laboratory analyzers - the Roche Cobas and Sysmex analyzers. Bland-Altman and either Passing-Bablok, or Deming regression analyses were used to determine agreement for each analyte in the panel. Additionally, linearity, sensitivity, and endogenous interfering substance studies were carried out for tests within the panel. ResultsOverall, the Truvian platform had a run reliability rate of > 95%. In the precision and detection capability studies, the evaluated tests successfully satisfied all predefined criteria for precision, linearity, and sensitivity. Moreover, the method comparison study revealed concordance with central laboratory analyzers. ConclusionsThis multi-site study demonstrated that the Truvian platform, currently in late-stage development, is capable of delivering the clinical performance and reliability needed for decentralized blood testing. The study also provided additional areas of focus to complete development.

BCR-ABL1 is a chimeric oncogene underlying chronic myeloid leukemia (CML) and serves as a key marker for monitoring minimal residual disease. Quantitative RT-qPCR analysis of BCR-ABL1 transcripts enables assessment of molecular response depth and timely detection of treatment failure or resistance. In international practice, the introduction of the International Scale (IS), along with method standardization, has significantly improved the comparability of results between laboratories. Participation in external quality assessment (EQA) programs is a mandatory accreditation requirement in countries with established CML monitoring systems, allowing laboratories to evaluate analytical accuracy and to adjust protocols when deviations are detected. Until recently, Russia lacked both standardized IS calibration and a national EQA program for BCR-ABL1 testing, which hindered the assessment of interlaboratory precision. This pilot study represents the first interlaboratory comparison of quantitative BCR-ABL1 measurement in the Russian Federation. Two panels of lyophilized control samples (five levels each, from M1 to M4.5) were distributed and analyzed by 14 laboratories (15 datasets) using their routine protocols without IS conversion. Interlaboratory variability was high: the overall coefficient of variation ranged from approximately 40 percent to 50 percent, with individual laboratory results at the high level (about 10 percent) varying from 3 percent to 27 percent. Most laboratories results were within plus/minus 3 standard deviations of the consensus median, but two laboratories showed consistent overestimation (bias about +3.8 percentage points) or underestimation (bias about -1.7 percentage points), leading to multi-fold errors at level M1. These findings highlight the urgent need to implement IS calibration and to establish a national EQA program for BCR-ABL1 testing in Russia to improve result comparability. Adoption of these measures will help align molecular monitoring of CML in Russia with international standards and strengthen clinician confidence in laboratory testing

BackgroundErythrocyte indices are essential for the diagnosis and monitoring of hematologic diseases, but their determination depends on automated hematology analyzers, which limits access in regions with limited laboratory infrastructure. Although artificial intelligence approaches have been proposed for hematologic analysis, they usually rely on slide scanners or digitization systems. To date, no validated approaches have been identified in the literature that estimate these indices directly from images obtained through the eyepiece of conventional optical microscopes. ObjectiveTo evaluate the feasibility of automated prediction of erythrocyte indices from blood smear images obtained directly through the eyepiece of conventional microscopes using convolutional neural networks. MethodsTwo hundred blood samples stained using the May-Grunwald-Giemsa method were analyzed and photographed using a standard optical microscope. Four architectures, DenseNet-121, EfficientNet-B0, ResNet-18, and ResNet-34, were evaluated at different resolutions using 10-fold K-Fold cross-validation. ResultsFor RBC, HGB, and HCT, ResNet-34 at a resolution of 1024x1024 pixels achieved superior performance, with R2 between 0.90 and 0.92, Pearson correlation r > 0.95, and mean absolute errors of 0.184 x106/{micro}L, 0.524 g/dL and 1.292%, respectively. For RDW-CV, DenseNet-121 achieved R2 = 0.49 and r = 0.71, reflecting the greater complexity of this parameter. Bland-Altman analysis confirmed adequate agreement, with biases close to zero and more than 94% of observations within the limits of agreement. ConclusionArtificial intelligence demonstrated excellent predictive performance in estimating the erythrocyte indices RBC, HGB, and HCT, with R2 > 0.90, from images obtained using a conventional microscope and accessible hardware. This approach has significant potential to democratize access to hematologic analysis in resource-limited settings, although multicenter validation and regulatory evaluation are required before clinical implementation.

