Low CT Research Articles

Cycle Threshold Values Predict COVID-19 Severity and Mortality but are not Correlated with Laboratory Markers

Many studies have evaluated the possible utility of cycle threshold (Ct) values as a predictor of Coronavirus disease 2019 (COVID-19) severity and patient outcome. Given the inconsistent results, we aimed to evaluate the association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Ct values and disease severity, inflammatory markers, and outcomes in Iranian patients with COVID-19.
 A retrospective study of 528 patients with COVID-19 hospitalized from September 2020 to October 2021 was conducted. Demographic, clinical, and laboratory data of patients were retrieved from electronic medical records. Ct values were analyzed as a continuous variable after subcategorizing into 3 groups: low (Ct values<20), medium (Ct values 20 to 30), and high (Ct values>30).
 Of the 528 patients (45.1% female) aged 13 to 97 years, 109 patients had low Ct values, 312 patients had medium, and 107 patients had high Ct values. Patients with low Ct values were more likely to present with critical COVID-19, require invasive mechanical ventilation and develop complications such as acute respiratory distress syndrome and pneumonia. Furthermore, patients with low or medium Ct values were more likely to die compared to patients with high Ct values.Multivariate analysis showed that patients with low or medium Ct values were more likely to have severe COVID-19 compared with patients with high Ct values. The multivariate analysis also showed a higher risk of mortality in patients with low Ct values compared to patients with high Ct values, although this was not statistically significant.
 Our findings revealed that Ct values were an independent predictor of COVID-19 severity. The risk of mortality was higher in patients with low Ct values. However, further investigation is needed to address the correlation between Ct values and inflammatory factors.

Identification and characterization of porcine Rotavirus A in Chilean swine population.

Rotavirus A (RVA) is a common cause of diarrhea in newborn pigs, leading to significant economic losses. RVA is considered a major public health concern due to genetic evolution, high prevalence, and pathogenicity in humans and animals. The objective of this study was to identify and characterize RVA in swine farms in Chile. A total of 154 samples (86 oral fluids and 68 fecal samples) were collected, from 22 swine farms. 58 (38%) samples belonging to 14 farms were found positive for RVA by real-time RT-PCR. The samples with low Ct values (21) and the two isolates were selected for whole genome sequencing. Nearly complete genomes were assembled from both isolates and partial genomes were assembled from five clinical samples. BLAST analysis confirmed that these sequences are related to human and swine-origin RVA. The genomic constellation was G5/G3-P[7]-I5-R1-C1-M1-A8-N1-T1-E1-H1. Phylogenetic analysis showed that VP4, VP1, VP2, NSP2, NSP3, NSP4, and NSP5 sequences were grouped in monophyletic clusters, suggesting a single introduction. The phylogenies for VP7, VP6, VP3, and NSP1 indicated two different origins of the Chilean sequences. The phylogenetic trees showed that most of the Chilean RVA sequences are closely related to human and swine-origin RVA detected across the world. The results highlight the potential zoonotic nature of RVA circulating in Chilean swine farms. Therefore, it is important to continue RVA whole genome sequencing globally to fully understand its complex epidemiology and early detection and characterization of zoonotic strains.

Diagnostic Performance Between Chest CT Severity Score and Initial Reverse Transcription-Polymerase Chain Reaction (RT-PCR) Cycle Values in COVID-19 Patients and Their Relation With the Clinical Status of Patients.

Reverse transcription-polymerase chain reaction (RT-PCR) is used as a standard test for the diagnosis of SARS-CoV-2 viral RNA from nasopharyngeal aspirates. However, this method lacks sensitivity and cannot assess disease severity. A CT scan of the thorax provides a CT severity score (CT-SS), which depicts lung involvement and disease severity. This study aims to investigate the diagnostic value of chest CT compared with RT-PCR cycle threshold (Ct) values in COVID-19 and relate it clinically with the disease severity of patients. This retrospective observational study was conducted in a tertiary center from April 2021 to March 2022. We included 511 patients who had tested RT-PCR positive for COVID-19, were hospitalized, and had undergone high-resolution CT (HRCT) thorax. Data was collected from patient records regarding name, age, sex, admission data, baseline investigations including Ct value, management, and outcome. HRCT was reviewed to assess lung involvement and calculate CT-SS. Data was analyzed using SPSS Statistics version 25 (IBM Corp. Released 2017. IBM SPSS Statistics for Windows, Version 25.0. Armonk, NY: IBM Corp.). The mean age of patients was 50.4 ± 13.7 years, and the majority (67.5%) were male. Gender-wise, there was no difference in RT-PCR cycle threshold (Ct) values; however, CT-SS was significantly higher in males (17.5 ± 4.8 vs.10.5 ± 6.6, t=-13.6, p<0.0001). ICU admission was needed for 34.8% of patients, and they had a significantly lower Ct value (21.7 ± 3.3 vs. 22.8 ± 3.7, t=21.10, p<0.0001) and higher CT-SS (16.3 ± 4.5 vs. 6.7 ± 5.1, t=-3.32, p=0.001). Ct values could not differentiate between moderate and severe patients. CT-SS was not related to the viral load at admission. Patients who succumbed had significantly lower Ct values and higher CT-SS.

