Clinical and Radiological Deterioration in a Case of Creutzfeldt–Jakob Disease following SARS-CoV-2 Infection: Hints to Accelerated Age-Dependent Neurodegeneration

Abstract

Systemic inflammation and the host immune responses associated with certain viral infections may accelerate the rate of neurodegeneration in patients with Creutzfeldt–Jakob disease (CJD), a rare, transmissible neurodegenerative disease. However, the effects of the newly emerged SARS-CoV-2 infection on the pathogenesis of CJD are unknown. In this study, we describe the case of an elderly female patient with sporadic CJD that exhibited clinical deterioration with the emergence of seizures and radiological neurodegenerative progression following an infection with SARS-CoV-2 and severe COVID-19. Despite efforts to control the progression of the disease, a dismal outcome ensued. This report further evidences the age-dependent neurological effects of SARS-CoV-2 infection and proposes a vulnerability to CJD and increased CJD progression following COVID-19.

Effect of Fucoidan on the Mitochondrial Membrane Potential (ΔΨm) of Leukocytes from Patients with Active COVID-19 and Subjects That Recovered from SARS-CoV-2 Infection

“…In the case of patients recovering from acute SARS-CoV-2 infection, they may develop long-term sequelae (pulmonary injury, inflammatory, neurodegenerative, etc.) caused by mitochondrial dysfunction [27][28][29][30][31][32][33][34]. Therefore, the search for alternative treatments is essential to reintegrate cellular homeostasis in SARS-CoV-2 infected subjects.…”

SARS-CoV-2 Invasion and Pathological Links to Prion Disease

“…Because of their unusual and atypical infective nature, PrDs and prion neurobiology have been intensively studied in considerable detail [ 19 , 20 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 ]. The brain- and CNS-abundant cellular prion sialoglycoprotein PrP c monomer consists of a constitutively expressed ~209-amino-acid, ~200 kDa glycosylated polypeptide containing a predominant internal α-helical region.…”

“…Typically, activated microglia accumulate around PrP sc aggregates and release cytokines such as IL-1β that play important roles in the inflammatory pathogenesis of PrD and the cytokine storm syndrome [ 19 , 20 , 47 , 51 , 59 ]. PrDs such as CJD appear to be initiated and driven by the accumulation of abnormally folded, protease-resistant isoforms of PrP sc , which leads to neuropathologic spongiform changes that coincide with neuroinflammation, microglial activation, and an irreversible and fatal pro-inflammatory neurodegeneration [ 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 ].…”

“…It is of a rather serious current concern that in association with SARS-CoV-2 infection, there are emerging case reports of COVID-19 patients developing PrD and/or are experiencing an acceleration or exacerbation in the development or propagation of this pre-existing, fatal, preclinical and/or already-established, age-dependent neurodegenerative disorder [ 48 , 53 , 56 ]. A number of interesting and fascinating associations have recently been made between SARS-CoV-2 infection, prion neurobiology, and PrD: (i) both SARS-CoV-2-mediated neurological complications and PrDs represent variably transmissible, pro-inflammatory diseases of the brain and CNS, involve a significant disruption in cytokine signaling patterns that is sometimes referred to as the cytokine storm syndrome , and are neurodegenerative, consistently neuro-disruptive, and/or lethal neurological disorders [ 58 , 59 ]; (ii) several recent reports link multiple aspects of the ‘S1’ spike protein structure and function, immunology, and epidemiology with PrD, prion-like spread, and prion neurobiology [ 44 , 48 , 60 , 61 ]; (iii) ‘S1’ spike proteins contain self-associating ‘prion-like’ domains [ 43 , 44 , 48 ]; (iv) ‘S1’ spike proteins are either bound to the SARS-CoV-2 lipoprotein envelope or are in free monomeric form and these domains also appear to play a role in systemic amyloidogenesis in aggregate ‘seeding’ and/or ‘spreading’, which in turn supports systemic inflammation and the formation of pathogenic pro-inflammatory lesions in the brain and CNS that sustain pro-inflammatory neurodegeneration, neuronal cell death, and/or PrD-type change [ 3 , 44 , 48 , 59 , 60 ]; (v) the SARS-CoV-2 ‘S1’ spike protein binds to aggregation-prone glycosaminoglycan heparin and heparin binding protein (HBP), amyloid-beta (Aβ) peptides, α-synuclein, tau and prion proteins, and TDP-43 (TAR DNA binding protein 43, critical for the regulation of the viral gene expression), thus facilitating and/or accelerating the coalescence and aggregation of multiple pathological amyloidogenic proteins in nervous tissues, all of which appear to further contribute to the protein-mis-folding characteristic of PrD infection [ 3 , 20 , 22 , 49 , 60 ]; and (vi) variations in the prion-like domains of the ‘S1’ spike protein differ among SARS-CoV-2 variants, thus modulating ‘S1’ affinity for the ACE2R and hence the success of SARS-CoV-2 infectivity [ …”

COVID-19 and Post-Acute COVID-19 Syndrome: From Pathophysiology to Novel Translational Applications

“…Other studies [ 20 ] have been published in this Special Issue, including some relevant case reports [ 21 , 22 ], all contributing to provide a stimulating insight into the pathophysiology and diagnostics of COVID-19 and post-acute COVID-19 syndrome. Some prognostic and therapeutic applications have been analyzed in both review and original articles, with interesting new findings and potentially relevant repercussions in clinical practice and future research.…”