key: cord-0792715-60zrs4zy
authors: Pieroni, Maurizio; Pieruzzi, Federico; Mignani, Renzo; Graziani, Francesca; Olivotto, Iacopo; Riccio, Eleonora; Ciabatti, Michele; Limongelli, Giuseppe; Manna, Raffaele; Bolognese, Leonardo; Pisani, Antonio
title: Potential resistance to SARS-CoV-2 infection in lysosomal storage disorders
date: 2021-02-18
journal: Clin Kidney J
DOI: 10.1093/ckj/sfab045
sha: bdfa94766dcaad007bfa36ffa5c034303dade49f
doc_id: 792715
cord_uid: 60zrs4zy

nan

On 11 March 2020, the World Health Organization declared the coronavirus disease 2019 (COVID-19) outbreak as a "pandemic". In the following months the spreading of the disease counted in Italy more than 2 millions of infected patients (3.7 % of the population) with more than 80000 COVID-19 related deaths. While vaccines have been developed, based on current knowledge of biology of coronaviruses infection, COVID-19 is empirically treated with antivirals, immunomodulatory and antimalarial drugs, but most of these approaches do not specifically target the cellular mechanisms involved in viral entry and spreading.

It has been demonstrated that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects human and some animal cell lines through the ACE2 receptor, but the endocytic pathway (Table 1) . Interestingly all but one of the infected Fabry patients were females. As Fabry disease is an X-linked disorder, females usually present a mild to moderate residual enzymatic activity leading to a partially preserved lysosomal function. Among the 143 patients receiving enzyme-replacement therapy, most (90%) continued treatment either in hospital (63%) or at home (37%) missing only 1,6% of scheduled therapy infusions. although in some cases being at higher risk of severe COVID-19 complications due to comorbidities or previous kidney transplant (Table 1) . Of note, 35% of the patient population was represented by patients resident in Italian regions Lombardia (21%) and Emilia-Romagna (25%), most affected by COVID-19 pandemic during the first pandemic wave.

Given the prevalence of COVID-19 in Italy, even considering the potential bias of a possible autoquarantine adopted by Fabry patients to avoid the contagion, these observations, together with the biological premises, support the hypothesis that an impaired lysosomal function may preserve patients with lysosomal storage disorders by SARS-CoV-2 infection and by severe clinical manifestations, although affected by a systemic multi-organ disease (6) . A similar hypothesis has been proposed for other lysosomal disorders including Niemann-Pick disease type C (2-3).

Our findings together with mechanistic premises, although not providing robust scientific evidence of a potential resistance to COVID-19 in Fabry disease, are hypothesis-generating and suggest that further studies including in vitro experiments and a more extensive epidemiological evaluation with widespread serological assessment of Fabry patients could confirm this hypothesis and provide new avenues for therapeutic strategies against SARS-CoV2 infection.

None declared. 

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