TT Virus Research Articles

Longitudinal monitoring of Torque Teno virus DNAemia in kidney transplant recipients correlates with long-term complications of inadequate immunosuppression.

Optimization of individual immunosuppression, which reduces the risks of both graft loss and patients' death, is considered the best approach to improve long-term outcomes of renal transplantation. Torque Teno Virus (TTV) DNAemia has emerged as a potential biomarker reflecting the depth of therapeutic immunosuppression during the initial year post-transplantation. However, its efficacy in long-term monitoring remains uncertain. In a cohort study involving 34 stable kidney transplant recipients and 124 healthy volunteers, we established lower and upper TTV DNAemia thresholds (3.75-5.1 log10 cp/mL) correlating with T-cell activatability, antibody response against flu vaccine, and risk for subsequent serious infections or cancer over 50 months. Validation in an independent cohort of 92 recipients confirmed that maintaining TTV DNAemia within this range in >50% of follow-up time points was associated with reduced risks of complications due to inadequate immunosuppression, including de novo DSA, biopsy-proven antibody-mediated rejection, graft loss, infections, or cancer. Multivariate analysis highlighted "in-target" TTV DNAemia as the sole independent variable significantly linked to decreased risk for long-term complications due to inadequate immunosuppression (odds ratio [OR]: 0.27 [0.09-0.77]; p = 0.019). Our data suggest that the longitudinal monitoring of TTV DNAemia in kidney transplant recipients could help preventing the long-term complications due to inadequate immunosuppression.

Combined Metagenomic Viral Detection and Donor-Derived Cell-Free DNA Quantification in Plasma From Kidney Transplant Recipients

BackgroundKidney transplant recipients require potent immunosuppression and are predisposed to opportunistic infections, many of which have a viral etiology. Currently, viral assays detect and quantify single pathogens using PCR or qPCR. An unbiased sequencing method with comparable accuracy would allow simultaneous monitoring of multiple viral pathogens and nonpathogenic Anelloviridae. The quantification of donor-derived cell-free DNA (dd-cfDNA) is an established method for the detection of allograft rejection, and a single workflow combining dd-cfDNA quantification and viral detection represents an opportunity to improve patient monitoring and management. MethodsWhole genome sequencing of cell-free DNA was performed using 1,980 plasma samples from 256 subjects enrolled in a multi-center study. Non-human sequences underwent reference-assisted assembly and taxonomic annotation of the viral DNA pathogens. ResultsOf the 1,980 samples tested, 1,453 (73.4%) had ≥1 viral detection(s), either a known viral pathogen or torque teno virus (TTV), with positivity rates generally declining 12–18 months post-transplant. Concordance of metagenomic NGS (mNGS) viral detection with qPCR detection was 97.7% (94.1% sensitivity, 98.2% specificity), and a linear relationship was demonstrated between mNGS viral quantitation and qPCR results. BK virus, cytomegalovirus, and Epstein-Barr virus were detected by sequencing up to 60 days prior to independently established clinical diagnoses. ConclusionsWhole-genome sequencing allows simultaneous quantification of dd-cfDNA as well as sensitive and early detection of viral infection through secondary analysis of the same sequencing results. In combination with dd-cfDNA, mNGS viral detection may provide additional pathogen surveillance results and serve as a useful biomarker for both over- and under-immunosuppression.

Clinical Characteristics and Prognosis of Patients With Severe Pneumonia With Pneumocystis jirovecii Colonization: A Multicenter, Retrospective Study

