SARS-CoV-2 antibodies, serum inflammatory biomarkers and clinical severity of hospitalized COVID-19 patients

Background The involvement of SARS-CoV-2 antibodies in mediating immunopathogenetic events in COVID-19 patients has been suggested. By using several experimental approaches, we investigated the potential association between SARS-CoV-2 IgGs recognizing the spike (S) protein receptor-binding domain (RBD), neutralizing antibodies (NtAb) targeting S, and COVID-19 severity. Patients and methods This unicenter, retrospective, observational study included 51 hospitalized patients (24 at the intensive care unit; ICU). A total of 93 sera from these patients collected at different time points from the onset of symptoms were analyzed. SARS-CoV-2 RBD IgGs were quantitated by ELISA and NtAb50 titers wer…

Active cytomegalovirus infection is not a risk factor for Epstein-Barr virus DNAemia in the allogeneic stem cell transplantation setting

T cell–mediated response to SARS‐CoV‐2 in liver transplant recipients with prior COVID‐19

Abstract Whether immunosuppression impairs severe acute respiratory syndrome coronavirus 2‐specific T‐cell‐mediated immunity (SARS‐CoV‐2‐CMI) after liver transplantation (LT) remains unknown. We included 31 LT recipients in whom SARS‐CoV‐2‐CMI was assessed by intracellular cytokine staining (ICS) and interferon (IFN)‐γ FluoroSpot assay after a median of 103 days from COVID‐19 diagnosis. Serum SARS‐CoV‐2 IgG antibodies were measured by ELISA. A control group of non‐transplant immunocompetent patients were matched (1:1 ratio) by age and time from diagnosis. Post‐transplant SARS‐CoV‐2‐CMI was detected by ICS in 90.3% (28/31) of recipients, with higher proportions for IFN‐γ‐producing CD4+ than …

Plasma metabolomics profiling for the prediction of cytomegalovirus DNAemia and analysis of virus–host interaction in allogeneic stem cell transplant recipients.

Metabolomics analysis of biofluids is increasingly being recognized as a useful tool for the diagnosis and management of a number of infectious diseases. Here we showed that plasma metabolomics profiling by untargeted 1H nuclear magnetic resonance may allow the anticipation of the occurrence of cytomegalovirus (CMV) DNAemia in allogeneic stem cell transplant. For this purpose, key discriminatory metabolites were total glutathione, taurine, methylamine, trimethylamine N-oxide and lactate, all of which were upregulated in patients eventually developing CMV DNAemia. The overall classification accuracy (predictability) of the projection to latent structure discriminant analysis (PLS-DA) model i…

Epstein-Barr virus DNA load kinetics analysis in allogeneic hematopoietic stem cell transplant recipients: Is it of any clinical usefulness?

Abstract Background There is a lack of clinical information regarding the usefulness of plasma Epstein-Barr virus (EBV) DNA load kinetics analyses in the management of EBV infections in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Namely, it remains unknown whether this type of analysis can help physicians to anticipate the development of high-level EBV DNAemia episodes requiring rituximab treatment or predict the risk of recurrent EBV DNAemia or post-transplant lymphoproliferative disorders (PTLDs). Study design Unicentric, retrospective, observational study including 142 consecutive patients undergoing T-cell replete allo-HSCT. The plasma EBV DNA load was mon…

Community-acquired respiratory virus lower respiratory tract disease in allogeneic stem cell transplantation recipient: Risk factors and mortality from pulmonary virus-bacterial mixed infections.

Abstract Risk factors (RFs) and mortality data of community‐acquired respiratory virus (CARVs) lower respiratory tract disease (LRTD) with concurrent pulmonary co‐infections in the setting of allogeneic hematopoietic stem cell transplantation (allo‐HSCT) is scarce. From January 2011 to December 2017, we retrospectively compared the outcome of allo‐HSCT recipients diagnosed of CARVs LRTD mono‐infection (n = 52, group 1), to those with viral, bacterial, or fungal pulmonary CARVs LRTD co‐infections (n = 15, group 2; n = 20, group 3, and n = 11, group 4, respectively), and with those having bacterial pneumonia mono‐infection (n = 19, group 5). Overall survival (OS) at day 60 after bronchoalveol…

Incidence and dynamics of active cytomegalovirus infection in allogeneic stem cell transplant patients according to single nucleotide polymorphisms in donor and recipient CCR5, MCP-1, IL-10, and TLR9 genes

Single nucleotide polymorphisms (SNPs) in genes involved in the activation or regulation of innate and adaptive immune responses may modulate the susceptibility to and the natural history of certain chronic viral infections. The current study aimed to investigate whether donor and recipient SNPs in the chemokine receptor 5 (rs1800023), monocyte chemoattractant protein 1 (rs13900), interleukin-10 (rs1878672), and Toll-like receptor 9 (rs352140) genes would exert any influence on the rate of incidence and features of CMV DNAemia in the allogeneic stem cell transplantation setting. This was a retrospective observational multicenter study. The cohort consisted of 102 non-consecutive allogeneic …

Efficacy and Safety of a Preemptive Antiviral Therapy Strategy Based on Combined Virological and Immunological Monitoring for Active Cytomegalovirus Infection in Allogeneic Stem Cell Transplant Recipients.

Preemptive antiviral therapy for active CMV infection in allogeneic stem cell transplant recipients guided by immunological and virological parameters minimizes the risk of recurrent viremia in a subset of patients.

Spontaneously‐resolving episodes of cytomegalovirus DNAemia in allogeneic hematopoietic stem cell transplant recipients: Virological features and clinical outcomes

It has been reported that low-plasma cytomegalovirus (CMV) DNA loads are associated with an increased risk of overall mortality in allogeneic hematopoietic stem cell transplantation (allo-HSCT). Utilizing a conservative strategy for initiation of preemptive antiviral therapy (>1500 IU/mL), we characterized the virological features of spontaneously-resolving episodes of CMV DNAemia and assessed their impact on mortality through the first year after transplantation. We reviewed the CMV DNA polymerase chain reaction results and clinical charts of 230 consecutive adult patients who underwent T-cell replete allo-HSCT at our center. A total of 280 episodes of CMV DNAemia were registered in 164 pa…

Monitoring of Trough Plasma Ganciclovir Levels and Peripheral Blood Cytomegalovirus (CMV)-Specific CD8 + T Cells To Predict CMV DNAemia Clearance in Preemptively Treated Allogeneic Stem Cell Transplant Recipients

ABSTRACT It is uncertain whether monitoring plasma ganciclovir (GCV) levels is useful in predicting cytomegalovirus (CMV) DNAemia clearance in preemptively treated allogeneic stem cell transplant recipients. In this observational study, including 13 episodes of CMV DNAemia treated with intravenous (i.v.) GCV or oral valganciclovir, we showed that monitoring trough plasma GCV levels does not reliably predict response to therapy. Rather, immunological monitoring (pp65 and immediate-early [IE]-1-specific gamma interferon [IFN-γ]-producing CD8 + T cells) appeared to perform better for this purpose.

