ABSTRACT
Background & Aim: With larger accessibility and increased number of patients being treated with CART cell therapy, real-world toxicity continues to remain a significant challenge to its widespread adoption. We have previously shown that allogeneic umbilical cord blood derived (UCB) regulatory T cells (Tregs) can resolve uncontrolled inflammation and can treat acute and immune mediated lung injury in a xenogenic model as well as in patients suffering from COVID-19 acute respiratory distress syndrome. The unique properties of UCB Tregs including: i) lack of plasticity when exposed to inflammatory micro-environments;ii) no requirement for HLA matching;iii) long shelf life of cryopreserved Tregs;and iv) immediate product availability for on demand treatment, makes them an attractive source for treating acute inflammatory syndromes. Therefore, we hypothesized that add-on therapy with UCB derived Tregs may resolve uncontrolled inflammation responsible for CART cell therapy associated toxicity. Methods, Results & Conclusion(s): UCB Tregs were added in 1:1 ratio to CART cells, where no interference in their ability to kill CD19+ Raji cells, was detected at different ratios : 8:1 (80.4% vs. 81.5%);4:1 (62.0% vs. 66.2%);2:1 (50.1% vs. 54.7%);1:1 (35.4% vs. 44.1%) (Fig 1A). In a xenogenic B cell lymphoma model, multiple injections of Tregs were administered after CART injection (Fig 1B), which did not impact distribution of CD8+ T effector cells (Fig 1C) or CART cells cells (Fig 1D) in different organs. No decline in the CAR T levels was observed in the Tregs recipients (Fig 1E). Specifically, no difference in tumor burden was detected between the two arms (Fig 2A). No tumor was detected in CART+Tregs in liver (Fig 2B) or bone marrow (Fig 2C). A corresponding decrease in multiple inflammatory cytokines in peripheral blood was observed in CART+Tregs when compared to CART alone (Fig 2D). Here we show "proof of concept" for add-on therapy with Tregs to mitigate hyper-inflammatory state induced by CART cells without interference in their on-target anti-tumor activity. The timing of Tregs administration after CART cells have had sufficient time for forming synapse with tumor cells allows for preservation of their anti-tumor cytotoxicity, such that the infused Tregs home to the areas of tissue damage to bind to the resident antigen presenting cells which in turn collaborate with Tregs to resolve inflammation. Such differential distribution of cells allow for a Treg "cooling blanket" and lays ground for clinical study. [Figure presented]Copyright © 2023 International Society for Cell & Gene Therapy
ABSTRACT
With the success of mRNA vaccines during the COVID-19 pandemic and CAR T-cell therapies in clinical trials, there is growing opportunity for immunotherapies in the treatment of many types of cancers. Lentiviral vectors have proven effective at delivery of genetic material or gene editing technology for ex vivo processing, but the benefits and promise of Adeno-associated virus (AAV) and mRNA tools for in vivo immunotherapy have garnered recent interest. Here we describe complete synthetic solutions for immuno-oncology research programs using either mRNA-vaccines or virus-mediated cell and gene engineering. These solutions optimize workflows to minimize screening time while maximizing successful research results through: (1) Efficiency in lentiviral packaging with versatility in titer options for high-quality particles. (2) A highthroughput viral packaging process to enable rapid downstream screening. (3) Proprietary plasmid synthesis and preparation techniques to maintain ITR integrity through AAV packaging and improve gene delivery. (4) Rapid synthesis, in vitro transcription, and novel sequencing of mRNA constructs for complete characterization of critical components such as the polyA tail. The reported research demonstrates a streamlined approach that improves data quality through innovative synthesis and sequencing methodologies as compared to current standard practices.
