Tag: long covid neurology

Chronic cough in post-COVID syndrome: Laryngeal electromyography findings in vagus nerve neuropathy

Abstract:

Background: Despite being a new entity, there is a large amount of information on the characteristics of SARS-CoV-2 infection and the symptoms of the acute phase; however, there are still many unknowns about the clinical features and pathophysiology of post-COVID syndrome. Refractory chronic cough is one of the most prevalent symptoms and carries both a medical problem and a social stigma. Many recent studies have highlighted the role of SARS-CoV-2 neurotropism, but no studies have demonstrated vagus nerve neuropathy as a cause of persistent chronic cough or other COVID-19 long-term effects.

Objective: The main objective was to assess the involvement of the vagus nerve neuropathy as a cause of chronic cough and other post-COVID syndrome symptoms.

Material and methods: This was a single-center observational study with prospective clinical data collected from 38 patients with chronic cough and post-COVID-19 syndrome. Clinical characteristics and laryngeal electromyographic findings were analyzed.

Results: Clinical data from 38 patients with chronic cough after 12 weeks of the acute phase of COVID-19 infection were analyzed. Of these patients, 81.6% suffered from other post-COVID conditions and, 73.6% reported fluctuating evolution of symptoms. Laryngeal electromyography (LEMG) of the thyroarytenoid (TA) muscles and cricothyroid (CT) muscles was pathological in 76.3% of the patients. Of the patients with abnormal LEMG, chronic denervation was the most frequent finding (82.8%), 10.3% presented acute denervation signs, and 6.9% presented myopathic pattern in LEMG.

Conclusions: LEMG studies suggest the existence of postviral vagus nerve neuropathy after SARS-CoV-2 infection that could explain chronic cough in post-COVID syndrome.

Source: García-Vicente P, Rodríguez-Valiente A, Górriz Gil C, Márquez Altemir R, Martínez-Pérez F, López-Pajaro LF, et al. (2023) Chronic cough in post-COVID syndrome: Laryngeal electromyography findings in vagus nerve neuropathy. PLoS ONE 18(3): e0283758. https://doi.org/10.1371/journal.pone.0283758 https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0283758 (Full text)

Neurocognitive and psychiatric symptoms following infection with COVID-19: Evidence from laboratory and population studies

Abstract:

Objective: The objective of the current investigation was to examine associations between symptomatic COVID-19 history, neurocognitive function, and psychiatric symptoms using cognitive task performance, functional brain imaging, and a prospective population survey.

Methods: Study 1 was a laboratory study conducted between 3 May 2022 and 16 Nov 2022 involving 120 fully vaccinated community dwelling adults between 18 and 84 years of age (Mage = 31.96 (SD = 20.71), 63.3% female). In this cross-sectional study we examined the association between symptomatic COVID-19 infection history and performance on three computer tasks assessing cognitive function (Flanker interference, delay discounting and simple reaction time) and measured oxygen saturation within the prefrontal cortex using functional near infrared spectroscopy (fNIRS). Study 2 was a 2-wave population survey undertaken between 28 September 2021 and 21 March 2022, examining the prospective relationship between symptomatic COVID-19 and self-reported symptoms of cognitive dysfunction, depressive symptoms, anxiety symptoms, and agitation at 6-month follow up. The sample (N = 2,002, M age = 37.0, SD = 10.4; 60.8% female) was collected using a quota process to ensure equal numbers of vaccinated and unvaccinated individuals. Structural equation modelling with latent variables was performed on the population-level data, evaluating the fit of the proposed mediational model of symptomatic COVID-19 to psychiatric symptoms through cognitive dysfunction.

Results: Findings from Study 1 revealed significant effects of symptomatic COVID-19 history on Flanker interference and delay discounting. Effects on flanker performance were significantly stronger among older adult women (effect: 9.603, SE = 4.452, t = 2.157, p = .033), and were accompanied by task-related changes cerebral oxygenation at the right superior frontal gyrus (F (1, 143.1) = 4.729, p = .031). Additionally, those with a symptomatic COVID-19 infection history showed evidence of amplified delay discounting (coefficient = 0.4554, SE = 0.2208, t = 2.0629, p = .041). In Study 2, baseline symptomatic COVID-19 history was associated with self-reported cognitive dysfunction and a latent variable reflecting psychiatric symptoms of anxiety, depression and agitation at follow-up. Mediational analyses revealed evidence of cognitive mediation of clinically significant psychiatric outcomes: depression (indirect effect = 0.077, SE = 0.026, p = .003) and generalized anxiety (indirect effect = 0.060, SE = 0.021, p = .004).

