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 solid organ 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-POET trial. 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 (IQR 5.3-8.9) was noted (p = 0.001); there was also a trend toward a 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.

No evidence of asymptomatic monkeypox infection in a highly sexually active MSM population in Austria.

BACKGROUND: The 2022 outbreak of monkeypox virus (MPXV) revealed new transmission routes. Incidence declined sharply in September 2022, and it remains unclear whether MPXV is circulating in asymptomatic individuals because of increased immunity. OBJECTIVES: Our study aimed to assesss the number of asymtomatic MPXV carriers in individuals at high risk for STI. METHODS: We analysed anal samples from asymptomatic highly sexually active men who have sex with men for the presence of MPXV. RESULTS: We detected a high number of concomitant sexually transmitted infections but did not find a single sample with MPXV. CONCLUSIONS: Our results indicate that the general recommendation to implement screening for MPXV is not currently justified.

Tumor necrosis factor α promotes clonal dominance of KIT D816V+ cells in mastocytosis: role of survivin and impact on prognosis.

ABSTRACT: Systemic mastocytosis (SM) is defined by the expansion and accumulation of neoplastic mast cells (MCs) in the bone marrow (BM) and extracutaneous organs. Most patients harbor a somatic KIT D816V mutation, which leads to growth factor-independent KIT activation and accumulation of MC. Tumor necrosis factor α (TNF) is a proapoptotic and inflammatory cytokine that has been implicated in the clonal selection of neoplastic cells. We found that KIT D816V increases the expression and secretion of TNF. TNF expression in neoplastic MCs is reduced by KIT-targeting drugs. Similarly, knockdown of KIT or targeting the downstream signaling cascade of MAPK and NF-κB signaling reduced TNF expression levels. TNF reduces colony formation in human BM cells, whereas KIT D816V+ cells are less susceptible to the cytokine, potentially contributing to clonal selection. In line, knockout of TNF in neoplastic MC prolonged survival and reduced myelosuppression in a murine xenotransplantation model. Mechanistic studies revealed that the relative resistance of KIT D816V+ cells to TNF is mediated by the apoptosis-regulator BIRC5 (survivin). Expression of BIRC5 in neoplastic MC was confirmed by immunohistochemistry of samples from patients with SM. TNF serum levels are significantly elevated in patients with SM and high TNF levels were identified as a biomarker associated with inferior survival. We here characterized TNF as a KIT D816V-dependent cytokine that promotes clonal dominance. We propose TNF and apoptosis-associated proteins as potential therapeutic targets in SM.

Effect of monovalent COVID-19 vaccines on viral interference between SARS-CoV-2 and several DNA viruses in patients with long-COVID syndrome.

Epstein-Barr virus (EBV) reactivation may be involved in long-COVID symptoms, but reactivation of other viruses as a factor has received less attention. Here we evaluated the reactivation of parvovirus-B19 and several members of the Herpesviridae family (DNA viruses) in patients with long-COVID syndrome. We hypothesized that monovalent COVID-19 vaccines inhibit viral interference between SARS-CoV-2 and several DNA viruses in patients with long-COVID syndrome, thereby reducing clinical symptoms. Clinical and laboratory data for 252 consecutive patients with PCR-verified past SARS-CoV-2 infection and long-COVID syndrome (155 vaccinated and 97 non-vaccinated) were recorded during April 2021-May 2022 (median 243 days post-COVID-19 infection). DNA virus-related IgG and IgM titers were compared between vaccinated and non-vaccinated long-COVID patients and with age- and sex-matched non-infected, unvaccinated (pan-negative for spike-antibody) controls. Vaccination with monovalent COVID-19 vaccines was associated with significantly less frequent fatigue and multiorgan symptoms (p < 0.001), significantly less cumulative DNA virus-related IgM positivity, significantly lower levels of plasma IgG subfractions 2 and 4, and significantly lower quantitative cytomegalovirus IgG and IgM and EBV IgM titers. These results indicate that anti-SARS-CoV-2 vaccination may interrupt viral cross-talk in patients with long-COVID syndrome (ClinicalTrials.gov Identifier: NCT05398952).

