Lysosomal storage diseases increase COVID-19 infection severity

Lysosomal storage diseases (LSDs) are a group of rare inherited conditions that cause toxic buildup of lipids, glycoproteins, and other substrates in cells due to dysfunctional lysosomal enzymes. LSDs are classified by which substrate accumulates, for example, sphingolipidoses, leading to a range of clinical presentations. Some diseases, like neuronal ceroid lipofuscinosis, affect the nervous system; others, like mucopolysaccharidosis, impact multiple organ systems.

Previous studies proposed LSDs might offer protection against COVID-19 infection due to inhibition of SARS-CoV-2 lysosomal viral shedding. However, an observational study analyzing these claims still needs to be completed. Here, we introduce an electronic health record (EHR) retrospective cohort study in the National COVID Cohort Collaborative (N3C). Our analysis found no evidence of LSDs being protective against severe COVID-19 infection.

Future studies can validate our results; in-vitro studies could simulate an LSD in cells to test the disruption of SARS-CoV-2 viral egress and observational studies in the All of Us program could test our regression model on patients with richer phenotyping data. Overall, our results indicate lysosomal storage diseases increase COVID-19 infection severity and validate the use of large EHR datasets such as the N3C as testbeds for basic science hypotheses.