A pilot randomized controlled trial of de novo belatacept-based immunosuppression following anti-thymocyte globulin induction in lung transplantation.

The development of donor-specific antibodies (DSA) after lung transplantation is common and results in adverse outcomes. In kidney transplantation, Belatacept has been associated with a lower incidence of DSA, but experience with Belatacept in lung transplantation is limited. We conducted a two-center pilot randomized controlled trial of de novo immunosuppression with Belatacept after lung transplantation to assess the feasibility of conducting a pivotal trial. Twenty-seven participants were randomized to Control (Tacrolimus, Mycophenolate Mofetil, and prednisone, n = 14) or Belatacept-based immunosuppression (Tacrolimus, Belatacept, and prednisone until day 89 followed by Belatacept, Mycophenolate Mofetil, and prednisone, n = 13). All participants were treated with rabbit anti-thymocyte globulin for induction immunosuppression. We permanently stopped randomization and treatment with Belatacept after three participants in the Belatacept arm died compared to none in the Control arm. Subsequently, two additional participants in the Belatacept arm died for a total of five deaths compared to none in the Control arm (log rank p = .016). We did not detect a significant difference in DSA development, acute cellular rejection, or infection between the two groups. We conclude that the investigational regimen used in this study is associated with increased mortality after lung transplantation.

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.

Utilization of a SARS-CoV-2-positive donor for liver transplantation.

Liver transplantation rates have been negatively affected by the pandemic caused by coronavirus disease 2019 (COVID-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Current practice in the liver transplant community is to avoid utilizing SARS-CoV-2-positive donors for liver transplantation unless there is a compelling reason such as recipient illness severity. In this case, we report the use of a donor who had a positive exposure to and symptom history for COVID-19 and tested positive for SARS-CoV-2 on admission for a liver transplant recipient with primary sclerosing cholangitis and a Model of End-Stage Liver Disease score of 23 with no known COVID-19 exposures. We focus on the decision to accept this particular organ, as well as the discussion with the recipient about the unknowns of disease transmission and risk associated with this donor. The current case argues that transplant programs should begin to consider low-risk donors with positive SARS-CoV-2 testing for recipients who have the potential to benefit from liver transplantation, which may not only be those with the most severe illness.

Highlights of the 33rd annual scientific meeting of the Association of Medical Laboratory Immunologists (AMLI).

The annual meeting of the Association of Medical Laboratory Immunologists (AMLI) was convened virtually over the month of August. Prior to the emergence of the COVID-19 pandemic, AMLI's scientific committee had chosen the following topics as the focus of its 2020 meeting: Histocompatibility Testing and Transplant Immunology; Secondary Immunodeficiency and Immunotherapy Monitoring; ANA Update; and Emerging Infectious Diseases and New Algorithms for Testing. Given the central role of the discipline in the evaluation of the host response to infection, it was apt to add a separate session on antibody testing for SARS-CoV-2 infections to the original program. The current report provides an overview of the subjects discussed in the course of this meeting.

COVID-19 convalescent plasma treatment of moderate and severe cases of SARS-CoV-2 infection: A multicenter interventional study.

OBJECTIVE: To study the effectiveness of COVID-19 convalescent plasma (CCP) therapy for patients with moderate and severe COVID-19 disease. METHODS: This non-randomized prospective cohort study was conducted from May 21 to June 30, 2020, at four major tertiary hospitals in Kuwait. CCP was administered to 135 patients. The control group comprised 233 patients who received standard treatment. All patients (N = 368, median age 54 [range 15-82]) had laboratory-confirmed SARS-CoV-2 infection and either moderate or severe COVID-19 disease. RESULTS: CCP treatment was associated with a higher rate of clinical improvement in patients with moderate or severe disease. Among those with moderate COVID-19 disease, time to clinical improvement was 7 days in the CCP group, versus 8 days in the control group (p = 0·006). For severe COVID-19 disease, time to clinical improvement was 7 days in the CCP group, versus 15.5 days in the control group (p = 0·003). In the adjusted analysis, patients with moderate disease treated with CCP had a significantly lower 30-day mortality rate. Compared to the control group, oxygen saturation improved within 3 days of CCP transfusion, and lymphocyte counts improved from day 7 in patients with moderate COVID-19 disease and day 11 in patients with severe disease. C-reactive protein levels declined throughout the first 14 days after CCP transfusion. None of the CCP patients developed a serious transfusion reaction. CONCLUSIONS: The data show that administration of CCP is a safe treatment option for patients with COVID-19 disease with a favorable outcome in the rate of, and time to, clinical improvement.