Impact of pathogen-reduction technologies on COVID-19 convalescent plasma potency.

Pathogen reduction technologies (PRT) have been recommended by many regulatory authorities to minimize the residual risk of transfusion-transmitted infections associated with COVID19 convalescent plasma. While its impact on safety and its cost-effectiveness are nowadays well proven, there is theoretical concern that PRT could impact efficacy of convalescent plasma by altering concentration and/or function of the neutralizing antibodies (nAb). We review here the evidence supporting a lack of significant detrimental effect from PRTs on nAbs.

Assessment of prevalence and load of torquetenovirus viraemia in a large cohort of healthy blood donors.

OBJECTIVES: Torquetenovirus (TTV) is an emerging marker of functional immune competence with the potential to predict transplant-related adverse events. A large-scale epidemiological study was performed to understand how basal values vary in healthy individuals according to age and gender. METHODS: We tested plasma from 1017 healthy blood donors aged 18-69 years. The presence and load of TTV were determined by a real-time PCR assay. A sub-cohort of 384 donors was tested for anti-cytomegalovirus IgG antibodies, and 100 participants were also tested for TTV viraemia on a paired whole blood sample. RESULTS: The overall prevalence of TTV was 65% (657/1017) with a mean (±SD) growth of 5 ± 4% every 10 years of age increase, but stably higher in males (465/690, 67%) than in females (192/327, 59%). Mean (±SD) TTV load was 2.3 ± 0.7 Log copies/mL with no sex difference. TTV viraemia showed modest increases along 10-year age intervals (mean ± SD: 0.3 ± 0.1). TTV viraemia in donors sampled 2 years later remained stable (mean ± SD: 2.3 ± 0.8 versus 2.2 ± 0.7 Log copies between samples). Twenty-six per cent (9/34) of blood donors with TTV-negative plasma scored positive when whole blood was tested, and the donors with positive plasma showed a mean (±SD) 1.4 ± 0.5 Log increase in copy numbers when whole blood was tested. CONCLUSIONS: This study establishes the mean value of TTV viraemia in plasma in healthy blood donors and suggests that ageing causes only minimal increases in TTV viraemia.

The kinetics of torque teno virus plasma DNA load shortly after engraftment predicts the risk of high-level CMV DNAemia in allogeneic hematopoietic stem cell transplant recipients.

Monitoring Torque teno virus (TTV) DNA load helps to estimate the risk of opportunistic infections in solid organ transplant recipients. We investigated whether the early kinetic pattern of plasma TTV DNA load after allogeneic hematopoietic stem cell transplantation (allo-HSCT) associates with subsequent CMV and EBV DNAemia. This study included 71 allo-HSCT patients. We found that the area under the curve (AUC) for log10 TTV DNA loads quantified by days 20 and 30 after transplantation (TTV DNA load AUC20-30), was significantly lower (P=0.036) in patients who subsequently developed CMV DNAemia requiring preemptive antiviral therapy (n=17) than in those who did not (n=8) or had no CMV DNAemia (n=19). Patients displaying TTV DNA load AUC20-30⩽2.8 copies × days × mL-1 were more likely to have high-level CMV DNAemia. A trend towards a direct correlation between TTV DNA AUC20-30 and CMV-specific interferon-γ CD8+ T-cell counts by day +30 was noted (P=0.095). However, this dynamic parameter was not useful for anticipating the occurrence of either CMV recurrences (n=12) or EBV DNAemia (n=34). In summary, it may be possible to identify a subset of allo-HSCT patients at a high risk of developing high-level CMV DNAemia by analyzing the kinetics of plasma TTV DNA load early after engraftment.

Torquetenovirus: the human virome from bench to bedside.

Torquetenovirus (TTV) is the most abundant component of human virome. Virologists have long ignored this orphan and highly divergent virus, in part because TTV cannot be cultured and because it lacks serology reagents and animal models. Nevertheless, it is almost endemic worldwide and is insensitive to current antiviral drugs, so its monitoring is useful in various conditions. To date, TTV as a marker has proved useful in at least two circumstances: to identify anthropogenic pollution and to assess functional immune competence in immunosuppressed individuals. This review summarizes recent findings about TTV and discusses the main hurdles in translating them into clinical diagnostics.

Induced pluripotent stem cells in hematology: current and future applications.

Reprogramming somatic cells into induced pluripotent stem (iPS) cells is nowadays approaching effectiveness and clinical grade. Potential uses of this technology include predictive toxicology, drug screening, pathogenetic studies and transplantation. Here, we review the basis of current iPS cell technology and potential applications in hematology, ranging from disease modeling of congenital and acquired hemopathies to hematopoietic stem and other blood cell transplantation.

Administering 25-hydroxyvitamin D3 in vitamin D-deficient young type 1A diabetic patients reduces reactivity against islet autoantigens.

