A case series of cutaneous phosphorylated α-synuclein in Long-COVID POTS

Miglis, Mitchell G.; Seliger, Jordan; Shaik, Ruba; Gibbons, Christopher H.

doi:10.1007/s10286-022-00867-0

Cited by 12 publications

(9 citation statements)

References 13 publications

(12 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…POTS has been described in smaller and larger case reports after the onset of the COVID-19 pandemic [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 17 , 18 , 19 , 20 ]. In our previous study of the first ten long-haul COVID-19 patients, we only observed POTS during a tilt test [ 13 ].…”

Section: Discussionmentioning

confidence: 99%

“…Since the outbreak of the pandemic by the particularly contagious respiratory virus SARS-CoV-2 (COVID-19) virus in March 2020, the early onset of orthostatic intolerance with postural orthostatic tachycardia syndrome (POTS) has been noted and described in several case reports [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 ]. POTS was found in the very early days of the COVID-19 infection, even on Day 1 of the infection [ 10 ], and can persist for more than two years [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Long-Haul COVID Patients: Prevalence of POTS Are Reduced but Cerebral Blood Flow Abnormalities Remain Abnormal with Longer Disease Duration

Campen¹,

Visser²

2022

Healthcare

View full text Add to dashboard Cite

Background: Postural orthostatic tachycardia syndrome (POTS) has been described early after the onset of the COVID-19 infection, but also orthostatic hypotension (OH). In the present study, we hypothesized that orthostatic intolerance decreases over time. Methods: In 29 long-haul COVID-19 (LHC) patients, a tilt test was performed, including measurements of cerebral blood flow (CBF) by extracranial Doppler. The time interval between the onset of infection and the tilt test varied between 3 and 28 months. Results: In the first 12 months after the infection, 71% of the LHC patients showed POTS and after 24 months none of them. In the first 12 months, 29% of patients had a normal heart rate and blood pressure response (normHRBP) and after 24 months 75% (distribution of POTS, OH, and a normHRBP over time: p < 0.0001). Linear regression showed that, over time, there was a decrease in the abnormal CBF during the tilt (p = 0.024) but remained abnormal. Conclusion: In LHC patients, hemodynamic abnormalities of a tilt test change over time. Patients studied early after the onset of the disease mainly exhibit POTS, but patients studied later in the time course mainly show a normHRBP or OH. In addition, the abnormal CBF reduction improves over time, but CBF remains abnormal.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Long-Haul COVID Patients: Prevalence of POTS Are Reduced but Cerebral Blood Flow Abnormalities Remain Abnormal with Longer Disease Duration

Campen¹,

Visser²

2022

Healthcare

View full text Add to dashboard Cite

show abstract

“…Similarly, Neuro-PASC patients exhibit higher T cell responses to the nucleocapsid protein compared with control convalescent patients, supporting the theory that a persistent reservoir of the N protein is responsible for the activation of unique immunological signatures biased towards N proteins in Neuro-PASC individuals [ 234 ]. Remarkably, skin biopsies obtained from several PASC patients with symptoms of POTS revealed unusual aggregation of cutaneously phosphorylated ⍺-synuclein amyloid fibrils [ 235 ].…”

Section: Sars-cov-2 Proteins Phase Separation Disrupt Host Biomolecul...mentioning

confidence: 99%

Melatonin: Regulation of Viral Phase Separation and Epitranscriptomics in Post-Acute Sequelae of COVID-19

