key: cord-0971208-0ehzvejf
authors: Ginns, Edward I.; Ryan, Emory; CPMP-BC; Sidransky, Ellen
title: Gaucher disease in the COVID-19 pandemic environment: The good, the bad and the unknown
date: 2021-02-24
journal: Mol Genet Metab
DOI: 10.1016/j.ymgme.2021.02.005
sha: 82e2928a10349cb4486ab00fa295164f1b78f6f7
doc_id: 971208
cord_uid: 0ehzvejf

nan

prototypic lysosomal disorder Gaucher disease, investigators were initially concerned that with SARS-CoV-2 infection, both the lysosomal involvement and the accompanying cytokine storm or dysregulation of inflammatory cytokines might augment Gaucher disease pathophysiology, resulting in increased mortality in infected patients.

During the early phase of the pandemic, a group of Gaucher investigators together identified potential Sars-CoV-2-related management challenges specifically for the Gaucher patient population, providing some suggestions and identifying concerns requiring additional research (Mistry et al., 2020) . These included the need for epidemiological studies, studies regarding the response of patients with Gaucher disease to Sars-CoV-2 and/or its pharmacological interventions and investigations into the impact of Sars-CoV-2 disease on the Gaucher patient community. Moreover, they addressed the challenges to maintaining ongoing requirements for health-sustaining medical treatments for lysosomal diseases, such as regular infusions of costly intravenous enzyme preparations that require access to providers and specialized clinics. There was also at least a theoretical concern that patients with Gaucher disease might be especially at risk if early Sars-CoV-2 treatments like hydroxychloroquine, that could disrupt autophagy needed to maintain homeostasis, were administered. In response to this call to action, both patient groups and physician investigators have attempted to educate and to survey the Gaucher patient population to assess the evolving impact of the Sars-CoV-2 disease and pandemic on their care and health (Elmonem et al., 2020; Fiumara et al., 2020; Riccio, Pieroni, Limoneglli, & Pisani, 2020; Sechi et al., 2020) .

Emerging clinical reports like the study by Fierro et al provide some preliminary reassurance for the Gaucher patient population (Fierro et al., 2021) . Focusing on patients exposed to the virus in the early New York City epicenter, the authors conducted a cross-sectional study in a cohort of 181 patients with Gaucher disease that included 150 adults and 31 children. Among this Gaucher cohort, 71% were chronically being treated with either enzyme replacement or substrate inhibitor therapy. Approximately one third of the adults reported being exposed to SARS-CoV-2, although the majority of these respondents did not develop symptoms. Of 94 patients tested by serology, 18 had positive results. Comorbidities, GBA1 genotype and the type of Gaucher disease therapy did not correlate with the probability of being symptomatic or testing positive.

Major confounding variables affecting the interpretation of this study are related to the rapid evolution of the pandemic and our understanding of SARS-CoV-2. Much of the data in this Gaucher study were collected early in the pandemic and did not include state-of-the-art quantitative testing or diagnostic confirmation. Instead, out of necessity in light of the period when the data was collected, the authors had to rely on a symptom scoring system based on patient reporting. Only 18 of the 181 patients surveyed reported having experienced three or more related symptoms. Fourteen of the 18 had clinical diagnostic testing, with 10 having SARS-CoV-2 positive results, making it more difficult to ascertain the true incidence of infection in this cohort. The Gaucher patient cohort studied was not particularly diverse, being mostly of were no mortalities. As the SARS-CoV-2 pandemic has evolved, additional reassurance against a high rate of infectivity or incidence of Sars-CoV-2-related complications in Gaucher or lysosomal disease patient cohorts has begun to emerge from reports of Sars-CoV-02 cases in patients with lysosomal storage disorders in Europe, (Andrade-Campos et al., 2020), Israel (Zimran, Szer, & Revel-Vilk, 2020) and Morocco (Naima Fdil, 2020). The series from Spain (Andrade-Campos et al., 2020) did describe one SARS-CoV-2 -related death in a 79-year-old patient with Gaucher disease who had various comorbidities including diabetes. As in the general population, it is logical that older age and other comorbidities are also negative prognostic factors for those with Gaucher disease.

It is anticipated that there will be many subsequent reports assessing the impact of the pandemic on specific populations of patients with rare disorders. Now that more quantitative testing and antibody assessment is more accessible, it should be easier to characterize such cohorts with increased precision and by more rigorous standardized clinical research criteria. Such criteria should encompass at least three aspects of disease acquisition and surveillance, including the type and route of clinical diagnostic determination of disease, as well as the presence or absence of Sars-CoV-2 antibodies, the detailed timeline and course of disease, and the impact on the underlying disorder. In order to facilitate comparisons to other cohorts, it is critical that descriptions of the disease course include an accurate timeline of the disease progression, the range of associated symptoms, and disease parameters reflecting the severity of infection.

Reports of the impact of Sars-CoV-2 on the patients' underlying disease should include relevant tracked biomarkers and other associated laboratory values, as well as assessments regarding potential exacerbation of underlying conditions or comorbidities. Rigorous longitudinal studies J o u r n a l P r e -p r o o f might also uncover unanticipated long-term disease sequelae. Such data may better guide treating providers in establishing consensus management guidelines for the remainder of this or future pandemics.

Another fascinating aspect mandating additional investigation is whether the relatively low incidence and relatively benign course of Sars-CoV-2-related complications in patients with Gaucher disease may be opening a window into an unanticipated phenomenon, protective of Sars-CoV-2 infection and/or its complications. There has been preliminary speculation, based on the low number of cases of Sars-CoV-2 among patients with Gaucher disease in Israel and Australia, that the accumulated glycosphingolipids in patients with Gaucher disease might promote immune tolerance rather than enhancing inflammation as a result of exposure to the virus (Zimran et al., 2020) . Similar to what has been hypothesized in Nieman Pick type C, it is possible that the inherent Gaucher disease and abnormal lysosomal environments in general may be an "unfavorable" milieu for SAR-CoV-2 infectivity (Ballout, Sviridov, Bukrinsky, & Remaley, 2020) . Additional carefully collected epidemiological data may help to determine whether the infectivity and disease manifestations in patients with Gaucher disease or other lysosomal storage disorders differs from the general population. If this indeed is true, further study of the factors underlying this observation could lead to novel and improved therapeutic avenues for patients infected with Sars-CoV-2.

Direct and indirect effects of the SARS-CoV-2 pandemic on Gaucher Disease patients in Spain: Time to reconsider home-based therapies?

The lysosome: A potential juncture between SARS-CoV-2 infectivity and Niemann-Pick disease type C, with therapeutic implications

The impact of COVID-19 pandemic on the diagnosis and management of inborn errors of metabolism: A global perspective

Gaucher disease and SARS-CoV-2 infection: Experience from 181 patients

COVID-19 Pandemic Outbreak and its Psychological Impact on Patients with Rare Lysosomal Diseases

beta-Coronaviruses Use Lysosomes for Egress Instead of the Biosynthetic Secretory Pathway

Gaucher disease and SARS-CoV-2 infection: Emerging management challenges

The Lysosomal Storage Diseases: A Promising Axis for future COVID-19 Future Therapies

Impact of COVID-19 pandemic on patients with Fabry disease: An Italian experience

Impact of COVID-19 related healthcare crisis on treatments for patients with lysosomal storage disorders, the first Italian experience

Impact of Gaucher disease on COVID-19