BackgroundFor decades, the incidence and clinical characteristics of Pneumocystis jirovecii (P. jirovecii) colonization in patients with severe pneumonia was remained unclear. Research questionWhat are the clinical features and outcomes associated with P. jirovecii colonization in individuals diagnosed with severe pneumonia? Study design and methodsIn this multicenter, retrospective, matched study, severe pneumonia patients who underwent bronchoalveolar lavage clinical metagenomics from 2019 to 2023 in the ICUs of 17 medical centers were enrolled. Patients were diagnosed based on clinical metagenomics, pulmonary CT scans, and clinical presentations. Clinical data were collected retrospectively, and according to propensity score matching and Cox multivariate regression analysis, the prognosis of patients with P. jirovecii colonization was compared to that of P. jirovecii-negative patients. Results40% of P. jirovecii positive patients are considered to have P. jirovecii colonization. P. jirovecii colonization group had a higher proportion of patients with immunosuppression and a lower lymphocyte count compared to P. jirovecii-negative group. More frequent detection of cytomegalovirus, Epstein–Barr virus, human herpesvirus-6B, human herpesvirus-7, and torque teno virus in the lungs was associated with P. jirovecii colonization than with P. jirovecii negativity. By constructing two cohorts through propensity score matching, we incorporated codetected microorganisms and clinical features into a Cox proportional hazards model and revealed that P. jirovecii colonization was an independent risk factor for mortality in severe pneumonia patients. According to sensitivity analyses, which included or excluded codetected microorganisms, as well as patients not receiving TMP-SMX treatment, similar conclusions were reached. InterpretationImmunosuppression and a reduced lymphocyte count were identified as risk factors for P. jirovecii colonization in non-PCP patients. More frequent detection of various viruses was observed in P. jirovecii colonization patients, and P. jirovecii colonization was associated with an increased 28-day mortality in patients with severe pneumonia.

Viral Load of HBV and HCV Correlation to Torque Teno Virus (TTV) Co-Infection in Iraqi Patients

Abstract Background: While hepatitis viruses A–E are established, emerging evidence points to additional, novel viral hepatitis agents. The torqueteno virus (TTV) has garnered interest due to its prevalence among patients with hepatitis, suggesting potential hepatotropism. Aim: This study was conducted to detect TTV antigens in individuals infected with chronic hepatitis B (HBV) and/or C (HCV) using molecular diagnostics and to explore any associations between TTV presence and demographic characteristics of the cohort. Materials and Methods: The current study was conducted from the period of September 2022 to April 2023, the investigation involved Iraqi patients aged between 32 and 83 years and diagnosed with HBV and HCV in National Iraqi Central Laboratories, Virology Section. We employed real-time PCR to quantify HBV and HCV viral loads and conventional PCR for TTV DNA detection. Results: TTV DNA was detected in 17 of the 60 patients (28.3%) with chronic HBV and HCV infections. Viral load distribution was found to be similar for both HBV and HCV. An age-related increase in viral load was noted, suggesting a trend where older individuals exhibited higher concentrations. However, no significant variation was observed that could link alterations in HBV and HCV viral loads to TTV status directly. Statistical analysis indicated a positive correlation between age and the likelihood of presenting with the virus, aligning with observed trends in other age-associated chronic conditions, such as Type 2 diabetes mellitus and chronic kidney disease. Conclusion: The presence of TTV in patients with enduring HBV or HCV infection could implicate the virus as a contributing factor to hepatitis pathology. Studies such as this are pivotal for elucidating the age-associated risk profiles for various pathologies and shaping corresponding public health policies and preventative approaches.

Detection and Genomic Characterization of Torque Teno Virus in Pneumoconiosis Patients in China.