Loh¹,

Reíter

2022

IJMS

View full text Add to dashboard Cite

The relentless, protracted evolution of the SARS-CoV-2 virus imposes tremendous pressure on herd immunity and demands versatile adaptations by the human host genome to counter transcriptomic and epitranscriptomic alterations associated with a wide range of short- and long-term manifestations during acute infection and post-acute recovery, respectively. To promote viral replication during active infection and viral persistence, the SARS-CoV-2 envelope protein regulates host cell microenvironment including pH and ion concentrations to maintain a high oxidative environment that supports template switching, causing extensive mitochondrial damage and activation of pro-inflammatory cytokine signaling cascades. Oxidative stress and mitochondrial distress induce dynamic changes to both the host and viral RNA m6A methylome, and can trigger the derepression of long interspersed nuclear element 1 (LINE1), resulting in global hypomethylation, epigenetic changes, and genomic instability. The timely application of melatonin during early infection enhances host innate antiviral immune responses by preventing the formation of “viral factories” by nucleocapsid liquid-liquid phase separation that effectively blockades viral genome transcription and packaging, the disassembly of stress granules, and the sequestration of DEAD-box RNA helicases, including DDX3X, vital to immune signaling. Melatonin prevents membrane depolarization and protects cristae morphology to suppress glycolysis via antioxidant-dependent and -independent mechanisms. By restraining the derepression of LINE1 via multifaceted strategies, and maintaining the balance in m6A RNA modifications, melatonin could be the quintessential ancient molecule that significantly influences the outcome of the constant struggle between virus and host to gain transcriptomic and epitranscriptomic dominance over the host genome during acute infection and PASC.

show abstract

“…124,125 Five cases have been reported in which skin biopsies of young people with POTS after COVID-19 infection showed alpha-synuclein deposition in nerve fibers, as seen in Parkinson disease. 126 These results may lead to further investigation of SARS-CoV-2 infection and protein accumulation associated with neurodegenerative disorders in the CNS. 127 Experiences for PASC Clinic of National Center of Neurology and Psychiatry…”

Section: Clinical Neurosciencesmentioning

confidence: 92%

“…Autonomic nervous system dysfunction may be associated with SARS‐CoV‐2 infection 124,125 . Five cases have been reported in which skin biopsies of young people with POTS after COVID‐19 infection showed alpha‐synuclein deposition in nerve fibers, as seen in Parkinson disease 126 . These results may lead to further investigation of SARS‐CoV‐2 infection and protein accumulation associated with neurodegenerative disorders in the CNS 127 …”

Section: Representative Neurological Symptoms Of Pascmentioning

confidence: 97%

Neurological post‐acute sequelae of SARS‐CoV‐2 infection

Takao

Ohira

2022

Psychiatry Clin Neurosci

View full text Add to dashboard Cite

The novel corona virus infectious disease, COVID‐19, caused by SARS‐CoV‐2, can have two phases: acute (generally 4 weeks after onset) and chronic (> 4 weeks after onset). Both phases include a wide variety of signs and symptoms including neurological and psychiatric symptoms. The signs and symptoms that are considered sequelae of COVID‐19 are termed post‐COVID condition, long COVID‐19, and post‐acute sequelae of SARS‐CoV‐2 infection (PASC). PASC symptoms include fatigue, dyspnea, palpitation, dysosmia, sub‐fever, hypertension, alopecia, sleep problems, loss of concentration, amnesia, numbness, pain, gastrointestinal symptoms, depression, and anxiety. Because the specific pathophysiology of PASC has not yet been clarified, there are no definite criteria of the condition, hence the World Health Organization’s definition is quite broad. Consequently, it is difficult to correctly diagnose PASC. Approximately 50% of patients may show at least one PASC symptom up to 12 months after COVID‐19 infection; however, the exact prevalence of PASC has not been determined. Despite extensive research in progress worldwide, there are currently no clear diagnostic methodologies or treatments for PASC. In this review, we discuss the currently available information on PASC and highlight the neurological sequelae of COVID‐19 infection. Furthermore, we provide clinical suggestions for diagnosing and caring for PASC patients based on our outpatient clinic experience. This article is protected by copyright. All rights reserved.

show abstract

A case series of cutaneous phosphorylated α-synuclein in Long-COVID POTS

Cited by 12 publications

References 13 publications

Long-Haul COVID Patients: Prevalence of POTS Are Reduced but Cerebral Blood Flow Abnormalities Remain Abnormal with Longer Disease Duration

Long-Haul COVID Patients: Prevalence of POTS Are Reduced but Cerebral Blood Flow Abnormalities Remain Abnormal with Longer Disease Duration

Melatonin: Regulation of Viral Phase Separation and Epitranscriptomics in Post-Acute Sequelae of COVID-19

Neurological post‐acute sequelae of SARS‐CoV‐2 infection

Contact Info

Product

Resources

About