To assess the respective performances of a HCV screening program in a hospital setting and a HCV screening model applied concomitantly in a primary care centre.
Adult patients consecutively admitted ...to hospital for ambulatory surgery were screened for anti-HCV antibodies (hospital screening cohort, HPSC), as were patients receiving blood tests for medical reasons in a primary care centre (primary care screening cohort, PCSC). Serum anti-HCV and HCV RNA levels were tested by ELISA and real-time PCR, respectively.
Seroprevalence of HCV infection was 2.2 % in the HPSC and 1.4 % in the PCSC (p = 0.044). All viraemic patients (0.2 % in HPSC and 0.1 % in PCSC) were treated with direct-acting antivirals and 85.7 % experienced a sustained virological response.
Hospital-based HCV screening outperformed primary care-centered screening, significantly increasing HCV case findings.
Graft versus host disease (GvHD) is the main complication of allogeneic hematopoietic stem cell transplantation (HSCT). Here we report studies of a patient with chronic GvHD (cGvHD) carrying ...persistent CD4
T cell clonal expansion harboring somatic mTOR, NFKB2, and TLR2 mutations. In the screening cohort (n = 134), we detect the mTOR P2229R kinase domain mutation in two additional cGvHD patients, but not in healthy or HSCT patients without cGvHD. Functional analyses of the mTOR mutation indicate a gain-of-function alteration and activation of both mTORC1 and mTORC2 signaling pathways, leading to increased cell proliferation and decreased apoptosis. Single-cell RNA sequencing and real-time impedance measurements support increased cytotoxicity of mutated CD4
T cells. High throughput drug-sensitivity testing suggests that mutations induce resistance to mTOR inhibitors, but increase sensitivity for HSP90 inhibitors. Our findings imply that somatic mutations may contribute to aberrant T cell proliferations and persistent immune activation in cGvHD, thereby paving the way for targeted therapies.
•Monoclonal anti-CD20+ antibodies are safe drugs in patients with multiple sclerosis infected with SARS-CoV-2.•Monoclonal anti-CD20+ antibodies may have some protective effect on the development of ...patients infected with SARS-CoV-2.•The presence of healthy humoral immunity may not be essential to ensure a good clinical course following SARS-CoV-2 infection.
In December 2019, the first cases of SARS-CoV-2 infection were detected in Wuhan. Within two months, it had begun to spread around the world in what became an unprecedented pandemic. Patients with Multiple Sclerosis (MS) in a state of immunosuppression may be considered at risk for complications in the COVID-19 pandemic, although there is increasing evidence postulating a possible protective role of selective immunosuppression. One group of such immunosuppressants used in MS comprises the anti-CD20 monoclonal antibodies (mAbs) ocrelizumab and rituximab. Anti-CD20 mAbs bind to the surface of B cells, causing their depletion. We describe our experience in seven cases of patients with multiple sclerosis who have been affected by SARS-COV-2 (with a clinical/serological diagnosis or PCR diagnosis) and who were being treated with anti-CD20+ monoclonal antibodies.
We review the development of patients during infection as well as the resolution of their clinical picture. We also analyze the serology status against SARS-CoV-2 after resolution of the infection.
Although the severity of the clinical pictures was variable, patients' development was good. Not all patients, however, developed antibodies against SARS-CoV-2.
Patients treated with anti-CD20+ have adequate resolution of COVID-19 despite the fact that the presence of antibodies against SARS-CoV-2 was not detected in all cases. It is possible that the presence of humoral immunity is not always necessary fora good clinical course of SARS-CoV-2 infection.