Mechanical thrombectomy in low Alberta stroke program early CT score (ASPECTS) in hyperacute stroke-a systematic review and meta-analysis.

Major randomized controlled trials of mechanical thrombectomy (MT) for acute ischemic stroke (AIS) failed to include a substantial number of patients presenting with low baseline Alberta Stroke Program Early CT Score (ASPECTS:0-5). Patients experiencing hyperacute strokes (last known well ≤ 6 h) can potentially benefit most from MT. We conducted a systematic review and meta-analysis to report presentation severity and radiographic and clinical outcomes for hyperacute stroke patients presenting with low-ASPECTS. Our comprehensive literature search of PubMed, Embase, and Cochrane databases up to August 31, 2022 included articles reporting patients presenting hyperacutely who underwent MT for anterior circulation large vessel occlusion AIS with an ASPECTS ≤ 5 on baseline imaging. Pooled averages were calculated for age and presenting National Institutes of Health Stroke Scale (NIHSS). Fixed- and random-effects meta-analyses for weighted estimation of overall rates were performed. Forest plots were generated for proportions and estimated overall outcome rates. 18 studies (1958 patients) were included (mean age = 64.1 years; presenting NIHSS = 18.4). Final modified thrombolysis in cerebral infarction 2b-3 grade was achieved in 76.4%, with symptomatic intracranial hemorrhage in 12.1%. Good (modified Rankin Scale [mRS] 0-2) and ambulatory (mRS 0-3) 3-month outcomes were achieved by 27.4 and 46.7%, respectively; 90-day mortality was 26.4%. MT in low-ASPECTS hyperacute stroke patients may result in ambulatory clinical outcomes with acceptable hemorrhage risk. Recanalization rates achieved were similar to those in patients presenting with ASPECTS ≥ 6; this did not fully translate to better clinical outcomes. MT should be considered for hyperacute strokes with low presenting ASPECTS.

Low-iodine 40-keV virtual monoenergetic CT angiography of the lower extremities.

To evaluate a reduced iodine volume protocol for lower extremity CT angiography (CTA) using dual-energy CT (DECT). This retrospective study included consecutive patients who underwent lower extremity CTA from June to December 2022. A 10 ml 1:1 mixed test bolus was performed, followed by a 40 ml full bolus at a 2.5/s injection rate, using 400 mg/ml iodine contrast media. Conventional and 40 keV virtual monoenergetic images (VMI) were reconstructed. For both reconstructions, five main artery segments were assessed with a 3-point image quality score as well as quantitative attenuation, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) measurements with diagnostic quality thresholds (respectively >150 HU and >3). Forty patients were included in the study (mean age 68 ± 12 yo). 200 artery segments were assessed. Median qualitative image scores were 3 [IQR, 3, 3] for both reconstructions. 40 keV VMI upgraded qualitative scores for 51 (26%) of patients, including 9 (5%) from nondiagnostic to diagnostic quality. 40 keV VMI obtained attenuation and CNR diagnostic quality for respectively 100% and 100% of segments, compared with 96% and 98% for conventional images (p < 0.001). Distal artery segments showed the most differences between 40 keV VMI and conventional images. A low-iodine lower extremity CTA protocol is feasible, with 40 keV virtual monoenergetic spectral reconstruction enabling maintained diagnostic image quality at the distal artery segments.