Pneumoconiosis is a common occupational disease that can worsen with accompanying infection. Torque teno virus (TTV) is a prevalent human virus with multiple genotypes that can chronically and persistently infect individuals. However, the prevalence of TTV in pneumoconiosis patients is still unclear. This research aims to detect the presence and prevalence of TTV in the alveolar lavage fluid of pneumoconiosis patients in the Hunan Province of China using PCR. As a result, a 65.5% positive rate (19 out of 29) of TTV was detected. The TTV detection rate varies among different stages of silicosis and different pneumoconiosis patient ages. Nine novel TTV genomes ranging in size from 3719 to 3908 nt, named TTV HNPP1, HNPP2, HNPP3, HNPP4, HNPP5, HNPP6-1, HNPP6-2, HNPP7-1 and HNPP7-2, were identified. A genomic comparison and phylogenetic analysis indicated that these nine TTVs represent five different species with high genetic diversity which belong to the genus Alphatorquevirus. HNPP6-1 and HNPP6-2 belong to TTV3, HNPP5 belongs to TTV13, HNPP1 belongs to TTV24, HNPP4 belongs to TTV20, and the others belong to TTV19. The genomes of TTV HNPP1, HNPP6-1, and HNPP6-2 contain three putative open reading frames (ORFs) coding for proteins, ORF1, ORF2, and ORF3, while the other six TTV genomes contain two ORFs coding for proteins, ORF1 and ORF2. These results provide the first description of TTV epidemiology in pneumoconiosis patients in China. The newly identified TTV genome sequences reveal the high genetic diversity of TTV in pneumoconiosis patients and could contribute to a deeper understanding of TTV retention and infection in humans.

Interactions of TTV with BKV, CMV, EBV, and HHV-6A and their impact on post-transplant graft function in kidney transplant recipients.

Mono and combined reactivation of latent viruses occurs frequently under immunosuppressive therapy in kidney transplant patients. Recently, monitoring torque teno virus (TTV) reactivation came more into focus as a potential biomarker for immune status. The surrogate characteristics of TTV reactivation on acute rejection, and the combined reactivation with other latent viruses such as cytomegalovirus (CMV), human BK virus (BKV), Epstein-Barr virus (EBV), and human herpes virus-6A (HHV-6A) on allograft function, are unknown so far. Blood samples from 93 kidney transplant recipients obtained during the first post-transplant year were analyzed for TTV/BKV/CMV/EBV/HHV-6A load. Clinical characteristics, including graft function [glomerular filtration rate (GFR)], were collected in parallel. TTV had the highest prevalence and viral loads at 100% and a mean of 5.72 copies/ml (cp/ml) (log10). We found 28.0%, 26.9%, 7.5%, and 51.6% of simultaneous reactivation of TTV with BKV, CMV, EBV, and HHV-6, respectively. These combined reactivations were not associated with a significantly reduced estimated GFR at month 12. Of interest, patients with lower TTV loads <5.0 cp/ml (log10) demonstrated not only a higher incidence of acute rejection, but also an unexpected significantly earlier occurrence and higher incidence of BKV and HHV-6A reactivation. Correlations between TTV loads, other latent viruses, and immunosuppressive medication were only significant from 6 months after transplant. We were able to observe and support previously introduced TTV load thresholds predicting kidney allograft rejection. However, due to a possible delayed relation between immunosuppressive medication and TTV viral load adaptation, the right time points to start using TTV as a biomarker might need to be further clarified by other and better designed studies.

#3028 Predictive validity of the Basel Assessment of Adherence to Immunosuppressive Medication Scale (BAASIS©) after renal transplantation