ELIMINATE: a PCR record-based macroelimination project for systematic recall of HCV-RNA-positive persons in Austria.

BACKGROUND AND AIMS: Micro-elimination projects targeted to specific hepatitis C virus (HCV) risk populations have been successful. Systematic identification of persons with HCV viremia, regardless of risk group, based on already available laboratory records may represent an effective macroelimination approach to achieve global HCV elimination. METHODS: Persons with a last positive HCV-RNA PCR result between 2008-2020 in the reference virology laboratories in eastern Austria were identified. First, (i) we described their demographic characteristics, (ii) we systematically recalled persons to the respective centers and (iii) started antiviral treatment if HCV-RNA viremia was confirmed, and (iv) recorded sustained virologic response (SVR). This interim report includes the preliminary results from 8 participating centers. RESULTS: During the study period 22,682 persons underwent HCV-RNA PCR testing, 11,216 (49.4%) were positive at any point in time, and 6006 (26.5%) showed detectable HCV-RNA at the last PCR test, suggesting ongoing HCV viremia. At the time of this interim report, 2546/6006 HCV-RNA PCR(+) persons were evaluated: 443/2546 (17.4%) had died, 852/2546 (33.5%) had invalid contact data, and 547/2546 (21.5%) had achieved SVR between data retrieval and recall. Contact could be established in 236/704 (33.5%) of the remaining target population with 97/236 (41.1%) presenting at the clinic for treatment evaluation. Ultimately, 71/236 (30.1%) started antiviral treatment and SVR was documented in 47/71 (66.2%). CONCLUSION: This ELIMINATE project based on systematic assessment of HCV-RNA PCR-records, identified 6006 persons with potential persisting HCV viremia. Invalid contact data and missed visits for treatment evaluation were the main barriers towards HCV elimination within this project. Importantly, many subjects with HCV viremia lost to follow-up were successfully linked to care and started antiviral treatment.

Inhibitory NKG2A+ and absent activating NKG2C+ NK cell responses are associated with the development of EBV+ lymphomas.

Epstein-Barr virus (EBV) is a ubiquitous herpesvirus, which infects over 90% of the adult human population worldwide. After primary infections, EBV is recurrently reactivating in most adult individuals. It is, however, unclear, why these EBV reactivations progress to EBV+ Hodgkin (EBV+HL) or non-Hodgkin lymphomas (EBV+nHL) only in a minority of EBV-infected individuals. The EBV LMP-1 protein encodes for a highly polymorphic peptide, which upregulates the immunomodulatory HLA-E in EBV-infected cells, thereby stimulating the inhibitory NKG2A-, but also the activating NKG2C-receptor on natural killer (NK) cells. Using a genetic-association approach and functional NK cell analyses, we now investigated, whether these HLA-E-restricted immune responses impact the development of EBV+HL and EBV+nHL. Therefore, we recruited a study cohort of 63 EBV+HL and EBV+nHL patients and 192 controls with confirmed EBV reactivations, but without lymphomas. Here, we demonstrate that in EBV+ lymphoma patients exclusively the high-affine LMP-1 GGDPHLPTL peptide variant-encoding EBV-strains reactivate. In EBV+HL and EBV+nHL patients, the high-expressing HLA-E*0103/0103 genetic variant was significantly overrepresented. Combined, the LMP-1 GGDPHLPTL and HLA-E*0103/0103 variants efficiently inhibited NKG2A+ NK cells, thereby facilitating the in vitro spread of EBV-infected tumor cells. In addition, EBV+HL and EBV+nHL patients, showed impaired pro-inflammatory NKG2C+ NK cell responses, which accelerated the in vitro EBV-infected tumor cells spread. In contrast, the blocking of NKG2A by monoclonal antibodies (Monalizumab) resulted in efficient control of EBV-infected tumor cell growth, especially by NKG2A+NKG2C+ NK cells. Thus, the HLA-E/LMP-1/NKG2A pathway and individual NKG2C+ NK cell responses are associated with the progression toward EBV+ lymphomas.