Development of highly sensitive one-step reverse transcription-quantitative PCR for SARS-CoV-2 detection in wastewater

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants is a major public health concern that has highlighted the need to monitor circulating strains to better understand the coronavirus disease 2019 (COVID-19) pandemic. This study was carried out to monitor SARS-CoV-2 RNA and its variant-specific mutations in wastewater using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). One-step RT-qPCR using the SARS-CoV-2 Detection RT-qPCR Kit for Wastewater (Takara Bio), which amplified two N-gene regions simultaneously using CDC N1 and N2 assays with a single fluorescence dye, demonstrated better performance in detecting SARS-CoV-2 RNA (positive ratio, 66 %) compared to two-step RT-qPCR using CDC N1 or N2 assay (40 % each, and 52 % when combined), with significantly lower Ct values. The one-step RT-qPCR assay detected SARS-CoV-2 RNA in 59 % (38/64) of influent samples collected from a wastewater treatment plant in Japan between January 2021 and March 2022. The correlation between the concentration of SARS-CoV-2 RNA in the wastewater and the number of COVID-19 cases reported each day for 7 days pre- and post-sampling was significant (p < 0.05, r = 0.76 ± 0.03). Thirty-one influent samples which showed two-well positive for SARS-CoV-2 RNA were further tested by six mutations site-specific one-step RT-qPCR (E484K, L452R, N501Y, T478K, G339D, and E484A mutations). The N501Y mutation was detected between March and June 2021 but was replaced by the L452R and T478K mutations between July and October 2021, reflecting the shift from Alpha to Delta variants in the study region. The G339D and E484A mutations were identified in January 2022 and later when the incidence of the Omicron variant peaked. These findings indicate that wastewater-based epidemiology has the epidemiological potential to complement clinical tests to track the spread of COVID-19 and monitor variants circulating in communities.

Comparison of Positive/Inconclusive Xpert Xpress SARS-CoV-2 with the Standard M nCoV Real-Time Detection.

COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can be diagnosed using rapid real-time PCR, real-time reverse transcription PCR (rRT-PCR), or rapid antigen testing. Among these, rRT-PCR is considered the gold standard assay. The Xpert Xpress SARS-CoV-2 assay is a rapid real-time PCR test, approved by the Korean Disease Control and Prevention Agency in 2020. The overall concordance and positive concordance rates of the Xpert assay with the STANDARD M nCoV Real-Time Detection kit were determined. All samples with positive or inconclusive Xpert test results from July 2021 to February 2023 that underwent confirmatory testing using the reference rRT-PCR assay were included in the analysis. Samples from 224 patients (93 men and 131 women) with a median age of 59 years (range 15 - 90 years) were included. Of 212 samples that tested positive using Xpert, 112 (52.8%) were true positves and 100 (47.2%) were false positives on rRT-PCR testing. The overall concordance and positive concordance rates were 52.8% (112/212) and 54.5% (112/224), respectively. In the Xpert positive group, the samples had a lower Ct value for the E gene than the N2 gene. The Ct values for the E and N2 genes were significantly lower in the positive group than in the inconclusive group. Positive or inconclusive Xpert results should be confirmed by the gold standard rRT-PCR for early control of this disease. Furthermore, Korea's policy should be reconsidered given the high false-positive rate of the rapid real-time PCR Xpert Xpress SARS-CoV-2 assay.

An Efficient Transformer Model for Synthesizing Dual Energy CT from Single Energy Scanner