Abstract Background and Aims Adherence towards immunosuppressive medication is crucial for allograft survival after renal transplantation. However, its assessment in daily clinical practice remains challenging. The BAASIS© questionnaire, is a validated self-report instrument to detect non-adherence. However, its predictive validity for clinical relevant consequences of non-adherence needs to be established. Method The prospective AdTorque-trial (DRKS00026674) includes a consecutive cohort of 226 adult kidney graft recipients transplanted at the Medical University of Vienna between 01/2018 and 12/2019. Medication adherence was monitored up to two years by a multi-component assessment including the BAASIS©, electronic drug monitoring, pharmacy refill records, tacrolimus trough level, records by medical personal, individual evaluation by a transplant psychologist and concurrent immune monitoring by the quantification of Torque Teno virus load. The BAASIS© was applied at three-month intervals during the first year and at 24 months during routine follow-up visits. The adherence phases implementation and persistence were assessed by three items (i.e. taking, timing and dose-reduction) and one item of the BAASIS©. Non-adherence was defined by YES on any of these items. The primary clinical outcome was the occurrence of biopsy-proven allograft rejection during a maximum clinical follow-up of up to 4 years after transplantation. Herein we present the preliminary analysis of the multimodal monitoring focusing on the BAASIS© questionnaire. Results Of all 226 recipients (33% female, median age 57 years), 153 completed the adherence monitoring for 2 years, resulting in a total of 973 BAASIS© assessments. Non-adherence was reported at least once by 124 (55%) recipients and 67 recipients (30%) revealed non-adherence multiple times. The proportion of non-adherent recipients increased from 11% to 31% within the first three months and was between 27% to 32% at subsequent visits from month 6 to 24 post-transplant. Issues in the punctual timing of dose taking was the most frequent cause for non-adherence. During the clinical follow-up of 44 months (median, IQR 12-48), non-adherent recipients had a significantly higher rate of biopsy-proven rejection than adherent recipients (25%, n = 30 vs. 7%, n = 7; p &amp;lt; 0.001). A time-dependent cox regression model showed that non-adherence assessed by the BAASIS© predicted an increased risk for allograft rejection (HR 2.87, 95% CI 1.47-5.6). Conclusion Medication non-adherence was substantially reported already in early phases post-transplant and was associated with an increased risk for allograft rejection. Our analysis demonstrated the predictive validity of the BAASIS©, a self-report instrument which can easily be integrated in daily transplant practice. Regular adherence assessments might identify patients at risk for poor clinical outcome due to medication non-adherence and provide rationale for intervention.

Immune monitoring in pediatric kidney transplant.

Long-term outcomes in pediatric kidney transplantation remain suboptimal, largely related to chronic rejection. Creatinine is a late marker of renal injury, and more sensitive, early markers of allograft injury are an active area of current research. This is an educational review summarizing existing strategies for monitoring for rejection in kidney transplant recipients. We summarize supporting currently available clinical tests, including surveillance biopsy, donor specific antibodies, and donor-derived cell free DNA, as well as the potential limitations of these studies. In addition, we review the current avenues of active research, including transcriptomics, proteomics, metabolomics, and torque tenovirus levels. Advancing the use of noninvasive immune monitoring will depend on well-designed multicenter trials that include patients with stable graft function, include biopsy results on all patients, and can demonstrate both association with a patient-relevant clinical endpoint such as graft survival or change in glomerular filtration rate and a potential timepoint for intervention.

Assessment of Torque Teno Virus (TTV) Frequency in Healthy Blood Donors in the Central Region of Iran, Yazd.

Background: Torque teno virus (TTV) is a globally prevalent virus in humans, yet comprehensive knowledge about its prevalence, predominant transmission routes, and pathogenesis remains limited. This study aimed to assess the frequency of TTV infection among healthy blood donors in Yazd, Iran. Materials and Methods: A total of 236 healthy blood donors, devoid of HIV/HBV/HCV infection markers, participated in the study from 2015 to 2016. Nested Polymerase Chain Reaction (PCR) utilizing a set of oligo primers for the 5΄- UTR region was employed to detect TTV DNA in serum samples. Results: The TTV genome was identified in 161 out of 236 (61.2%) healthy blood donors. The mean age for men and women was 43 and 57 years, respectively. Of the participants, 156 were male, and 107 were female. Donor age exhibited a significant association with virus presence (P=0.007); however, gender did not show a statistically significant association with the frequency of TTV infection in healthy blood donors (P=0.3). Conclusion: The study revealed a notably high frequency of the Torque teno virus in Yazd province, aligning with similar findings globally. Further investigations are warranted to elucidate the clinical implications of the virus in the healthy population.

