Deaths Due to COVID-19 in Patients With Cancer During Different Waves of the Pandemic in the US.

Importance: With the ongoing relaxation of guidelines to prevent COVID-19 transmission, particularly in hospital settings, medically vulnerable groups, such as patients with cancer, may experience a disparate burden of COVID-19 mortality compared with the general population. Objective: To evaluate COVID-19 mortality among US patients with cancer compared with the general US population during different waves of the pandemic. Design, Setting, and Participants: This cross-sectional study used data from the Center for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research database to examine COVID-19 mortality among US patients with cancer and the general population from March 1, 2020, to May 31, 2022. The number of deaths due to COVID-19 during the 2021 to 2022 winter Omicron surge was compared with deaths during the preceding year's COVID-19 winter surge (when the wild-type SARS-CoV-2 variant was predominant) using mortality ratios. Data were analyzed from July 21 through August 31, 2022. Exposures: Pandemic wave during which the wild-type variant (December 2020 to February 2021), Delta variant (July 2021 to November 2021), or Omicron variant (December 2021 to February 2022) was predominant. Main Outcomes and Measures: Number of COVID-19 deaths per month. Results: The sample included 34 350 patients with cancer (14 498 females [42.2%] and 19 852 males [57.8%]) and 628 156 members of the general public (276 878 females [44.1%] and 351 278 males [55.9%]) who died from COVID-19 when the wild-type (December 2020-February 2021), Delta (July 2021-November 2021), and winter Omicron (December 2021-February 2022) variants were predominant. Among patients with cancer, the greatest number of COVID-19 deaths per month occurred during the winter Omicron period (n = 5958): at the peak of the winter Omicron period, there were 18% more deaths compared with the peak of the wild-type period. In contrast, among the general public, the greatest number of COVID-19 deaths per month occurred during the wild-type period (n = 105 327), and at the peak of the winter Omicron period, there were 21% fewer COVID-19 deaths compared with the peak of the wild-type period. In subgroup analyses by cancer site, COVID-19 mortality increased the most, by 38%, among patients with lymphoma during the winter Omicron period vs the wild-type period. Conclusions and Relevance: Findings of this cross-sectional study suggest that patients with cancer had a disparate burden of COVID-19 mortality during the winter Omicron wave compared with the general US population. With the emergence of new, immune-evasive SARS-CoV-2 variants, many of which are anticipated to be resistant to monoclonal antibody treatments, strategies to prevent COVID-19 transmission should remain a high priority.

Endothelial Cyp26b1 restrains murine heart valve growth during development.

Endothelial cells (ECs) are critical to proper heart valve development, directly contributing to the mesenchyme of the cardiac cushions, which progressively transform into mature valves. To date, investigators have lacked sufficient markers of valve ECs to evaluate their contributions during valve morphogenesis fully. As a result, it has been unclear whether the well-characterized regional differentiation of valves correlates with any endothelial domains in the heart. Furthermore, it has been difficult to ascertain whether endothelial heterogeneity in the heart influences underlying mesenchymal zones in an angiocrine manner. To identify regionally expressed EC genes in the heart valves, we screened publicly available databases and assembled a toolkit of endothelial-enriched genes. We identified Cyp26b1 as one of many endothelial enriched genes found to be expressed in the endocardium of the developing cushions and valves. Here, we show that Cyp26b1 is required for normal heart valve development. Genetic ablation of Cyp26b1 in mouse embryos leads to abnormally thickened aortic valve leaflets, which is due in part to increased endothelial and mesenchymal cell proliferation in the remodeling valves. In addition, Cyp26b1 mutant hearts display ventricular septal defects (VSDs) in a portion of null embryos. We show that loss of Cyp26b1 results in upregulation of retinoic acid (RA) target genes, supporting the observation that Cyp26b1 has RA-dependent roles. Together, this work identifies a novel role for Cyp26b1 in heart valve morphogenesis and points to a role of RA in this process. Understanding the spatiotemporal expression dynamics of cardiac EC genes will pave the way for investigation of both normal and dysfunctional heart valve development.