Neurological manifestations of long-COVID syndrome: a narrative review

Therapeutic Advances in Chronic Disease, Journal Year: 2022, Volume and Issue: 13

Published: Jan. 1, 2022

Accumulating evidence points toward a very high prevalence of prolonged neurological symptoms among coronavirus disease 2019 (COVID-19) survivors. To date, there are no solidified criteria for 'long-COVID' diagnosis. Nevertheless, is conceptualized as multi-organ disorder with wide spectrum clinical manifestations that may be indicative underlying pulmonary, cardiovascular, endocrine, hematologic, renal, gastrointestinal, dermatologic, immunological, psychiatric, or disease. Involvement the central peripheral nervous system noted in more than one-third patients antecedent severe acute respiratory syndrome 2 (SARS-CoV-2) infection, while an approximately threefold higher incidence recorded observational studies including patient-reported data. The most frequent encompass fatigue; 'brain fog'; headache; cognitive impairment; sleep, mood, smell, taste disorders; myalgias; sensorimotor deficits; and dysautonomia. Although limited exists to date on pathophysiological mechanisms implicated manifestation 'long-COVID', neuroinflammatory oxidative stress processes thought prevail propagating sequelae. In this narrative review, we sought present comprehensive overview our current understanding features, risk factors, Moreover, propose diagnostic therapeutic algorithms aid prompt recognition management causes persist beyond resolution COVID-19. Furthermore, causal treatments currently unavailable, approaches symptom-oriented symptoms. addition, emphasize collaborative research initiatives urgently needed expedite development preventive strategies

Language: Английский

---

SARS-CoV-2 spike S1 subunit induces neuroinflammatory, microglial and behavioral sickness responses: Evidence of PAMP-like properties

Brain Behavior and Immunity, Journal Year: 2021, Volume and Issue: 100, P. 267 - 277

Published: Dec. 13, 2021

Language: Английский

---

Cerebrospinal fluid findings in COVID-19: a multicenter study of 150 lumbar punctures in 127 patients

Journal of Neuroinflammation, Journal Year: 2022, Volume and Issue: 19(1)

Published: Jan. 20, 2022

Abstract Background Comprehensive data on the cerebrospinal fluid (CSF) profile in patients with COVID-19 and neurological involvement from large-scale multicenter studies are missing so far. Objective To analyze systematically CSF COVID-19. Methods Retrospective analysis of 150 lumbar punctures 127 PCR-proven symptoms seen at 17 European university centers Results The most frequent pathological finding was blood-CSF barrier (BCB) dysfunction (median QAlb 11.4 [6.72–50.8]), which present 58/116 (50%) samples without pre-/coexisting CNS diseases (group I). remained elevated > 14d (47.6%) even 30d (55.6%) after onset. total protein 54/118 (45.8%) 65.35 mg/dl [45.3–240.4]) strongly correlated QAlb. white cell count (WCC) increased 14/128 (11%) (mostly lympho-monocytic; median 10 cells/µl, 100 only 4). An albuminocytological dissociation (ACD) found 43/115 (37.4%) samples. l -lactate 26/109 (24%; 3.04 mmol/l [2.2–4]). CSF-IgG 50/100 (50%), but peripheral origin, since QIgG normal almost all cases, as were QIgA QIgM. In 58/103 (56%) pattern 4 oligoclonal bands (OCB) compatible systemic inflammation present, while CSF-restricted OCB 2/103 (1.9%). SARS-CoV-2-CSF-PCR negative 76/76 Routine findings 35%. Cytokine levels frequently (often associated BCB dysfunction) serum, partly remaining positive high for weeks/months (939 tests). Of note, a SARS-CoV-2-IgG-antibody index (AI) 2/19 (10.5%) unusually WCC both them interleukin-6 (IL-6) one (not tested other). Anti-neuronal/anti-glial autoantibodies mostly absent serum (1509 disorders II [ N = 19]; including multiple sclerosis, JC-virus-associated immune reconstitution inflammatory syndrome, HSV/VZV encephalitis/meningitis, lymphoma, anti-Yo subarachnoid hemorrhage), representative respective disease. Conclusions is mainly characterized by disruption absence intrathecal inflammation, endotheliopathy. Persistent cytokine may contribute to acute ‘long COVID’. Direct infection SARS-CoV-2, if occurring all, seems be rare. Broad differential diagnostic considerations recommended avoid misinterpretation treatable coexisting complications