ABSTRACT
The most common non-Hodgkin's lymphoma (NHL) is diffuse large B-cell lymphoma (DLBCL), an aggressive lymphoma that can be cured with standard frontline chemo-immunotherapy in 60%-70% of patients but with historically poor outcomes for relapsed/refractory disease. Patients with relapsed DLBCL after autologous stem cell transplant (ASCT) or with chemotherapy-refractory disease have a particularly dismal prognosis, with a median overall survival (OS) of only 6 months. Chimeric antigen receptor (CAR) T-cell therapy has significantly improved outcomes for patients with relapsed/refractory large B-cell lymphoma, mantle cell lymphoma and follicular lymphoma, with multiple FDA approved CAR T products now commercially available in many developed world including European countries. Ongoing studies seek to move CAR T cells to earlier lines of therapy and to characterise the efficacy and safety of CAR T-cell approaches in additional lymphoma histologies including relapsed/refractory follicular lymphoma and chronic lymphocytic leukaemias. Other areas of active research address CAR T in combination with other lymphoma-directed therapies, and mechanisms of CAR T resistance. We conducted a retrospective observational study assessing the outcomes of patients referred to our tertiary centre, University College London hospital NHS foundation Trust (UCLH) from January 2018 to December 2022, over a 48-month period. We collected data including patients' demographics, types of lymphomas, prior lines of therapies including stem cell transplantation, bridging therapies as appropriate, complications and overall response rate. We also analysed the communication between teams during the challenging period of the COVID-19 pandemic.
ABSTRACT
Commercially available human platelet lysate (hPL) is produced using expired human platelets obtained from accredited blood banks in the United States. These platelets were originally intended for use in patient transfusion. The safety of platelets used in transfusion is managed by the U.S. Food Drug Administration (FDA), as well as the American Association of Blood Banks (AABB). These organizations set standards, including testing for transmissible diseases. The United States record for blood safety is well established, with extremely low rates of disease transmission, making the platelet units used for hPL manufacture low risk. The Covid-19 pandemic has increased awareness of emerging infectious diseases, even though transmission of Covid-19 via blood transfusion has not been documented. For that reason, gamma irradiated hPL offers an additional safety measure in the clinic. Chimeric Antigen Receptor (CAR) expressing T-cells have demonstrated potent clinical efficacy in patients with hematological malignancies. In addition, there are several phase I clinical trials evaluating the use of CAR-T-cells for targeting of solid tumorassociated antigens. Some of the challenging issues found during production of CAR-T cells are the efficiency of T cell transduction to generate CAR-T cells, the expansion of T cells to clinically relevant numbers and the long-term survival in vivo of the therapeutic cells. The use of human platelet lysate has been demonstrated to improve these issues. Our data from experiments performed using human CD3+ from donors demonstrates that human platelet lysates offer an improved performance on T cell expansion versus serum derived products. hPL efficiently promotes T cell expansion, with higher cell yields and lower cell exhaustion rate. Additionally, we efficiently developed a protocol for suspension culture of T cells, which could facilitate the large-scale expansion of allogeneic CAR-T cells.
ABSTRACT
Background: The ZUMA-1 safety management Cohort 6 (N=40), which evaluated whether prophylactic corticosteroids and earlier corticosteroids and/or tocilizumab could improve safety outcomes, demonstrated an improved safety profile (no Grade >=3 cytokine release syndrome [CRS];15% Grade >=3 neurologic events [NEs]) vs pivotal Cohorts 1+2, without compromising response rate or durability (95% ORR, 80% CR rate, and 53% ongoing response rate with >=1 y of follow-up;Oluwole, et al. ASH 2021. 2832). Here, 2-y updated outcomes are reported. Method(s): Eligible pts with R/R LBCL underwent leukapheresis (followed by optional bridging therapy) and conditioning chemotherapy, then a single axi-cel infusion. Pts received corticosteroid prophylaxis (once-daily oral dexamethasone 10 mg on Days 0 [before axi-cel], 1, and 2) and earlier corticosteroids and/or tocilizumab for CRS and NE management vs Cohorts 1+2 (Oluwole, et al. Br J Haematol. 