IntroductionEvaluating the accuracy and imprecision of Point-of-Care Testing (POCT) devices is an important prerequisite for ensuring proper diagnosis. The objective of this study was to assess the reliability of POCT hemoglobin (Hb), conducting a method comparison study on HemoCue Hb 801 and Sysmex XN 9000 as reference. MethodsThirty EDTA whole blood samples previously tested for Hb on Sysmex XN 9000 were also analysed on HemoCue Hb 801 within the measurement range 6.4-21.9 g/dL. Data were assessed by linear regression and correlation with a 95% confidence interval (CI) for the slope and intercept, a paired Students t-test, bias calculations and a Bland-Altman plot. Twelve independent measurements on the same sample material determined the imprecision of HemoCue Hb 801. ResultsWe found a strong correlation coefficient (r2) of 0.992 between Hb measured on HemoCue Hb 801 and Sysmex XN 9000 with a slope of 0.984 (CI: 0.956 to 1.021) and an intercept of 0.181 (CI: -0.283 to 0.544). The paired Students t-test indicated that the mean Hb differences between the methods were not statistically significant (p=0.84). Bias (-0.01 g/dL) did not deviate from the allowed maximum absolute bias ({+/-}0.35 g/dL). The values were within the 95% limits of agreement ({+/-}1.40 g/dL) for the differences. The coefficient of variation was 1.0%. ConclusionThere was a strong correlation and good agreement between Hb measured on HemoCue Hb 801 and Sysmex XN 9000, as well as an acceptable bias and imprecision, supporting a good accuracy.

Background and ObjectivesBlood center Nucleic Acid Testing (NAT) laboratories primarily utilize Individual testing(ID-NAT) and minipool testing(MP-NAT) modes. ID-NAT offers higher sensitivity, while MP-NAT is more cost-effective. While direct comparisons of the two modes exist, the efficacy of a parallel implementation combining both modes has been less explored. Materials and MethodsThis laboratory employs both testing systems in parallel. From March to August 2024, the ID-NAT system was suspended for equipment upgrades. NAT indicators during this suspension period were retrospectively analyzed and compared with data from the preceding seven years to assess impacts on economic benefits and positive yield. ResultsDuring the suspension period, 96,941 specimens were tested. The NAT yield rate was 0.0536%, NAT resolution reactive rate was 0.8624%, NAT resolution efficiency rate was 49.06%, MP-NAT reagent utilization rate was 82.35%, NAT invalid rate was 1.5228%, and NAT invalid pool rate was 0.0328%. Comparisons with the same period in 2023 and other months in 2024 showed no statistically significant differences (p > 0.05). Testing costs decreased by approximately 28.57%. When compared to historical data from the same period, the NAT yield rate,and MP-NAT yield rate, showed statistically significant differences (p < 0.05). ConclusionDifferences exist in NAT yield detection between the parallel ID-NAT/MP-NAT mode and the single MP-NAT mode, requiring cautious interpretation. Economically, the parallel mode demonstrated superior performance.

IntroductionFree light chain kappa (FLC{kappa}) are a newer sensitive biomarker to detect intrathecal immunoglobulin synthesis. Here we report the study protocol of the ORCAS study which will evaluate a novel laboratory work flow recently proposed including FLC{kappa} analysis simplifying cerebrospinal fluid (CSF) analysis. MethodsThe ORCAS study is a prospective multicenter diagnostic biomarker study across at least 4 study sites. The study protocol does not specify which assays should be applied in the participating laboratories to detect oligoclonal bands (OCB) or measure FLC{kappa} or Ig synthesis to represent real world data. Primary outcome parameter is the sensitivity and negative predictive value of the absence of local FLC{kappa} synthesis for the absence of intrathecal synthesis according to OCB and/or intrathecal IgG, IgA, IgM synthesis in quotient diagrams. The reference range of FLC{kappa} will be indicated by the FLC{kappa} quotient diagram. This study was designed according to the STARD criteria. PerspectiveThe establishment of a newer biomarker in routine practice is associated with significant difficulties, such as the inconsistent comparability of different measurement platforms, the establishment of suitable cut-offs or insufficient knowledge regarding sensitivity and specificity of the biomarker. If the ORCAS study objective is achieved, the use of the proposed workflow integrating FLC{kappa} analysis in routine practice in CSF diagnostics could help to better characterize the intraindividual and disease-specific intrathecal humoral immune response in a resource-efficient manner.