Early kinetics of Torque Teno virus DNA load and BK polyomavirus viremia after kidney transplantation

Kinetics of Torque Teno virus DNA in stools may predict occurrence of acute intestinal graft versus host disease early after allogeneic hematopoietic stem cell transplantation

Torque Teno virus (TTV) DNA load in blood may act as a marker of immune competence after allogeneic hematopoietic stem cell transplant recipients (allo-HSCT). Conflicting data have been reported as to the value of this biomarker for anticipating acute Graft-versus-host disease (aGvHD) occurrence. Here, we hypothesized that quantitation of TTV DNA load in stool specimens early after allo-HSCT could be used to identify patients at high risk of acute intestinal graft-versus-host disease (aIGvHD). In this prospective two-center study we recruited a total of 83 non-consecutive adult patients undergoing allo-HSCT. The study period comprised the first 120 days after allo-HSCT. TTV DNA was quantita…

B and T cell immune responses elicited by the Comirnaty® COVID-19 vaccine in nursing home residents

Objectives The immunogenicity of the Comirnaty® COVID-19 vaccine is understudied in elderly people with comorbidities. SARS-CoV-2-S-targeted antibody and T cell responses following full vaccination were assessed in nursing home residents. Methods Sixty nursing home residents (44 female; age, 53-100 years), of whom 10 had previously been diagnosed of COVID-19, and 18 healthy controls (15 female; age, 27-54 years) were recruited. Pre- and post-vaccination blood specimens were available for quantitation of total antibodies binding SARS-CoV-2 S protein and enumeration of SARS-CoV-2-S-reactive IFN-γ CD4+ and CD8+ T cells by flow cytometry. Results The seroconversion rate in presumably SARS-CoV-2…

Would Kinetic Analyses of Plasma Cytomegalovirus DNA Load Help to Reach Consensus Criteria for Triggering the Initiation of Preemptive Antiviral Therapy in Transplant Recipients?: Table 1.

The impact of virus population diversity on the dynamics of cytomegalovirus DNAemia in allogeneic stem cell transplant recipients

Mixed cytomegalovirus (CMV) infections are associated with delayed viral clearance in solid organ transplant recipients. We investigated whether this could be extrapolated to allogeneic stem cell transplant (allo-SCT) recipients. A total of 48 plasma specimens, obtained during 29 episodes of active CMV infection in 25 non-consecutive allo-SCT patients, were analysed. Baseline blood specimens, drawn shortly prior to the inception of pre-emptive antiviral therapy (pre-treatment specimen; n=29), as well as follow-up samples obtained either after the initiation of antiviral therapy (post-treatment specimen; n=15) or during recurrent episodes (n=4) were analysed. Plasma CMV DNA loads were quanti…

Assessment of immunodeficiency scoring index performance in enterovirus/rhinovirus respiratory infection after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Enterovirus/rhinoviruses (EvRh) are the most common cause of respiratory virus infections in recipients of allogeneic stem cell transplantation (allo-HSCT).; OBJECTIVE: We sought to analyze the value of the immunodeficiency scoring index (ISI) in predicting lower respiratory tract disease (LRTD) progression and mortality in a prospective cohort of consecutive adult (> 16 years) allo-HSCT recipients with EvRh infection from December 1 2013 to December 1 2019 at two Spanish transplant centers.; RESULTS: We included 234 allo-HSCT recipients with 383 EvRh episodes. Out of 383 EvRh episodes, 98 (25%) had LRTD. Multivariate logistic regression analysis identified three independent fac…

Need to evaluate the performance of real-time PCR assays for the quantitation of cytomegalovirus DNA load in lower respiratory tract specimens

There is an increasing appreciation for the potential clinical value of the quantitation of cytomegalovirus (CMV) DNA in the lower respiratory tract in critically ill patients lacking canonical immunosuppression, in view of the possible pathogenic role of CMV in these patients [1]. No data have been published on the analytical performance of real-time PCR assays for this purpose. We present our data on the performance of the COBAS® AmpliPrep/COBAS® TaqMan CMV PCR Assay (Roche Diagnostics, Mannheim, Germany) for the quantitation of CMV DNA in tracheal aspirates (TA). This CMV PCR assay has been approved recently by the US Food and Drug Administration for use with plasma specimens [2]. We cho…

An investigation of the potential association between gastrointestinal viral and bacterial infection and development of intestinal acute graft versus host disease following allogeneic hematopoietic stem cell transplantation.

It is uncertain whether gastrointestinal (GI) infection caused by viral and bacterial pathogens may predispose to gastrointestinal acute Graft-versus-host disease (aGvHD-GI) in allogeneic hematopoietic stem cell transplant recipients (allo-HSCT). We investigated the potential association between detection of enteropathogenic viruses or bacteria in stools and subsequent occurrence of aGvHD-GI in a cohort of 121 allo-HSCT patients. Eighty-six out of 121 patients (71%) had acute diarrhea and underwent screening for primary GI pathogens by molecular diagnostic methods. One or more GI pathogens were detected in 27 out of the 86 patients with diarrhea (31.3%). Specifically, Clostridioides diffici…

Effect of Sirolimus Exposure on the Need for Preemptive Antiviral Therapy for Cytomeglovirus Infection after Allogeneic Hematopoietic Stem Cell Transplantation

The current study evaluates the clinical effect of sirolimus exposure on the occurrence of cytomegalovirus (CMV) DNAemia necessitating preemptive antiviral therapy. A total of 167 consecutive recipients of reduced-intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (allo-HSCT) who received sirolimus- and tacrolimus-based graft-versus-host disease (GVHD) prophylaxis and whose CMV serostatus was positive for donors and/or recipients were included in this multicenter retrospective study. A parametric model with consecutive sirolimus blood levels describing the time to CMV DNAemia-RAT was developed using NONMEM version 7.4. Overall, 122 of 167 patients (73%) were all…

Immunological response against SARS-CoV-2 following full-dose administration of Comirnaty® COVID-19 vaccine in nursing home residents

6 páginas, 2 figuras, 3 tablas. Se puede acceder al texto completo de este artículo desde PubMedCentral: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490129 . Los datos de investigación utilizados en el mismo, se encuentran disponibles en: https://doi.org/10.1016/j.cmi.2021.09.031.