2021). The primary endpoints were incidence and severity of CRS and NEs. Secondary endpoints included ORR (investigator-assessed), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and chimeric antigen receptor (CAR) T-cell levels in blood. Result(s): As of December 16, 2021, the median follow-up time for the 40 treated pts was 26.9 mo. Since the 1-y analysis, no new CRS events were reported (no pts had Grade >=3 CRS to date). The incidence of Grade >=3 NEs increased from 15% to 18%between the 1-y and 2-y analyses. Two new NEs occurred in 2 pts: 1 pt had Grade 2 dementia (onset on Day 685 and ongoing at time of data cutoff;not related to axi-cel) and 1 had Grade 5 axi-cel-related leukoencephalopathy. Since the 1-y analysis, 6 new infections were reported (Grades 1, 2, and 5 COVID-19 [n=1 each], Grade 3 Pneumocystis jirovecii pneumonia [n=1], Grade 3 unknown infectious episode with inflammatory syndrome [n=1], and Grade 2 herpes zoster [n=1]). In total, 8 deaths occurred since the 1-y analysis (progressive disease [n=5], leukoencephalopathy [n=1], and COVID-19 [n=2]). The ORR was 95% (80% CR), which was unchanged from the 1-y analysis. Median DOR and PFS were since reached (25.9 mo [95% CI, 7.8-not estimable] and 26.8 mo [95% CI, 8.7-not estimable], respectively). Median OS was still not reached. Kaplan- Meier estimates of the 2-y DOR, PFS, and OS rates were 53%, 53%, and 62%, respectively. Of 18 pts (45%) in ongoing response at data cutoff, all achieved CR as the best response. By Month 24, 14/20 pts with evaluable samples (70%) had detectable CAR T cells (vs 23/36 pts [64%] in Cohorts 1+2). Conclusion(s): With 2 y of follow-up, the ZUMA-1 Cohort 6 toxicity management strategy continued to demonstrate an improved long-term safety profile of axi-cel in pts with R/R LBCL. Further, responses remained high, durable, and similar to those observed in Cohorts 1+2 (Locke, et al. Lancet Oncol. 2019).Copyright © 2023 American Society for Transplantation and Cellular Therapy
ABSTRACT
Background: Cyclophosphamide (Cy) is used in hematopoietic stem cell transplant (HSCT) preparative regimens and lymphodepletion for chimeric antigen receptor T-cell (CAR-T) therapy. We describe a case of cyclophosphamide hypersensitivity in a pediatric patient during CAR-T therapy. Case description: A 13 year old boy was diagnosed with very high risk ALL in 2015 and had 2 isolated CNS relapses treated with intensified chemotherapy (chemo) and cranial radiation (1st relapse) and Blinatumomab with intrathecal (IT) chemo followed by sibling donor HSCT (2nd relapse). At age 19, and 18 months after HSCT, he had a 3rd CNS relapse treated with IT chemo and referral for CAR-T therapy. At our center, leukapheresis and CAR-T production (Novartis) were performed. Later, during lymphodepletion with fludarabine (Flu) and Cy, physiologic replacement hydrocortisone (HC) was briefly held to prevent interference with CAR-T function. After 3 days of Flu/Cy, he developed fever and hypotension requiring inotropic support. Hypotension and fever resolved with stress dose HC and antibiotics and was attributed to culture-negative sepsis and adrenal crisis. CAR-T infusion was subsequently delayed by skin GVHD requiring glucocorticoids and COVID-19 infection treated with convalescent plasma and nirmatrelvir/ritonavir. Physiologic HC replacement was continued when he was re-admitted for CAR-T therapy, but he again developed fever, diffuse erythema and shock in hours following the first dose of Cy necessitating stress dose HC, antibiotics, inotropes, and mechanical ventilation. Negative blood cultures and ongoing physiologic HC replacement suggested an alternative explanation for shock. Case reports of anaphylaxis to Cy metabolites implicated Cy as the causative agent so it was discontinued. After recovery, CAR-T cells were infused without complications. In the following weeks, he had no evidence of recurrent leukemia but was persistently pancytopenic. A sibling donor stem cell boost was proposed but the patient accepted only palliative care. He had several opportunistic infections before succumbing to E. coli sepsis. Discussion(s): The first episode of shock was initially attributed to adrenal crisis and sepsis, although no organism was identified. The second episode appeared anaphylactic in timing and clinical presentation with adequate HC replacement and negative cultures, suggesting Type I hypersensitivity. The patient previously received Cy uneventfully before HSCT, suggesting that the donor-derived immune system was the source of new Cy hypersensitivity. Onset of anaphylaxis within hours rather than minutes after Cy administration supports hypersensitivity to Cy metabolites rather than to the drug itself. This case highlights the importance of consideration of sensitivity to Cy metabolites as well as acquired donor-specific allergy even when alternative explanations are likely.Copyright © 2023 American Society for Transplantation and Cellular Therapy
