Tag: long covid neurology

An Unexpected Journey: The Lived Experiences of Patients with Long-Term Cognitive Sequelae After Recovering from COVID-19

Abstract:

This current study explored the lived experiences of patients with long-term cognitive sequelae after recovering from COVID-19. A qualitative design with in-depth interviews and an analysis inspired by Ricoeur’s interpretation theory was utilised. Contracting COVID-19 and suffering long-term sequelae presented as a life-altering event with significant consequences for one’s social, psychological and vocational being in the world in the months following the infection.

Patients living with long-term cognitive sequelae after COVID-19 were in an unknown life situation characterised by feelings of anxiety, uncertainty and concerns about the future, significantly disrupting their life trajectory and forcing them to change their ways of life. While awaiting studies on treatment, symptom management and recovery after persistent sequelae of COVID-19, clinicians and researchers may find inspiration in experiences of other health conditions with similar phenomenology, such as ME/chronic fatigue syndrome and chronic headaches.

Source: Loft MI, Foged EM, Koreska M. An Unexpected Journey: The Lived Experiences of Patients with Long-Term Cognitive Sequelae After Recovering from COVID-19. Qual Health Res. 2022 May 21:10497323221099467. doi: 10.1177/10497323221099467. Epub ahead of print. PMID: 35603563. https://pubmed.ncbi.nlm.nih.gov/35603563/

Neurological and Psychiatric Symptoms of COVID-19: A Narrative Review

Abstract:

Recently dubbed Long COVID or Long-Haul COVID, those recovering from the initial COVID-19 infection may maintain clinical signs for longer than two or more weeks following the initial onset of the infection. The virus can gain entry into the CNS through axonal transport mediated through the olfactory nerve or hematogenous spread and can also cross the blood–brain barrier to access the temporal lobe and the brainstem. The neurologic and neuropsychiatric symptoms associated with COVID-19 patients are becoming a highly studied area due to the increased frequency of reported cases.
Multiple hospital case series and observational studies have found a headache to be a common symptom among patients who are symptomatic with the SARS-CoV-2 virus. The headache described by many of these patients is similar to new daily persistent headache (NDPH). NDPH potentially develops in response to pro-inflammatory cytokines during a persistent systemic or CNS inflammation, mostly due to the initial infection. The treatments investigated were high-dose steroids, tetracycline derivatives, onabotulinum toxin type A, and long-term multidrug regimens. Among the identified symptoms of post-COVID-19 viral illness, fatigue appears to be the most ubiquitous. High-dose vitamin C is currently a suggested therapy proposed for its antioxidant, anti-inflammatory, and immunomodulatory properties.
The mental health consequences of this diagnosis are being identified among large portions of COVID-19 survivors. Among these consequences, cases of major depressive disorder (MDD) and anxiety are being reported and closely examined. The aim of this narrative review is to highlight the neurological and psychiatric symptoms that have been associated with Long-Haul COVID and their possible treatments.
Source: Edinoff AN, Chappidi M, Alpaugh ES, Turbeville BC, Falgoust EP, Cornett EM, Murnane KS, Kaye AM, Kaye AD. Neurological and Psychiatric Symptoms of COVID-19: A Narrative Review. Psychiatry International. 2022; 3(2):158-168. https://doi.org/10.3390/psychiatryint3020013 https://www.mdpi.com/2673-5318/3/2/13/htm (Full text)

SARS-CoV-2 is associated with changes in brain structure in UK Biobank

Abstract:

There is strong evidence for brain-related abnormalities in COVID-19 1-13 . It remains unknown however whether the impact of SARS-CoV-2 infection can be detected in milder cases, and whether this can reveal possible mechanisms contributing to brain pathology. Here, we investigated brain changes in 785 UK Biobank participants (aged 51-81) imaged twice, including 401 cases who tested positive for infection with SARS-CoV-2 between their two scans, with 141 days on average separating their diagnosis and second scan, and 384 controls. The availability of pre-infection imaging data reduces the likelihood of pre-existing risk factors being misinterpreted as disease effects.

We identified significant longitudinal effects when comparing the two groups, including: (i) greater reduction in grey matter thickness and tissue-contrast in the orbitofrontal cortex and parahippocampal gyrus, (ii) greater changes in markers of tissue damage in regions functionally-connected to the primary olfactory cortex, and (iii) greater reduction in global brain size. The infected participants also showed on average larger cognitive decline between the two timepoints. Importantly, these imaging and cognitive longitudinal effects were still seen after excluding the 15 cases who had been hospitalised. These mainly limbic brain imaging results may be the in vivo hallmarks of a degenerative spread of the disease via olfactory pathways, of neuroinflammatory events, or of the loss of sensory input due to anosmia. Whether this deleterious impact can be partially reversed, or whether these effects will persist in the long term, remains to be investigated with additional follow up.