Dual-energy CT can be used to optimize radiation treatment. Recently, deep learning has been demonstrated to synthesize high-energy CT images from low-energy ones for dose reduction and lower CT system burden. As the state-of-the-art deep learning architecture, the computation burden of Transformer increases quadratically with the feature size, making the model training resource-demanding or even infeasible. Here, we introduce an efficient transformer for the balance between CT image synthesis quality and computational burden. The model is a U-shape deep neural network with encoders and decoders built by Transformer blocks. The model input is low-energy 100kVp CT image and the output is high-energy 140kVp one. Each block has a Self Channel Correlation Unit (SCCU) and a Self Spatial Attention Unit (SSAU). Local shortcuts are applied for both units. Under-sampling operation achieved by pixel shuffling is used to obtain multi-scale feature maps, and the transformer block is applied on each feature scale. Symmetric skip connection sending features from shallow layers to deep layers, thus an additional 1 × 1 convolution is used for feature fusion in each decoder. In a SCCU, the feature is first mapped to one Query, one Key, and one Value. Then the Query and the Key tensors perform matrix multiplication to compute cross covariance of feature channels. The channel correlation score can be obtained by normalization of the covariance, and it is used to weight the Value tensor. As a result, the model complexity only increases linearly with the feature size. Besides the channel weighting, we enhance spatial information using SSAU, where the feature is mapped to two tensors. One tensor after activation is used to point-wisely calibrate another tensor. Additional Transformer blocks are cascaded to the last decoder for feature refinement. Because of the structure similarity of low- and high-energy CT images, a global shortcut is used to ease model training. Clinical iodine contrast-enhanced dual energy CT image datasets of 19 patients are used in this study. The dual-energy scanning is performed by a SOMATOM Definition Flash DECT scanner. We split the datasets into training dataset of 15 patients, validation dataset of 1 patient, and testing dataset of 3 patients. The image size is 512 × 512 with pixel size 0.5 × 0.5 mm2. The U-Net model with 1.95M parameters and 44.87G FLOPS achieved the averaged PSNR value of 44.55 dB (s.t.d. 1.34) and averaged RMSE value of 0.0060 (s.t.d. 0.001). In comparison, our efficient Transformer with 1.408M parameters and 31.375G FLOPS achieved the averaged PSNR value of 44.78 dB (s.t.d. 1.37) and RMSE value of 0.0059 (s.t.d. 0.001), demonstrating our model has better performance with small model size and less computation. The efficient Transformer model allows high-resolution CT image synthesis with small model scale and computation burden from low-energy CT image.

The Synergic Role of Emerging and Endemic Swine Virus in the Porcine Respiratory Disease Complex: Pathological and Biomolecular Analysis.

Porcine respiratory disease complex (PRDC) represents a significant threat to the swine industry, causing economic losses in pigs worldwide. Recently, beyond the endemic viruses PRRSV and PCV2, emerging viruses such as TTSuV, PCV3, and PPV2, have been associated with PRDC, but their role remains unclear. This study investigates the presence of PCV2 and PRRSV and emerging viruses (PCV3, TTSuV, and PPV2) in the lungs of swine belonging to different age groups by histopathology and real-time PCR. The prevalent lung lesion was interstitial pneumonia with increased severity in post-weaning pigs. PRRSV was detected in 33% of piglets' lungs and in 20% of adults and post-weaning pigs with high Ct, while PCV2 was found in 100% of adult pigs, 33% of post-weaning pigs, and 22% of piglets, with low Ct in post-weaning pigs. PCV3 was present in all categories and coexisted with other viruses. TTSuV was detected in all swine in combination with other viruses, possibly influencing the disease dynamics, while PPV2 was detected in 100% of adults' and 90% of piglets' lungs. The detection of TTSuV, PCV3, and PPV2 in affected pigs prioritizes the need for comprehensive approaches in implementing appropriate control measures and minimizing economic losses associated with PRDC.

Usefulness of 3D reconstruction of low dose pelvic CT as an innovative tool for surgical planning in definitive correction of cloacal malformations

PurposeTo describe the results of the use of a low dose pelvic CT protocol for preoperative imaging in cloacal anomalies at a referral center. MethodsWe reviewed 43 cases of cloacal anomalies treated at our institution from 2012 to 2022. The patients underwent a cystoscopy under general anesthesia, with measurement of the common channel and the urethra, and visualization of the Müllerian structures, and a Foley catheter was placed in the bladder. Then the patient was transferred to the CT suite for a low dose pelvic CT, filling the bladder, the vagina (by overflow) and the sigmoid/rectum (as in a distal colostogram) with diluted meglumine. Volume rendering was obtained at the CT station. Results43 girls with cloaca were treated our institution, 40 of them operated on for correction. The median effective radiation dose was of 2.19mSv (0.81 - 2.96 mSv). The measurement of the common channel had a Pearson coefficient of 0.96 when correlated with the actual measurement. The length was < 1 cm in 3, 1-3 cm in 18, 3-5 cm in 15, and >5 cm in 4. Total urogenital mobilization was possible in 28 patients. We found vaginal duplication in 16, and vaginal reconstruction was performed in 13 others. ConclusionThis technique provided the spatial anatomy of the urinary, vaginal, and colorectal components, with a higher fidelity than fluoroscopy. Since we do not have rotational fluoroscopy, we overcame that limitation with this modality, and found it to be an improvement for planning, allowing for better outcomes.

Cycle threshold and viral load in SARS-CoV-2-infected patients in Sonora, Mexico.