BackgroundAutomated hematology analyzers offer precise hemoglobin measurements, but are expensive and impractical for field, point of care, primary care and remote settings use. The portable and cost-effective Hemocue device provides an alternative. Comparing their accuracies is crucial to prevent diagnostic discrepancies and misdiagnoses. This study aimed to determine the accuracy of Hb HemoCue machine by comparing its performance to automated analyzer at KCMC clinical laboratory where both equipment are used. MethodsA cross-sectional study was conducted at Kilimanjaro Christian Medical Centre (KCMC) Clinical Laboratory among adult patients whose hemoglobin concentrations were measured in May to June 2024. Hemoglobin levels were estimated using two distinct methods: the Hb HemoCue machine and repeatedly tested using an automated hematology analyzer. ResultsHemoglobin (Hb) concentration values obtained from the HemoCue machine and the automated analyzer, had a mean difference of 0.001 g/dl (95% Cl: -0.036 to 0.038), t value of 0.062, and a p-value of 0.95, indicating a non-statistically significant differences between the two measurement methods. The Bland-Altman plot analysis indicated that the mean difference (bias) between the two methods was 0.0012 g/dL, and the limits of agreement ranged from - 0.481 to 0.482 g/dL, suggesting that the HemoCue machine tends to slightly overestimate Hb values compared to the automated hematology analyzer. The Pearson correlation coefficient for the Hb concentrations measured using HemoCue and automated analyzer was 0.995, indicating a very strong positive correlation. Receiver operating characteristics (ROC) curve showed that the area under the curve (AUC) for analyzer and HemoCue was 1.000 indicating that both methods have good diagnostic accuracy of measuring Hb concentrations. ConclusionThe study revealed strong agreement between HemoCue and automated hematology analyzer for measuring hemoglobin concentrations. Both methods demonstrated high diagnostic accuracy suitable for clinical use. Although HemoCue slightly overestimated hemoglobin, this difference was deemed insignificant. The study endorses HemoCue as a reliable tool for hemoglobin concentration measurement alongside automated analyzers.

Heparin-induced thrombocytopenia (HIT) is a potentially life-threatening disorder characterized by antibodies to Platelet Factor 4 (PF4)-polyanion complexes which cause thrombocytopenia and thrombosis. Currently used technically-simple frontline assays such as the PF4-polyanion enzyme-linked immunosorbent assays (ELISAs) lack specificity, and more accurate functional assays such as the serotonin release assay (SRA) and PF4-dependent P-selectin expression assay (PEA) have long turnaround times due to technical complexity and availability only in the reference laboratory setting. There is a critical need for accurate near-patient functional testing to guide patient management, but a key barrier to attaining this goal is the short-term viability of platelets. Here, we detail a process of platelet cryopreservation that renders them viable for at least one year and show that PF4-treated cryopreserved platelets, when coupled with ELISA-based measurement of thrombospondin-1 release (a platelet -granule protein), detects pathogenic HIT antibodies with high accuracy. Furthermore, testing of a cohort of non-pathogenic HIT antibodies that were strongly reactive in PF4/polyanion ELISA but negative in functional assays demonstrated negative results in the thrombospondin-1 release assay, confirming high specificity of this technique. These findings have the potential to transform the diagnostic testing paradigm in HIT by making in-hospital functional testing available for rapid and accurate diagnosis.

BACKGROUNDIn December 2019, a novel coronavirus (SARS-CoV-2)-infected pneumonia (COVID-19) occurred in Wuhan, China. Travel-associated cases have also been reported in other countries. The number of cases has increased rapidly but laboratory diagnosis is limited. METHODSWe collect two groups of cases diagnosed with COVID-19 for experiments. One group collected 63 samples for Enzyme-linked immunosorbent assay (ELISA) IgG and IgM antibodies. The other group collected 91 plasma samples for colloidal gold-immunochromatographic assay (GICA). RESULTSThe sensitivity of the combined ELISA IgM and ELISA IgG detection was 55/63 ( 87.3%), The sensitivity of the combined GICA IgM and GICA IgG detection was 75/91 ( 82.4%), Both methods are negative for healthy controls, specificity of 100%. There is no significant difference between the sensitivity of between ELISA and GICA (IgM+ IgG). CONCLUSIONSELISA and GICA for specific IgM and IgG antibodies are conventional serological assays, they are simple, fast, and safe, the results can be used for clinical reference, and the huge clinical diagnosis and treatment pressure can be greatly relieved.