Epidemiologic and Clinical Characteristics of Coronavirus and Bocavirus Respiratory Infections after Allogeneic Stem Cell Transplantation: A Prospective Single-Center Study

Highlights • Human coronavirus are common after allogeneic stem cell transplantation and can progress to LRTDs, and in some cases this leads to hospitalization and requires supportive care. • Human bocavirus are quite rare after allogeneic stem cell transplantation and are commonly detected in conjunction with other viral co-pathogens.

Pulmonary cytomegalovirus (CMV) DNA shedding in allogeneic hematopoietic stem cell transplant recipients: Implications for the diagnosis of CMV pneumonia

Highlights • CMV DNA is frequently detected in BAL fluid specimens from allo-HSCT. • CMV DNA detection in BAL fluids is comparable across pneumonia etiologies. • CMV DNA loads in BAL fluids are comparable across pneumonia etiologies. • CMV DNA load in BAL may predict attributable-pneumonia mortality.

Plasma Torquetenovirus (TTV) DNA load as a surrogate marker of reconstitution of CMV-specific immunity in the allogeneic stem cell transplantation setting

Assessment of the association between cytomegalovirus DNAemia and subsequent acute graft-versus-host disease in allogeneic peripheral blood stem cell transplantation: A multicenter study from the Spanish hematopoietic transplantation and cell therapy group.

The potential role of active CMV infection in promoting acute Graft-versus-Host Disease (aGvHD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a matter of debate. We further addressed this issue conducting a retrospective, observational, multicenter study of 632 patients subjected to allogeneic peripheral blood HSCT at 20 Spanish centers. Monitoring of CMV DNA load in plasma or whole blood was performed by real-time PCR assays. Cumulative incidence of CMV DNAemia was 48.9% (95% CI, 45%-52.9%), of any grade aGvHD, 45.6; 95% (CI, 41.3%-50.1%), and of grade II-IV aGvHD, 30.7 (95% CI, 24.9%-36.4%). Overall, development of CMV DNAemia at any level resulted in an increa…

Role of cytomegalovirus (CMV)-specific polyfunctional CD8+ T-cells and antibodies neutralizing virus epithelial infection in the control of CMV infection in an allogeneic stem-cell transplantation setting

The role of cytomegalovirus (CMV)-specific polyfunctional CD8+ T-cells and that of antibodies neutralizing virus epithelial infection (AbNEI) in the control of CMV DNAemia were investigated in 39 CMV-seropositive allogeneic stem-cell transplant (Allo-SCT) recipients with (n = 24) or without (n = 15) CMV DNAemia. AbNEI levels were monitored prospectively by means of a neutralization assay employing retinal epithelial cells (ARPE-19) and the recombinant CMV strain BADrUL131-Y4. Quantification of CMV-specific polyfunctional CD8+ T-cells (expressing two or three of the following markers: IFN-γγ, TNF-α and CD107a) in whole blood was performed by flow cytometry for intracellular cytokine staining…

BD MAX Enteric Bacterial, Bacterial Plus, and Virus Panels for Diagnosis of Acute Infectious Gastroenteritis: a Cost-Benefit Analysis

Economic assessment is required to gauge the value of implementing PCR syndromic platforms in the microbiology laboratory for the diagnosis of community-acquired acute gastroenteritis (AGE) in pediatric and adult in- and outpatients. A cost-benefit analysis was conducted from a health care system perspective using BD MAX Enteric Bacterial, Bacterial Plus, and Virus panels. Two 6-month periods were selected, in which either conventional procedures (in 2017) or BD MAX PCR multiplex panels (in 2018) were used. We retrospectively reviewed medical records of all patients with positive results and a representative sample of negative ones. A Markov model was used to represent transition probabilit…

Cytomegalovirus DNAemia and risk of mortality in allogeneic hematopoietic stem cell transplantation: Analysis from the Spanish Hematopoietic Transplantation and Cell Therapy Group

The net impact of cytomegalovirus (CMV) DNAemia on overall mortality (OM) and nonrelapse mortality (NRM) following allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a matter of debate. This was a retrospective, multicenter, noninterventional study finally including 749 patients. CMV DNA monitoring was conducted by real-time polymerase chain reaction (PCR) assays. Clinical outcomes of interest were OM and NRM through day 365 after allo-HSCT. The cumulative incidence of CMV DNAemia in this cohort was 52.6%. A total of 306 out of 382 patients with CMV DNAemia received preemptive antiviral therapy (PET). PET use for CMV DNAemia, but not the occurrence of CMV DNAemia, taken …

Clinical effectiveness of influenza vaccination after allogeneic hematopoietic stem cell transplantation: A cross-sectional prospective observational study.

Abstract Background Vaccination is the primary method for preventing influenza respiratory virus infection (RVI). Although the influenza vaccine is able to achieve serological responses in some allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients, its clinical benefits are still uncertain. Methods In this prospective, cross-sectional study, we retrospectively analyzed the effect of inactivated trivalent influenza vaccination on the prevalence of influenza RVI in a consecutive cohort of 136 allo-HSCT adult recipients who developed 161 RVI over 5 flu seasons (from 2013 to 2018). Respiratory viruses in upper– and/or lower–respiratory tract specimens were tested using multi…

SARS-CoV-2-specific Cell-mediated Immunity in Kidney Transplant Recipients Recovered From COVID-19.

BACKGROUND: The magnitude and kinetics of severe acute respiratory syndrome coronavirus 2-specific cell-mediated immunity (SARS-CoV-2-CMI) in kidney transplant (KT) recipients remain largely unknown. METHODS: We enumerated SARS-CoV-2-specific interferon-I³-producing CD69+ CD4+ and CD8+ T cells at months 4 and 6 from the diagnosis of coronavirus disease 2019 (COVID-19) in 21 KT recipients by intracellular cytokine staining. Overlapping peptides encompassing the SARS-CoV-2 spike (S) glycoprotein N-terminal 1- to 643-amino acid sequence and the membrane protein were used as stimulus. SARS-CoV-2 IgG antibodies targeting the S1 protein were assessed by ELISA at month 6. RESULTS: Detectable (≥0.1…

Cytomegalovirus DNAemia Burden and Mortality Following Allogeneic Hematopoietic Stem Cell Transplantation: An Area Under a Curve-Based Investigational Approach.

Dynamics of Torque Teno virus plasma DNAemia in allogeneic stem cell transplant recipients

Abstract Background Torque Teno virus (TTV) plasma DNA load directly correlate with the level of immunosuppresion in different clinical settings. It is uncertain whether this may be the case in allogeneic hematopoietic stem cell transplant recipients (allo-HSCT). Objectives We characterized the dynamics of TTV DNAemia in patients undergoing T-cell replete allo-SCT. Study design Retrospective single-center observational study including 72 allo-HSCT patients. Plasma TTV DNA loads were quantified before initiating the conditioning regimen and at different time-points after transplant by real-time PCR. White blood cells (WBC) and absolute lymphocyte counts (ALC) were measured by flow cytometry.…

Diversity and dynamic changes of anelloviruses in plasma following allogeneic hematopoietic stem cell transplantation.

