ABSTRACT
Objective: To better characterize the intersection of the HIV and SARS-CoV-2 pandemics, including our robust statewide panel of people living with HIV, in the State of Delaware. Methods: We conducted a retrospective descriptive case-series that identified people living with HIV ≥ 18 years old co-infected with SARS-CoV-2 from 1 March 2020 through 9 March 2021 who attended our ambulatory HIV program, through review of testing results, electronic medical records and external clinical records. Results: There were 105 confirmed cases of SARS-CoV-2 infection and 4 attributable deaths from COVID-19 among adult people living with HIV from 1 March 2020 through 9 March 2021. Co-infected patients had very high rates of ART prescription and virologic suppression, with robust CD4 counts. 24/105 (22.9%) SARS-CoV-2 cases were hospitalized due to COVID-19 and had a significant burden of co-morbidities; a vast majority were AIDS-defined. Age, BMI >30 kg/m2, cardiovascular disease, chronic kidney disease and cirrhosis were independently associated with hospitalization by logistic regression. Black patients appeared to have lower rates of testing and higher rates of hospitalization. Additionally, those with history of natural immunity to hepatitis B virus exhibited a low rate of hospitalization. Conclusions: Our cohort data is the first to capture the experience of patients co-infected with HIV/SARS-CoV-2 in Delaware, demonstrating the risk of long-term immunosuppression and burden of comorbid disease, even in the setting of virologic suppression. Although not reaching statistical significance, we identified high rates of resolved hepatitis B virus infection amongst non-hospitalized co-infected patients and postulate there may be an underlying immunologic mechanism to this hypothesis-generating observation. Our results also highlight the role that healthcare disparities have played during these overlapping pandemics. Policy Implications: Pronounced healthcare disparities are known to worsen outcomes in a variety of disease states. From our descriptive data, we suggest continued efforts to address the social determinants of health, especially as they pertain to common chronic comorbid conditions and certain Black communities.
ABSTRACT
L1-cell adhesion molecule (L1-CAM) belongs to a functionally conserved group of neural cell adhesion molecules that are implicated in many aspects of nervous system development. In many neuronal cells the adhesive function of L1-type CAMs induces cellular signaling processes that involves the activation of neuronal tyrosine protein kinases and among other functions regulates axonal growth and guidance. Mutations in the human L1-CAM gene are responsible for a complex neurodevelopmental condition, generally referred to as L1 syndrome. Several pathogenic L1-CAM mutations have been identified in humans that cause L1 syndrome in affected individuals without affecting the level of L1-CAM-mediated homophilic cell adhesion when tested in vitro. In this study, an analysis of two different pathogenic human L1-CAM molecules indicates that although both induce normal L1-CAM-mediated cell aggregation, they are defective in stimulating human epidermal growth factor receptor tyrosine kinase activity in vitro and are unable to rescue L1 loss-of-function conditions in a Drosophila transgenic model in vivo. These results indicate that the L1 syndrome-associated phenotype might involve the disruption of L1-CAM's functions at different levels. Either by reducing or abolishing L1-CAM protein expression, by interfering with L1-CAM's cell surface expression, by reducing L1-CAM's adhesive ability or by impeding further downstream adhesion-dependent signaling processes.