SARS-CoV-2 infection is confirmed with the polymerase chain reaction test. Its positivity is determined by the cycle threshold (Ct), which is inversely proportional to viral load. To describe clinical and epidemiological characteristics of SARS-CoV-2-infected patients according to their viral load estimated by Ct. Cross-sectional study that included 21,110 confirmed cases, which were stratified according to their viral load: low (Ct > 30), medium (Ct 25-30) and high (Ct < 25). High viral load was identified in 53% of the cases, hospitalization was more common in subjects with medium viral load, and deaths were more prevalent in those with high viral load. Median Ct was lower during the first five days and linearly increased with the days of clinical evolution. There was a higher prevalence of deaths, hospitalizations and ventilatory support in subjects with confirmed SARS-CoV-2 infection who had a medium and high viral load. The Ct value, correlated with other patient characteristics, can guide the prognosis, as well as the design of interventions that limit the spread of the virus within the population.

Expression of the Purinergic P2X7 Receptor in Murine MOPC315.BM Myeloma Cells

The adenosine-5’ triphosphate (ATP)-gated, ion channel, P2X receptor superfamily has seven members expressed by many cancer types. Subtype 7 (P2X7 receptor) is expressed consistently at levels higher than in comparatively healthy tissues. Moreover, transcript variant heterogeneity is associated with drug resistance. We have previously described the role of the P2X7 receptor in myeloma, a rare blood disease that uniquely presents with aggressive bone destruction. In this study, we used known agonists of the P2X7 receptor to induce calcium influx and YO-PRO-1 uptake in murine MOPC315.BM myeloma cells as readouts of P2X7 receptor-mediated channel activation and pore formation, respectively. Neither ATP- nor BzATP-induced calcium influx and YO-PRO-1 indicated an absence of the P2X7 receptor function on MOPC315.BM cells. TaqMan revealed low (Ct &gt; 35) P2rx7 but high P2rx4 gene expression in MOPC315.BM; the latter was downregulated with BzATP treatment. The concomitant downregulation of CD39/Entpd1, Icam-1, and Nf-kb1 and the upregulation of Casp-1 genes regulated during purinergic signaling and with established roles in myeloma progression suggest P2RX4-mediated survival adaptation by cancer cells. Further studies are needed to characterize the P2RX4 pharmacology on MOPC315.BM since transcriptional regulation may be utilized by cancer cells to overcome the otherwise toxic effects of high extracellular ATP.

Clinical, epidemiological, and virological features of Mpox in Beijing, China – May 31–June 21, 2023

ABSTRACT The first locally acquired case in the Chinese mainland was reported on May 31, 2023, lagging behind other countries. In this study, we aimed to examine the early clinical and epidemiological characteristics of the earliest cases of Mpox in Beijing, China. Additionally, we investigated the sequence and transmission patterns of the Mpox virus (MPXV). We analyzed 37 reported cases of Mpox in Beijing from May 31, 2023 to June 21, 2023. The age range of the subjects was 24–51 years. Thirty-six cases (97.3%) were identified in men who have sex with men (MSM), and 19 cases (51.4%) tested positive for the human immunodeficiency virus. Thirty-three cases were symptomatic, while four were asymptomatic. Skin lesions were observed in 32 cases (97.0%), fever in 26 (78.8%), and swollen lymph nodes in 17 (51.5%). Rash typically appeared in the genital or perianal area 1–3 days before fever onset, with a minimum incubation period of 2 days. For individuals with skin rashes, the skin lesion samples showed 100% positivity and low Ct values. There were high oropharyngeal swab (75.8%) and blood (84.6%) positivity rates. All MPXV strains belonged to the B.1.3 branch of the West African lineage. These strains carried 76–86 nucleotide substitutions compared with the reference human MPXV genome, and genetic diversity was observed. Our findings provide the first insights into the landscape of early transmission of Mpox in Beijing and help inform policy formulation in the Chinese mainland.