Conclusions: Converging findings from laboratory and population survey data support the conclusion that symptomatic COVID-19 infection is associated with task-related, functional imaging and self-reported indices of cognitive dysfunction as well as psychiatric symptoms. In some cases, these findings appear to be more amplified among women than men, and among older women than younger.

Source: Hall PA, Ayaz H, Meng G, Hudson A, Sakib MN, Quah ACK, Agar TK, Lee JA, Boudreau C, Fong GT. Neurocognitive and psychiatric symptoms following infection with COVID-19: Evidence from laboratory and population studies. Brain Behav Immun Health. 2023 Mar;28:100595. doi: 10.1016/j.bbih.2023.100595. Epub 2023 Jan 24. PMID: 36713476; PMCID: PMC9870612. https://www.sciencedirect.com/science/article/pii/S2666354623000091?via%3Dihub (Full study)

The original strain of SARS-CoV-2, the Delta variant, and the Omicron variant infect microglia efficiently, in contrast to their inability to infect neurons: Analysis using 2D and 3D cultures

Highlights:

  • None of the SARS-CoV-2 original, delta, or omicron strains can infect neurons.
  • The SARS-CoV-2 original, delta, and omicron strains can infect microglia.
  • The CNS cells differentiated from hiPSCs are useful to investigate the infectivity of the virus.

Abstract:

COVID-19 causes neurological damage, systemic inflammation, and immune cell abnormalities. COVID-19-induced neurological impairment may be caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which directly infects cells of the central nervous system (CNS) and exerts toxic effects. Furthermore, SARS-CoV-2 mutations occur constantly, and it is not well understood how the infectivity of the virus to cells of the CNS changes as the virus mutates.

Few studies have examined whether the infectivity of cells of CNS – neural stem/progenitor cells (NS/PCs), neurons, astrocytes, and microglia – varies among SARS-CoV-2 mutant strains. In this study, therefore, we investigated whether SARS-CoV-2 mutations increase infectivity to CNS cells, including microglia.

Since it was essential to demonstrate the infectivity of the virus to CNS cells in vitro using human cells, we generated cortical neurons, astrocytes, and microglia from human induced pluripotent stem cells (hiPSCs). We added pseudotyped lentiviruses of SARS-CoV-2 to each type of cells, and then we examined their infectivity. We prepared three pseudotyped lentiviruses expressing the S protein of the original strain (the first SARS-CoV-2 discovered in the world), the Delta variant, and the Omicron variant on their envelopes and analyzed differences of their ability to infect CNS cells. We also generated brain organoids and investigated the infectivity of each virus.

The viruses did not infect cortical neurons, astrocytes, or NS/PCs, but microglia were infected by the original, Delta, and Omicron pseudotyped viruses. In addition, DPP4 and CD147, potential core receptors of SARS-CoV-2, were highly expressed in the infected microglia, while DPP4 expression was deficient in cortical neurons, astrocytes, and NS/PCs.

Our results suggest that DPP4, which is also a receptor for Middle East respiratory syndrome-coronavirus (MERS-CoV), may play an essential role in the CNS. Our study is applicable to the validation of the infectivity of viruses that cause various infectious diseases in CNS cells, which are difficult to sample from humans.

Source: Kase Y, Sonn I, Goto M, Murakami R, Sato T, Okano H. The original strain of SARS-CoV-2, the Delta variant, and the Omicron variant infect microglia efficiently, in contrast to their inability to infect neurons: Analysis using 2D and 3D cultures. Exp Neurol. 2023 Mar 11;363:114379. doi: 10.1016/j.expneurol.2023.114379. Epub ahead of print. PMID: 36914084; PMCID: PMC10008041. https://www.sciencedirect.com/science/article/pii/S0014488623000638?via%3Dihub (Full text)

Potential Prion Involvement in Long COVID-19 Neuropathology, Including Behavior

Abstract:

Prion is a term used to describe a protein infectious particle responsible for several neurodegenerative diseases in mammals, e.g., Creutzfeldt-Jakob disease. The novelty is that it is protein based infectious agent not involving a nucleic acid genome as found in viruses and bacteria.