Monitoring of alphatorquevirus (torque teno virus [TTV]) DNA in plasma may prove to be useful to assess the net state of immune competence following allogeneic hematopoietic stem cell transplantation (allo-HSCT). There are scarce data published on the prevalence of beta (torque teno mini virus [TTMV]) and gammatorqueviruses (torque teno midi virus [TTMDV]) and, in particular, on the dynamics of anelloviruses in allo-HSCT patients. Twenty-five allo-HSCT recipients with available plasma specimens obtained before conditioning and after engraftment were included. Degenerated primers targeting a highly conserved genomic sequence across all anelloviruses were designed for genomic amplification an…

Clinical significance of Pneumocystis jirovecii DNA detection by real-time PCR in hematological patient respiratory specimens

Are pathogenic intestinal bacteria present in stool specimens from patients with chronic heart failure?

It has been reported that patients with chronic heart failure exhibit an intestinal overgrowth of primary gut bacterial pathogens, such as Shigella spp., Salmonella spp., Campylobacter spp., and Yersinia enterocolitica. We failed to reproduce these findings in a cohort of 39 patients admitted to the hospital with decompensated heart failure by means of conventional stool bacterial cultures and a multiplexed polymerase chain reaction assay.

Comparison of two methods skipping cell lysis and protein extraction for identification of bacteria from blood cultures by matrix-assisted laser desorption/ ionization time-of-flight mass-spectrometry

ABSTRACT Objective Matrix-assisted laser desorption/ionization time-of-flight mass-spectrometry (MALDI-TOF MS) is widely used for fast identification of bacteria from blood cultures (BC). We compared the performance of two procedures, one including a pre-enrichment step in brain heart infusion and the other a direct method using vacutainer separator gel tubes (DI), for identification of bacteria from blood cultures by MALDI-TOF MS. Material and methods We first prepared a training set of 20 simulated bacteremia specimens, including 10 Gram-negative and 10 Gram-positive species. A total of 145 non-consecutive BCs flagged as positive (68 Gram-negative rods, and 77 Gram-positive cocci) were pr…

Assessing the risk of cytomegalovirus DNAaemia in allogeneic stem cell transplant recipients by monitoring oxidative-stress markers in plasma

The level of antioxidants, such as thiol-containing tripeptide glutathione (GSH), in cytomegalovirus (CMV)-infected cells is notably increased. We previously showed that GSH levels in plasma, as measured by untargeted 1H nuclear magnetic resonance, are higher in allogeneic stem cell transplant (allo-SCT) recipients who subsequently develop CMV viraemia. We hypothesized that the net level of oxidative-stress markers present in plasma may be reduced in patients who develop CMV DNAaemia compared to those who do not. We serially monitored the levels of malondialdehyde (MDA) and carbonylated proteins (CPs) early after allo-SCT and assessed whether they could predict the occurrence of CMV DNAaemi…

Kinetics of torque teno virus DNA load in saliva and plasma following allogeneic hematopoietic stem cell transplantation

Plasma torque teno virus (TTV) DNA load directly correlates with the degree of T-cell immune reconstitution early after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Here, the kinetics of oral TTV DNA shedding was examined to assess whether quantitation of TTV DNA load in saliva may either replace or complement that in plasma for predicting lymphocyte (ALC) reconstitution after engraftment. This prospective observational study enrolled 38 nonconsecutive allo-HSCT recipients. Saliva and plasma specimens were collected at baseline (pretransplant) and at around days +30, +50, and +90 after allo-HSCT. TTV DNA was quantitated in both specimen types by real-time PCR. ALCs were m…

Performance of a Highly Sensitive Mycobacterium tuberculosis Complex Real-Time PCR Assay for Diagnosis of Pulmonary Tuberculosis in a Low-Prevalence Setting: a Prospective Intervention Study

ABSTRACT The potential impact of routine real-time PCR testing of respiratory specimens from patients with presumptive tuberculosis in terms of diagnostic accuracy and time to tuberculosis treatment inception in low-prevalence settings remains largely unexplored. We conducted a prospective intervention cohort study. Respiratory specimens from 1,020 patients were examined by acid-fast bacillus smear microscopy, tested by a real-time Mycobacterium tuberculosis complex PCR assay (Abbott RealTi me MTB PCR), and cultured in mycobacterial media. Seventeen patients tested positive by PCR (5 were acid-fast bacillus smear positive and 12 acid-fast bacillus smear negative), and Mycobacterium tubercul…

An investigation on the relationship between the occurrence of CMV DNAemia and the development of invasive aspergillosis in the allogeneic stem cell transplantation setting

Cytomegalovirus (CMV) infection might increase the risk of fungal superinfection in allogeneic stem cell transplant patients. The potential association between the occurrence of CMV DNAemia and the development of invasive aspergillosis in this clinical setting was investigated. The current retrospective observational study included 167 patients undergoing T cell-replete allogeneic stem cell transplantation. Virological monitoring of active CMV infection was performed by the pp65 antigenemia assay and/or by a plasma real-time PCR assay. A total of 109 out of 167 patients developed CMV DNAemia. Twenty-three patients had proven (n = 4) or probable (n = 19) invasive aspergillosis. The occurrenc…

SARS‐CoV‐2‐reactive interferon‐γ‐producing CD8+ T cells in patients hospitalized with coronavirus disease 2019

Abstract There is limited information on severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) T‐cell immune responses in patients with coronavirus disease 2019 (COVID‐19). Both CD4+ and CD8+ T cells may be instrumental in resolution of and protection from SARS‐CoV‐2 infection. Here, we tested 25 hospitalized patients either with microbiologically documented COVID‐19 (n = 19) or highly suspected of having the disease (n = 6) for presence of SARS‐CoV‐2‐reactive CD69+ expressing interferon‐γ (IFN‐γ) producing CD8+ T cells using flow‐cytometry for intracellular cytokine staining assay. Two sets of overlapping peptides encompassing the SARS‐CoV‐2 Spike glycoprotein N‐terminal 1 to 643 am…

Cytomegalovirus‐specific T‐cell immunity and DNAemia in patients with chronic lymphocytic leukaemia undergoing treatment with ibrutinib

Evaluation of the Architect Epstein-Barr Virus (EBV) Viral Capsid Antigen (VCA) IgG, VCA IgM, and EBV Nuclear Antigen 1 IgG Chemiluminescent Immunoassays for Detection of EBV Antibodies and Categorization of EBV Infection Status Using Immunofluorescence Assays as the Reference Method

