Allogeneic, off-the-shelf, SARS-CoV-2-specific T cells (ALVR109) for the treatment of COVID-19 in high-risk patients.

Defects in T-cell immunity to SARS-CoV-2 have been linked to an increased risk of severe COVID-19 (even after vaccination), persistent viral shedding and the emergence of more virulent viral variants. To address this T-cell deficit, we sought to prepare and cryopreserve banks of virus-specific T cells, which would be available as a partially HLA-matched, off-the-shelf product for immediate therapeutic use. By interrogating the peripheral blood of healthy convalescent donors, we identified immunodominant and protective T-cell target antigens, and generated and characterized polyclonal virus-specific T-cell lines with activity against multiple clinically important SARS-CoV-2 variants (including 'delta' and 'omicron'). The feasibility of making and safely utilizing such virus-specific T cells clinically was assessed by administering partially HLA-matched, third-party, cryopreserved SARS-CoV-2-specific T cells (ALVR109) in combination with other antiviral agents to four individuals who were hospitalized with COVID-19. This study establishes the feasibility of preparing and delivering off-the-shelf, SARS-CoV-2-directed, virus-specific T cells to patients with COVID-19 and supports the clinical use of these products outside of the profoundly immune compromised setting (ClinicalTrials.gov number, NCT04401410).

Practical aspects of recruitment and retention in clinical trials of rare genetic diseases: the phenylketonuria (PKU) experience.

Bringing treatments for rare genetic diseases to patients requires clinical research. Despite increasing activism from patient support and advocacy groups to increase access to clinical research studies, connecting rare disease patients with the clinical research opportunities that may help them has proven challenging. Chief among these challenges are the low incidence of these diseases resulting in a very small pool of known patients with a particular disease, difficulty of diagnosing rare genetic diseases, logistical issues such as long distances to the nearest treatment center, and substantial disease burden leading to loss of independence. Using clinical studies of phenylketonuria as an example, this paper discusses how, based on the authors' collective experience, partnership among clinicians, patients, study coordinators, genetic counselors, dietitians, industry, patient support groups, and families can help overcome the challenges of recruiting and retaining patients in rare disease clinical trials. We discuss specific methods of collaboration, communication, and education as part of a long-term effort to build a community committed to advancing the medical care of patients with rare genetic diseases. By talking to patients and families regularly about research initiatives and taking steps to make study participation as easy as possible, rare disease clinic staff can help ensure adequate study enrollment and successful study completion.

Anesthetic complications in pediatric patients undergoing cochlear implantation.

OBJECTIVES/HYPOTHESIS: Cochlear implantation (CI) is effective in the treatment of childhood sensorineural hearing loss and is associated with minimal surgical complications. We investigated the incidence of anesthetic complications in young patients undergoing general anesthesia for CI. STUDY DESIGN: Retrospective chart review. METHODS: A retrospective chart review of 123 patients younger than 18 years, who underwent CI between 2007 and 2008, was conducted for identification of intra- and postoperative anesthesia-related complications. The relation of collected variable to the complication events was analyzed using logistic regression. RESULTS: Of the 123 CI procedures, eight patients had nine anesthesia-related complications, yielding a complication rate of 6.5% and included the following: postoperative wheezing/stridor (5 cases), laryngospasm (3 cases), and emesis during inhalational induction (1 case). Divided by age group, 12 patients were <12 months with one complication (8%), 18 patients were between 1 and 2 years with one complication (5.6%), 35 patients were between 2 and 5 years with one complication (3%), 39 patients were between 5 and 12 years with five complications (13%), and 19 patients were older than 12 years with no complication (0%). Logistic regression failed to identify a significant association of any collected variable(s) with the observed complications. The incidence of complications is similar to that previously reported in elderly patients (4.3%) (Pearson χ(2) , P = .523). CONCLUSIONS: General anesthesia is well tolerated by pediatric patients undergoing CI, even under 1 year of age. Significant perioperative complications are primarily respiratory, are usually free of long-term sequelae, and occur with an incidence similar to other reported age groups.