Prion disorders exhibit, in part, incubation periods, neuronal loss, and induce abnormal folding of specific normal cellular proteins due to enhancing reactive oxygen species associated with mitochondria energy metabolism. These agents may also induce memory, personality and movement abnormalities as well as depression, confusion and disorientation.

Interestingly, some of these behavioral changes also occur in COVID-19 and mechanistically include mitochondrial damage caused by SARS-CoV-2 and subsequent production of reactive oxygen species. Taken together, we surmise, in part, long COVID may involve the induction of spontaneous prion emergence, especially in individuals susceptible to its origin may thus explain some of its manisfestions post-acute viral infection.

Source: Stefano GB, Büttiker P, Weissenberger S, Anders M, Raboch J, Ptacek R, Kream RM. Potential Prion Involvement in Long COVID-19 Neuropathology, Including Behavior. Cell Mol Neurobiol. 2023 Mar 28:1–6. doi: 10.1007/s10571-023-01342-8. Epub ahead of print. PMID: 36977809; PMCID: PMC10047479. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10047479/ (Full text)

Sleep Disorders in Post-COVID Syndrome: A Psychiatric or Neurological Problem?

Abstract:

The coronavirus pandemic that began in 2019 continues. COVID-19 adversely affects human health not only in the acute, but also in the long-term period of the disease: in a large percentage of cases, health is not fully restored after long periods, requires medical intervention, and is often difficult to correct.

Researchers noted during the first wave of the pandemic in 2020 that about 10-20% of patients did not fully recover by three weeks from disease onset and the possible duration of the recovery period remains insufficiently clear, as do the reasons for differences in course during this period. Prolonged recovery after viral infection is not a feature exclusive to COVID-19, which does not facilitate the management of patients with post-COVID syndrome (PCS).

The mental health impact of COVID-19 is significant, with at least 30% of recovered patients likely to have symptoms of anxiety and/or depression after the acute phase has passed. Since the onset of COVID-19, there has been an increase in sleep disorders by 42%, with every third COVID-19 survivor reporting sleep complaints. In PCS, this condition is referred to as coronasomnia.

The success of therapy for this condition depends on identifying and correcting patients’ mental disorders, as anxiety and depression are often accompanied by sleep disorders this results in a bidirectional interaction between mental disorders and sleep quality. This article presents data on the anti-anxiety drugs Noofen and Adaptol, which help to correct the manifestations of PCS with sleep disorders.

Source: Kotova OV, Medvedev VE, Poluektov MG, Belyaev AA, Akarachkova ES. Sleep Disorders in Post-COVID Syndrome: A Psychiatric or Neurological Problem? Neurosci Behav Physiol. 2023;53(1):16-20. doi: 10.1007/s11055-023-01385-w. Epub 2023 Mar 11. PMID: 36969358; PMCID: PMC10006556. https://link.springer.com/article/10.1007/s11055-023-01385-w (Full text available as PDF file)

 

Neurologic manifestations of long COVID differ based on acute COVID-19 severity

Abstract:

Objective: To characterize neurologic manifestations in post-hospitalization Neuro-PASC (PNP) and non-hospitalized Neuro-PASC (NNP) patients.

Methods: Prospective study of the first 100 consecutive PNP and 500 NNP patients evaluated at a Neuro-COVID-19 clinic between 5/2020 and 8/2021.

Results: PNP were older than NNP patients (mean 53.9 vs 44.9 y; p < 0.0001) with a higher prevalence of pre-existing comorbidities. An average 6.8 months from onset, the main neurologic symptoms were “brain fog” (81.2%), headache (70.3%), and dizziness (49.5%) with only anosmia, dysgeusia and myalgias being more frequent in the NNP compared to the PNP group (59 vs 39%, 57.6 vs 39% and 50.4 vs 33%, all p < 0.003). Moreover, 85.8% of patients experienced fatigue. PNP more frequently had an abnormal neurologic exam than NNP patients (62.2 vs 37%, p < 0.0001). Both groups had impaired quality of life in cognitive, fatigue, sleep, anxiety, and depression domains. PNP patients performed worse on processing speed, attention, and working memory tasks than NNP patients (T-score 41.5 vs 55, 42.5 vs 47 and 45.5 vs 49, all p < 0.001) and a US normative population. NNP patients had lower results in attention task only. Subjective impression of cognitive ability correlated with cognitive test results in NNP but not in PNP patients.