SARS-CoV-2'nin Rt-PCR Döngüsü Eşik Değerlerinin ve COVID-19 hastalarının epidemiyolojik verilerinin değerlendirilmesi

Introduction: COVID-19 infection is diagnosed by RT-PCR. In this test results interpreted according to the cycle threshold (Ct) values, provide indirect measurements of viral load. In this study we aimed to the evalaute the relationship between Ct values and demographics and sypmtoms of patients. Material and Methods: The nasopharyngeal swab of the patients suspected with COVID-19 were collected and tested by RT-PCR for SARS-CoV-2. Demographics, medical history, timelines for exposure and symptoms of the patients diagnosed as COVID-19 by RT-PCRwere obtained from the hospital information system. Results: Total of 619 patient result was enrolled in the study. Ct values were determined as 24.74 (20.95-27.64) for 18&amp;gt; years-old and 22.85 (20.14-26.22) ≥18 years-old, there was no statistically difference according to the age among Ct values. Hypertension was the most common comorbid disease (13.3%) among COVID-19 patients. A positive correlation was detected among the onset of the symptoms and Ct values, Ct values were lowest (corresponding to a higher viral RNA concentration) soon after symptom onset. Patients who had fever, headache, muscle-joint pain significantly had lower Ct values were than patients who did not have these sypmtoms. Conclusion: It is important to early testing for SARS-CoV-2 among persons who have respiratory symptoms, and isolation of them when their viral load and transmission rate is higher.

Effects of 6 Weeks of Low-Volume Combined Training on Muscle Power, Muscular Strength, and Aerobic Power in Active Young Adults

The effects of combined training (CE) on athletic performance are well established, as is the potential of low-volume exercise on physical fitness. However, the efficacy of low-volume CT on measures of physical fitness requires further investigation. Therefore, the aim of this study was to analyze the effects of 6-week low-volume CT on muscle power, muscle strength, and maximal aerobic power (Wmax). Eighteen healthy and active young adult men (mean ± SD, 20.06 ± 1.66 years; 22.23 ± 2.76 kg/m2) underwent low-volume CE (GE, n=9) or maintained a normal life (GC, n=9). The EC was composed of strength training (EF), 2 series of 3 exercises with 80 to 85% 1RM) followed by high intensity interval training (HIIT), 5 series of 60'' with 95% Wmax). Measurements of jump height, 1 repetition maximum (1RM) in bench press and back squat, Wmax, and internal load were obtained before and after training for analysis. In addition, an ANOVA test of repeated measures and paired samples with p ≤ 0.05 was used. The main results demonstrated that the low volume CT increased jump height (p ≤ 0.05), bench press and back squat 1RM (p &lt; 0.001 and p &lt; 0.001, respectively) and Wmax (p ≤ 0.01). , despite the fact that the internal load did not have significant differences between weeks (p &gt; 0.05). For active young adults, low-volume CT is an effective and time-efficient strategy to improve jump height, bench press and squat 1RM, and Wmax without increasing internal load. Keywords: Exercise, Concurrent training, Physical fitness, Performance, Cardiorespiratory fitness, Untrained.

CT Number Accuracy and Association With Object Size: A Phantom Study Comparing Energy-Integrating Detector CT and Deep Silicon Photon-Counting Detector CT.

BACKGROUND. Variable beam hardening based on patient size causes variation in CT numbers for energy-integrating detector (EID) CT. Photon-counting detector (PCD) CT more accurately determines effective beam energy, potentially improving CT number reliability. OBJECTIVE. The purpose of the present study was to compare EID CT and deep silicon PCD CT in terms of both the effect of changes in object size on CT number and the overall accuracy of CT numbers. METHODS. A phantom with polyethylene rings of varying sizes (mimicking patient sizes) as well as inserts of different materials was scanned on an EID CT scanner in single-energy (SE) mode (120-kV images) and in rapid-kilovoltage-switching dual-energy (DE) mode (70-keV images) and on a prototype deep silicon PCD CT scanner (70-keV images). ROIs were placed to measure the CT numbers of the materials. Slopes of CT number as a function of object size were computed. Materials' ideal CT number at 70 keV was computed using the National Institute of Standards and Technology XCOM Photon Cross Sections Database. The root mean square error (RMSE) between measured and ideal numbers was calculated across object sizes. RESULTS. Slope (expressed as Hounsfield units per centimeter) was significantly closer to zero (i.e., less variation in CT number as a function of size) for PCD CT than for SE EID CT for air (1.2 vs 2.4 HU/cm), water (-0.3 vs -1.0 HU/cm), iodine (-1.1 vs -4.5 HU/cm), and bone (-2.5 vs -10.1 HU/cm) and for PCD CT than for DE EID CT for air (1.2 vs 2.8 HU/cm), water (-0.3 vs -1.0 HU/cm), polystyrene (-0.2 vs -0.9 HU/cm), iodine (-1.1 vs -1.9 HU/cm), and bone (-2.5 vs -6.2 HU/cm) (p < .05). For all tested materials, PCD CT had the smallest RMSE, indicating CT numbers closest to ideal numbers; specifically, RMSE (expressed as Hounsfield units) for SE EID CT, DE EID CT, and PCD CT was 32, 44, and 17 HU for air; 7, 8, and 3 HU for water; 9, 10, and 4 HU for polystyrene; 31, 37, and 13 HU for iodine; and 69, 81, and 20 HU for bone, respectively. CONCLUSION. For numerous materials, deep silicon PCD CT, in comparison with SE EID CT and DE EID CT, showed lower CT number variability as a function of size and CT numbers closer to ideal numbers. CLINICAL IMPACT. Greater reliability of CT numbers for PCD CT is important given the dependence of diagnostic pathways on CT numbers.

