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Background/Objectives: Pediatric patients with autism spectrum disorder (ASD) face unique challenges, especially amongst individuals from historically minoritized racial groups. ASD has also been associated with an increased mortality from COVID-19. This study aims to explore the differences in sociodemographic factors and health outcomes (as measured by length of stay) amongst hospitalized pediatric patients with COVID-19 infections and a diagnosis of ASD compared to individuals with a COVID-19 infection alone; Methods: We performed a retrospective cohort study examining pediatric patients (ages birth to 21) who were hospitalized with a diagnosis of ASD and COVID-19 compared to patients with a diagnosis of COVID-19 alone between January 2019 and June 2023 using Epic Systems Corporation’s Cosmos, a de-identified dataset aggregated from electronic health record data. We examined differences in demographic factors and length of stay (LOS) between groups by utilizing chi-square and Wilcoxon rank sum tests. Multiple logistic regression models were utilized to assess the association between length of stay and diagnosis; Results: A total of 21,708 distinct pediatric patients with a diagnosis of ASD and COVID-19 or COVID-19 alone were included in the analytical dataset. Patients with ASD and COVID-19, compared to patients with COVID-19 alone, had a higher proportion of individuals identifying as male and White. Patients with COVID-19 alone, compared to individuals with ASD and COVID-19, had higher proportions of individuals identifying as Black or African American. Higher proportions of individuals with ASD and COVID-19 had public insurance, compared to individuals with COVID-19 alone. Having a diagnosis of ASD and COVID, after controlling for covariates, was associated with higher odds of having a length of stay greater than the three days (cutoff value determined by the median LOS of three days) compared to having a diagnosis of COVID alone (aOR 1.19, 95% CI 1.04–1.35); Conclusions: Our study highlights the health disparities experienced during hospitalizations by pediatric patients with ASD and COVID-19. Further studies should address barriers and support health outcomes for pediatric patients with ASD.

The democratization of genomic technologies has revealed profound sex biases in expression patterns in every adult tissue, even in organs with no conspicuous differences, such as the heart. With the increasing awareness of the disparities in cardiac pathophysiology between males and females, there are exciting opportunities to explore how sex differences in the heart are established developmentally. Although sexual dimorphism is traditionally attributed to hormonal influence, expression and epigenetic sex biases observed in early cardiac development can only be accounted for by the difference in sex chromosome composition, i.e., XX in females and XY in males. In fact, genes linked to the X and Y chromosomes, many of which encode regulatory factors, are expressed in cardiac progenitor cells and at every subsequent developmental stage. The effect of the sex chromosome composition may explain why many congenital heart defects originating before gonad formation exhibit sex biases in presentation, mortality, and morbidity. Some transcriptional and epigenetic sex biases established soon after fertilization persist in cardiac lineages, suggesting that early epigenetic events are perpetuated beyond early embryogenesis. Importantly, when sex hormones begin to circulate, they encounter a cardiac genome that is already functionally distinct between the sexes. Although there is a wealth of knowledge on the effects of sex hormones on cardiac function, we propose that sex chromosome-linked genes and their downstream targets also contribute to the differences between male and female hearts. Moreover, identifying how hormones influence sex chromosome effects, whether antagonistically or synergistically, will enhance our understanding of how sex disparities are established. We also explore the possibility that sexual dimorphism of the developing heart predicts sex-specific responses to environmental signals and foreshadows sex-biased health-related outcomes after birth.