BackgroundThe international consensus group suggested criteria for action following automated complete blood count and white blood cell differential analysis. These criteria were set based on data from laboratories of developed countries. It is highly important to validate the criteria in developing countries where infectious diseases are still rampant that can affect blood cell count and morphology. Thus, this study was aimed to validate the consensus group criteria for slide review at Jimma Medical Center, Ethiopia from February 1 to May 30, 2020. MethodThe study comprised a total of 1685 patient samples from the daily laboratory workload of CBC analysis. The samples were collected in K2-EDTA tubes (Becton Dickinson) and analyzed using Coulter DxH 800 and Sysmex XT-1880 hematology analyzers. Slide review was done on two Wright-stained slides for each sample. All statistical analysis were performed using SPSS version 20 software. ResultThere were 39.8% positive findings, majority of which were related to red blood cells. The false negative and false positive rates for Sysmex and Coulter analyzer were 2.4% vs. 4.8%; and 4.6% vs. 4.7%, respectively. The false negative rate was unacceptably higher when we used physicians triggered slide review, which was 17.3% and 17.9% for Sysmex and Coulter analyzer, respectively. ConclusionGenerally, the consensus group rules are suitable to use in our setting. However, we might still need to modify the rules, particularly to reduce the review rates. It is also necessary to confirm the rules with case mixes proportionally derived from the source population.

Monitoring the change of cell populations within patients after hematopoietic stem cell transplant (HSCT) is crucial for determining the success of treatment. With current studies largely focused on determining mixed chimerism of nucleated cells, mixed chimerism for non-nucleated red blood cell (RBC) populations was rarely studied. In this study, based on the differences between donor and recipient ABO blood group surface markers and using commercially available mouse monoclonal antibodies (mAbs) for anti-A1 and anti-glycophorin A (GlyA), a flow cytometry (FCM) based assay was tested to monitor RBC chimerism for post-HSCT patients with combinations A1/O, A1B/O, A1/B, and A1B/B blood group difference. Titration curves of mixed blood type combinations with 10% margins were made. These titration curves had a consistent R2 value > 0.99 and a standard deviation (SD) value < 5%. This suggests that the proposed assay was valid, precise, and reliable. Furthermore, a patient sample with recipient A and donor O mixed blood type was tested and showed that the proposed assay was accurate. Since anti-A2 and anti-B mAbs were not tested, next steps would be testing these antibodies such that the assay can monitor post-HSCT patients with combinations A2/O, A2B/O, A2/B, A2B/B, AB/B, and B/O blood type difference.

POEMS syndrome is a rare form of plasma cell dyscrasia with multiple clinical features including polyneuropathy and sclerotic bone lesions. As various signs and symptoms can be observed, diagnosis is often delayed and we need an accurate diagnosis tool for these patients. Vascular endothelial growth factor (VEGF) is known to play a major role in the pathology and is frequently increased in sera of the patients but is not specific. This condition is also associated with the presence of a monoclonal immunoglobulin light chain composed of highly restricted variable domains (IGLV1-40, IGLV1-44, IGLV1-36 and IGJV3*02 genes). Using RNA-based high-throughput sequencing (5 RACE RepSeq), we previously showed mutated consensus stretches in the CDR1/FR2 regions of the variable domains of the light chains: (P/A)VNWYQ and (D/G)VNWYQ. We have now added 70 light chain sequences to our cohort and confirmed the variable domain restriction, the consensus stretches and found a new YSVNWYQ pattern on IGLV1-44 light chains. When correlated with our clinical database of POEMS patients, these mutation patterns had an accuracy of 89% and a specificity of 100%. 5RACE RepSeq is an important tool to ensure the diagnosis of patients suspected of having POEMS syndrome, even with a small secretory clone. Samples from an involved organ are mandatory in the case of localized disease.

