Our staff editors continue to share exciting, interesting, and thought-provoking reading material in the recommended articles series.
This week, we would like to share several imteresting articles on COVID-19 and the brain.
Title: Neurological complications associated with Covid-19; molecular mechanisms and therapeutic approaches
Authors: Mohammad Mahboubi Mehrabani,Mohammad Sobhan Karvandi,Pedram Maafi,Mohammad Doroudian
Type: Review of Reviews in Medical Virology
With the progression of investigations on the pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), neurological complications have emerged as a critical aspect of the ongoing coronavirus disease 2019 (Covid-19) pandemic. Besides the well-known respiratory symptoms, many neurological manifestations such as anosmia/ageusia, headaches, dizziness, seizures, and strokes have been documented in hospitalised patients. The neurotropism background of coronaviruses has led to speculation that the neurological complications are caused by the direct invasion of SARS-CoV-2 into the nervous system. This invasion is proposed to occur through the infection of peripheral nerves or via systemic blood circulation, termed neuronal and haematogenous routes of invasion, respectively. On the other hand, aberrant immune responses and respiratory insufficiency associated with Covid-19 are suggested to affect the nervous system indirectly. Deleterious roles of cytokine storm and hypoxic conditions in blood-brain barrier disruption, coagulation abnormalities, and autoimmune neuropathies are well investigated in coronavirus infections, as well as Covid-19. Here, we review the latest discoveries focussing on possible molecular mechanisms of direct and indirect impacts of SARS-CoV-2 on the nervous system and try to elucidate the link between some potential therapeutic strategies and the molecular pathways.
Access this article: https://doi.org/10.1002/rmv.2334
Title: Metabolic correlates of olfactory dysfunction in COVID-19 and Parkinson’s disease (PD) do not overlap
Authors: Silvia Morbelli, Silvia Chiola, Maria Isabella Donegani, Dario Arnaldi, Matteo Pardini, Raffaele Mancini, Francesco Lanfranchi, Francesca D’amico, Matteo Bauckneht, Alberto Miceli, Erica Biassoni, Beatrice Orso, Emanuela Barisione, Luana Benedetti, Sambuceti Gianmario, Flavio Nobili
Type: Original Article of European Journal of Nuclear Medicine and Molecular Imaging
Hyposmia is a common feature of COVID-19 and Parkinson’s disease (PD). As parkinsonism has been reported after COVID-19, a link has been hypothesized between SARS-CoV2 infection and PD. We aimed to evaluate brain metabolic correlates of isolated persistent hyposmia after mild-to-moderate COVID-19 and to compare them with metabolic signature of hyposmia in drug-naïve PD patients.
Forty-four patients who experienced hyposmia after SARS-COV2 infection underwent brain [18F]-FDG PET in the first 6 months after recovery. Olfaction was assessed by means of the 16-item “Sniffin’ Sticks” test and patients were classified as with or without persistent hyposmia (COVID-hyposmia and COVID-no-hyposmia respectively). Brain [18F]-FDG PET of post-COVID subgroups were compared in SPM12. COVID-hyposmia patients were also compared with eighty-two drug-naïve PD patients with hyposmia. Multiple regression analysis was used to identify correlations between olfactory test scores and brain metabolism in patients’ subgroups.
COVID-hyposmia patients (n = 21) exhibited significant hypometabolism in the bilateral gyrus rectus and orbitofrontal cortex with respect to COVID-non-hyposmia (n = 23) (p < 0.002) and in middle and superior temporal gyri, medial/middle frontal gyri, and right insula with respect to PD-hyposmia (p < 0.012). With respect to COVID-hyposmia, PD-hyposmia patients showed hypometabolism in inferior/middle occipital gyri and cuneus bilaterally. Olfactory test scores were directly correlated with metabolism in bilateral rectus and medial frontal gyri and in the right middle temporal and anterior cingulate gyri in COVID-hyposmia patients (p < 0.006) and with bilateral cuneus/precuneus and left lateral occipital cortex in PD-hyposmia patients (p < 0.004).
Metabolic signature of persistent hyposmia after COVID-19 encompasses cortical regions involved in olfactory perception and does not overlap metabolic correlates of hyposmia in PD.
Access this article: https://doi.org/10.1007/s00259-021-05666-9
Title: Covid-19 Infection and Parkinsonism: Is There a Link?
Authors: Rabia Bouali-Benazzouz, Abdelhamid Benazzouz
Type: Review of Movement Disorders
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an opportunistic pathogen that infects the upper respiratory tract in humans and causes serious illness, including fatal pneumonia and neurological disorders. Several studies have reported that SARS-CoV-2 may worsen the symptoms of Parkinson's disease (PD), with the potential to increase mortality rates in patients with advanced disease. The potential risk of SARS-CoV-2 to induce PD has also been suggested because the virus can enter the brain, where it can trigger cellular processes involved in neurodegeneration. In this review, we will discuss the potential of SARS-CoV-2 to exacerbate and cause certain neurological disorders, including PD. We will then elucidate its impact on the brain while examining its pathways and mechanisms of action.
