Bioinformatic analysis of SMN1–ACE/ACE2 interactions hinted at a potential protective effect of spinal muscular atrophy against COVID-19-induced lung injury

Abstract

Patients with spinal muscular atrophy (SMA) are susceptible to the respiratory infections and might be at a heightened risk of poor clinical outcomes upon contracting coronavirus disease 2019 (COVID-19). In the face of the COVID-19 pandemic, the potential associations of SMA with the susceptibility to and prognostication of COVID-19 need to be clarified. We documented an SMA case who contracted COVID-19 but only developed mild-to-moderate clinical and radiological manifestations of pneumonia, which were relieved by a combined antiviral and supportive treatment. We then reviewed a cohort of patients with SMA who had been living in the Hubei province since November 2019, among which the only 1 out of 56 was diagnosed with COVID-19 (1.79%, 1/56). Bioinformatic analysis was carried out to delineate the potential genetic crosstalk between SMN1 (mutation of which leads to SMA) and COVID-19/lung injury-associated pathways. Protein-protein interaction analysis by STRING suggested that loss-of-function of SMN1 might modulate COVID-19 pathogenesis through CFTR, CXCL8, TNF and ACE. Expression quantitative trait loci analysis also revealed a link between SMN1 and ACE2, despite low-confidence protein-protein interactions as suggested by STRING. This bioinformatic analysis could give hint on why SMA might not necessarily lead to poor outcomes in patients with COVID-19.

Psychosocial impact of the COVID-19 pandemic and shielding in adults and children with early-onset neuromuscular and neurological disorders and their families: a mixed-methods study

“…This study, our clinical experience, and the limited available body of evidence suggest that COVID-19, particularly with severe outcomes, was uncommon in patients with NMD during and after the first pandemic wave: in a Spanish paediatric NMD registry, 29 individuals tested positive for SARS-CoV-2 to November 2020: 10% were hospitalised and 3% were admitted to ICU. 13 In addition, in a cohort of 56 patients with spinal muscular atrophy in Hubei province, only one developed COVID-19, 21 and in a small study of 7 patients with Duchenne muscular dystrophy and COVID-19 infection confirmed on PCR testing, no patients developed moderate–severe disease despite complications including cardiomyopathy and respiratory failure. 12 …”

Impact of the Renin-Angiotensin System on the Pathogeny and Pharmacotherapeutics of Neurodegenerative Diseases

“…Other studies have demonstrated an interaction between the survival motor neuron 1 (SMN1) gene and the loss of function of the SMN protein, which is involved in ribonucleoprotein synthesis, intra- and intercellular trafficking of vesicles and organelles, and ACE/ACE2 expression [ 182 , 183 ].…”

A Comprehensive Review of Neuromuscular Manifestations of COVID-19 and Management of Pre-Existing Neuromuscular Disorders in Children

“…The authors of the study concluded that the protective role of young age seemed to outweigh the risk factors associated with having a neuromuscular condition [39]. Interestingly, a bioinformatics analysis investigating the possible interaction between the SMN gene and ACE2, a receptor involved in SARS-CoV-2 entry into the cell, suggests that SMN1 deficiency may modulate ACE2 levels and therefore have a direct impact on the pathogenesis of COVID-19 [69].…”