Microbiological and Virological Knowledge-Based Alert Service.

Hospital wards need immediate information about multi-resistant pathogens and contagious viruses in their hospitalized patients. An alert service configurable with Arden-Syntax-based alert definitions passing through an ontology service to complement results from microbiology and virology with high-level terms was implemented as proof of concept. Integration into the University Hospital Vienna's IT landscape is ongoing.

Durable Anti-SARS-CoV-2 Antibody Response after mRNA-1273 Booster in Peritoneal Dialysis Patients during the Omicron Wave.

Anti-SARS-CoV-2 vaccination of dialysis patients has been proven to be safe and effective to reduce COVID-19-related morbidity and mortality. However, data on the durability of anti-SARS-CoV-2 antibodies post-vaccination in peritoneal dialysis (PD) patients are scarce. In this prospective single-center cohort study we measured anti-SARS-CoV-2 RBD antibodies 3 and 6 months after the 3rd dose of the mRNA-1273 vaccine in 27 adult PD patients and recorded breakthrough infections. Furthermore, in a mixed model analysis, we analyzed potential factors influencing the humoral response following vaccination. Anti-SARS-CoV-2 RBD antibody levels declined from 21,424 BAU/mL at 1 month to 8397 BAU/mL at 3 months and to 5120 BAU/mL at 6 months after the 3rd dose, but remained higher than pre-3rd dose levels (212 BAU/mL). Eight patients (29.6%) were infected with SARS-CoV-2 within six months from the 3rd dose during the Omicron wave. Previous high antibody levels, high glomerular filtration rate (GFR) and low Davies Comorbidity Score were associated with higher anti-SARS-CoV-2 antibody levels after the booster. In conclusion, PD patients exhibited a robust and durable humoral response after a third dose of the mRNA-1273 vaccine. A high GFR and low comorbidity as well as previous high antibody levels predicted a better humoral response to vaccination.

Eligibility for antiviral therapy and treatment uptake in chronic hepatitis B patients referred to a European tertiary care center.

BACKGROUND AND AIMS: Treatment indications for chronic hepatitis B (CHB) differ among recommendations by European Association for the Study of the Liver (EASL), American Association for the Study of Liver Diseases (AASLD) and World Health Organization (WHO). We aimed to assess treatment eligibility and linkage to therapy at a large tertiary care center. METHODS: All CHB patients who were evaluated for treatment at the Vienna General Hospital between January 2010 and December 2020 were retrospectively included. Clinical, virological, and long-term treatment efficacy data were analyzed. RESULTS: A total of 751 CHB patients were included (53.3% male; median age: 39.5 years; HBeAg-positive: 10.8%). The median Hepatitis B Virus (HBV)-DNA and HBsAg levels were 569 (68-11,750) IU/mL and 3467.65 (620.05-11,935.43) IU/mL, respectively. Overall, 9.2% of patients had severe fibrosis/cirrhosis, and 5.7% were coinfected with hepatitis D virus (HDV), which was highly prevalent in cirrhosis. According to the recent EASL nomenclature, 3.2% of patients had HBeAg-positive chronic infection, 7.6% had HBeAg-positive chronic hepatitis, 58.9% had HBeAg-negative chronic infection, and 30.4% had HBeAg-negative chronic hepatitis. At the time of evaluation, 36.4% had HBV-DNA >2000 IU/mL, and 37.3% showed alanine aminotransferase >40 U/L. Ultimately, 26.9% (EASL), 29.0% (AASLD) and 23.4% (WHO) met the treatment criteria. Treatment was initiated in most patients, mainly with tenofovir (61.8%) or entecavir (34.9%). Treatment efficiently suppressed HBV-DNA in all patients; however, HBsAg loss was observed only in 2.8% at 5 years of therapy. CONCLUSIONS: Severe fibrosis/cirrhosis was found in 9.2% of CHB patients at presentation, and 23.4%-29.5% met current treatment recommendations with a high treatment uptake of 79.8%-89.2% among eligible patients.