Source: Douaud G, Lee S, Alfaro-Almagro F, Arthofer C, Wang C, McCarthy P, Lange F, Andersson JLR, Griffanti L, Duff E, Jbabdi S, Taschler B, Keating P, Winkler AM, Collins R, Matthews PM, Allen N, Miller KL, Nichols TE, Smith SM. SARS-CoV-2 is associated with changes in brain structure in UK Biobank. medRxiv [Preprint]. 2022 Mar 2:2021.06.11.21258690. doi: 10.1101/2021.06.11.21258690. Update in: Nature. 2022 Mar 7;: PMID: 34189535; PMCID: PMC8240690. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9046077/ (Full text)

Dissecting the Molecular Mechanisms Surrounding Post-COVID-19 Syndrome and Neurological Features

Abstract:

Many of the survivors of the novel coronavirus disease (COVID-19) are suffering from persistent symptoms, causing significant morbidity and decreasing their quality of life, termed “post-COVID-19 syndrome” or “long COVID”. Understanding the mechanisms surrounding PCS is vital to developing the diagnosis, biomarkers, and possible treatments.

Here, we describe the prevalence and manifestations of PCS, and similarities with previous SARS epidemics. Furthermore, we look at the molecular mechanisms behind the neurological features of PCS, where we highlight important neural mechanisms that may potentially be involved and pharmacologically targeted, such as glutamate reuptake in astrocytes, the role of NMDA receptors and transporters (EAAT2), ROS signaling, astrogliosis triggered by NF-κB signaling, KNDy neurons, and hypothalamic networks involving Kiss1 (a ligand for the G-protein-coupled receptor 54 (GPR54)), among others. We highlight the possible role of reactive gliosis following SARS-CoV-2 CNS injury, as well as the potential role of the hypothalamus network in PCS manifestations.

Source: Mohamed MS, Johansson A, Jonsson J, Schiöth HB. Dissecting the Molecular Mechanisms Surrounding Post-COVID-19 Syndrome and Neurological Features. Int J Mol Sci. 2022 Apr 12;23(8):4275. doi: 10.3390/ijms23084275. PMID: 35457093. https://www.mdpi.com/1422-0067/23/8/4275/htm (Full text)

Post-COVID-19 syndrome: persistent neuroimaging changes and symptoms 9 months after initial infection

Abstract:

A previously healthy and active middle-aged woman acquired COVID-19 as an occupational exposure with subsequent persistent post-COVID-19 symptoms including headache, dyspnoea on exertion, chest pressure, tachycardia, anosmia, parosmia, persistent myalgia, vertigo, cognitive decline and fatigue. She presented to a tertiary medical centre for further evaluation after 9 months of persistent symptoms and had a largely unremarkable workup with the exception of a persistently elevated monocyte chemoattractant protein 1, blunted cardiovagal response and non-specific scattered areas of low-level hypometabolism at the bilateral frontal, left precuneus, occipital and parietal regions on PET scan.

Source: Grach SL, Ganesh R, Messina SA, Hurt RT. Post-COVID-19 syndrome: persistent neuroimaging changes and symptoms 9 months after initial infection. BMJ Case Rep. 2022 Apr 8;15(4):e248448. doi: 10.1136/bcr-2021-248448. PMID: 35396239. https://casereports.bmj.com/content/15/4/e248448.long (Full text)

The use of amantadine in the prevention of progression and treatment of COVID-19 symptoms in patients infected with the SARS-CoV-2 virus (COV-PREVENT): Study rationale and design

Abstract:

Background: COVID-19, a disease caused by infection with the SARS-CoV-2 virus, is asymptomatic or mildly symptomatic in most cases. Some patients, usually burdened with risk factors develop acute respiratory failure and other organ dysfunction. In such cases, the mortality rate is very high despite the use of intensive therapy. Amantadine has complex activity including antiviral, antiinflammatory and dopaminergic effects. This clinical trial will assess the efficacy and safety of amantadine in the prevention of COVID-19 progression toward acute respiratory failure and neurological complications.

Methods and results: The trial will enroll 200 patients who are positive for SARS-CoV-2 infection and have one or more risk factors for worsening the disease. These patients will be included as hospitalized or ambulatory subjects for early treatment of illness. The recruitment will take place in 8 centers covering different regions of Poland. For 14 days they will be given either 200 mg of amantadine a day or placebo. Our hypothesis is a considerable reduction in the number of patients with progression toward respiratory insufficiency or neurological complications thanks to the treatment of amantadine.

