Mortality Risk Among Patients Hospitalized Primarily for COVID-19 During the Omicron and Delta Variant Pandemic Periods - United States, April 2020-June 2022.

The risk for COVID-19-associated mortality increases with age, disability, and underlying medical conditions (1). Early in the emergence of the Omicron variant of SARS-CoV-2, the virus that causes COVID-19, mortality among hospitalized COVID-19 patients was lower than that during previous pandemic peaks (2-5), and some health authorities reported that a substantial proportion of COVID-19 hospitalizations were not primarily for COVID-19-related illness,* which might account for the lower mortality among hospitalized patients. Using a large hospital administrative database, CDC assessed in-hospital mortality risk overall and by demographic and clinical characteristics during the Delta (July-October 2021), early Omicron (January-March 2022), and later Omicron (April-June 2022) variant periods† among patients hospitalized primarily for COVID-19. Model-estimated adjusted mortality risk differences (aMRDs) (measures of absolute risk) and adjusted mortality risk ratios (aMRRs) (measures of relative risk) for in-hospital death were calculated comparing the early and later Omicron periods with the Delta period. Crude mortality risk (cMR) (deaths per 100 patients hospitalized primarily for COVID-19) was lower during the early Omicron (13.1) and later Omicron (4.9) periods than during the Delta (15.1) period (p<0.001). Adjusted mortality risk was lower during the Omicron periods than during the Delta period for patients aged ≥18 years, males and females, all racial and ethnic groups, persons with and without disabilities, and those with one or more underlying medical conditions, as indicated by significant aMRDs and aMRRs (p<0.05). During the later Omicron period, 81.9% of in-hospital deaths occurred among adults aged ≥65 years and 73.4% occurred among persons with three or more underlying medical conditions. Vaccination, early treatment, and appropriate nonpharmaceutical interventions remain important public health priorities for preventing COVID-19 deaths, especially among persons most at risk.

Environmental overlap influences goal-oriented coding of spatial sequences differently along the long-axis of hippocampus.

When navigating our world we often first plan or retrieve a route to our goal, avoiding alternative paths to other destinations. Inspired by computational and animal models, we have recently demonstrated evidence that the human hippocampus supports prospective spatial coding, mediated by interactions with the prefrontal cortex. But the relationship between such signals and the need to discriminate possible routes based on their goal remains unclear. In the current study, we combined human fMRI, multi-voxel pattern analysis, and an established paradigm for contrasting memories of nonoverlapping routes with those of routes that cross paths and must be disambiguated. By classifying goal-oriented representations at the initiation of a navigational route, we demonstrate that environmental overlap modulates goal-oriented representations in the hippocampus. This modulation manifest through representational shifts from posterior to anterior components of the right hippocampus. Moreover, declines in goal-oriented decoding due to overlapping memories were predicted by the strength of the alternative memory, suggesting co-expression and competition between alternatives in the hippocampus during prospective thought. Moreover, exploratory whole-brain analyses revealed that a region of frontopolar cortex, which we have previously tied to prospective route planning, represented goal-states in new overlapping routes. Together, our findings provide insight into the influences of contextual overlap on the long-axis of the hippocampus and a broader memory and planning network that we have long-associated with such navigation tasks.

Environmental overlap and individual encoding strategy modulate memory interference in spatial navigation.

There has been great interest in how previously acquired knowledge interacts with newly learned knowledge and how prior knowledge facilitates semantic and "schema" learning. In studies of episodic memory, it is broadly associated with interference. Very few studies have examined the balance between interference and facilitation over the course of temporally-extended events and its individual differences. In the present study, we recruited 120 participants for a two-day spatial navigation experiment, wherein participants on Day 2 navigated virtual routes that were learned from Day 1 while also learning new routes. Critically, half of the new mazes overlapped with the old mazes, while the other half did not, enabling us to examine interference and facilitation in the context of spatial episodic learning. Overall, we found that navigation performance in new mazes that overlapped with previously-learned routes was significantly worse than the new non-overlapping mazes, suggesting proactive interference. Interestingly, we found memory facilitation for new routes in familiar environments in locations where there was no direct overlap with the previously-learned routes. Cognitive map accuracy positively correlated with proactive interference. Moreover, participants with high self-report spatial ability and/or a preference for place-based learning experienced more proactive interference. Taken together, our results show that 1) both memory interference and facilitation can co-occur as a function of prior learning, 2) proactive interference within a route varied as a function of the degree of overlap with old knowledge, and 3) individual differences in spatial ability and strategy can modulate proactive interference.

The Complex Nature of Hippocampal-Striatal Interactions in Spatial Navigation.

Decades of research have established the importance of the hippocampus for episodic and spatial memory. In spatial navigation tasks, the role of the hippocampus has been classically juxtaposed with the role of the dorsal striatum, the latter of which has been characterized as a system important for implementing stimulus-response and action-outcome associations. In many neuroimaging paradigms, this has been explored through contrasting way finding and route-following behavior. The distinction between the contributions of the hippocampus and striatum to spatial navigation has been supported by extensive literature. Convergent research has also underscored the fact that these different memory systems can interact in dynamic ways and contribute to a broad range of navigational scenarios. For example, although familiar routes may often be navigable based on stimulus-response associations, hippocampal episodic memory mechanisms can also contribute to egocentric route-oriented memory, enabling recall of context-dependent sequences of landmarks or the actions to be made at decision points. Additionally, the literature has stressed the importance of subdividing the striatum into functional gradients-with more ventral and medial components being important for the behavioral expression of hippocampal-dependent spatial memories. More research is needed to reveal how networks involving these regions process and respond to dynamic changes in memory and control demands over the course of navigational events. In this Perspective article, we suggest that a critical direction for navigation research is to further characterize how hippocampal and striatal subdivisions interact in different navigational contexts.