Long COVID symptoms in hospital employees after post-vaccination SARS-CoV-2 infection in Austria: A study on self-reported incidence and associated factors.

PURPOSE: Post acute sequelae of SARS-CoV-2 infection are defined by persistence or re-occurrence of symptoms six to 12 weeks after SARS-CoV-2 infections. METHODS: Twice vaccinated hospital employees after mild to moderate post-vaccination SARS-CoV-2 infection completed a questionnaire on the incidence of general, respiratory, neuropsychiatric, dermatological and gastrointestinal symptoms, experienced during their acute infection and eight weeks after recovery. Post acute sequelae of SARS-CoV-2 infection were analysed in relation to socio-demographic-, health-, virus- and acute infection-related characteristics. RESULTS: 73 participants, 25 women and 48 men with a mean age of 40.9 years, with a post-vaccination SARS-CoV-2 infection completed the survey. Out of these 93 % reported at least one symptom at time of initial SARS-CoV-2 infection, 31.5 %, predominantly women, reported post acute sequelae at least eight weeks after the acute infection stage. Fatigue, dysgeusia and dysosmia, headache or difficulty concentrating and shortness of breath during acute infection, BMI> 25 and pre-existing pulmonary disorders were associated with post acute sequelae of SARS-CoV-2 infection. Participants with initially more than five symptoms were four times more likely to report post acute sequelae. CONCLUSION: It is suggested that the multiplicity of symptoms during acute SARS-CoV-2 infections increases the risk for post acute symptoms.

The natural killer cell-associated rs9916629-C allele is a novel genetic risk factor for fatal COVID-19.

The severity of COVID-19 is associated with individual genetic host factors. Among these, genetic polymorphisms affecting natural killer (NK) cell responses, as variations in the HLA-E- (HLA-E*0101/0103), FcγRIIIa- (FcγRIIIa-158-F/V), and NKG2C- (KLRC2wt/del ) receptor, were associated with severe COVID-19. Recently, the rs9916629-C/T genetic polymorphism was identified that indirectly shape the human NK cell repertoire towards highly pro-inflammatory CD56bright NK cells. We investigated whether the rs9916629-C/T variants alone and in comparison to the other risk factors are associated with a fatal course of COVID-19. We included 1042 hospitalized surviving and 159 nonsurviving COVID-19 patients as well as 1000 healthy controls. rs9916629-C/T variants were genotyped by TaqMan assays and were compared between the groups. The patients' age, comorbidities, HLA-E*0101/0103, FcγRIIIa-158-F/V, and KLRC2wt/del variants were also determined. The presence of the rs9916629-C allele was a risk factor for severe and fatal COVID-19 (p < 0.0001), independent of the patients' age or comorbidities. Fatal COVID-19 was more frequent in younger patients (<69.85 years) carrying the FcγRIIIa-158-V/V (p < 0.006) and in older patients expressing the KLRC2del variant (p < 0.003). Thus, patients with the rs9916629-C allele have a significantly increased risk for fatal COVID-19 and identification of the genetic variants may be used as prognostic marker for hospitalized COVID-19 patients.

Low mortality despite temporary liver dysfunction in severe courses of acute hepatitis E.