ABSTRACTCommercial immunoassays for detecting IgG and IgM antibodies against Epstein-Barr virus (EBV), viral capsid antigens (VCA), and IgGs toward EBV nuclear antigen-1 (EBNA-1) are routinely used in combination to categorize EBV infection status. In this study, we evaluated the performances of the Architect EBV VCA IgG, VCA IgM, and EBNA-1 IgG chemiluminescent microparticle assays (CMIAs) in EBV serological analyses using indirect immunofluorescence assays and anticomplement immunofluorescence assays as the reference methods for VCA IgG, VCA IgM, and EBNA-1 IgG antibody detection, respectively. A total of 365 serum samples representing different EBV serological profiles were included in t…

Combined kinetic analysis of SARS-CoV-2 RNAemia, N-antigenemia and virus-specific antibodies in critically ill adult COVID-19 patients

Combined kinetic analysis of plasma SARS-CoV-2 RNAemia, Nucleocapsid (N)-antigenemia and virus-specific antibodies may help ascertain the role of antibodies in preventing virus dissemination in COVID-19 patients. We performed this analysis in a cohort of 71 consecutive critically ill COVID-19 patients (49 male; median age, 65 years) using RT-PCR assay, lateral flow immunochromatography method and receptor binding domain (RBD) and N-based immunoassays. A total of 338 plasma specimens collected at a median of 12 days after symptoms onset were available for analyses. SARS-CoV-2 RNAemia and N-antigenemia were detected in 37 and 43 specimens from 26 (36.5%) and 30 (42.2%) patients, respectively.…

B and T cell immune responses elicited by the BNT162b2 (Pfizer–BioNTech) COVID-19 vaccine in nursing home residents

ABSTRACTObjectivesThe immunogenicity of the BNT162b2 COVID-19 vaccine is understudied in elderly people with comorbidities. We assessed SARS-CoV-2-S-targeted antibody and T cell responses following full vaccination in nursing home residents (NHR).MethodsWe recruited 60 NHR (44 female; median age, 87.5 years), of whom 10 had previously had COVID-19, and 18 healthy controls (15 female; median age, 48.5 years). Pre- and post-vaccination blood specimens were available for quantitation of total antibodies binding RBD and enumeration of SARS-CoV-2-S-reactive IFN-γ CD4+ and CD8+ T cells by flow cytometry.ResultsThe seroconversion rate in presumably SARS-CoV-2 naïve NHR (95.3%), either with or with…

Comparison of the performance of 2 commercial multiplex PCR platforms for detection of respiratory viruses in upper and lower tract respiratory specimens

The performance of the CLART® PneumoVir system with that of the Luminex xTAG RVP Fast v1 assay for detection of most common respiratory viruses in upper and lower tract respiratory specimens (n = 183) from unique patients with influenza-like syndrome or lower tract respiratory infection. Nested PCR coupled to automated sequencing was used for resolution of discrepancies. Fully concordant results were obtained for a total of 122 specimens, whereas 56 specimens gave partially (n = 21) or fully discordant (n = 35) results (Kappa coefficient, 0.62). The overall specificity of the Luminex xTAG RVP Fast v1 assay was slightly higher than that of the CLART® PneumoVir assay for human bocavirus, infl…

Pre-emptive antiviral therapy for active CMV infection in adult allo-SCT patients guided by plasma CMV DNAemia quantitation using a real-time PCR assay: clinical experience at a single center

Pre-emptive antiviral therapy for active CMV infection in adult allo-SCT patients guided by plasma CMV DNAemia quantitation using a real-time PCR assay: clinical experience at a single center

An evaluation of the role of NKG2C+natural killer cells in protection from cytomegalovirus DNAemia early following allogeneic stem cell transplantation

The role of natural killer (NK) cells in affording protection against human cytomegalovirus (CMV) in allogeneic stem cell transplant recipients is largely unknown. The current study was aimed at determining whether NKG2C+ NK cells confer protection from CMV DNAemia early following transplantation in patients lacking mono and polyfunctional CMV pp65 and IE-1-specific CD4+ and CD8+ T-cell responses, as measured by flow cytometry for intracellular cytokine staining. Fourteen out of the 36 patients included in this study developed CMV DNAemia between days +30 and +60 after transplant. Three patients did so after day +60. Peripheral blood levels of CD56(bright) CD16(-/low) and CD56(dim) CD16+ NK…

Incidence, risk factors, and outcome of pulmonary invasive fungal disease after respiratory virus infection in allogeneic hematopoietic stem cell transplantation recipients

Abstract Background There is growing evidence that community‐acquired respiratory virus (CARV) increases the risk of pulmonary invasive fungal disease (IFD) in the allogeneic hematopoietic stem cell transplantation (allo‐HSCT) setting. To date, there is a lack of knowledge regarding the risk factors (RFs), as well as the most critical period for subsequent onset of IFD after CARV infections in allo‐HSCT recipients. Methods In this prospective longitudinal observational CARV survey, we analyzed the effect of CARV on subsequent IFD development in 287 adult allo‐HSCT recipients diagnosed with 597 CARV episodes from December 2013 to December 2018. Multiplex PCR panel assays were used to test CA…

Cytomegalovirus Infection Management in Allogeneic Stem Cell Transplant Recipients: a National Survey in Spain.

ABSTRACT This study gathered information about current practices of cytomegalovirus (CMV) infection management in allogeneic stem cell transplant recipients at Spanish centers. A wide variety of preemptive antiviral therapy strategies for CMV infection guided by real-time PCR assays was found, yet the incidence of CMV disease was low (<3%).

Incidence, features, and outcomes of cytomegalovirus DNAemia in unmanipulated haploidentical allogeneic hematopoietic stem cell transplantation with post‐transplantation cyclophosphamide

Background Conflicting data have been published as to the risk of cytomegalovirus (CMV) DNAemia and CMV disease in patients undergoing haploidentical hematopoietic stem cell transplantation (haplo-HSCT) with post-transplantation cyclophosphamide. Methods We conducted a multicenter retrospective study including 118 patients subjected to unmanipulated haplo-HSCT to further clarify this issue. An historic cohort comprising 165 patients undergoing other transplant modalities (HLA-matched related, matched unrelated or mismatched) was built for comparison purposes. Plasma CMV DNA monitoring was performed using two highly sensitive real-time PCR assays. Results Overall, the cumulative incidence of…

Initial viral load and decay kinetics of SARS-CoV-2 lineage B.1.1.7 in the upper respiratory tract of adults and children

We read with interest the systematic review published by Walsh et al. in the Journal of Infection,1 focusing on the dynamics of SARS-CoV-2 RNA at the upper respiratory tract (URT). In this context, a novel SARS-CoV-2 variant lineage (B.1.1.7), first detected in the UK at the end of 2020 has transmission advantage over other lineages.2 Increased transmissibility of the B.1.1.7 variant has been linked to enhanced ACE2 affinity3 allegedly resulting in higher viral loads in URT, an observation that has been reported in some,3, 4, 5, 6 but not all7 large series published to date. In addition, longer duration of SARS-CoV-2 RNA shedding in URT has been reported in individuals infected by the B.1.1…

Comparison of the new Abbott Real Time CMV assay and the Abbott CMV PCR Kit for the quantitation of plasma cytomegalovirus DNAemia

CMV DNA loads measured by the new Abbott RealTime CMV PCR were significantly higher than those quantitated by the Abbott CMV PCR kit (approximately 1 log(10)), and provided a better estimate of the actual CMV load present in plasma specimens as inferred by the use of the WHO standard.