ABSTRACT
Background: The Sarah Cannon Transplant and Cellular Therapy Network (SCTCTN), which offers community access to transplant and cell therapy, implemented a coordinated approach to deliver CAR-T therapy through 5 programs. We conducted a retrospective review of clinical outcomes after FDA-approved anti-CD19+ CAR-T in B-cell NHL. Method(s): All patients referred for evaluation within SCTCTN were tracked in our prospective registry (Stafa-CT). We identified 110 patients who received FDA-approved anti-CD19+ CAR-T for NHL within the network between 12/10/2018 and 3/7/2022. All patients received care through standardized eligibility criteria, process, care pathways, toxicity management protocols, and a single quality plan. Result(s): The median age at referral was 60 years (range 23-82), 63% were male, the referral indication was diffuse large B-cell lymphoma (70%), mantle cell lymphoma (7%), follicular lymphoma (15%), or other B-NHL (8%). 35% had received a prior autologous transplant. The median time from referral to infusion was 143 days (range 89- 224), and from collection to infusion was 32 days. The infusion year was 2018 (1), 2019 (20), 2020 (31), 2021 (48), 2022 (10). The CAR-T cell products were Axi-cel (70), Tisa-cel (27), Brexu-cel (9), and Liso-cel (4). 16 patients (15%) were infused as outpatient, of which 10 patients were subsequently hospitalized at a median of 8 days (range 1-26) after infusion. Of the 94 patients (85%) infused as inpatient, the median length of stay was 15 days (range 6 to 85). Cytokine release syndrome (CRS) was observed in 78% with a median maximum grade 1. Maximum grade CRS was none, grade 1, grade 2, grade 3, grade 4, grade 5 in 22%, 36%, 32%, 7%, 2 % and <1%, respectively. The median times to onset and resolution of symptoms were day 3 and 8, respectively. Tocilizumab was administered to 39% for a median of 2 doses. Neurotoxicity was observed in 55% with a median maximum grade 1. Maximum grade neurotoxicity was none, grade 1, grade 2, grade 3, grade 4, grade 5 in 45%, 19%, 13%, 18%, 4 % and 0%, respectively. The median times to onset and resolution of symptoms were day 7 and 13, respectively. Neutropenia (<0.5/ muL) and thrombocytopenia (<20K/muL) at day 30 were reported in 11% and 12%, respectively. 18% required ICU stay. 37 deaths (34%) were reported from disease progression (23), infections (7, including 5 from COVID), CRS (2) and other causes (5).(Figure Presented) Conclusion(s): Administration of anti-CD19+ CAR-T is feasible in specialized community hospitals with outcomes similar to registrational clinical trials. Outpatient administration is feasible in selected patients, but subsequent hospitalization needs to be anticipated. CRS, neurotoxicity, cytopenias and infection remain challenges, while disease progression was the commonest cause of deathCopyright © 2023 American Society for Transplantation and Cellular Therapy
ABSTRACT
Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows:. To assess the benefits and adverse effects of vaccines for the prevention of infections in adults with haematological malignancies.Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
ABSTRACT
T-lineage acute lymphoblastic leukemia (T-ALL) is curable for most children and adolescent and young adult patients with contemporary frontline chemotherapy regimens. During the past decade, improved survival rates have resulted from the optimization of frontline chemotherapy regimens, the use of minimal residual disease (MRD) assessment for evaluating a patient's risk for relapse, and the intensification of treatment based on the persistence of MRD. Optimization of initial therapy is critical because relapsed T-ALL after initial intensive chemotherapy is incurable for most adult patients. Current T-ALL salvage chemotherapy regimens are minimally effective, and unlike in B-cell ALL, there are no approved antibody therapies or chimeric antigen receptor T-cell therapies for relapsed disease. Immunotherapy and small-molecule inhibitors are beginning to be tested in relapsed T-ALL and have the potential to advance the treatment. Until effective salvage strategies are discovered, however, intensive frontline therapy is required for cure. In this article I review the current frontline chemotherapy regimens for adult patients with T-ALL, summarize the novel targeted and immune therapeutics currently in early-phase clinical trials, and outline how these therapies are helping to define an optimal approach for T-ALL.Copyright © 2022 by The American Society of Hematology.