Amyotrophic lateral sclerosis stratification: unveiling patterns with virome, inflammation, and metabolism molecules

Amyotrophic lateral sclerosis (ALS) is an untreatable and clinically heterogeneous condition primarily affecting motor neurons. The ongoing quest for reliable biomarkers that mirror the disease status and progression has led to investigations that extend beyond motor neurons’ pathology, encompassing broader systemic factors such as metabolism, immunity, and the microbiome. Our study contributes to this effort by examining the potential role of microbiome-related components, including viral elements, such as torque tenovirus (TTV), and various inflammatory factors, in ALS. In our analysis of serum samples from 100 ALS patients and 34 healthy controls (HC), we evaluated 14 cytokines, TTV DNA load, and 18 free fatty acids (FFA). We found that the evaluated variables are effective in differentiating ALS patients from healthy controls. In addition, our research identifies four unique patient clusters, each characterized by distinct biological profiles. Intriguingly, no correlations were found with site of onset, sex, progression rate, phenotype, or C9ORF72 expansion. A remarkable aspect of our findings is the discovery of a gender-specific relationship between levels of 2-ethylhexanoic acid and patient survival. In addition to contributing to the growing body of evidence suggesting altered peripheral immune responses in ALS, our exploratory research underscores metabolic diversity challenging conventional clinical classifications. If our exploratory findings are validated by further research, they could significantly impact disease understanding and patient care customization. Identifying groups based on biological profiles might aid in clustering patients with varying responses to treatments.Graphical abstract

Polyomavirus Nephropathy in ABO Blood Group-Incompatible Kidney Transplantation: Torque Teno Virus and Immunosuppressive Burden as an Approximation to the Problem

IntroductionEarlier reports suggest that patients after ABO-incompatible kidney transplantation (ABOi) are at enhanced risk to develop BK-virus (BKV) nephropathy (BKPyVAN). It remains elusive whether this is a result of more intense immunosuppression or an ABOi-associated ‘intrinsic attribute’. To address this question, we measured Torque-Teno-Virus (TTV) loads as a quantitative proxy for immunosuppressive depth in ABOi recipients and compared them to HLA-incompatible (HLAi, i.e. pre-transplant donor-specific antibody-positive) and standard-risk transplant recipients. MethodsOur retrospective study screened 2256 consecutive kidney transplantations performed between 2007-2020 at the Medical University of Vienna. Out of 629 in-principle eligible transplantations, we were able to include 465 patients: 42 ABOi, 106 HLAi and 317 control recipients. Longitudinal TTV- and BKV-PCR was carried out at pre-defined timepoints and ranged from pre-transplant until month 24 post-transplantation. TTV loads and immunosuppression were evaluated in the context of BKV-associated-complications. ResultsABOi recipients had a higher TTV load compared to HLAi and controls both at month three (median 1.5x109 vs. 2.4x108 vs. 9.1x107, p=0.010) and month six (3.1x109 vs. 1.4x107 vs. 6.4x107, p=0.014) post-transplantation. Tacrolimus exposure was significantly higher in ABOi patients compared to HLAi and control patients (ABOi vs. HLAi: p=0.007, ABOi vs. controls: p<0.0001). Biopsy-proven BKPyVAN was more frequent in ABOi recipients when compared to HLAi- and control-recipients (11.9% vs. 2.8% vs. 4.1%, p=0.046). ConclusionOur data support the assumption that ABOi patients are indeed at higher risk to develop BKPyVAN. A higher TTV load and immunosuppressive burden suggest that intense immunosuppression, rather than an ‘intrinsic attribute’ conferred by ABOi, may contribute to this finding.

(662) - Torque Teno Virus Level as Predictor of Acute Rejection in Lung Transplant Recipients

(662) - Torque Teno Virus Level as Predictor of Acute Rejection in Lung Transplant Recipients

The association of Torque Teno viral load with CMV and BKV infection in pediatric and adolescent kidney transplant patients.