BACKGROUND: Hepatitis E virus (HEV) infection can cause severe viral hepatitis and eventually liver failure. We aim to provide novel data on the epidemiology and the course of HEV infections from Q1/2008 to Q3/2018 at the Vienna General Hospital. METHODS: Of the 88,945 people tested, we identified HEV-IgM positive (+) or HEV-PCR (+) patients and retrospectively collated information on the course of infection from patient records. RESULTS: Among 151 HEV-IgM or PCR (+) (median age 51 years, 45.8% female), 7 (4.6%) had non-severe acute HEV infection (ALT ≥ 2-5-fold upper limit of normal, ULN), 11 (7.3%) had severe HEV infection without liver dysfunction (LD) (ALT > 5-fold ULN), and 9 (6.0%) with LD (ikterus or bilirubin > 5 mg/dL, OR coagulopathy or INR > 1.5, OR encephalopathy or ammonia > 100 µmol/L). HEV-RNA-PCR was performed in 58/190 (30.5%) HEV-IgM (+) patients and was positive in 19 (30.6%). Rates of HEV IgM/PCR positivity remained stable over the observation period. The HEV genotype (GT) was GT­1 in 71.4% (n = 5) and GT­3 in 28.6% (n = 2). Travel history was recorded for 9/20 (45.0%) of severe HEV and 12/20 (60.0%) patients with severe HEV infection were hospitalized. One patient with pre-existing liver disease and concomitant EBV infection required intensive care. No patient required transplantation and the 30-day mortality was 3/151 (1.9%). Despite the increased testing rates, the absolute number of diagnosed HEV infections at Vienna General Hospital remained constant between 2008 to 2018. CONCLUSION: Although approximately half of the patients with severe acute HEV infection required hospitalization, admissions to the intensive care unit (ICU) and short-term mortality were low.

Viral infections in pediatric brain tumor patients treated with targeted therapies.

BACKGROUND: Brain tumors are the most common solid malignancies and the leading cause of cancer-related mortality in children. While numerous studies report on viral infections in children with hematologic malignancies and solid organ transplantation, epidemiologic data on the incidence and outcome of viral infections in pediatric patients with brain tumors treated with targeted therapies are still lacking. OBJECTIVES/STUDY DESIGN: We retrospectively reviewed all children with brain tumors receiving targeted therapies in a primary or recurrent setting at the Medical University of Vienna from 2006 to 2021. Demographic variables, quantitative and qualitative parameters of possible infections, and treatment outcomes were recorded. RESULTS: In our cohort (n = 117), 36% of the patients developed at least one PCR-proven viral infection. Respiratory and gastrointestinal tract infections were most common, with 31% and 25%, respectively. Central nervous system (CNS) infections occurred in approximately 10%, with an almost equal distribution of varicella-zoster virus, John Cunningham virus (JCV), and enterovirus. Two patients tested PCR-positive for SARS-CoV-2 infection, with one virus-related death caused by a SARS-CoV-2-related acute respiratory distress syndrome. Patients receiving bevacizumab or mTOR inhibitors seem to have a greater susceptibility to viral infections. CONCLUSION: Pediatric patients with brain tumors receiving targeted therapies have a higher risk of viral infections when compared to children receiving conventional chemotherapy or the general population, and life-threatening infections can occur. Fast detection and upfront treatment are paramount to prevent life-threatening infections in immunocompromised children suffering from brain tumors receiving targeted therapies.

Increasing test specificity without impairing sensitivity: lessons learned from SARS-CoV-2 serology.

BACKGROUND: Serological tests are widely used in various medical disciplines for diagnostic and monitoring purposes. Unfortunately, the sensitivity and specificity of test systems are often poor, leaving room for false-positive and false-negative results. However, conventional methods were used to increase specificity and decrease sensitivity and vice versa. Using SARS-CoV-2 serology as an example, we propose here a novel testing strategy: the 'sensitivity improved two-test' or 'SIT²' algorithm. METHODS: SIT² involves confirmatory retesting of samples with results falling in a predefined retesting zone of an initial screening test, with adjusted cut-offs to increase sensitivity. We verified and compared the performance of SIT² to single tests and orthogonal testing (OTA) in an Austrian cohort (1117 negative, 64 post-COVID-positive samples) and validated the algorithm in an independent British cohort (976 negatives and 536 positives). RESULTS: The specificity of SIT² was superior to single tests and non-inferior to OTA. The sensitivity was maintained or even improved using SIT² when compared with single tests or OTA. SIT² allowed correct identification of infected individuals even when a live virus neutralisation assay could not detect antibodies. Compared with single testing or OTA, SIT² significantly reduced total test errors to 0.46% (0.24-0.65) or 1.60% (0.94-2.38) at both 5% or 20% seroprevalence. CONCLUSION: For SARS-CoV-2 serology, SIT² proved to be the best diagnostic choice at both 5% and 20% seroprevalence in all tested scenarios. It is an easy to apply algorithm and can potentially be helpful for the serology of other infectious diseases.