Language: Английский

---

COVID-19 and the Vasculature: Current Aspects and Long-Term Consequences

Frontiers in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 10

Published: Feb. 15, 2022

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was first identified in December 2019 as a novel respiratory pathogen and is the causative agent of Corona Virus disease (COVID-19). Early on during this pandemic, it became apparent that SARS-CoV-2 not only restricted to infecting tract, but virus also found other tissues, including vasculature. Individuals with underlying pre-existing co-morbidities like diabetes hypertension have been more prone develop severe illness fatal outcomes COVID-19. In addition, critical clinical observations made COVID-19 patients include hypercoagulation, cardiomyopathy, heart arrythmia, endothelial dysfunction, which are indicative for an involvement vasculature pathology. Hence, review summarizes impact infection details how promotes (chronic) vascular inflammation. We provide general overview SARS-CoV-2, its entry determinant Angiotensin-Converting Enzyme II (ACE2) detection extrapulmonary tissue. Further, we describe relation between cardiovascular diseases (CVD) their Clinical findings changes reviewed detail recent evidence from vitro studies susceptibility cells discussed. conclude current notions contribution events long term consequences COVID-19, known “Long-COVID-syndrome”. Altogether, our provides detailed perspectives influence

Language: Английский

---

Neuropilin-1 Mediates SARS-CoV-2 Infection of Astrocytes in Brain Organoids, Inducing Inflammation Leading to Dysfunction and Death of Neurons

mBio, Journal Year: 2022, Volume and Issue: 13(6)

Published: Oct. 31, 2022

Coronavirus disease 2019 (COVID-19) is frequently associated with neurological deficits, but how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces these effects remains unclear. Here, we show that astrocytes are readily infected by SARS-CoV-2, surprisingly, neuropilin-1, not angiotensin-converting enzyme (ACE2), serves as the principal receptor mediating cell entry. Infection further positively modulated two-pore segment channel (TPC2) protein regulates membrane trafficking and endocytosis. Astrocyte infection produces a pathological response closely resembling reactive astrogliosis characterized elevated type I interferon (IFN) production, increased inflammation, decreased expression of transporters water, ions, choline, neurotransmitters. These combined events initiated within produce hostile microenvironment promotes dysfunction death uninfected bystander neurons.

Language: Английский

---

Acute and Post-Acute Neurological Complications of COVID-19

Neurology International, Journal Year: 2021, Volume and Issue: 13(1), P. 102 - 119

Published: March 9, 2021

Coronavirus disease 2019 (COVID-19) is an emerging global health emergency caused by the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The outbreak of SARS-CoV-2 infection has been declared a pandemic World Health Organization (WHO). clinical presentation depends on severity and may range from asymptomatic to lethal illness. Fever, cough, shortness breath are among most common symptoms associated with infection. Accumulating evidence indicates that COVID-19 patients commonly develop neurological symptoms, such as headache, altered mental status, anosmia, myalgia. In this comprehensive literature review, we have summarized complications reported case studies COVID-19, side effects treatments. Additionally, post-acute long-term were discussed. We also explained proposed mechanisms involved in pathogenesis these complications.

Language: Английский

---

COVID‐19 and the peripheral nervous system. A 2‐year review from the pandemic to the vaccine era

Journal of the Peripheral Nervous System, Journal Year: 2022, Volume and Issue: 27(1), P. 4 - 30

Published: Feb. 9, 2022

Abstract Increasing literature has linked COVID‐19 to peripheral nervous system (PNS) diseases. In addition, as we move from the pandemic vaccination era, interest is shifting towards potential association between vaccines and PNS manifestations. We reviewed published on COVID‐19, manifestations 1 January 2020 December 2021. For Guillain‐Barré syndrome (GBS), isolated cranial neuropathy (ICN) myositis associated with demographic, clinical, laboratory, electrophysiological imaging features were included in a narrative synthesis. identified 169 studies COVID‐19‐associated complications, including 63 papers (92 patients) GBS, 29 (37 ICN 11 (18 myositis. Additional clinical phenotypes chronic inflammatory demyelinating polyneuropathy, vasculitic neuropathies, neuralgic amyotrophy, critical care‐related myasthenia gravis. complications secondary have been reported during randomized trials, real‐world case reports, large‐scale surveillance programs. These mainly include cases of Bell's palsy, amyotrophy. Based our extensive review literature, any conclusion about pathophysiological correlation disorders remains premature, solely supported by their temporal association, while epidemiological pathological data are insufficient. The occurrence after seems limited possible higher risk facial nerve palsy degree that widespread access ongoing campaign should not be discouraged, awaiting for more definitive studies.

