Fabry disease and COVID-19: international expert recommendations for management based on real-world experience

Abstract

The rapid spread of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 has raised questions about Fabry disease (FD) as an independent risk factor for severe COVID-19 symptoms. Available real-world data on 22 patients from an international group of healthcare providers reveals that most patients with FD experience mild-to-moderate COVID-19 symptoms with an additional complication of Fabry pain crises and transient worsening of kidney function in some cases; however, two patients over the age of 55 years with renal or cardiac disease experienced critical COVID-19 complications. These outcomes support the theory that pre-existent tissue injury and inflammation may predispose patients with more advanced FD to a more severe course of COVID-19, while less advanced FD patients do not appear to be more susceptible than the general population. Given these observed risk factors, it is best to reinforce all recommended safety precautions for individuals with advanced FD. Diagnosis of FD should not preclude providing full therapeutic and organ support as needed for patients with FD and severe or critical COVID-19, although a FD-specific safety profile review should always be conducted prior to initiating COVID-19-specific therapies. Continued specific FD therapy with enzyme replacement therapy, chaperone therapy, dialysis, renin-angiotensin blockers or participation to clinical trials during the pandemic is recommended as FD progression will only increase susceptibility to infection. In order to compile outcome data and inform best practices, an international registry for patients affected by Fabry and infected by COVID-19 should be established.

Keywords: COVID-19; Fabry disease; SARS-CoV-2; chloroquine; enzyme replacement therapy; lysosome; pathogenesis; prevention.

FIGURE 1:

Common features in the pathogenesis and clinical manifestations of FD and COVID-19. Attribution of parts of the image: Wolfdog406 at English Wikipedia; Author: Peter van Driel, NL. Source: https://thenounproject.com/search/? q=kidney&i=524431

FIGURE 2:

Risk of severe or critical COVID-19 in patients with FD. Given the scarcity of Fabry-specific information, this figure has extrapolated knowledge from the general population and the natural history of FD [1, 2]. It shows two scales, depending on whether data are available for specific patients on the extent of target organ injury. When this is known, the ‘Based on target organ injury’ scale should be used. When this is unknown, the ‘Based on age and sex’ scale provides some guidance. TIA, transient ischaemic attack; WML, white matter lesion; LVH, left ventricular hypertrophy.