Background: Long-term allograft and patient survival after kidney transplantation (KTX) depends on the balance between over- and under-immunosuppression (IS). High levels of IS predispose to opportunistic infections. Plasma load of Torque Teno Virus (TTV), a non-pathogenic highly prevalent Annellovirus, is associated with its hosts immune status, especially after solid organ transplantation. Objectives: To investigate the association of plasma TTV load and opportunistic viral infections after pediatric KTX. Study design: This retrospective study includes all pediatric KTX patients followed at the Medical University of Vienna 2014–2020. PCR for Cytomegalovirus (CMV), Epstein-Barr virus (EBV), BK virus (BKV), and TTV was performed every 4–8 weeks at routine follow-up visits. Results: 71 pediatric KTX patients were followed with TTV measurements for a median of 2.7 years. TTV plasma load was associated with CMV DNAemia at the next visit with an OR of 2.37 (95 % CI 1.15–4.87; p = 0.03) after adjustment for time after KTX and recipient age. For a cut-off of 7.68 log10 c/mL TTV a sensitivity of 100 %, a specificity of 61 %, a NPV 100 %, and a PPV of 46 % to detect CMV DNAemia at the next visit was calculated. TTV plasma loads were also associated with BKV DNAuria and BKV DNAemia at the next visit, but not with EBV DNAemia. Conclusions: This is the first study to analyse associations between TTV plasma loads and opportunistic viral infections in pediatric KTX. We were able to present a TTV cut-off for the prediction of clinically relevant CMV DNAemia that might be useful in clinical care.

Microbiomes detected by cerebrospinal fluid metagenomic next-generation sequencing among patients with and without HIV with suspected central nervous system infection.

Opportunistic infections in the central nervous system (CNS) can be a serious threat to people living with HIV. Early aetiological diagnosis and targeted treatment are crucial but difficult. Metagenomic next-generation sequencing (mNGS) has significant advantages over traditional detection methods. However, differences in the cerebrospinal fluid (CSF) microbiome profiles of patients living with and without HIV with suspected CNS infections using mNGS and conventional testing methods have not yet been adequately evaluated. We conducted a retrospective cohort study in the first hospital of Changsha between January 2019 and June 2022 to investigate the microbiomes detected using mNGS of the CSF of patients living with and without HIV with suspected CNS infections. The pathogens causing CNS infections were concurrently identified using both mNGS and traditional detection methods. The spectrum of pathogens identified was compared between the two groups. Overall, 173 patients (140 with and 33 without HIV) with suspected CNS infection were enrolled in our study. In total, 106 (75.7%) patients with and 16 (48.5%) patients without HIV tested positive with mNGS (p = 0.002). Among the enrolled patients, 71 (50.7%) with HIV and five (15.2%) without HIV tested positive for two or more pathogens (p < 0.001). Patients with HIV had significantly higher proportions of fungus (20.7% vs. 3.0%, p = 0.016) and DNA virus (59.3% vs. 21.2%, p < 0.001) than those without HIV. Epstein-Barr virus (33.6%) was the most commonly identified potential pathogen in the CSF of patients living with HIV using mNGS, followed by cytomegalovirus (20.7%) and torque teno virus (13.8%). The top three causative pathogens identified in patients without HIV were Streptococcus (18.2%), Epstein-Barr virus (12.1%), and Mycobacterium tuberculosis (9.1%). In total, 113 patients living with HIV were diagnosed as having CNS infections. The rate of pathogen detection in people living with HIV with a CNS infection was significantly higher with mNGS than with conventional methods (93.8% vs. 15.0%, p < 0.001). CSF microbiome profiles differ between patients living with and without HIV with suspected CNS infection. mNGS is a powerful tool for the diagnosis of CNS infection among people living with HIV, especially in those with mixed infections.

Torque Teno Virus DNA Load in Blood as an Immune Status Biomarker in Adult Hematological Patients: The State of the Art and Future Prospects.