Conclusions: Demonstrating the efficacy and safety of amantadine treatment in improving the clinical condition of patients diagnosed with COVID-19 is of great importance in combating the effects of the pandemic. It has potential to influence on the severity and course of neurological complications, which are very common and persist long after the infection as long-COVID syndrome.

Clinical trial registration: www.

Clinicaltrials: gov identification no. NCT04854759; Eudra CT number: 2021-001144-98 (dated 27 February 2021).

Source: Rejdak K, Fiedor P, Bonek R, Goch A, Gala-Błądzińska A, Chełstowski W, Łukasiak J, Kiciak S, Dąbrowski P, Dec M, Król ZJ, Papuć E, Zasybska A, Segiet A, Grieb P. The use of amantadine in the prevention of progression and treatment of COVID-19 symptoms in patients infected with the SARS-CoV-2 virus (COV-PREVENT): Study rationale and design. Contemp Clin Trials. 2022 Apr 4;116:106755. doi: 10.1016/j.cct.2022.106755. Epub ahead of print. PMID: 35390511; PMCID: PMC8978450. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8978450/ (Full text)

Neuropathology and virus in brain of SARS-CoV-2 infected non-human primates

Abstract:

Neurological manifestations are a significant complication of coronavirus disease (COVID-19), but underlying mechanisms aren’t well understood. The development of animal models that recapitulate the neuropathological findings of autopsied brain tissue from patients who died from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are critical for elucidating the neuropathogenesis of infection and disease.

Here, we show neuroinflammation, microhemorrhages, brain hypoxia, and neuropathology that is consistent with hypoxic-ischemic injury in SARS-CoV-2 infected non-human primates (NHPs), including evidence of neuron degeneration and apoptosis. Importantly, this is seen among infected animals that do not develop severe respiratory disease, which may provide insight into neurological symptoms associated with “long COVID”. Sparse virus is detected in brain endothelial cells but does not associate with the severity of central nervous system (CNS) injury.

We anticipate our findings will advance our current understanding of the neuropathogenesis of SARS-CoV-2 infection and demonstrate SARS-CoV-2 infected NHPs are a highly relevant animal model for investigating COVID-19 neuropathogenesis among human subjects.

Source: Rutkai I, Mayer MG, Hellmers LM, Ning B, Huang Z, Monjure CJ, Coyne C, Silvestri R, Golden N, Hensley K, Chandler K, Lehmicke G, Bix GJ, Maness NJ, Russell-Lodrigue K, Hu TY, Roy CJ, Blair RV, Bohm R, Doyle-Meyers LA, Rappaport J, Fischer T. Neuropathology and virus in brain of SARS-CoV-2 infected non-human primates. Nat Commun. 2022 Apr 1;13(1):1745. doi: 10.1038/s41467-022-29440-z. PMID: 35365631. https://www.nature.com/articles/s41467-022-29440-z (Full text)

Magnetic Resonance Imaging Confirmed Olfactory Bulb Reduction in Long COVID-19: Literature Review and Case Series

Abstract:

An altered sense of smell and taste was recognized as one of the most characteristic symptoms of coronavirus infection disease (COVID-19). Despite most patients experiencing a complete functional resolution, there is a 21.3% prevalence of persistent alteration at 12 months after infection. To date, magnetic resonance imaging (MRI) findings in these patients have been variable and not clearly defined. We aimed to clarify radiological alterations of olfactory pathways in patients with long COVID-19 characterized by olfactory dysfunction.
A comprehensive review of the English literature was performed by analyzing relevant papers about this topic. A case series was presented: all patients underwent complete otorhinolaryngology evaluation including the Sniffin’ Sticks battery test. A previous diagnosis of SARS-CoV-2 infection was confirmed by positive swabs. The MRIs were acquired using a 3.0T MR scanner with a standardized protocol for olfactory tract analysis. Images were first analysed by a dedicated neuroradiologist and subsequently reviewed and compared with the previous available MRIs.
The review of the literature retrieved 25 studies; most cases of olfactory dysfunction more than 3 months after SARS-CoV-2 infection showed olfactory bulb (OB) reduction. Patients in the personal case series had asymmetry and a reduction in the volume of the OB. This evidence was strengthened by the comparison with a previous MRI, where the OBs were normal. The results preliminarily confirmed OB reduction in cases of long COVID-19 with an altered sense of smell. Further studies are needed to clarify the epidemiology, pathophysiology and prognosis.
Source: Frosolini A, Parrino D, Fabbris C, Fantin F, Inches I, Invitto S, Spinato G, Filippis CD. Magnetic Resonance Imaging Confirmed Olfactory Bulb Reduction in Long COVID-19: Literature Review and Case Series. Brain Sciences. 2022; 12(4):430. https://doi.org/10.3390/brainsci12040430 (Full text)