Epidemiology of COVID-19 and the Utility of Cycle Threshold (Ct) Values in Predicting the Severity of Disease.

Advanced molecular diagnostic methods like real-time polymerase chain reaction (PCR) play a vital role in the early recognition of viral infections, including the coronavirus disease 2019 (COVID-19). Therefore, in the context of the recent COVID-19 pandemic, this study aimed to determine the correlation of cycle threshold (Ct) values with symptoms in COVID-19-positive patients. A retrospective study was conducted in a virus research diagnostic laboratory (VRDL) at a COVID-19-dedicated tertiary care hospital in South India. A total of 5563 COVID-19-positive patients were analyzed for symptom spectrum and duration of illness with Ct values of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Around 80% (n= 4401) of the patients were symptomatic and the rest were asymptomatic. Among the symptomatic patients, fever (66%) was the most common symptom. About 44% of symptomatic patients had a low Ct value (Ct ≤ 24). There was a significant difference in symptoms among patients with low, medium, and high Ct values. In the subpopulation of symptomatic patients analyzed for the association of Ct value and duration of illness, the mean duration of illness was three days and almost 88% of the patients were tested within five days of onset of symptoms. It has been observed that a shorter duration of illness lowers the Ct values. A significant association was seen between the mean Ct value and days since symptom onset (p-value = 0.016). Most of the symptomatic patients had lower Ct values in comparison to the asymptomatic patients. A significant association between low Ct values and the duration of symptoms observed in our study explains the viral dynamics, i.e., higher viral shedding at the onset of symptoms and declinesthereafter.

Infection and tissue distribution of highly pathogenic avian influenza A type H5N1 (clade 2.3.4.4b) in red fox kits (Vulpes vulpes)

ABSTRACT Avian influenza H5N1 is a highly pathogenic virus that primarily affects birds. However, it can also infect other animal species, including mammals. We report the infection of nine juvenile red foxes (Vulpes vulpes) with Highly Pathogenic Avian Influenza A type H5N1 (Clade 2.3.4.4b) in the spring of 2022 in the central, western, and northern regions of New York, USA. The foxes displayed neurologic signs, and examination of brain and lung tissue revealed lesions, with brain lesions ranging from moderate to severe meningoencephalitis. Analysis of tissue tropism using RT-PCR methods showed a comparatively lower Ct value in the brain, which was confirmed by in situ hybridization targeting Influenza A RNA. The viral RNA labelling was highly clustered and overlapped the brain lesions, observed in neurons, and grey matter. Whole viral genome sequences obtained from the affected foxes were subjected to phylogenetic and mutation analysis to determine influenza A clade, host specificity, and potential occurrence of viral reassortment. Infections in red foxes likely occurred due to preying on infected wild birds and are unlikely due to transmission between foxes or other mammals.

Viral load dynamics and shedding kinetics of mpox infection: a systematic review and meta-analysis.