Interpretation: PNP and NNP patients both experience persistent neurologic symptoms affecting their quality of life. However, they harbor significant differences in demographics, comorbidities, neurologic symptoms and findings, as well as pattern of cognitive dysfunction. Such differences suggest distinct etiologies of Neuro-PASC in these populations warranting targeted interventions.

Source: Perez Giraldo GS, Ali ST, Kang AK, Patel TR, Budhiraja S, Gaelen JI, Lank GK, Clark JR, Mukherjee S, Singer T, Venkatesh A, Orban ZS, Lim PH, Jimenez M, Miller J, Taylor C, Szymanski AL, Scarpelli J, Graham EL, Balabanov RD, Barcelo BE, Cahan JG, Ruckman K, Shepard AG, Slutzky MW, LaFaver K, Kumthekar PU, Shetty NK, Carroll KS, Ho SU, Lukas RV, Batra A, Liotta EM, Koralnik IJ. Neurologic manifestations of long COVID differ based on acute COVID-19 severity. Ann Neurol. 2023 Mar 26. doi: 10.1002/ana.26649. Epub ahead of print. PMID: 36966460. https://onlinelibrary.wiley.com/doi/abs/10.1002/ana.26649 (Full text available as PDF file)

 

Immunometabolic rewiring in long COVID patients with chronic headache

Abstract:

Almost 20% of patients with COVID-19 experience long-term effects, known as post-COVID condition or long COVID. Among many lingering neurologic symptoms, chronic headache is the most common. Despite this health concern, the etiology of long COVID headache is still not well characterized. Here, we present a longitudinal multi-omics analysis of blood leukocyte transcriptomics, plasma proteomics and metabolomics of long COVID patients with chronic headache. L

ong COVID patients experienced a state of hyper-inflammation prior to chronic headache onset and maintained persistent inflammatory activation throughout the progression of chronic headache. Metabolomic analysis also revealed augmented arginine and lipid metabolisms, skewing towards a nitric oxide-based pro-inflammation. Furthermore, metabolisms of neurotransmitters including serotonin, dopamine, glutamate, and GABA were markedly dysregulated during the progression of long COVID headache.

Overall, these findings illustrate the immuno-metabolomics landscape of long COVID patients with chronic headache, which may provide insights to potential therapeutic interventions.

Source: Foo SS, Chen W, Jung KL, Azamor T, Choi UY, Zhang P, Comhair SA, Erzurum SC, Jehi L, Jung JU. Immunometabolic rewiring in long COVID patients with chronic headache. bioRxiv [Preprint]. 2023 Mar 6:2023.03.06.531302. doi: 10.1101/2023.03.06.531302. PMID: 36945569; PMCID: PMC10028820. https://www.biorxiv.org/content/10.1101/2023.03.06.531302v1.full (Full text)

Neurological Dysfunction in Long COVID Should Not Be Labelled as Functional Neurological Disorder

Abstract:

There have been suggestions that Long COVID might be purely functional (meaning psychological) in origin. Labelling patients with neurological dysfunction in Long COVID as having functional neurological disorder (FND) in the absence of proper testing may be symptomatic of that line of thought. This practice is problematic for Long COVID patients, as motor and balance symptoms have been reported to occur in Long COVID frequently.
FND is characterized by the presentation of symptoms that seem neurological but lack compatibility of the symptom with a neurological substrate. Although diagnostic classification according to the ICD-11 and DSM-5-TR is dependent predominantly on the exclusion of any other medical condition that could account for the symptoms, current neurological practice of FND classification allows for such comorbidity. As a consequence, Long COVID patients with motor and balance symptoms mislabeled as FND have no longer access to Long COVID care, whereas treatment for FND is seldom provided and is ineffective.
Research into underlying mechanisms and diagnostic methods should explore how to determine whether motor and balance symptoms currently diagnosed as FND should be considered one part of Long COVID symptoms, in other words, one component of symptomatology, and in which cases they correctly represent FND. Research into rehabilitation models, treatment and integrated care are needed, which should take into account biological underpinnings as well as possible psychological mechanisms and the patient perspective.
Source: Van der Feltz-Cornelis CM, Moriarty AS, Strain WD. Neurological Dysfunction in Long COVID Should Not Be Labelled as Functional Neurological Disorder. Viruses. 2023; 15(3):783. https://doi.org/10.3390/v15030783 https://www.mdpi.com/1999-4915/15/3/783 (Full text)

