ALVR109, an off-the-shelf partially HLA matched SARS-CoV-2-specific T cell therapy, to treat refractory severe COVID-19 pneumonia in a heart transplant patient: Case report.

An unvaccinated adult male heart transplant recipient patient with recalcitrant COVID-19 due to SARS-CoV-2 delta variant with rising nasopharyngeal quantitative viral load was successfully treated with ALVR109, an off-the-shelf SARS-CoV-2-specific T cell therapy. Background immunosuppression included 0.1 mg/kg prednisone, tacrolimus, and mycophenolate mofetil 1 gm twice daily for historical antibody-mediated rejection. Prior therapies included remdesivir, corticosteroids, and tocilizumab, with requirement for high-flow nasal oxygen. Lack of clinical improvement and acutely rising nasopharyngeal viral RNA more than 3 weeks into illness prompted the request of ALVR109 through an emergency IND. The day following the first ALVR109 infusion, the patient's nasopharyngeal SARS-CoV-2 RNA declined from 7.43 to 5.02 log10 RNA copies/ml. On post-infusion day 4, the patient transitioned to low-flow oxygen. Two subsequent infusions of ALVR109 were administered 10 and 26 days after the first; nasopharyngeal SARS-CoV-2 RNA became undetectable on Day 11, and he was discharged the following day on low-flow oxygen 5 weeks after the initial diagnosis of COVID-19. The clinical and virologic improvements observed in this patient following administration of ALVR109 suggest a potential benefit that warrants further exploration in clinical trials.

COVID-19 Adaptations in the Care of Patients with Opioid Use Disorder: a Survey of California Primary Care Clinics.

BACKGROUND: With the onset of the COVID-19 crisis, many federal agencies relaxed policies regulating opioid use disorder treatment. The impact of these changes has been minimally documented. The abrupt nature of these shifts provides a naturalistic opportunity to examine adaptations for opioid use disorder treatment in primary care. OBJECTIVE: To examine change in medical and behavioral health appointment frequency, visit type, and management of patients with opioid use disorder in response to COVID-19. DESIGN: A 14-item survey queried primary care practices that were enrolled in a medications for opioid use disorder statewide expansion project. Survey content focused on changes in service delivery because of COVID-19. The survey was open for 18 days. PARTICIPANTS: We surveyed 338 clinicians from 57 primary care clinics located in California, including federally qualified health centers and look-alikes. A representative from all 57 clinics (100%) and 118 staff (34.8% of all staff clinicians) participated in the survey. MAIN MEASURES: The survey consisted of seven dimensions of practice: medical visits, behavioral health visits, medication management, urine drug screenings, workflow, perceived patient demand, and staff experience. KEY RESULTS: A total of 52 of 57 (91.2%) primary care clinics reported practice adaptations in response to COVID-19 regulatory changes. Many clinics indicated that both medical (40.4%) and behavioral health visits (53.8%) were now exclusively virtual. Two-thirds (65.4%) of clinics reported increased duration of buprenorphine prescriptions and reduced urine drug screenings (67.3%). The majority (56.1%) of clinics experienced an increase in patient demand for behavioral health services. Over half (56.2%) of clinics described having an easier or unchanged experience retaining patients in care. CONCLUSIONS: Many adaptations in the primary care approach to patients with opioid use disorder may be temporary reactions to COVID-19. Further evaluation of the impact of these adaptations on patient outcomes is needed to determine whether changes should be maintained post-COVID-19.