Viral load dynamics and shedding kinetics are critical factors for studying infectious diseases. However, evidence on the viral dynamics of mpox remains limited and inconclusive. Thus, we aimed to provide a comprehensive understanding of viral load and viability of the re-emerged mpox virus since 2022. For this systematic review and meta-analysis, we searched PubMed/MEDLINE, Embase, and Google Scholar for published articles which are related to mpox viral dynamics up to April, 2023. From 19 studies, 880 samples and 1477 specimens were collected. The pooled median Ct values appeared in the following order: skin lesion (Ct value 21.7 [IQR 17.8-25.5]), anorectal (22.3 [16.9-27.6]), saliva (25.9 [22.5-31.1]), oral (29.0 [24.5-32.8]), semen (29.6 [25.9-33.4]), urine (30.5 [24.6-36.4]), pharyngeal (31.9 [26.5-37.3]), urethra (33.0 [28.0-35.0]), and blood (33.2 [30.4-36.1]). People living with HIV have lower Ct value in the skin (skin HIV+, 19.2 [18.3-20.0] versus skin HIV-, 25.4 [21.2-29.0]). From the Ct values and test day since symptom onset, we identified temporal trends of viral load for each specimen type. Changes in the trend were observed at 4days in saliva, 5days in blood, 6days in skin, 7days in anorectal, urine, semen, pharyngeal, and 8days in urethra. We determined optimal Ct cutoff values for anorectal (34.0), saliva (27.7), and urethra (33.0) specimens, where a Ct value above each cutoff suggests minimal viral viability. Using these cutoff values, we derived the duration of viable viral isolation in each specific specimen type (anorectal 19days; saliva 14days; and urethra 14days). Skin lesion, anorectal, and saliva samples contained the highest viral load. The peak viral load manifests within 4-8days after symptom onset, and viable virus detection was presumed to cease within 14-19days from symptom onset in anorectal, saliva and urethra samples.

Automated antigen assays display a high heterogeneity for the detection of SARS-CoV-2 variants of concern, including several Omicron sublineages

Diagnostic tests for direct pathogen detection have been instrumental to contain the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) pandemic. Automated, quantitative, laboratory-based nucleocapsid antigen (Ag) tests for SARS-CoV-2 have been launched alongside nucleic acid-based test systems and point-of-care (POC) lateral-flow Ag tests. Here, we evaluated four commercial Ag tests on automated platforms for the detection of different sublineages of the SARS-CoV-2 Omicron variant of concern (VoC) (B.1.1.529) in comparison with “non-Omicron” VoCs. A total of 203 Omicron PCR-positive respiratory swabs (53 BA.1, 48 BA.2, 23 BQ.1, 39 XBB.1.5 and 40 other subvariants) from the period February to March 2022 and from March 2023 were examined. In addition, tissue culture-expanded clinical isolates of Delta (B.1.617.2), Omicron-BA.1, -BF.7, -BN.1 and -BQ.1 were studied. These results were compared to previously reported data from 107 clinical “non-Omicron” samples from the end of the second pandemic wave (February to March 2021) as well as cell culture-derived samples of wildtype (wt) EU-1 (B.1.177), Alpha VoC (B.1.1.7) and Beta VoC (B.1.351)). All four commercial Ag tests were able to detect at least 90.9% of Omicron-containing samples with high viral loads (Ct < 25). The rates of true-positive test results for BA.1/BA.2-positive samples with intermediate viral loads (Ct 25–30) ranged between 6.7% and 100.0%, while they dropped to 0 to 15.4% for samples with low Ct values (> 30). This heterogeneity was reflected also by the tests’ 50%-limit of detection (LoD50) values ranging from 44,444 to 1,866,900 Geq/ml. Respiratory samples containing Omicron-BQ.1/XBB.1.5 or other Omicron subvariants that emerged in 2023 were detected with enormous heterogeneity (0 to 100%) for the intermediate and low viral load ranges with LoD50 values between 23,019 and 1,152,048 Geq/ml. In contrast, detection of “non-Omicron” samples was more sensitive, scoring positive in 35 to 100% for the intermediate and 1.3 to 32.9% of cases for the low viral loads, respectively, corresponding to LoD50 values ranging from 6181 to 749,792 Geq/ml. All four assays detected cell culture-expanded VoCs Alpha, Beta, Delta and Omicron subvariants carrying up to six amino acid mutations in the nucleocapsid protein with sensitivities comparable to the non-VoC EU-1. Overall, automated quantitative SARS-CoV-2 Ag assays are not more sensitive than standard rapid antigen tests used in POC settings and show a high heterogeneity in performance for VoC recognition. The best of these automated Ag tests may have the potential to complement nucleic acid-based assays for SARS-CoV-2 diagnostics in settings not primarily focused on the protection of vulnerable groups. In light of the constant emergence of new Omicron subvariants and recombinants, most recently the XBB lineage, these tests’ performance must be regularly re-evaluated, especially when new VoCs carry mutations in the nucleocapsid protein or immunological and clinical parameters change.