ABSTRACT
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), disproportionately affects immunocompromised and elderly patients. Not only are hematopoietic cell transplantation (HCT) and chimeric antigen receptor (CAR) T-cell recipients at greater risk for severe COVID-19 and COVID-19-related complications, but they also may experience suboptimal immune responses to currently available COVID-19 vaccines. Optimizing the use, timing, and number of doses of the COVID-19 vaccines in these patients may provide better protection against SARS-CoV-2 infection and better outcomes after infection. To this end, current guidelines for COVID-19 vaccination in HCT and CAR T-cell recipients from the American Society of Transplantation and Cellular Therapy Transplant Infectious Disease Special Interest Group and the American Society of Hematology are provided in a frequently asked questions format.
ABSTRACT
Currently, experience with COVID-19 in multiple myeloma (MM) is still very limited. Terefore, we conducted this analysis of MM patients infected by COVID-19 from two prominent hematology centers in Wuhan and Wurzburg (Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China and University Hospital of Wurzburg, Wurzburg, Germany) as of 9 June 2020. In total, we identifed fve Caucasian patients from Wurzburg and three Asian patients from Wuhan. The majority of the patients were male (n=5, 63%), and the median age at COVID-19 diagnosis was 57 (range 39-83 years). Tree patients had newly diagnosed (ND) MM, and two of them were therapy naive at diagnosis of COVID-19. One patient from Wuhan was receiving the second cycle of VTD (bortezomib, thalidomide, and dexamethasone) as the first line therapy. In Wuhan, a patient with extramedullary progression (No. 6) received leukapheresis to prepare for a salvage chimeric antigen receptor T-cell (CAR-T) therapy. Due to COVID-19 infection, systemic anti-MM treatment was discontinued in all eight patients. Notably, two patients in Wurzburg showed no COVID-19 symptoms, and the other three patients exhibited only mild symptoms such as fever, cough, and nausea, which did not require an intensive care unit (ICU) admission. Tree patients did not receive any COVID-19 treatment, and all fve patients in Wurzburg recovered. In contrast, two patients from Wuhan developed severe respiratory syndrome so that mechanical ventilation and circulatory support were needed. The patient who was receiving the frontline therapy with VTD also had an elevated procalcitonin value (30.05 ng/ml), suggesting an additional bacterial infection, and this patient died due to acute respiratory failure. In addition, two out of fve patients in our cohort did not show positive IgM or IgG for COVID-19 afer recovery. In summary, our observations showed that COVID-19 infection could be severe especially in NDMM, and also suggested inadequate humoral immune response in MM patients, probably due to secondary immune defciency caused by the treatments or the disease itself. Surprisingly, the MM patients in Wurzburg did not present any signs of severe COVID-19 infection. Other than Wuhan where COVID-19 was reported for the first time, in Europe, the pandemic had already been announced, and in Germany the lock-down came relatively early in comparison to other countries.