Current clinical management of multiple myeloma (MM) relies on bone marrow (BM) biopsies for minimal residual disease (MRD) assessment. While BM biopsies are the gold standard, their invasive nature and potential to miss extramedullary or patchy disease necessitate sensitive, non-invasive liquid biopsy platforms. In this study, we evaluated the analytical performance of the CellSearch CMMC assay to determine its utility for deep-MRD monitoring. Using a standard 4 mL whole blood input, the assay achieves a WBC-normalized sensitivity of 2.45 x 10-7, supported by a limit of quantitation of 5 cells per run. Given this high analytical sensitivity, the assay provides a robust negative predictive value, rendering false-negative findings highly unlikely in populations with detectable peripheral disease. These findings characterize the CellSearch CMMC assay as a highly sensitive, analytically validated platform for non-invasive deep-MRD level longitudinal surveillance monitoring. When integrated into a clinical workflow that accounts for its specificity profile, the platform offers a patient-friendly complement to serial BM biopsies, with the potential to reduce their frequency in appropriate clinical contexts.

Serological assays for anti-SARS-CoV-2 antibodies are now of critical importance to support diagnosis, guide epidemiological intervention, and understand immune response to natural infection and vaccine administration. We developed and validated new anti-SARS-CoV-2 IgG, IgM and IgA ELISA tests (ENZY-WELL SARS-CoV-2 ELISA, DIESSE Diagnostica Senese S.p.a.) based on whole-virus antigens. We used a total of 553 serum samples including samples from COVID-19 suspected and confirmed cases, healthy donors, and patients positive for other infections or autoimmune conditions. Overall, the assays showed good concordance with the indirect immunofluorescence reference test in terms of sensitivity and specificity. Especially for IgG and IgA, we observed high sensitivity (92.5 and 93.6%, respectively); specificity was high (>96%) for all antibody types ELISAs. In addition, sensitivity was linked to the days from symptoms onset (DSO) due to the seroconversion window, and for ENZY-WELL SARS-CoV-2 IgG and IgA ELISAs resulted 100% in those samples collected after 10 and 12 DSO, respectively. The results showed that ENZY-WELL SARS-CoV-2 ELISAs may represent a valid option for both diagnostic and epidemiological purposes, covering all different antibody types developed in SARS-CoV-2 immune response.

BackgroundThe complete blood count (CBC) is one of the most beneficial biological tests used in routine medical practice. The reference intervals (RIs) of the hematological parameters are of major importance for clinical orientations and therapeutic decisions and it is necessary to establish RIs that are population specific. The objective of this study was to establish population-specific reference intervals for hematological parameters among healthy adult Eritreans. MethodUsing a DXH500 analyzer, CBC values were evaluated in samples taken from 401 healthy Eritreans in Asmara city, ranging in age from 18 to 60. For the blood tests, a sample of venous blood was drawn into a tube containing the anticoagulant EDTA. Data analysis was done using SPSS version 25, and a P value of 0.05 or above was deemed significant. The upper (97.5th percentile) and lower (2.5th percentile) reference interval boundaries with 95% CI were determined using a non-parametric test. The necessity for gender-based reference interval partitioning was determined using the Harris and Boyd Rule. ResultsThe established 95% reference intervals combined median (2.5th-97.5th percentile) were: that represent both males and females as per the suggestion of Harris and Boyd WBCs, Lymphocytes, Monocytes, Neutrophils, Eosinophils, Basophils, MCV, RDW, RDW-SD and MPV (fl) were 6.3(3.62-11.56x103/L), 39.53(22.10-60.55 %), 8.67(5.70-13.61 %), 49.32(27.09-69.25 %), 1.19(0.22-7.13%), 0.17(0.02-0.61%), 88.10(79.32-96.07fl), 13.50(12.50-15.90 %), 37.25(33.00-43.29%), and 9.29(7.76-11.51fl) respectively. RBCs, Hb, HCT, MCH, MCHC, and platelets were the parameters that required separate RI. Their respective median (2.5th - 97.5th percentile) for males versus females were 5.40 (4.57-6.21 x106/L) versus 4.88 (4.25-5.61x106/L), 15.66 (13.56-18.13 g/dl) versus 13.50 (11.95-15.68 g/dl, 48 (42.02-53.93%) versus 42.60 (36.40-48.52%), 29.10 (26.02-34.74 pg) versus 28.30 (24.79-31.02 pg), 32.55 (31.60-36.14 g/dl) versus 32.20 (31.10-33.50 14 g/dl) and 273.15 (155.67-399.34) versus 314.35 (113.96-499.55 103/L). ConclusionThe reference intervals established in this study differ from currently used RIs and thus should be used for the interpretation of laboratory results in diagnosis and safety monitoring in clinical trials in Asmara