Monitoring of alphatorquevirus DNA levels for the prediction of immunosuppression-related complications after kidney transplantation

The replication kinetics of nonpathogenic anelloviruses belonging to the Alphatorquevirus genus (such as torque teno virus) might reflect the overall state of posttransplant immunosuppression. We analyzed 221 kidney transplant (KT) recipients in whom plasma alphatorquevirus DNA load was quantified by real-time polymerase chain reaction at baseline and regularly through the first 12 posttransplant months. Study outcomes included posttransplant infection and a composite of opportunistic infection and/or de novo malignancy (immunosuppression-related adverse event [iRAE]). Alphatorquevirus DNA loads at month 1 were higher among patients who subsequently developed posttransplant infection (P  = …

Effect of the IL28B Rs12979860 C/T polymorphism on the incidence and features of active cytomegalovirus infection in allogeneic stem cell transplant patients

The current study was aimed at investigating whether the single nucleotide polymorphism (SNP) (rs12979860), upstream of the IL28B gene, had any effect on the incidence rate and the features of active CMV infection in the Allogeneic stem cell transplantation setting. This was a retrospective observational study including 151 patients undergoing T cell-replete Allo-SCT. Donor and recipient IL28 SNP genotype was determined by allele-specific real-time PCR. The incidence rate of active CMV infection was not significantly associated with either the donor or the recipient IL28B SNP genotype. Nevertheless, a trend towards a lower incidence of active CMV infection was noted in the donor T/T populat…

Re-examining the relationship between active cytomegalovirus (CMV) infection and acute graft-versus-host disease in allogeneic stem cell transplant recipients in the era of real-time PCR CMV assays.

Factors influencing cytomegalovirus DNA load measurements in whole blood and plasma specimens from allogeneic hematopoietic stem cell transplant recipients

We assessed the impact of several parameters, including the nature of the episode of Cytomegalovirus (CMV) DNAemia, the use of preemptive antiviral therapy, and the blood cell content in CMV DNA loads measured in whole blood (WB) and plasma (PL). CMV DNA load was quantified in 245 paired specimens collected within 43 postengraftment episodes of CMV DNAemia by using the CMV RealTime CMV PCR (Abbott Molecular). Concordant categorical results were obtained for 78.4% of paired specimens (Kappa index, 0.385; P = 0.001). Overall, CMV DNA loads in PL were higher than those in WB (mean bias, +0.115 log IU/mL) in both initial and recurrent episodes; this was so in post-antiviral treatment but not in…

Validation of a plasma metabolomics model that allows anticipation of the occurrence of cytomegalovirus DNAaemia in allogeneic stem cell transplant recipients.

A plasma metabolomic model obtained by means of untargeted 1H nuclear magnetic resonance, to which taurine, choline, methylamine, total glutathione, trimethylamine N-oxide, lactate, lysine, isoleucine, total fatty acids and unsaturated fatty acids contributed, was validated for the prediction of first episodes of cytomegalovirus (CMV) DNAaemia in a cohort of 79 allogeneic stem haematopoietic stem cell transplant (allo-HSCT) recipients. The predictive success rate was nearly 65 % for patients at both low and high risk of CMV-related complications according to their baseline characteristics. Plasma metabolomics profiling shortly after engraftment (day 21 after transplantation) allowed the ant…

A New Clinical and Immunovirological Score for Predicting the Risk of Late Severe Infection in Solid Organ Transplant Recipients: The CLIV Score

Abstract Background We aimed at constructing a composite score based on Epstein-Barr virus DNAemia (EBVd) and simple clinical and immunological parameters to predict late severe infection (LI) beyond month 6 in solid organ transplantation (SOT) recipients. Methods Kidney and liver transplant recipients between May 2014 and August 2016 at 4 participating centers were included. Serum immunoglobulins and complement factors, peripheral blood lymphocyte subpopulations, and whole blood EBVd were determined at months 1, 3, and 6. Cox regression analyses were performed to generate a weighted score for the prediction of LI. Results Overall, 309 SOT recipients were followed-up for a median of 1000 da…

Failure of Cytomegalovirus-Specific CD8+ T Cell Levels at Viral DNAemia Onset to Predict the Eventual Need for Preemptive Antiviral Therapy in Allogeneic Hematopoietic Stem Cell Transplant Recipients

Suitability of two rapid lateral flow immunochromatographic assays for predicting SARS‐CoV‐2 neutralizing activity of sera

Purpose: Assessment of commercial SARS-CoV-2 immunoassays for their capacity to provide reliable information on sera neutralizing activity is an emerging need. We evaluated the performance of two commercially-available lateral flow immunochromatographic assays (LFIC) (Wondfo SARS-CoV-2 Antibody test and the INNOVITA 2019-nCoV Ab test) in comparison with a SARS-CoV-2 neutralization pseudotyped assay for COVID-19 diagnosis in hospitalized patients, and investigate whether the intensity of the test band in LFIC associates with neutralizing antibody (NtAb) titers. Patients and Methods: Ninety sera were included from 51 patients with moderate to severe COVID-19. A green fluorescent protein (GFP)…

SARS-CoV-2-reactive interferon-γ-producing CD8+ T cells in patients hospitalized with Coronavirus viral disease-2019

There is limited information on SARS-CoV-2 T-cell immune responses in patients with Covid-19. Both CD4+ and CD8+ T cells may be instrumental in the resolution of and protection from SARS-CoV-2 infection. Here, we tested 25 hospitalized patients with either microbiologically documented Covid-19 (n=19) or highly suspected of having the disease (n=6) for the presence of SARS-CoV-2-reactive- CD69+-expressing interferon-gamma;-producing-(IFN-gamma;) CD8+ T cells by a flow-cytometry for intracelular cytokine staining assay. Two sets of overlapping peptides encompassing the SARS-CoV-2 Spike glycoprotein N-terminal 1-643 amino acid sequence and the entire sequence of SARS-CoV-2 M protein were used …