The systemic renin-angiotensin system in COVID-19.

SARS-CoV-2 gains cell entry via angiotensin-converting enzyme (ACE) 2, a membrane-bound enzyme of the "alternative" (alt) renin-angiotensin system (RAS). ACE2 counteracts angiotensin II by converting it to potentially protective angiotensin 1-7. Using mass spectrometry, we assessed key metabolites of the classical RAS (angiotensins I-II) and alt-RAS (angiotensins 1-7 and 1-5) pathways as well as ACE and ACE2 concentrations in 159 patients hospitalized with COVID-19, stratified by disease severity (severe, n = 76; non-severe: n = 83). Plasma renin activity (PRA-S) was calculated as the sum of RAS metabolites. We estimated ACE activity using the angiotensin II:I ratio (ACE-S) and estimated systemic alt-RAS activation using the ratio of alt-RAS axis metabolites to PRA-S (ALT-S). We applied mixed linear models to assess how PRA-S and ACE/ACE2 concentrations affected ALT-S, ACE-S, and angiotensins II and 1-7. Median angiotensin I and II levels were higher with severe versus non-severe COVID-19 (angiotensin I: 86 versus 30 pmol/L, p < 0.01; angiotensin II: 114 versus 58 pmol/L, p < 0.05), demonstrating activation of classical RAS. The difference disappeared with analysis limited to patients not taking a RAS inhibitor (angiotensin I: 40 versus 31 pmol/L, p = 0.251; angiotensin II: 76 versus 99 pmol/L, p = 0.833). ALT-S in severe COVID-19 increased with time (days 1-6: 0.12; days 11-16: 0.22) and correlated with ACE2 concentration (r = 0.831). ACE-S was lower in severe versus non-severe COVID-19 (1.6 versus 2.6; p < 0.001), but ACE concentrations were similar between groups and correlated weakly with ACE-S (r = 0.232). ACE2 and ACE-S trajectories in severe COVID-19, however, did not differ between survivors and non-survivors. Overall RAS alteration in severe COVID-19 resembled severity of disease-matched patients with influenza. In mixed linear models, renin activity most strongly predicted angiotensin II and 1-7 levels. ACE2 also predicted angiotensin 1-7 levels and ALT-S. No single factor or the combined model, however, could fully explain ACE-S. ACE2 and ACE-S trajectories in severe COVID-19 did not differ between survivors and non-survivors. In conclusion, angiotensin II was elevated in severe COVID-19 but was markedly influenced by RAS inhibitors and driven by overall RAS activation. ACE-S was significantly lower with severe COVID-19 and did not correlate with ACE concentrations. A shift to the alt-RAS axis because of increased ACE2 could partially explain the relative reduction in angiotensin II levels.

Performance Evaluation of the Fully Automated NeuMoDx RT-PCR Platform for the Quantification of CMV and EBV DNA in EDTA Plasma: Implications for Clinical Management and Establishment of a Conversion Formula.