We aimed to evaluate the correct assignment of HCV genotypes by three commercial methods-Trugene HCV genotyping kit (Siemens), VERSANT HCV Genotype 2.0 assay (Siemens), and Real-Time HCV genotype II ...(Abbott)-compared to NS5B sequencing. We studied 327 clinical samples that carried representative HCV genotypes of the most frequent geno/subtypes in Spain. After commercial genotyping, the sequencing of a 367 bp fragment in the NS5B gene was used to assign genotypes. Major discrepancies were defined, e.g. differences in the assigned genotype by one of the three methods and NS5B sequencing, including misclassification of subtypes 1a and 1b. Minor discrepancies were considered when differences at subtype levels, other than 1a and 1b, were observed. The overall discordance with the reference method was 34% for Trugene and 15% for VERSANT HCV2.0. The Abbott assay correctly identified all 1a and 1b subtypes, but did not subtype all the 2, 3, 4 and 5 (34%) genotypes. Major discordances were found in 16% of cases for Trugene HCV, and the majority were 1b- to 1a-related discordances; major discordances were found for VERSANT HCV 2.0 in 6% of cases, which were all but one 1b to 1a cases. These results indicated that the Trugene assay especially, and to a lesser extent, Versant HCV 2.0, can fail to differentiate HCV subtypes 1a and 1b, and lead to critical errors in clinical practice for correctly using directly acting antiviral agents.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Antibody detection is essential to establish exposure, infection, and immunity to SARS-CoV-2, as well as to perform epidemiological studies. The worldwide urge for new diagnostic tools to control the ...pandemic has led to a quick incorporation in clinical practice of the recently developed serological assays. However, as only few comparative studies have been published, there is a lack of data about the diagnostic accuracy of currently available assays. We evaluated the diagnostic accuracy to detect Ig G, Ig M+A, and/or IgA anti SARS-CoV-2 of 10 different assays: lateral flow card immunoassays, 4 enzyme-linked immunosorbent assay (ELISA), and 3 chemiluminescent particle immunoassays (CMIA). Using reverse transcriptase polymerase chain reaction (RT-PCR) for COVID-19 as gold standard, sensitivity, specificity, PPV, and NPV were determined. Each assay was tested in 2 groups, namely, positive control, formed by 50 sera from 50 patients with SARS-CoV-2 pneumonia with positive RT-PCR; and negative control, formed by 50 sera from 50 patients with respiratory infection non-COVID-19. Sensitivity range of the 10 assays evaluated for patients with positive COVID-19 RT-PCR was 40–77% (65–81% considering IgG plus IgM). Specificity ranged 83–100%. VPP and VPN were respectively 81–100% and 61.6–81%. Among the lateral flow immunoassays, the highest sensitivity and specificity results were found in Wondfo® SARS-CoV-2 Antibody Test. ELISA IgG and IgA from EUROIMMUN® were the most sensitive ELISA. However, poor results were obtained for isolated detection of IgG. We found similar sensitivity for IgG with SARS-CoV-2 for Architect by Abbott® and ELISA by Vircell®. Results obtained varied widely among the assays evaluated. Due to a better specificity, overall diagnostic accuracy of the assays evaluated was higher in case of positive result. On the other side, lack of antibody detection should be taken with care because of the low sensitivity described. Highest diagnostic accuracy was obtained with ELISA and CMIAs, but they last much longer.
Early kinetics of SARS‐CoV‐2 viral load (VL) in plasma determined by quantitative reverse‐transcription polymerase chain reaction (RT‐PCR) was evaluated as a predictor of poor clinical outcome in a ...prospective study and assessed in a retrospective validation cohort. Prospective observational single‐center study including consecutive adult patients hospitalized with COVID‐19 between November 2020 and January 2021. Serial plasma samples were obtained until discharge. Quantitative RT‐PCR was performed to assess SARS‐CoV‐2 VL. The main outcomes were in‐hospital mortality, admission to the Intensive Care Unit (ICU), and their combination (Poor Outcome). Relevant viremia (RV), established in the prospective study, was assessed in a retrospective cohort including hospitalized COVID‐19 patients from April 2021 to May 2022, in which plasma samples were collected according to clinical criteria. Prospective cohort: 57 patients were included. RV was defined as at least a twofold increase in VL within ≤2 days or a VL > 300 copies/ml, in the first week. Patients with RV (N = 14; 24.6%) were more likely to die than those without RV (35.7% vs. 0%), needed ICU admission (57% vs. 0%) or had Poor Outcome (71.4% vs. 0%), (p < 0.001 for the three variables). Retrospective cohort: 326 patients were included, 18.7% presented RV. Patients with RV compared with patients without RV had higher rates of ICU‐admission (odds ratio OR: 5.6 95% confidence interval CI: 2.1–15.1); p = 0.001), mortality (OR: 13.5 95% CI: 6.3–28.7; p < 0.0001) and Poor Outcome (OR: 11.2 95% CI: 5.8–22; p < 0.0001). Relevant SARS‐CoV‐2 viremia in the first week of hospitalization was associated with higher in‐hospital mortality, ICU admission, and Poor Outcome. Findings observed in the prospective cohort were confirmed in a larger validation cohort.
Summary
Evaluation of SARS‐CoV‐2 viral load kinetics in plasma assessed by quantitative RT‐PCR as an indicator of poor prognosis in hospitalized COVID‐19 patients.
