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Background and objectives The optimal iron hypothesis (OIH) posits that risk for infection is lowest at a mild level of iron deficiency. The extent to which this protection results from arms race dynamics in the evolution of iron acquisition and sequestration mechanisms is unclear. We evaluated the OIH with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an emerging infectious agent. Methodology We tested 304 healthcare workers at baseline for iron deficiency (zinc protoporphyrin:heme), anemia (hemoglobin), and SARS-CoV-2 (salivary PCR), and followed them for ~3 months with biweekly SARS-CoV-2 tests. We fit logistic regression models based on Akaike Information Criterion. Results Adequate data were available for 199 participants. Iron replete (OR: 2.87, 95% CI: 0.85, 9.75) and anemia (OR: 2.48; 95% CI: 0.82, 7.85) were associated with higher risk for SARS-CoV-2 infection after control for covariates. Logistic regression and Cox proportional hazards models of the SARS-CoV-2 outcome were similar. Anemia (OR: 1.81; 95% CI: 0.88, 3.71) was associated with respiratory symptoms regardless of SARS-CoV-2 infection. Conclusions and implications These findings provide partial support for the OIH: SARS-CoV-2 infection risk was elevated at the high end of the range of iron availability; however, the elevated risk among those with anemia was not, as expected, specific to severe iron deficiency. Narrowly, for COVID-19 epidemiology, these findings accord with evidence that SARS-CoV-2's ability to establish infection is enhanced by access to iron. More broadly, these findings suggest that the OIH does not hinge on a long history of evolutionary arms race dynamics in access to host iron. [ABSTRACT FROM AUTHOR]

Lysosomal storage diseases (LSDs) encompass a group of rare inherited metabolic disorders characterized by the accumulation of undegraded substrates within lysosomes, leading to multisystemic manifestations, including profound neurological involvement. This article provides a concise overview of the neurological manifestations of LSDs, with a focus on central nervous system (CNS) involvement and treatment strategies. While the paper intricacies of each LSD subtype and its associated CNS manifestations, it aims to provide a summary of the essential findings and implications. The neurological manifestations of LSDs encompass a spectrum of symptoms, including cognitive impairment, motor dysfunction, seizures, and sensory deficits, which significantly impact patients' quality of life and pose therapeutic challenges. Current treatment strategies primarily aim to alleviate symptoms and slow disease progression, with limited success in reversing established neurological damage. Enzyme replacement therapy, substrate reduction therapy, and emerging gene therapies hold promise for addressing CNS involvement in LSDs. However, challenges such as blood-brain barrier penetration and long-term efficacy remain. In addition to discussing treatment modalities, this article highlights the importance of early diagnosis, multidisciplinary care, and patient advocacy in optimizing outcomes for individuals affected by LSDs. Ethical considerations are also addressed, including equitable access to emerging treatments and integrating personalized medicine approaches. Overall, this article underscores the complex interplay between genetics, neuroscience, and clinical care in understanding and managing the neurological manifestations of LSDs while emphasizing the need for continued research and collaboration to advance therapeutic interventions and improve patient outcomes., Competing Interests: The views and opinions expressed in this paper are solely those of the authors and do not necessarily reflect any institution or organization’s official policy or position. The authors declare no conflicts of interest or financial disclosures related to this research.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)