A solid body of scientific evidence supports the assumption that Torque teno virus (TTV) DNA load in the blood compartment may behave as a biomarker of immunosuppression in solid organ transplant recipients; in this clinical setting, high or increasing TTV DNA levels precede the occurrence of infectious complications, whereas the opposite anticipates the development of acute rejection. The potential clinical value of the TTV DNA load in blood to infer the risk of opportunistic viral infection or immune-related (i.e., graft vs. host disease) clinical events in the hematological patient, if any, remains to be determined. In fact, contradictory data have been published on this matter in the allo-SCT setting. Studies addressing this topic, which we review and discuss herein, are highly heterogeneous as regards design, patient characteristics, time points selected for TTV DNA load monitoring, and PCR assays used for TTV DNA quantification. Moreover, clinical outcomes are often poorly defined. Prospective, ideally multicenter, and sufficiently powered studies with well-defined clinical outcomes are warranted to elucidate whether TTV DNA load monitoring in blood may be of any clinical value in the management of hematological patients.

Torque Teno Virus (TTV) in Renal Transplant Recipients: Species Diversity and Variability.

Torque Teno Virus (TTV) is a nonpathogenic and ubiquitous ssDNA virus, a member of the Anelloviridae family. TTV has been postulated as a biomarker in transplant patients. This study aimed to determine the TTV species diversity and variability in renal transplant recipients and to associate species diversity with the corresponding TTV viral load. From 27 recipients, 30 plasma samples were selected. Viral load was determined using two real-time PCR assays, followed by RCA-NGS and ORF1 phylogenetic analysis. The TTV diversity was determined in all samples. Variability was determined in three patients with two sequential samples (pre- and post-transplantation). Most of the samples presented multiple TTV species, up to 15 different species were detected. In the pre-transplant samples (n = 12), the most prevalent species were TTV3 (75%) and TTV13 (75%), and the median number of species per sample was 5 (IQR: 4-7.5). TTV3 was also the most prevalent (56%) in the post-transplant samples (n = 18), and the median number of species was 2 (IQR: 1.8-5.5). No significant correlation between the number of species and viral load was found. The number and type of TTV species showed total variability over time. We report high TTV species diversity in Argentinian recipients, especially in pre-transplant period, with total intra-host variability. However, we found no significant correlation between this high diversity and TTV viral load.

Evaluation of Torque Teno Virus DNA Load as a Predictive Biomarker in Kidney Transplant Recipients Converted from Calcineurin Inhibitors to Belatacept

Belatacept is a relevant alternative to calcineurin inhibitors (CNIs) after kidney transplantation (KT). Circulating Torque Teno virus (TTV) DNA load is correlated to infections and rejection risks post-KT in patients treated with CNIs. The aim of this study was to assess the TTV DNA load profile in kidney transplant recipients converted from CNIs to belatacept and explore its use as a predictive biomarker. Sixty-eight single-center kidney transplanted recipients who were converted from CNIs to belatacept between June, 2015 and December, 2020 were included in this study. Whole blood TTV DNA load was measured before, at 3, 6, and 12 months post-belatacept conversion. Our primary end point was to assess the TTV DNA load profile and correlate the results with rejection and opportunistic infection (OPI). TTV DNA load remained stable after belatacept conversion, that is, 3.8 (3.1-4.9), 4.4 (3.2-5.4), 4.0 (3.0-5.7) and 4.2 (3.0-5.2) log10 copies/ml at baseline, 3, 6, and 12 months, respectively. No correlation was found between TTV DNA load and post-KT complications. Chronic allograft dysfunction at 1 year postconversion was associated with a lower TTV DNA load after 6 and 12-months (P= 0.014 and P= 0.021, respectively). A higher TTV DNA load was found in older patients and in those with higher body mass index (BMI) (P= 0.023 and P= 0.005, respectively). Conversion from CNIs to belatacept did not affect TTV DNA load. OPIs or acute rejection occurrences were not associated with TTV DNA load. However, low TTV (lTTV) DNA load after 6 months postconversion may be a promising tool to predict graft dysfunction risk at 1-year postconversion.