ABSTRACT
Toxicities after chimeric antigen receptor T cell (CAR-T) therapy are well known, yet the patient experience during and after CAR-T therapy has not been well described outside of the trial setting. We explored the patient experience after CAR-T therapy to inform the patient-reported outcomes (PRO) measurement approach for the Center for International Blood and Marrow Transplant Research (CIBMTR). We recruited (1) adult patients diagnosed with a hematologic malignancy 14 days to 6 months after receiving a commercial CAR T cell product who had agreed to be contacted by the CIBMTR, (2) caregivers of those patients, and (3) clinical experts in CAR-T therapy. Telephone interviews were conducted following a semistructured guide that included open-ended questions about symptoms and functioning. We conducted a systematic content analysis of each transcript using prespecified codes representing common domains of health, as well as open coding for emergent themes. Forty patients at 29 centers, 15 of their caregivers, and 15 experts from 9 centers participated, representing diversity with respect to age, sex, race/ethnicity, and years in practice (experts). Patients, caregivers, and experts shared largely consistent impressions of the patient experience after CAR-T therapy. Commonly described themes included anxiety, cognitive dysfunction, depression, fatigue, pain, impaired physical function, gastrointestinal symptoms, sexual dysfunction, sleep difficulties, need for support, financial impact, hospitalization, communication with healthcare providers, and the COVID-19 pandemic. Limitations in patients' ability to participate in social roles and activities was the most prevalent theme, found in nearly all interviews. In the setting of CAR-T therapy, a multidimensional approach to PRO measurement is needed that includes physical, mental, and social health, as well as the financial impact of this novel treatment. High-quality existing PRO tools are available to measure these concepts. Results will inform the CIBMTR measurement of PROs after CAR-T therapy and may be applicable to other CAR-T studies that aim to represent patient experiences.
Subject(s)
COVID-19 , Receptors, Chimeric Antigen , Adult , Humans , Pandemics , COVID-19/epidemiology , Patient Reported Outcome Measures , AnxietyABSTRACT
INTRODUCTION: Chimeric antigen receptor T-cells (CAR-T) represent a promising immunotherapeutic approach in the treatment of refractory malignancies, but carry the risk of unique inflammatory toxicities including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). In moderate to severe cases, these toxicities necessitate intensive care unit (ICU) admission for aggressive support and management. DESCRIPTION: A 63-year-old male with a history of pulmonary embolism, prostate cancer with resection and relapsed/refractory IgG-kappa multiple myeloma (diagnosed 4 years earlier and status-post multiple chemotherapy regimens) was admitted for conditioning chemotherapy and CAR-T cell infusion. 1 day post-infusion on the ward, he developed CRS and ICANS, with fever and altered mental status, for which he received tocilizumab, dexamethasone, and anakinra, in addition to empiric antibiotics. He progressed with worsening hypotension and encephalopathy and was admitted to the ICU and required vasopressors, pulse-dose steroids, and siltuximab. A nasal swab was performed to rule out COVID-19, following which he developed persistent epistaxis, requiring packing and, after aspiration of blood, intubation for airway protection. Laboratory data showed anemia and thrombocytopenia, prolonged PT and aPTT, low fibrinogen, and elevated levels of ferritin of 44,124 mg/ mL, D-Dimer of 1.35 mug/mL, interleukin-6 of 8,595 pg/ mL, interleukin-10 of 1,042 pg/mL, tumor necrosis factor- alpha of 103 pg/mL, and interferon-gamma above 244 pg/mL. The patient received numerous red cell and platelet transfusions, aminocaproic acid, cryoprecipitate, and additional packing and thrombin application by ENT before his epistaxis was controlled. Ultimately, he was weaned from vasopressors, extubated after two weeks and transferred out of the ICU, discharged to rehabilitation, and later home. DISCUSSION: Severe CRS can be associated with hemophagocytic lymphohistiocytosis and disseminated intravascular coagulation (DIC), which can lead to lifethreatening bleeding as demonstrated in our patient. Effective and timely treatment of bleeding associated with DIC and severe CRS can be life-saving. It behooves the intensivist to recognize the toxicities of CAR-T as therapeutic applications broaden in the coming years.