Enumeration of NKG2C+natural killer cells early following allogeneic stem cell transplant recipients does not allow prediction of the occurrence of cytomegalovirus DNAemia

The role of Natural killer (NK) cells in the control of cytomegalovirus (CMV) infection in allogeneic stem cell transplant recipients has not been precisely characterized. The current study is aimed at investigating the potential role of NK cells expressing the activating receptor NKG2C in affording protection against the development of CMV DNAemia in patients exhibiting detectable CMV-specific CD8+ T-cell responses early following transplantation. A total of 61 nonconsecutive patients were included in the study. Peripheral levels of CD56brightCD16−/low and CD56dimCD16+ NKG2C+ NK cells and CMV pp65/IE-1-specific IFN-γ-producing CD8+ T-cells were enumerated by flow cytometry at days +30 and …

Effect of long-term prophylaxis in the development of cytomegalovirus-specific T-cell immunity in D+/R- solid organ transplant recipients.

Background This study aimed to characterize the dynamics of acquisition of cytomegalovirus (CMV)-specific cell-mediated immunity (CMI) in CMV donor positive/recipient negative solid organ transplant (SOT) patients receiving long-term antiviral prophylaxis, and to determine whether development of CMI confers protection against CMV disease. Methods A prospective multicenter study was conducted in Spain from September 2009 to September 2012. Whole blood specimens were prospectively collected at 30, 90, 120, 200, and 365 days after SOT, and CMI was determined by enumeration of CMV pp65 and IE-1-specific CD69+/interferon-γ-producing CD8+ and CD4+ T cells by flow cytometry for intracellular cytok…

Lack of evidence for a reciprocal interaction between bacterial and cytomegalovirus infection in the allogeneic stem cell transplantation setting

Summary Pathogenic interactions between bacteria and cytomegalovirus (CMV) may potentially occur early after allogeneic stem cell transplantation (Allo-SCT). This possibility nevertheless has not been investigated in depth. This was a retrospective study that included 170 consecutive patients who underwent 173 Allo-SCTs. Both bacterial infection (most of which were bacteremic) and CMV DNAemia were detected in 78 Allo-SCTs (62.9%). In total, 51 and 32 episodes of bacterial infection preceded or occurred after CMV DNAemia detection, respectively. Both events were diagnosed concurrently in four Allo-SCTs. The cumulative incidence of bacterial infection (of any type) over the study period was c…

Comparison of the artus Epstein-Barr virus (EBV) PCR kit and the Abbott RealTime EBV assay for measuring plasma EBV DNA loads in allogeneic stem cell transplant recipients.

The ability of the artus Epstein-Barr virus (EBV) PCR kit and the Abbott RealTime EBV PCR assay to detect and quantify plasma EBV DNAemia was compared. The agreement between these assays was 95.8%. The EBV DNA loads measured by the two assays significantly correlated (P=< 0.0001).

The effect of timing on community acquired respiratory virus infection mortality during the first year after allogeneic hematopoietic stem cell transplantation: a prospective epidemiological survey.

The effect of timing of community acquired respiratory virus (CARV) infection after allogeneic hematopoietic stem cell transplant (allo-HCT) is an as yet unsettled issue. We evaluate this issue by including all consecutive allo-HCT recipients with molecularly-documented CARV infection during the first year after transplant. The study cohort was drawn from a prospective longitudinal survey of CARV in allo-HCT recipient having respiratory symptoms conducted from December 2013 to December 2018 at two Spanish transplant centers. Respiratory viruses in upper and/or lower respiratory specimens were tested using multiplex PCR panel assays. The study cohort comprised 233 allo-HCT recipients with 37…

High vancomycin MICs within the susceptible range in Staphylococcus aureus bacteraemia isolates are associated with increased cell wall thickness and reduced intracellular killing by human phagocytes

Vancomycin minimum inhibitory concentrations (MICs) at the upper end of the susceptible range for Staphylococcus aureus have been associated with poor clinical outcomes of bloodstream infections. We tested the hypothesis that high vancomycin MICs in S. aureus bacteraemia isolates are associated with increased cell wall thickness and suboptimal bacterial internalisation or lysis by human phagocytes. In total, 95 isolates were evaluated. Original vancomycin MICs were determined by Etest. The susceptibility of S. aureus isolates to killing by phagocytes was assessed in a human whole blood assay. Internalisation of bacterial cells by phagocytes was investigated by flow cytometry. Cell wall thic…

Features of Cytomegalovirus DNAemia Blips in Allogeneic Hematopoietic Stem Cell Transplant Recipients: Implications for Optimization of Preemptive Antiviral Therapy Strategies.

Cytomegalovirus (CMV) DNAemia occurs frequently in allogeneic hematopoietic stem cell transplant recipients (allo-HSCT). There is limited information about the incidence, features, and clinical impact of CMV DNAemia blips (episodes defined by an isolated positive PCR result) in this setting. In this retrospective study, 225 consecutive adult patients undergoing any modality of allo-HSCT at our center between May 2012 and July 2019 were included. Plasma CMV DNA load was monitored using a highly sensitive real-time PCR assay. In all, 187 of 225 patients had CMV DNAemia through day 365 after allo-HSCT (total number of episodes, n = 379). Eighty-three of the 187 patients had 1 or more blips (n …

Impact of cytomegalovirus DNAemia on overall and non-relapse mortality in allogeneic stem cell transplant recipients.

Background We conducted a retrospective single-center study to investigate the potential impact of cytomegalovirus (CMV) DNAemia on mortality in allogeneic stem cell transplant recipients (allo-SCT). Methods A total of 151 consecutive patients who underwent T-cell replete allo-SCT were included in the study. Patients with CMV DNAemia were treated pre-emptively with antivirals upon detection of plasma CMV DNA loads >1500 IU/mL. Results At least one episode of CMV DNAemia occurred in 109 (72.2%), and 67 of these patients (61.5%) required one or more courses of antiviral therapy. The cumulative incidence of 1-year overall and non-relapse mortality (NRM) was 28.5% (95% confidence interval [CI],…

An update on the management and prevention of cytomegalovirus infection following allogeneic hematopoietic stem cell transplantation

ABSTRACT  A significant progress has been made in deciphering critical aspects of the biology and immunology of CMV infection in the allogeneic stem cell transplantation setting. Genetic traits predisposing to active CMV infection and CMV end-organ disease have begun to be delineated. Reliable molecular assays for CMV DNA load quantitation in body fluids have been developed. Elucidation of immune mechanisms affording control of CMV infection will help to improve the management of active CMV infection. Finally, the advent of new CMV-specific antivirals and promising vaccine prototypes as well as the development of fine procedures for large-scale ex vivo generation of functional CMV-specific…