The kinetics of Torque Teno virus plasma load following calcineurin inhibitor dose change in kidney transplant recipients.

Torque Teno virus (TTV)is nonpathogenic, highly prevalent, and reflects the immune status of its host. Thus, TTV plasma load was suggested for the guidance of immunosuppression post solidorgan transplantation. The present study was designed to determine the kinetics of TTV following changes in calcineurin inhibitor (CNI)dose. A total of 48 adult recipients of a kidney graft transplanted at the Medical University of Vienna between 2018 and 2019 with isolated changes in CNI dose were selected from the prospective TTV-POETtrial. TTV plasma load was quantified by in-house PCR. At Day 30 following CNI dose adaptation (median 33% of daily dose) no changes in TTV load were noted. However, at Day 60, following CNI dose reduction a lower TTV load of 6.4 log10 c/mL (median; interquartile range[IQR] 4.9-8.1) compared with the baseline of 7.1 log10 c/mL (IQR5.3-8.9) was noted (p = 0.001); there was also a trend towarda higher TTV load following CNI increase (6.6 log10 c/mL, IQR 4.1-9.7 vs. 5.2 log10 c/mL, IQR 4.5-6.8; p = 0.09). The data suggested that TTV load changes become noticeable only 2 months after CNI dose adaptation, which might be the ideal time point for TTV load monitoring.

High Torque teno virus load and outcome of patients undergoing allogeneic hematopoietic cell transplantation.

Quantification of Torque teno virus (TTV) load emerged as a marker of immunosuppression. Associations of TTV load with complications and survival after allogeneic hematopoietic cell transplantation (allo-HCT) were controversial in published studies. In this prospective study, we aimed to identify factors influencing TTV load after allo-HCT and to determine whether the TTV load is associated with complications or outcomes. Seventy allo-HCT recipients were included. TTV DNA load was quantified in 469 plasma samples of 70 patients from Day (D) 15 before D120 after transplantation. The influence of transplant characteristics on TTV load and the associations of TTV load with viral infections, acute graft versus host disease, mortality, and relapse were analyzed. More than 80% of patients were TTV DNA positive from D30 after transplantation onwards. Median TTV load increased between D30 and D60 post-transplantation. Patients with lymphoid malignancies had higher TTV load than those with myeloid malignancies. Myeloablative conditioning was associated with higher TTV loads. Patients with no measurable residual disease at transplant had higher TTV loads. High TTV load at D90 post-transplantation was associated with lower overall survival and at D120 post-transplantation was associated with higher relapse rate. In conclusion, TTV load at time points later than D90 after allo-HCT may be useful to assess prognosis.

Association of dynamics of anellovirus loads with hospital-acquired pneumonia in brain-injured patients during the intensive care unit stay.

Critical illness induces immune disorders associated with an increased risk of hospital-acquired pneumonia (HAP) and acute respiratory distress syndrome (ARDS). Torque Teno Virus (TTV), from the Anelloviridae family, are proposed as a biomarker to measure the level of immunosuppression. Our objective was to describe the kinetics of TTV DNA loads and their association with critical-illness related complications. We performed a longitudinal study in 115 brain-injured patients from a prospective cohort, collected endotracheal and blood samples at three time points (T1, T2, T3) during the two weeks post-admission in intensive care unit, and measured viral DNA loads using the TTV R-gene® kit (Biomerieux) and a pan-Anelloviridae in house qRT-PCR. TTV DNA was detected in the blood of 69, 71, and 64% of brain-injured patients at T1, T2 and T3 respectively. Time-associated variations of TTV and Anellovirus (AV) DNA loads were observed. Using a linear mixed-effects model, we found that HAP and ARDS were associated with lower blood AV DNA loads. Our results show that HAP or ARDS in critically ill patients are associated to changes in AV DNA loads, and should be evaluated further as a biomarker of immune disorders leading to these complications.