Access this article: https://doi.org/10.1002/mds.28680
Title: Brain Disease Network Analysis to Elucidate the Neurological Manifestations of COVID-19
Authors: Kartikay Prasad, Suliman Yousef AlOmar, Saeed Awad M. Alqahtani, Md. Zubbair Malik, Vijay Kumar
Type: Original Article of Molecular Neurobiology
Although COVID-19 largely causes respiratory complications, it can also lead to various extrapulmonary manifestations resulting in higher mortality and these comorbidities are posing a challenge to the health care system. Reports indicate that 30–60% of patients with COVID-19 suffer from neurological symptoms. To understand the molecular basis of the neurologic comorbidity in COVID-19 patients, we have investigated the genetic association between COVID-19 and various brain disorders through a systems biology-based network approach and observed a remarkable resemblance. Our results showed 123 brain-related disorders associated with COVID-19 and form a high-density disease-disease network. The brain-disease-gene network revealed five highly clustered modules demonstrating a greater complexity of COVID-19 infection. Moreover, we have identified 35 hub proteins of the network which were largely involved in the protein catabolic process, cell cycle, RNA metabolic process, and nuclear transport. Perturbing these hub proteins by drug repurposing will improve the clinical conditions in comorbidity. In the near future, we assumed that in COVID-19 patients, many other neurological manifestations will likely surface. Thus, understanding the infection mechanisms of SARS-CoV-2 and associated comorbidity is a high priority to contain its short- and long-term effects on human health. Our network-based analysis strengthens the understanding of the molecular basis of the neurological manifestations observed in COVID-19 and also suggests drug for repurposing.
Access this article: https://doi.org/10.1007/s12035-020-02266-w
Title: COVID-19 associated nervous system manifestations
Authors: Fatima Khatoon, Kartikay Prasad, Vijay Kumar
Type: Original Article of Sleep Medicine
The novel coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a global pandemic in the last year. Along with major respiratory distress, a myriad of neurological manifestations was also reported to be associated with COVID-19 patients. These cases indicate that SARS-CoV-2 can be considered as an opportunistic pathogen of the brain. SARS-CoV-2 enters the brain through the olfactory bulb, retrograde axonal transport from peripheral nerve endings, or via hematogenous or lymphatic routes. Notably, COVID-19 infection can cause or even present with different neurological features including encephalopathy, impaired consciousness, confusion, agitation, seizure, ataxia, headache, anosmia, ageusia, neuropathies, and neurodegenerative diseases. In this paper, we provide a brief review of observed neurological manifestations associated with COVID-19.
Access this article: https://doi.org/10.1016/j.sleep.2021.07.005
Title: Hyperactivation of P2X7 receptors as a culprit of COVID-19 neuropathology
Authors: Deidiane Elisa Ribeiro, Ágatha Oliveira-Giacomelli, Talita Glaser, Vanessa F. Arnaud-Sampaio, Roberta Andrejew, Luiz Dieckmann, Juliana Baranova, Claudiana Lameu, Mariusz Z. Ratajczak, Henning Ulrich
Type: Review Article of Molecular Psychiatry
Scientists and health professionals are exhaustively trying to contain the coronavirus disease 2019 (COVID-19) pandemic by elucidating viral invasion mechanisms, possible drugs to prevent viral infection/replication, and health cares to minimize individual exposure. Although neurological symptoms are being reported worldwide, neural acute and long-term consequences of SARS-CoV-2 are still unknown. COVID-19 complications are associated with exacerbated immunoinflammatory responses to SARS-CoV-2 invasion. In this scenario, pro-inflammatory factors are intensely released into the bloodstream, causing the so-called “cytokine storm”. Both pro-inflammatory factors and viruses may cross the blood–brain barrier and enter the central nervous system, activating neuroinflammatory responses accompanied by hemorrhagic lesions and neuronal impairment, which are largely described processes in psychiatric disorders and neurodegenerative diseases. Therefore, SARS-CoV-2 infection could trigger and/or worse brain diseases. Moreover, patients with central nervous system disorders associated to neuroimmune activation (e.g. depression, Parkinson’s and Alzheimer’s disease) may present increased susceptibility to SARS-CoV-2 infection and/or achieve severe conditions. Elevated levels of extracellular ATP induced by SARS-CoV-2 infection may trigger hyperactivation of P2X7 receptors leading to NLRP3 inflammasome stimulation as a key mediator of neuroinvasion and consequent neuroinflammatory processes, as observed in psychiatric disorders and neurodegenerative diseases. In this context, P2X7 receptor antagonism could be a promising strategy to prevent or treat neurological complications in COVID-19 patients.
Access this article: https://doi.org/10.1038/s41380-020-00965-3