AimsTo evaluate the association between platelet indices and platelet count severity in patients with primary immune thrombocytopenia during routine post-treatment follow-up. MethodsThis retrospective observational study included patients with primary immune thrombocytopenia followed at a single tertiary care center between 2011 and 2025. Demographic and laboratory data were obtained from medical records. Platelet count severity was categorized as less than 30 x 10^9/L, 30 to 100 x 10^9/L, and greater than 100 x 10^9/L. Platelet indices, including mean platelet volume (MPV) and platelet distribution width (PDW), were analyzed using the most recent complete blood count obtained during routine follow-up after treatment initiation. Continuous variables were summarized as median and interquartile range. Comparisons across platelet count categories were performed using the Kruskal-Wallis test with post hoc Mann-Whitney U testing. Correlation analysis and simple linear regression were also conducted. ResultsA total of 243 patients were identified, of whom 232 met the inclusion criteria. Platelet distribution width differed significantly across platelet count severity categories (Kruskal-Wallis p < 0.001) and demonstrated a strong inverse association with platelet count. Mean platelet volume also showed a statistically significant difference across platelet count groups (Kruskal-Wallis p = 0.007), although the association was weaker and less consistent compared with PDW. Regression analysis confirmed a significant association between platelet count and PDW. ConclusionPlatelet distribution width is more closely associated with platelet count severity than mean platelet volume in patients with primary immune thrombocytopenia during routine post-treatment follow-up. PDW may represent a useful adjunctive laboratory parameter when interpreted alongside platelet count in routine clinical practice.

BACKGROUNDNucleic acid test and antibody assay have been employed in the diagnosis for SARS-CoV-2 infection, but the use of viral antigen for diagnosis has not been successfully developed. Theoretically, viral antigen is the specific marker of the virus and precedes antibody appearance within the infected population. There is a clear need of detection of viral antigen for rapid and early diagnosis. METHODSWe included a cohort of 239 participants with suspected SARS-CoV-2 infection from 7 centers for the study. We measured nucleocapsid protein in nasopharyngeal swab samples in parallel with the nucleic acid test. Nucleic acid test was taken as the reference standard, and statistical evaluation was taken in blind. We detected nucleocapsid protein in 20 urine samples in another center, employing nasopharyngeal swab nucleic acid test as reference standard. RESULTSWe developed a fluorescence immunochromatographic assay for detecting nucleocapsid protein of SARS-CoV-2 in nasopharyngeal swab sample and urine within 10 minutes. 100% of nucleocapsid protein positive and negative participants accord with nucleic acid test for same samples. Further, earliest participant after 3 days of fever can be identified by the method. In an additional preliminary study, we detected nucleocapsid protein in urine in 73.6% of diagnosed COVID-19 patients. CONCLUSIONSThose findings indicate that nucleocapsid protein assay is an accurate, rapid, early and simple method for diagnosis of COVID-19. Appearance of nucleocapsid protein in urine coincides our finding of the SARS-CoV-2 invading kidney and might be of diagnostic value.

BackgroundO_ST_ABSAbstractC_ST_ABSReliable SARS-CoV-2 serological assays are required for diagnosing infections, for the serosurveillance of past exposures and for assessing the response to future vaccines. In this study, the analytical and clinical performances of a chemiluminescent immunoassays for SARS-CoV-2 IgM and IgG detection (Mindray CL-1200i), targeting Nucleocapsid (N) and receptor binding domain (RBD) portion of the Spike protein, were evaluated. MethodsPrecision and linearity were evaluated using standardized procedures. A total of 157 leftover serum samples from 81 hospitalized confirmed COVID-19 patients (38 with moderate and 43 with severe disease) and 76 SARS-CoV-2 negative subjects (44 healthcare workers, 20 individuals with rheumatic disorders, 12 pregnant women) were included in the study. In an additional series of 44 SARS-CoV-2 positive, IgM and IgG time kinetics were also evaluated in a time-period of 38 days. ResultsPrecision was below or equal to 4% for both IgM and IgG, in all the studied levels, whilst a slightly significant deviation from linearity was observed for both assays in the range of values covering the manufacturers cut-off. Considering a time frame [&ge;] 12 days post symptom onset, sensitivity and specificity for IgM were 92.3% (95%CI:79.1%-98.4%) and 92.1% (95%CI:83.6%-97.0%). In the same time frame, sensitivity and specificity for IgG were 100% (95%CI:91.0%-100%) and 93.4% (95%CI:85.3%-97.8%). The assays agreement was 73.9% (Cohens kappa of 0.373). Time kinetics showed a substantial overlapping of IgM and IgG response, the latter values being elevated up to 38 days from symptoms onset. ConclusionsAnalytical imprecision is satisfactory as well as the linearity, particularly when taking into account the fact that both assays are claimed to be qualitative. Diagnostic sensitivity of IgG was excellent, especially considering specimens collected [&ge;]12 days post symptom onset. Time kinetics suggest that IgM and IgG are detectable early in the course of infection, but the role of SARS-CoV-2 antibodies in clinical practice still requires further evaluations.