Severe Course of COVID-19 and Long-COVID-19 in Children: Difficulties in Diagnosis

Abstract:

The question of COVID-19 and long-COVID-19 course in children remains unsolved. This infection in children, which is associated with COVID-19, can vary from asymptomatic to systemic damage of various systems. Multisystem inflammatory syndrome in children, associated with SARS-CoV-2 (MIS-C), is a serious condition in children and adolescents after experiencing COVID-19.
Published data on MIS-C have indicated that the inflammation can be registered in the gastrointestinal tract (60–100%), as well as in cardiovascular (80%), nervous (29–58%), and respiratory (21–65%) systems. However, with the changing characteristics of SARS-CoV-2, the manifestations of COVID-19 and long-COVID-19 in children have also been changing. Currently, there is no clear understanding of the development of severe COVID-19 and MIS-C in children, especially after being exposed to patients with COVID-19.
We presented two new clinical courses of multisystem inflammatory syndrome in children with severe multisystem damage after close contact to relatives with COVID-19 or long-COVID-19. Thus, high-risk children, who are positive for SARS-CoV-2 infection after contact with COVID-19 patients, should be clinically managed during the first few months. The identification of the disease complexity requires the involvement of neurologists, cardiologists, and other specialists.
Source: Vasichkina E, Kofeynikova O, Fetisova S, Starshinova AY, Sheyanova E, Vershinina T, Ryzhkov A, Skripnik A, Alekseeva D, Nechaeva E, Glushkova A, Kudlay D, Pervunina T, Starshinova A. Severe Course of COVID-19 and Long-COVID-19 in Children: Difficulties in Diagnosis. Life. 2023; 13(3):781. https://doi.org/10.3390/life13030781 https://www.mdpi.com/2075-1729/13/3/781 (Full text)

Not myopathic, but autonomic changes in patients with long-COVID syndrome: a case series

Abstract:

Introduction: Neurological sequelae following SARS-CoV-2 infection still represent a serious concern both for neurologists and neuroscientists. In our paper, we investigated pain, myalgia, and fatigue as symptoms in long-COVID patients with an electrophysiological approach, comprising the evaluation of sympathetic skin responses (SSRs) and quantitative electromyography (qEMG).

Materials and methods: Twelve patients were enrolled (mean age, 47.7 ± 11.6 years), referred to our attention because of myalgia, pain, or muscle cramps, which persisted about 6 months after the diagnosis of SARS-CoV-2 infection. They underwent conventional electroneurography (ENG), needle electromyography (EMG), and SSRs; moreover, qEMG was performed by sampling at least 20 motor unit potentials (20-30 MUPs) during weak voluntary contraction in deltoid and tibialis anterior muscles. The mean duration, amplitude, and percentage of polyphasic potentials were assessed and compared with healthy and age-matched volunteers.

Results: ENG did not disclose significant changes compared to healthy subjects; needle EMG did not reveal denervation activity. In addition, qEMG showed MUPs similar to those recorded in healthy volunteers in terms of polyphasia (deltoid: p = 0.24; TA: p = 0.35), MUP area (deltoid: p = 0.45; TA: p = 0.44), mean duration (deltoid: p = 0.06; TA: p = 0.45), and amplitude (deltoid: p = 0.27; TA: p = 0.63). SSRs were not recordable from lower limbs in seven patients (58%) and from the upper ones in three of them (25%).

Conclusion: Our data suggest an involvement of the autonomic system, with a focus on cholinergic efferent sympathetic activity, without any evidence of myopathic changes.

Source: Bocci T, Bertini A, Campiglio L, Botta S, Libelli G, Guidetti M, Priori A. Not myopathic, but autonomic changes in patients with long-COVID syndrome: a case series. Neurol Sci. 2023 Apr;44(4):1147-1153. doi: 10.1007/s10072-023-06637-8. Epub 2023 Feb 3. PMID: 36735149; PMCID: PMC9896447. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9896447/ (Full study)