Remdesivir was recently approved by the Food and Drug Administration for the treatment of hospitalized patients with COVID-19. Remdesivir is the prodrug of an adenosine analogue that inhibits viral replication of several RNA virus families including Coronaviridae. Preclinical data in animal models of coronavirus diseases, including COVID-19, have demonstrated that early treatment with remdesivir leads to improved survival, decreased lung injury and decreased quantification of viral RNA. Recent clinical data have demonstrated the clinical activity of remdesivir in terms faster time to recovery in patients with severe COVID-19 and higher odds of improved clinical status in patients with moderate COVID-19. Clinical trials published to date are presented and appraised. Remdesivir's potential benefits and its favorable adverse event profile make it an option for the treatment of COVID-19. This article examines the available literature describing remdesivir's pharmacology, pharmacokinetics, and preclinical and clinical data.

CAR T-cell (CAR-T) therapy has revolutionized the treatment of hematologic malignancies, though its use may be complicated by toxicities including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and infections. Invasive fungal disease (IFD) has been reported following CAR-T therapy, but the incidence in the absence of antifungal prophylaxis is unknown. Optimal screening, prophylaxis, and preemptive treatment strategies are widely debated. We performed a single-center retrospective study of 280 adults receiving CD19 CAR-T therapy for Non-Hodgkin's lymphoma (NHL) between December 2017 and September 2021 (n=280). Patients did not receive routine anti-yeast or mold prophylaxis. Proven and probable IFD was identified between day of cell infusion and last follow up. Cumulative Incidence Functions were calculated at 100 days and 18 months based on time to IFD using dates of IFD-free death, initiation of salvage treatment following relapse, and hematopoietic cell transplantation as competing risks. Eight patients (2.9%) developed IFD, including 3 Pneumocystis jirovecii pneumonia (PJP), 3 invasive mold infections (IMIs), and 2 invasive yeast infections (IYIs). Five infections (3 IMI; 2 IYI) occurred prior to day 100 and the 100-day cumulative incidence of IFD accounting for competing risks was 1.8% (95% CI 0.8 - 4.4%). Amongst the 280 patients, many developed early toxicity including CRS (85%) and ICANS (55%). Late toxicities after day 30 including grade 3/4 neutropenia (41%), hypogammaglobulinemia (35%), and low CD4 T-cell count (20%) were common. IFD was rare amongst patients who received CD19 CAR-T therapy for NHL in the absence of routine antifungal prophylaxis despite frequent toxicities including CRS, ICANS, and late neutropenia. This study suggests that in settings with low institutional rates of IFD, routine antifungal prophylaxis may not be indicated.

No abstract