ABSTRACT
Background. Determining if a patient with SARS-CoV-2 remains infectious is an infection control challenge in healthcare settings;specially, among critically ill or profoundly immunosuppressed patients. We use an assay that detects minus-strand RNA as a surrogate for actively replicating SARS-CoV-2. We report positive strand-specific assays in relationship to time since admission and describe patients with a detectable strand-specific assay >20 days since admission. Methods. We use a 2-step rRT-PCR specific to the minus strand of the SARS-CoV-2 envelope gene. The strand-specific assay is used to evaluate for infectivity in asymptomatic patients with a positive admission screening or pre-procedural test or if ongoing replication is suspected (critical illness or profound immunosuppression). We retrieved strand-specific test results for patients hospitalized at Stanford Healthcare during August 2020-March 2022. We describe clinical characteristics for patients with a detectable minus strand-specific test >20 days since admission. Results. A total of 774 strand-specific tests were collected from 624 hospitalized patients. A total of 523 patients had only one test (84%) and 101 (16%) had >=2 tests. The test positivity rate varied by time since admission: 19% in tests performed 0-5 days, 28% in 6-10 days, 22% in 11-20 days, and 41% in those >20 days since admission. Among 35 patients tested >20 days since admission, 13 (37%) had >=1 detectable minus strand-specific test. Most were male (n=8, 62%) and mean age was 59. Of 13 patients with a detectable assay, seven (54%) had prolonged viral replication with persistent symptoms and detectable minus strand assays for >20 days from symptom onset. Of these seven patients, four had a transplant (3 lung, 1 liver), 1 ovarian cancer, 1 CAR-T cell therapy, and 1 ESRD without immunosuppression. The remaining eight patients with a detectable assay >20 days since admission had illness onset while hospitalized. Conclusion. Among hospitalized patients with SARS-CoV-2 infection, we found a varying positivity rate according to the timing of testing, possibly reflecting different indications for the test. The strand-specific assay may help assess for infectiousness in profoundly immunocompromised patients.
ABSTRACT
The proceedings contain 1886 papers. The topics discussed include: clinical features and burden of post-acute sequelae of SARS-CoV-2 infection in children and adolescents;demonstration of stable clusters of symptoms in long covid;longitudinal analysis of t cells in COVID-19 survivors with post-acute sequelae of COVID-19 reveals associations between individual symptoms and inflammatory indexes;long-term health outcomes of individuals who are infected with SARS-CoV-2 and develop COVID-19;SARS-CoV-2 infection is associated with decreased reported physical fitness in a us military longitudinal cohort;impact of early post-transplant multidrug-resistant organism detection among renal transplant recipients, 2005-2021;incidence rates of invasive aspergillosis among lung transplant recipients in timeperiods with universal and targeted antifungal prophylaxis - a nationwide cohort study;infectious outcomes of car t-cell therapy: longitudinal follow up and risk stratification;and one-month humoral response following two doses of COVID-19 vaccines in specific populations - anrs0001s COV POPART cohort study.
ABSTRACT
The proceedings contain 15 papers. The topics discussed include: eplet analysis: a tool for risk assessment of de novo donor-specific HLA-DQ-antibodies in patients after lung transplantation;beta-2-microglobulin the neglected edge of HLA class I;temporal loss of HLA heterozygosity in an AML patient prior to stem cell transplantation: does it affect HLA typing strategies?;in-vivo monitoring of CAR-T cell expansion using TaqMan real time PCR;immunogenetic features with SARS-COV-2 breakthrough infections: analyzing 1st/2nd and omicron waves;uterus transplantation from the immunological point of view - experiences from the first center in Germany;follow-up of HLA class I antibodies in neonatal thrombocytopenia;monitoring the in-vivo persistence and expansion of CAR-T cells by TaqMan real-time PCR;and detection of complement-fixing anti-HLA antibodies by a C3D-detecting Luminex technique. is there any additional diagnostic value not available through the use of standard antibody specification at the single antigen level?.