Mechanisms of coronavirus infectious disease 2019-related neurologic diseases

Abstract:

Purpose of review: As of January 8, 2022, a global pandemic caused by infection with severe acute respiratory syndrome coronavirus (SARS-CoV)-2, a new RNA virus, has resulted in 304,896,785 cases in over 222 countries and regions, with over 5,500,683 deaths (www.worldometers.info/coronavirus/). Reports of neurological and psychiatric symptoms in the context of coronavirus infectious disease 2019 (COVID-19) range from headache, anosmia, and dysgeusia, to depression, fatigue, psychosis, seizures, delirium, suicide, meningitis, encephalitis, inflammatory demyelination, infarction, and acute hemorrhagic necrotizing encephalopathy. Moreover, 30-50% of COVID-19 survivors develop long-lasting neurologic symptoms, including a dysexecutive syndrome, with inattention and disorientation, and/or poor movement coordination. Detection of SARS-CoV-2 RNA within the central nervous system (CNS) of patients is rare, and mechanisms of neurological damage and ongoing neurologic diseases in COVID-19 patients are unknown. However, studies demonstrating viral glycoprotein effects on coagulation and cerebral vasculature, and hypoxia- and cytokine-mediated coagulopathy and CNS immunopathology suggest both virus-specific and neuroimmune responses may be involved. This review explores potential mechanistic insights that could contribute to COVID-19-related neurologic disease.

Recent findings: While the development of neurologic diseases during acute COVID-19 is rarely associated with evidence of viral neuroinvasion, new evidence suggests SARS-CoV-2 Spike (S) protein exhibits direct inflammatory and pro-coagulation effects. This, in conjunction with immune dysregulation resulting in cytokine release syndrome (CRS) may result in acute cerebrovascular or neuroinflammatory diseases. Additionally, CRS-mediated loss of blood-brain barrier integrity in specific brain regions may contribute to the expression of proinflammatory mediators by neural cells that may impact brain function long after resolution of acute infection. Importantly, host co-morbid diseases that affect vascular, pulmonary, or CNS function may contribute to the type of neurologic disease triggered by SARS-COV-2 infection.

Summary: Distinct effects of SARS-CoV-2 S protein and CNS compartment- and region-specific responses to CRS may underlie acute and chronic neuroinflammatory diseases associated with COVID-19.

Source: Klein RS. Mechanisms of coronavirus infectious disease 2019-related neurologic diseases. Curr Opin Neurol. 2022 Mar 11. doi: 10.1097/WCO.0000000000001049. Epub ahead of print. PMID: 35283461. https://pubmed.ncbi.nlm.nih.gov/35283461/

Long-term follow-up of dynamic brain changes in patients recovered from COVID-19 without neurological manifestations

Abstract:

BACKGROUND. After the initial surge in COVID-19 cases, large numbers of patients were discharged from a hospital without assessment of recovery. Now, an increasing number of patients report postacute neurological sequelae, known as “long COVID” — even those without specific neurological manifestations in the acute phase.

METHODS. Dynamic brain changes are crucial for a better understanding and early prevention of “long COVID.” Here, we explored the cross-sectional and longitudinal consequences of COVID-19 on the brain in 34 discharged patients without neurological manifestations. Gray matter morphology, cerebral blood flow (CBF), and volumes of white matter tracts were investigated using advanced magnetic resonance imaging techniques to explore dynamic brain changes from 3 to 10 months after discharge.

RESULTS. Overall, the differences of cortical thickness were dynamic and finally returned to the baseline. For cortical CBF, hypoperfusion in severe cases observed at 3 months tended to recover at 10 months. Subcortical nuclei and white matter differences between groups and within subjects showed various trends, including recoverable and long-term unrecovered differences. After a 10-month recovery period, a reduced volume of nuclei in severe cases was still more extensive and profound than that in mild cases.

CONCLUSION. Our study provides objective neuroimaging evidence for the coexistence of recoverable and long-term unrecovered changes in 10-month effects of COVID-19 on the brain. The remaining potential abnormalities still deserve public attention, which is critically important for a better understanding of “long COVID” and early clinical guidance toward complete recovery.

Source: Tian Tian, et al. Long-term follow-up of dynamic brain changes in patients recovered from COVID-19 without neurological manifestations. Published February 22, 2022
Citation Information: JCI Insight. 2022;7(4):e155827. https://doi.org/10.1172/jci.insight.155827. (Full text)