Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine Immunogenicity among Chimeric Antigen Receptor T Cell Therapy Recipients.

Patients receiving chimeric antigen receptor T cell (CAR-T) therapy may have impaired humoral responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinations owing to their underlying hematologic malignancy, prior lines of therapy, and CAR-T-associated hypogammaglobulinemia. Comprehensive data on vaccine immunogenicity in this patient population are limited. A single-center retrospective study of adults receiving CD19 or BCMA-directed CAR-T therapy for B cell non-Hodgkin lymphoma or multiple myeloma was conducted. Patients received at least 2 doses of SARS-CoV-2 vaccination with BNT162b2 or mRNA-1273 or 1 dose of Ad26.COV2.S and had SARS-CoV-2 anti-spike antibody (anti-S IgG) levels measured at least 1 month after the last vaccine dose. Patients were excluded if they received SARS-CoV-2 monoclonal antibody therapy or immunoglobulin within 3 months of the index anti-S titer. The seropositivity rate (assessed by an anti-S assay cutoff of ≥.8 U/mL in the Roche assay) and median anti-S IgG titers were analyzed. Fifty patients were included in the study. The median age was 65 years (interquartile range [IQR], 58 to 70 years), and the majority were male (68%). Thirty-two participants (64%) had a positive antibody response, with a median titer of 138.5 U/mL (IQR, 11.61 to 2541 U/mL). Receipt of ≥3 vaccines was associated with a significantly higher anti-S IgG level. Our study supports current guidelines for SARS-CoV-2 vaccination among recipients of CAR-T therapy and demonstrates that a 3-dose primary series followed by a fourth booster increases antibody levels. However, the relatively low magnitude of titers and low percentage of nonresponders demonstrates that further studies are needed to optimize vaccination timing and determine predictors of vaccine response in this population.

SARS-CoV-2 vaccine immunogenicity among chimeric antigen receptor T-cell therapy recipients

Introduction Patients receiving chimeric antigen receptor T-cell (CAR T-cell) therapy may have impaired humoral responses to SARS-CoV-2 vaccinations due to their underlying hematologic malignancy, prior lines of therapy, and CAR T-cell-associated hypogammaglobulinemia. Comprehensive data on vaccine immunogenicity in this patient population are limited. Methods A single-center retrospective study of adults receiving CD19 or BCMA-directed CAR T-cell therapy for B-cell non-Hodgkin lymphoma or multiple myeloma was conducted. Patients received at least two doses of SARS-CoV-2 vaccinations with BNT162b2, mRNA-1273, or one dose of Ad26.COV2.S and had SARS-CoV-2 anti-spike antibody (anti-S IgG) levels measured at least one month after the last vaccine dose. Patients were excluded if they received SARS-CoV-2 monoclonal antibody therapy or immunoglobulin within three months of the index anti-S titer. The seropositivity rate (assessed by anti-S assay cutoff of ≥0.8 U/mL, Roche assay) and median anti-S IgG titers were analyzed. Results Fifty patients were included in the study. Median age was 65 years (IQR 58–70), and a majority of patients were male (68%). Thirty-two (64%) participants had a positive antibody response, with a median titer of 138.5 U/mL (IQR 11.61–2541). Receiving ≥3 vaccines was associated with a significantly higher anti-S IgG. Conclusion Our study supports current guidelines for SARS-CoV-2 vaccination among CAR T-cell recipients and demonstrates that a three-dose primary series followed by a fourth booster increases antibody levels. However, the relatively low magnitude of titers and percent of non-responders demonstrates that further studies are needed to optimize vaccination timing and determine predictors of vaccine response in this population. Graphical Image, graphical

New Perspectives on Antimicrobial Agents: Remdesivir Treatment for COVID-19.

Remdesivir was recently approved by the Food and Drug Administration for the treatment of hospitalized patients with coronavirus disease 2019 (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 levels of viral RNA. Recent clinical data have demonstrated the clinical activity of remdesivir in terms of faster time to recovery in patients with severe COVID-19 and higher odds of improved clinical status in patients with moderate COVID-19. Here, 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.