The NeuMoDx96 platform is a fully automated real-time PCR (RT-PCR) system. To provide continued testing quality with the introduction of new assays, the primary aim of this study was to evaluate the analytical and clinical performance of the NeuMoDx platform for the detection and quantification of CMV and EBV DNA in EDTA plasma. As no conversion from log10 international units per milliliter to copies per milliliter was provided, the secondary aim was to calculate and establish a conversion factor for the output of results in copies per milliliter for CMV and EBV. Archived ETDA plasma samples (cytomegalovirus [CMV], n = 290; Ebstein-Barr virus [EBV], n = 254) were used to evaluate the analytical performance of the NeuMoDx96 platform against the routine real-time quantitative PCR (qPCR) assays. Additionally, the first WHO international standards (WHO-IS) for CMV (n = 70) and EBV (n = 72) were used for the calculation of the intra- and interassay variation. WHO-IS qualitative agreement between the assays was 100%. Intra-assay variability was low for both CMV assays (coefficient of variation [CV], phosphate-buffered saline [PBS], 3 log10 IU/mL NeuMoDx, 3.67%; Abbott RealTime, CMV, 3.35%) and NeuMoDx EBV assay (CV, PBS, 3 log10 IU/mL, 3.05%) but high for the Altona EBV assay (CV, PBS, 3 log10 IU/mL, 26.13%). The overall qualitative concordance in clinical samples was 96.8% (270/279) for CMV and 96.7% (237/245) for EBV. The mean difference between the assays was -0.2 log10 IU/mL (CMV) and -0.18 log10 IU/mL (EBV). High qualitative concordance and a significant correlation of quantitative values for both assays make NeuMoDx CMV and EBV assays suitable for routine diagnostic testing. The new RT-PCR system and conversion formulas to report results in copies per milliliter are now applied in clinical routine testing. IMPORTANCE Clinical management of solid organ transplant (SOT) patients requires the careful monitoring of immunosuppression and viral infection or reactivation. qPCR is the gold standard for the detection and quantification of very small amounts of viral DNA and allows for an early assessment of viral load kinetics. The tested NeuMoDx 96 platform provides faster results than the previously used RT-PCR workflows for CMV (Abbott m2000 and RealTime CMV assay) and EBV (LightCycler 480 II, Roche high pure extraction, and Altona RealStar EBV assay) DNA detection. The implemented conversion formulas allow the continued reporting in clinically established copies per milliliter, important for long-term care of SOT patients.

The impact of COVID-19 on liver transplantation programs in Austria.

BACKGROUND: Coronavirus disease of 2019 (COVID-19) has affected liver disease management. The impact of the COVID-19 pandemic on the Austrian orthotopic liver transplantation (OLT) programs, however, has not been systematically investigated. METHODS: All patients listed for OLT in Austria during 2020-2021 were studied. Data on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing, vaccinations, infections, mortality and the overall number of OLTs (vs. pre-COVID-19: 2015-2019) were analyzed. RESULTS: Overall, 490 patients (median age: 58.0 years, 70.4% men, hepatocellular carcinoma: 27.3%) were listed for OLT in Austria in 2020-2021. Alcohol-related cirrhosis (35.3%), cholestatic (16.7%) and viral liver disease (13.9%) were the main etiologies. Of the patients 61.2% underwent OLT and 8.8% died while on the waiting list. The number of OLTs performed during COVID-19 (2020: n = 150; 2021: n = 150) remained unchanged compared to pre-COVID-19 (median: n = 152). Among waiting list patients, 7.7% (n = 31/401) were diagnosed with COVID-19 and 7 (22.6%) of these patients died. By the end of 2021, 45.1% (n = 176/390; 82.8% mRNA vaccinations) and 28.8% (105/365) of patients received 2 and 3 SARS-CoV­2 vaccinations, respectively. After two SARS-CoV­2 vaccinations, antibodies more often remained undetectable in patients vaccinated post-OLT (25.6% vs. 6.5% in patients vaccinated pre-OLT; p = 0.034). Patients with three vaccinations after OLT had lower antibody titers than patients vaccinated pre-OLT (post-OLT: 513.5, IQR 44.4-2500.0 vs. pre-OLT: 2500.0, IQR 1462.0-2500.0 BAU/mL; p = 0.020). CONCLUSION: The number of OLTs in Austria remained unchanged during COVID-19. SARS-CoV­2 infections were rare but associated with high mortality in patients on the Austrian OLT waiting lists. SARS-CoV­2 vaccination rates at the end of 2021 were suboptimal, while serological response was better in patients vaccinated pre-OLT vs. post-OLT.