Sirolimus exposure and the occurrence of cytomegalovirus DNAemia after allogeneic hematopoietic stem cell transplantation

Sirolimus appears to protect against cytomegalovirus (CMV) in organ transplant recipients. The effect of this drug in allogeneic hematopoietic stem cell transplantation recipients remains unexplored. By means of multivariate continuous-time Markov model analyses, we identified 3 independent covariates that significantly impacted the risk of CMV DNAemia: recipient/donor CMV serostatus, tacrolimus exposure, and sirolimus exposure. CMV-seropositive recipients with CMV-seronegative donors had a significantly higher probability of having detectable CMV DNAemia. Increasing the tacrolimus trough concentration from 0 to 16 ng/mL increased the probability of patients having detectable CMV DNAemia by…

Cytomegalovirus DNA load monitoring in stool specimens for anticipating the occurrence of intestinal acute graft‐versus‐host disease following allogeneic hematopoietic stem cell transplantation: Is it of any value?

Background Data have been published suggesting a bidirectional interaction between cytomegalovirus (CMV) infection and acute graft-versus-host disease (aGvHD) in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients. Here, we hypothesized that prospective CMV DNA monitoring in stool specimens may be useful for predicting subsequent occurrence of intestinal aGvHD (IaGvHD). Methods This two-center study enrolled 121 consecutive adult patients undergoing any modality of allo-HSCT. A total of 1,009 stool specimens were collected (a median of 7 specimens/patient; range, 1-18). CMV DNA monitoring in stools and plasma was performed using real-time PCR assays. Results CMV DNA was det…

Neutralizing antibodies against SARS-CoV-2 variants of concern elicited by the comirnaty COVID-19 vaccine in nursing home residents.

Immunosenescence may impact the functionality and breadth of vaccine-elicited humoral immune responses. The ability of sera to neutralize the SARS-CoV-2 spike protein (S) from Beta, Gamma, Delta, and Epsilon variants of concern (VOCs) relative to the ancestral Wuhan-Hu-1 strain was compared in Comirnaty COVID-19-vaccinated elderly nursing home residents, either SARS-CoV-2 naïve (n = 22) or experienced (n = 8), or SARS-CoV-2 naïve younger individuals (n = 18) and non-vaccinated individuals who recovered from severe COVID-19 (n = 19). In all groups, except that including SARS-CoV-2-experienced nursing home residents, some participants lacked NtAb against one or more VOCs, mainly the Beta vari…

Evolution of SARS-CoV-2 immune responses in nursing home residents following full dose of the Comirnaty® COVID-19 vaccine

ABSTRACTObjectivesThere is scarce information as to the durability of immune responses elicited by the Comirnaty® COVID-19 vaccine in nursing home residents. Here, we assessed SARS-CoV-2-Spike (S)-targeted antibody and functional T cell responses at around 6 months after complete vaccination.MethodsThe sample comprised 46 residents (34 females; age, 60-100 years), of whom 10 had COVID-19 prior to vaccination. Baseline (median of 17.5 days after vaccination) and follow-up (median, 195 days) plasma specimens were available for quantitation of SARS-CoV-2-S antibodies and enumeration of SARS-CoV-2-S-reactive IFN-γ CD4+ and CD8+ T cells by flow cytometry.ResultsIn total, 44/45 participants had d…

Sirolimus versus cyclosporine in haploidentical stem cell transplantation with posttransplant cyclophosphamide and mycophenolate mofetil as graft‐versus‐host disease prophylaxis

Sirolimus has emerged as an alternative to calcineurin inhibitors-based (CNI) graft-versus-host disease (GVHD) prophylaxis. This retrospective study compares the outcome of 133 consecutive adult patients with haematological malignancies undergoing haploidentical stem cell transplantation with posttransplant cyclophosphamide (PTCy) and mycophenolate mofetil (MMF), combined with cyclosporine A (PTCy-CsA-MMF,

Functional patterns of cytomegalovirus (CMV) pp65 and immediate early-1-specific CD8+T cells that are associated with protection from and control of CMV DNAemia after allogeneic stem cell transplantation

Background The functional profile of cytomegalovirus (CMV)-specific CD8+ T cells that associate with protection from and control of CMV DNAemia in allogeneic stem cell transplant (allo-SCT) recipients remains incompletely characterized. Methods We enumerated pp65 and immediate early (IE)-1-specific CD8+ T cells expressing interferon-gamma, tumor necrosis factor-alpha, and CD107a, by flow cytometry in 94 patients at days +30 and +60 after allo-SCT. Results Fifty of 94 patients had CMV DNAemia within the first 100 days after transplant. CMV-specific CD8+ T-cell responses (of any functional type) were more likely to be detected in patients who did not display CMV DNAemia than in those who did …

Cytomegalovirus DNAemia in patients with de novo acute myeloid leukemia undergoing cytotoxic chemotherapy

There is evidence suggesting that cytomegalovirus (CMV) reactivation following allogeneic hematopoietic stem cell transplantation (allo-HSCT) may be associated with a lower relapse incidence in acu...

Looking for biological factors to predict the risk of active cytomegalovirus infection in non-immunosuppressed critically ill patients

The identification of non-immunosuppressed critically ill patients most at risk for developing cytomegalovirus (CMV) reactivation is potentially of great clinical relevance. The current study was aimed at determining (i) whether single nucleotide polymorphisms in the genes coding for chemokine receptor 5 (CCR5), interleukin-10 IL-10), and monocyte chemoattractant protein-1 (MCP-1) have an impact on the incidence rate of active CMV infection, (ii) whether serum levels of CMV-specific IgGs are associated with the risk of CMV reactivation, and (iii) whether detection of CMV DNA in saliva precedes that in the lower respiratory tract or the blood compartment. A total of 36 out of 78 patients (46…

Regular monitoring of cytomegalovirus-specific cell-mediated immunity in intermediate-risk kidney transplant recipients: predictive value of the immediate post-transplant assessment

Abstract Objective Previous studies on monitoring of post-transplant cytomegalovirus (CMV)-specific cell-mediated immunity (CMI) are limited by single-centre designs and disparate risk categories. We aimed to assess the clinical value of a regular monitoring strategy in a large multicentre cohort of intermediate-risk kidney transplant (KT) recipients. Methods We recruited 124 CMV-seropositive KT recipients with no T-cell-depleting induction pre-emptively managed at four Spanish institutions. CMV-specific interferon-γ-producing CD4+ and CD8+ T cells were counted through the first post-transplant year by intracellular cytokine staining after stimulation with pp65 and immediate early-1 peptide…