Language: Английский

---

Plasma Markers of Neurologic Injury and Inflammation in People With Self-Reported Neurologic Postacute Sequelae of SARS-CoV-2 Infection

Neurology Neuroimmunology & Neuroinflammation, Journal Year: 2022, Volume and Issue: 9(5)

Published: June 14, 2022

The biologic mechanisms underlying neurologic postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) are incompletely understood.We measured markers injury (glial fibrillary acidic protein [GFAP], neurofilament light chain [NfL]) and soluble inflammation among a cohort people with prior confirmed SARS-CoV-2 at early late recovery after the initial illness (defined as less than greater 90 days, respectively). primary clinical outcome was presence self-reported CNS PASC symptoms during time point. We compared fold changes in marker values between those without using linear mixed-effects models examined relationships immunologic rank correlations.Of 121 individuals, 52 reported symptoms. During recovery, who went on to report had elevations GFAP (1.3-fold higher mean ratio, 95% CI 1.04-1.63, p = 0.02), but not NfL (1.06-fold 0.89-1.26, 0.54). neither nor levels were elevated Although absolute did differ, demonstrated stronger downward trend over comparison (p 0.041). Those also exhibited interleukin 6 (48% 38% recovery), monocyte chemoattractant 1 (19% tumor necrosis factor α 13% recovery). correlated several immune activation recovery; these correlations attenuated recovery.Self-reported present approximately 4 months associated earlier points. Some inflammatory pathways seem be involved infection. Additional work will needed better characterize processes identify interventions prevent or treat this condition.

Language: Английский

---

Neurological symptoms in COVID-19: a cross-sectional monocentric study of hospitalized patients

Neurological Research and Practice, Journal Year: 2021, Volume and Issue: 3(1)

Published: March 12, 2021

Abstract Background The SARS-Coronavirus-2 (SARS-CoV-2) invades the respiratory system, causing acute and sometimes severe pulmonary symptoms, but turned out to also act multisystematically with substantial impact on brain. A growing number of studies suggests a diverse spectrum neurological manifestations. To investigate we here describe manifestations complications patients proven SARS-CoV-2 infection who have been hospitalized at RWTH University Hospital Aachen, Germany. Methods Between March September 2020, evaluated common clinical characteristics, laboratory (including cerebrospinal fluid (CSF) analysis), radiological, electroencephalography (EEG) data from 53 admitted positive polymerase chain reaction (PCR). We used Montreal Cognitive Assessment Test (MoCA) screen for cognitive impairment, when feasible. compared critically ill non-critically categorized according presence Acute Respiratory Distress Syndrome (ARDS). Results Major features COVID-19 were coordination deficits (74%), impairment (61.5%), paresis (47%), abnormal reflex status (45%), sensory abnormalities general muscle weakness pain (32%), hyposmia (26%), headache (21%). Patients ARDS more severely affected than non-ADRS patients. 29.6% presented subarachnoid bleedings, 11.1% showed ischemic stroke associated infection. mainly executive functions, attention, language, delayed memory recall. obtained by lumbar puncture in nine patients, none which had PCR. Conclusions In line previous findings, our results provide evidence range SARS-CoV-2-associated 26% reported hyposmia, emphasizing neuro-invasive potential SARS-CoV-2, can enter olfactory bulb. It therefore be speculated that may caused direct invasion virus CNS; however, PCR did not reveal intrathecal SARS-CoV-2. Therefore, hypothesize it is likely para-infectious pro-inflammatory responsible including impairment. Future comprehensive longitudinal assessment are required determine long-term COVID-19.

Language: Английский

---

SARS-CoV-2 and the Brain: What Do We Know about the Causality of ‘Cognitive COVID?

Journal of Clinical Medicine, Journal Year: 2021, Volume and Issue: 10(15), P. 3441 - 3441

Published: Aug. 2, 2021

The second year of the COVID-19 (coronavirus disease) pandemic has seen need to identify and assess long-term consequences a SARS-CoV-2 infection on an individual’s overall wellbeing, including adequate cognitive functioning. ‘Cognitive COVID’ is informal term coined interchangeably refer acute changes in cognition during and/or sequelae with various deficits following infection. These may manifest as altered levels consciousness, encephalopathy-like symptoms, delirium, loss memory domains. Dysexecutive syndrome peculiar manifestation well. In previous major outbreaks viruses like SARS-CoV, MERS-CoV Influenza. There have been attempts understand underlying mechanisms describing causality similar symptoms This review, therefore, attempting highlight current understanding direct indirect mechanisms, focusing role neurotropism SARS-CoV-2, general pro-inflammatory state, pandemic-associated psychosocial stressors COVID.’ Neurotropism associated retrograde neuronal transmission via olfactory pathway, hematogenous spread, virus using immune cells vectors. high amounts inflammation caused by COVID-19, compounded potential intubation, are deleterious effect Finally, pandemic’s unique impact raised alarm due its possible cognition. Furthermore, surfacing reports post-COVID-vaccination impairments after vaccines containing mRNA encoding for spike glycoprotein we hypothesize their ways mitigate risk. quality life individual fact that even minor proportion cases developing impairment could be significant burden already overwhelmed healthcare systems across world make it vital gather further evidence regarding prevalence, presentation, correlations, these events reevaluate our approach accommodate early identification, management, rehabilitation patients exhibiting symptoms.

Language: Английский

---