Tumors harbor multiple genetic alterations, yet treatment decisions are commonly based on single biomarkers, leading to underutilization of genomic information by comprehensive molecular tests, uncertainty in clinical practice, and frequent treatment failures. Although molecular tumor boards can assist personalized treatments, this process is not scalable or standardized, resulting in highly discordant recommendations. Validated digital solutions for personalized decision support are highly needed. The Digital Drug Assignment (DDA) system is a computational reasoning model that scores treatment options based on the full tumor genomic data. We retrospectively analyzed data of 111 lung cancer patients and found that high-score MTAs (1000≦DDA score) provided significant clinical benefit over other treatments, in terms of ORR, PFS, and OS. These results demonstrate that the DDA system is predictive of relative benefit of the various agents used in lung cancer care. Digital drug assignment can potentially address challenges with complex molecular profiles in routine clinical settings.

Advanced age, comorbidities, and immunocompromised states remain major risk factors for severe or persistent COVID-19 despite vaccination and antivirals, underscoring the need for innovative treatments such as adoptive T-cell therapy (ATT). In this prospective single-center study, we evaluated the safety, feasibility, and efficacy of two ATT approaches in immunocompromised patients with high-risk or persistent SARS-CoV-2 infection: interferon-γ cytokine capture system virus-specific T cells (IFN-γ CCS VST, n = 12; median age 59) and CD45RA + T-cell depleted donor lymphocyte infusion (CD45RA⁺ TCD DLI, n = 11; median age 46). Most patients (73.9%) had undergone prior hematopoietic stem cell transplantation (HSCT). Both treatments were safe, with no adverse events observed. One-year overall survival (OS) did not differ significantly between groups (p = 0.8907 overall; p = 0.5907 in HSCT recipients). However, CD45RA⁺ TCD DLI showed a trend toward improved 1-year COVID-19–free survival (p = 0.058) and significantly better survival among HSCT recipients (p = 0.0362). Viral clearance was achieved in most patients (90.9% vs. 83.3%). Immunomonitoring revealed distinct immune dynamics: between weeks 5–8, IFN-γ CCS VST promoted naïve T-cell expansion with broad cytokine elevation, while CD45RA⁺ TCD DLI expanded memory T cells with a more restricted cytokine profile. IFN-γ CCS VST also elicited stronger in vivo expansion of SARS-CoV-2–specific CD4 + and CD8 + T cells. In summary, both ATT approaches are safe and effective in immunocompromised patients with persistent COVID-19. CD45RA⁺ TCD DLI, which can be generated from convalescent donors as an off-the-shelf product, may provide a practical strategy for pandemic preparedness and treatment of vulnerable patients with immune senescence.