ObjectiveTo establish and validate reference intervals for the peripheral blood systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) in healthy children from the Zigong region of china. MethodsA total of 2014 healthy children undergoing physical examination at The First Peoples Hospital of Zigong from April 2023 to February 2025 were enrolled. Blood cell parameters were measured using the XN-1000 hematology analyzer, and SII, NLR, PLR, and LMR were calculated. The non-parametric method was employed to establish the 95% reference intervals. ResultsNo statistically significant differences were observed in SII, NLR, PLR, or LMR between genders (P > 0.05). Participants were stratified into three age groups: 28 days to 2 years, 2 to 6 years, and 6 to 18 years. The established reference intervals for SII were 28.60x109/L to 298.85x109/L, 83.09x109/L to 601.33x109/L, and 140.02x109/L to 657.19x109/L, respectively, for the three age groups. The corresponding NLR reference intervals were 0.10-0.92, 0.35-1.88, and 0.57-2.30. PLR reference intervals were 29.39-115.15, 39.93-150.46, and 56.74-172.55. LMR reference intervals were 3.42-13.84, 2.81-13.03, and 2.41-10.56. A validation study conducted on 92 children from the Department of Child Health Care of the same hospital between April 2025 and September 2025 confirmed the applicability of these reference intervals. This indicates that the established reference intervals for peripheral blood SII, NLR, PLR, and LMR in children from the Zigong region are suitable for local clinical practice. ConclusionThis study is the first to establish reference intervals for NLR, PLR, SII, and LMR in children from the Zigong region, providing a basis for the assessment of inflammatory diseases in local pediatric populations.

IntroductionSerological detection of antibodies against SARS-CoV-2 has become an essential tool to test vaccine efficacy and epidemiological surveillance of COVID-19. There have been limited published studies documenting the performance of SARS-CoV-2 antibody assays within hispanic populations. Materials and methodsWe evaluated the diagnostic performance of a chemiluminescence enzyme immunoassay (CLIA) on a set of 1,035 samples including pre-pandemic samples, healthcare workers (HCW), blood donors (BD) and COVID-19 positive confirmed by RT-PCR collected from April to December 2020. ResultsThrough a ROC curve the CLIA test had a high diagnostic performance, with an AUC of 0.9854 (CI95% 95.68-100), P <0.0001. The analysis yielded a cut-off point 0.1950, sensitivity of 98.4% (CI95% 95 91.54-99.9), and specificity of 93.8% (CI95% 79.8 - 98.9). The diagnostic performance was also evaluated comparing the results with those obtained using other diagnostic techniques. Substantial agreement with the lateral flow chromatography and RT-PCR tests was found, and a high level of agreement with ELISA, with %PPA of 91.3 (CI95% 84.0-95.5), % NPA of 97.7 (CI95% 96.3-98.6), % OPA of 97.7 (CI95% 96.3-98.6) and Cohens kappa value of 90.4 (CI95% 85.8-94.9). A logistic regression was used to determine which of the independent variables predicted reactivity to CLIA test. A higher age was associated with an odds ratio (OR) of 1.043 (CI95% 1.022-1.065), while the presence of at least one chronic disease was associated with an OR of 5.649 (CI95% 3.089-10.329) greater likelihood of reactivity. ConclusionsCLIA test exhibited excellent performance making it a suitable test for seroprevalence surveillance at the community level.