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Differential COVID-19 Outcomes Across Lysosomal Disorders
Medrxiv : the Preprint Server for Health Sciences
|July 3, 2026
Summary
Individuals with lysosomal disorders (LDs) face higher odds of COVID-19 hospitalization, particularly those with neurodegenerative types. However, LDs do not worsen survival rates once hospitalized, highlighting the need for personalized care.
Area of Science:
- Rare inherited diseases
- Infectious disease epidemiology
- Genetics and genomics
Background:
- Lysosomal disorders (LDs) are rare inherited conditions impacting multiple systems.
- LDs present concerns for severe COVID-19 due to comorbidities.
- SARS-CoV-2's reliance on endolysosomal pathways suggests potential LD protective effects, creating conflicting hypotheses.
Purpose of the Study:
- To investigate the association between lysosomal disorders and COVID-19 outcomes.
- To resolve conflicting hypotheses regarding LDs' impact on SARS-CoV-2 infection.
- To estimate population-level outcomes using large-scale health data.
Main Methods:
- Retrospective cohort study utilizing nationwide U.S. electronic health records (N3C).
- Inclusion of longitudinal records from January 1, 2018, to July 11, 2024.
- Comparison of 5,460 patients with LDs against 10,920 matched controls for COVID-19 outcomes.
Main Results:
- Patients with LDs had 1.86 times higher odds of COVID-19 hospitalization (95% CI: 1.70-2.04).
- Neurodegenerative LDs (e.g., neuronal ceroid lipofuscinosis, metachromatic leukodystrophy) showed significantly elevated hospitalization odds, even after comorbidity adjustment.
- Hospitalized LD patients had comparable one-year survival rates (82.1%) to controls (82.0%).
Conclusions:
- Lysosomal disorders increase COVID-19 hospitalization odds, influenced by comorbidities and specific LD effects.
- The primary excess risk associated with LDs is in the transition to hospitalization.
- Personalized clinical management is recommended for LD patients to mitigate COVID-19 consequences.
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