BACKGROUND & AIMS: We investigated whether improving 25-hydroxyvitamin D status in young type 1A diabetic patients reduces reactivity of peripheral blood mononuclear cells against islet autoantigens and associates with beta-cell functional changes. METHODS: Eight patients with 25-hydroxyvitamin D deficiency (<20 ng/ml), out of 15 consecutive young type 1A diabetic subjects received 25-hydroxyvitamin D3 to achieve and maintain levels above 50 ng/ml for up to one year. Peripheral blood mononuclear cell reactivity (Interferon-γ spots) against beta-cell autoantigens (glutamic acid decarboxylase 65-kD isoform, proinsulin and tyrosine phosphatase-like protein IA-2) and C-peptide during mixed meal were assessed before and after 25-hydroxyvitamin D3 replenishment. RESULTS: Target 25-hydroxyvitamin D blood levels were safely reached and maintained. Peripheral blood mononuclear cell reactivity against glutamic acid decarboxylase 65-kD isoform (3.8 ± 4.0 vs. 45 ± 16) and proinsulin (3.5 ± 3.2 vs. 75 ± 51) decreased significantly (p < 0.001 and p < 0.02) upon 25-hydroxyvitamin D3 replenishment, which was correlated with 25-hydroxyvitamin D concentrations. C-peptide values remained stable after one year of treatment. CONCLUSIONS: Safely restored and maintained 25-hydroxyvitamin D levels associated with reduced peripheral blood mononuclear cell reactivity against beta-cell autoantigens with no significant decrease of beta-cell function in this cohort of patients.

Xenotropic murine leukaemia virus-related virus is not found in peripheral blood cells from treatment-naive human immunodeficiency virus-positive patients.

The human pathogen xenotropic murine leukaemia virus-related virus (XMRV) has been tentatively associated with prostate cancer and chronic fatigue syndrome. Unfortunately, subsequent studies failed to identify the virus in various clinical settings. To determine whether XMRV circulates in humans and the relationship with its host, we searched for the virus in 124 human immunodeficiency virus-infected patients who might have been exposed to XMRV, might be prone to infection as a result of progressive immunodeficiency, and had not yet been treated with antiretroviral drugs. Using nested PCR and single-step TaqMan real-time PCR, both designed on the XMRV gag gene, we could not find any positive samples. These findings add to the growing amount of scepticism regarding XMRV.

Immunosuppressive monoclonal antibodies: current and next generation.

Monoclonal antibodies (mAbs) are well-established therapeutics, as evidenced by the large number of Food and Drug Administration-approved mAbs for the treatment of cancers, and inflammatory or autoimmune diseases, and for the prevention and treatment of solid organ transplant rejection. Although, in many cases, mAbs have improved patient survival, they are also associated with an increased incidence of opportunistic infections. We review here the current and next generation of mAbs and the risks that infectious disease specialists should be aware of.

Ultrasound findings guided a successful hemicolectomy in a leukemic patient with neutropenic enterocolitis.

INTRODUCTION: Neutropenic enterocolitis (NEC) can be a life-threatening complication of chemotherapy in leukemic patients. Early diagnosis and treatment is therefore crucial. METHODS: A 38-year-old woman with acute lymphoblastic leukemia and chemotherapy-induced neutropenia suddenly developed symptoms suspicious of NEC. Transabdominal ultrasound showed features consistent with NEC, later confirmed by computed tomography (CT) scan. RESULTS: The patient was scanned using portable ultrasound (US) equipment (Esaote My Lab 25). US findings showed involvement of the cecum, appendix, ascending colon and proximal middle transverse colon, with features resembling gas containing fissures within the colon wall itself. The risk of colon rupture was confirmed by CT scan. The patient underwent successful hemicolectomy after intravenous treatment with broad spectrum antibiotics, granulocyte-colony stimulating factor (G-CSF), platelets and fresh frozen plasma transfusion. DISCUSSION: A prompt bedside US examination upon development of symptoms allowed an early diagnosis of NEC and identified features consistent with imminent colon wall rupture, shifting the management of this life-threatening complication from medical to surgical. Multidisciplinary intervention was crucial for a successful hemicolectomy in a severely affected neutropenic patient.

Doxorubicin cardiomyopathy via TLR-2 stimulation: potential for prevention using current anti-retroviral inhibitors such as ritonavir and nelfinavir.

Doxorubicin remains a useful anti-cancer drug but as lifetime dose approaches 500 mg/m2 and particularly when this dose is exceeded, iatrogenic life-threatening cardiomyopathy becomes progressively more likely. This note reviews evidence indicating that doxorubicin induced cardiomyopathy is partly mediated by stimulation of Toll-like receptors (TLR) 2 and 4 which are expressed on cardiomyocytes. Indinavir, nelfinavir, ritonavir, and saquinavir are currently marketed protease inhibitors used to suppress human immunodeficiency virus. They have recently been shown to inhibit signalling at TLR 2 and 4 as well as intracellular events downstream from these receptors. It is possible that these FDA-approved anti-retroviral protease inhibitors could be used off-label to diminish likelihood of doxorubicin cardiotoxicity permitting higher doxorubicin doses. We suggest that currently marketed anti-viral protease inhibitors be investigated in animal models of doxorubicin cardiomyopathy and if such studies do indeed show protection, human studies be initiated.