Graft-versus-host disease (GVHD) is the main complication after allogeneic hematopoietic stem cell transplantation. We previously unveiled a correlation between proportions of C-C motif chemokine ...receptor 7 (CCR7)
T cells in the apheresis and the risk of developing GVHD. We wanted to evaluate in vivo whether apheresis with low proportion of CCR7
cells or treatment with an anti-human CCR7 monoclonal antibody (mAb) were suitable strategies to prevent or treat acute GVHD in preclinical xenogeneic models. Therapeutic anti-CCR7 mAb was the most effective strategy in both prophylactic and therapeutic settings where antibody drastically reduced in vivo lymphoid organ infiltration of donor CCR7
T cells, extended lifespan and solved clinical signs. The antibody neutralized in vitro migration of naïve and central memory T cells toward CCR7 ligands and depleted target CCR7
subsets through complement activation. Both mechanisms of action spared CCR7
subsets, including effector memory and effector memory CD45RA
T cells which may mediate graft versus leukemia effect and immunity against infections. Accordingly, the numbers of donor CCR7
T cells in the apheresis were not associated to cytomegalovirus reactivation or the recurrence of the underlying disease. These findings provide a promising new strategy to prevent and treat acute GVHD, a condition where new specific, safety and effective treatment is needed.
Background. Quantification of cytomegalovirus (CMV) load is central to the management of CMV infections in immunocompromised patients, but quantitative results currently differ significantly across ...methods and laboratories. Methods. The COBAS AmpliPrep/COBAS TaqMan CMV Test (CAP/CTM CMV test), developed using the first World Health Organization CMV standard in the calibration process, was compared to local assays used by 5 laboratories at transplant centers in the United States and Europe. Blinded plasma panels (n = 90) spiked with 2.18–6.7 log10 copies/mL and clinical plasma samples from immunocompromised patients (n = 660) were tested. Results. Observed mean panel member concentrations by site and 95% confidence intervals (CIs) of the data combined across sites were narrower for CAP/CTM CMV test compared with local assays. The 95% CI in log10 copies/mL of the combined data per panel member for CAP/CTM CMV test vs comparator assays was .17 vs 1.5 at 2.18 log 10 copies/mL; .14 vs .52 at 2.74 log 10 copies/mL; .16 vs .6 at 3.3 log 10 copies/mL; .2 vs 1.11 at 4.3 log 10 copies/mL; .21 vs 1.13 at 4.7 log 10 copies/mL; and .18 vs 1.4 at 6.7 log 10 copies/mL. In clinical specimens, constant and variable quantification differences between the CAP/CTM CMV test and comparator assays were observed. Conclusions. High interlaboratory agreement and precision of CAP/CTM CMV test results across 5 different laboratories over 4 orders of magnitude suggest that this assay could be valuable in prospective studies identifying clinical viral load thresholds for CMV treatment.
Can COVID‐19 cause severe neutropenia? López‐Pereira, Patricia; Iturrate, Isabel; de La Cámara, Rafael ...
Clinical case reports,
December 2020, Letnik:
8, Številka:
12
Journal Article
Recenzirano
Odprti dostop
This is the first case of acquired severe neutropenia in the context of COVID‐19 reported to date. This could illustrate another less frequent hematological disorder related to this novel viral ...infection.
This is the first case of acquired severe neutropenia in the context of COVID‐19 reported to date. This could illustrate another less frequent hematological disorder related to this novel viral infection.
Patients with coronavirus disaese 2019 (COVID-19) can develop a cytokine release syndrome that eventually leads to acute respiratory distress syndrome requiring invasive mechanical ventilation (IMV). ...Because IL-6 is a relevant cytokine in acute respiratory distress syndrome, the blockade of its receptor with tocilizumab (TCZ) could reduce mortality and/or morbidity in severe COVID-19.
We sought to determine whether baseline IL-6 serum levels can predict the need for IMV and the response to TCZ.
A retrospective observational study was performed in hospitalized patients diagnosed with COVID-19. Clinical information and laboratory findings, including IL-6 levels, were collected approximately 3 and 9 days after admission to be matched with preadministration and postadministration of TCZ. Multivariable logistic and linear regressions and survival analysis were performed depending on outcomes: need for IMV, evolution of arterial oxygen tension/fraction of inspired oxygen ratio, or mortality.
One hundred forty-six patients were studied, predominantly males (66%); median age was 63 years. Forty-four patients (30%) required IMV, and 58 patients (40%) received treatment with TCZ. IL-6 levels greater than 30 pg/mL was the best predictor for IMV (odds ratio, 7.1; P < .001). Early administration of TCZ was associated with improvement in oxygenation (arterial oxygen tension/fraction of inspired oxygen ratio) in patients with high IL-6 (P = .048). Patients with high IL-6 not treated with TCZ showed high mortality (hazard ratio, 4.6; P = .003), as well as those with low IL-6 treated with TCZ (hazard ratio, 3.6; P = .016). No relevant serious adverse events were observed in TCZ-treated patients.
Baseline IL-6 greater than 30 pg/mL predicts IMV requirement in patients with COVID-19 and contributes to establish an adequate indication for TCZ administration.
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