https://cronfa.swan.ac.uk/Record/cronfa54196/Download/54196__17493__47815979be224dde9a7b3f9b037ce7ec.pdf

Multidisciplinary research priorities for the COVID-19 pandemic: a call for action for mental health science.

http://academic.oup.com/milmed/article-pdf/146/7/506/24126715/milmed-146-7-506.pdf

Goodman and Gilman's The Pharmacological Basis of Therapeutics

The recent outbreak of coronavirus infectious disease 2019 (COVID-19) has gripped the world with apprehension and has evoked a scare of epic proportion regarding its potential to spread and infect ...

/pdf/evidence-of-the-covid-19-virus-targeting-the-cns-tissue-34hjln8bvw.pdf

Evidence of the COVID-19 Virus Targeting the CNS: Tissue Distribution, Host–Virus Interaction, and Proposed Neurotropic Mechanisms

Viral infections have detrimental impacts on neurological functions, and even to cause severe neurological damage. Very recently, coronaviruses (CoV), especially severe acute respiratory syndrome CoV 2 (SARS-CoV-2), exhibit neurotropic properties and may also cause neurological diseases. It is reported that CoV can be found in the brain or cerebrospinal fluid. The pathobiology of these neuroinvasive viruses is still incompletely known, and it is therefore important to explore the impact of CoV infections on the nervous system. Here, we review the research into neurological complications in CoV infections and the possible mechanisms of damage to the nervous system.

/pdf/nervous-system-involvement-after-infection-with-covid-19-and-1wvkcokhlc.pdf

Nervous system involvement after infection with COVID-19 and other coronaviruses

The newly identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19, a pandemic respiratory disease. Moreover, thromboembolic events throughout the body, including in the CNS, have been described. Given the neurological symptoms observed in a large majority of individuals with COVID-19, SARS-CoV-2 penetrance of the CNS is likely. By various means, we demonstrate the presence of SARS-CoV-2 RNA and protein in anatomically distinct regions of the nasopharynx and brain. Furthermore, we describe the morphological changes associated with infection such as thromboembolic ischemic infarction of the CNS and present evidence of SARS-CoV-2 neurotropism. SARS-CoV-2 can enter the nervous system by crossing the neural-mucosal interface in olfactory mucosa, exploiting the close vicinity of olfactory mucosal, endothelial and nervous tissue, including delicate olfactory and sensory nerve endings. Subsequently, SARS-CoV-2 appears to follow neuroanatomical structures, penetrating defined neuroanatomical areas including the primary respiratory and cardiovascular control center in the medulla oblongata.

/pdf/olfactory-transmucosal-sars-cov-2-invasion-as-a-port-of-2djge43d7c.pdf

Olfactory transmucosal SARS-CoV-2 invasion as a port of central nervous system entry in individuals with COVID-19.

The recent outbreak of COVID-19 caused by SARS-CoV-2 coronavirus has turned the world into chaos with its ominously high rate of transmissions. As the SARS-CoV-2 infection has become pandemic, the scientific community is in a race against time to beat the COVID19 by unraveling molecular targets and discover epitopes in the protein sequences of SARS-CoV-2 for vaccines/antibodies synthesis. It has been reported that in addition to the conventional respiratory complains of flu, patients are also exhibiting neurological signs and symptoms. Recently, the report of a patient with COVID-19 exhibiting loss of the involuntary process of breathing1 controlled by the inspiratory area in the brainstem, is alarming. Additionally, neurological deficits reported in uncomplicated and complicated patients with COVID-192 from hospitals in Wuhan, China, are convincing enough that the neurological deficits could be ongoing in the recent outbreak without getting noticed. As the recent outbreak has now spread to almost all of the continents and has become pandemic, we are in the early phases of our attempts to understand the syndromic complexity of the COVID-19. The SARS-CoV-2 causing COVID-19 can take two pathways to involve the brain (Figure 1). Early occurrences of loss of smell, ataxia, and convulsions should be further evaluated for CNS involvement by SARS-CoV-2. The clinicians throughout the world in general, and Wuhan, China, in particular, are getting the firsthand to study and report the real-time clinical presentations of the patients affected by COVID19. The prognostic and diagnostic significance of neurological sign and symptoms in COVID-19 patients can be gauged by fact that the protocol designed to investigate the First Few X cases (FFX) and their close contacts by the World Health Organization (WHO), includes a separate section for “other neurological signs” in addition to separate columns for respiratory symptoms.3 Additionally, reports of COVID-19-affected individuals experiencing convulsions in prevalent areas is alarming and need to be distinguished from febrile convolution that is expected to occur with high-grade fever in patients with COVID-19. Our experience with taxonomically related SARS-CoV patients in the past has proven beyond doubt the coronaviruses to affect the brain. Of many examples from the past, was a case where SARS-CoV was isolated from the brain of a patient who had exhibited features of neurological deficits on 28th day of infection.4 In past outbreaks with SARS-CoV, it has been shown that it targets the CNS5 and the reports that the brain also is an additional target of SARS-CoV4 raises the possibility of the presentation of more patients with neurological manifestations in the ongoing outbreak of COIVD-19. Also, SARS-CoV has been isolated from brain tissue with edema and neuronal degeneration as seen at autopsies with immunohistochemistry, in situ hybridization, and electron microscopic confirmation of viral infection of the neurons.6 It would not be surprising to see the COVID-19 virus following the same trend as both viruses are near identical taxonomically. As the pandemic is in effect at present, a detailed timeline of the syndromic neurological manifestation in COVID-19 will emerge as more studies get published on complicated and uncomplicated cases of COVID-19. Though the understanding of the pathogenetic mechanisms underlying the CNS invasion will be revealed in time, there is an urgent need to distinguish between neurologically affected CVOID-19 patients and those who do not exhibit the sign and symptoms of CNS involvement. The hematogenous route appears to be the likely pathway for SARS-CoV-2 to reach the brain, but other routes to the CNS like across the cribriform plate (Figure 1B) of the ethmoid bone in proximity to the olfactory bulb7 should be taken into consideration in cases of early-phase COVID-19-affected patients who exhibit loss of smell and taste accompanied with neurological signs and symptoms. Studies believe that direct SARS-CoV infection of the human CNS does occur in some patients.8 It is also important to mention here that the neurological signs and symptoms observed in the COVID-19 cases could be a manifestation of hypoxia, respiratory, and metabolic acidosis at an advanced stage of the disease, but reasonably, a differential diagnosis of these cases is needed, which could prove lifesaving. The later distinction also appears to be important from the vantage point of selecting a treatment regimen, as management of the COVID-19 cases with neurological involvement would require more specific and aggressive treatments as compared to the patients without it. The significance of a thorough neurological assessment of COVID19 patients cannot be overemphasized which can rule-in or rule out a neurological deficit of a patient admitted after serological tests confirming the diagnosis of COVID-19. Presence of neurological deficits

https://onlinelibrary.wiley.com/doi/pdf/10.1111/cns.13372

Neurological manifestations in COVID-19 caused by SARS-CoV-2.

With the ongoing pandemic of coronavirus diseases (COVID-19) caused by SARS-CoV-2, there has been a surge in research and publications related to its pathogenesis and the clinical presentation of the affected patients. Many aspects of this novel virus have raised confusion including the naming of the virus and the disease it causes, the staging of its clinical presentation to highlight a few such occurrences. An emerging aspect of the clinical presentation related to COVID-19 is the long-term effects, which in the absence of any consensus has been termed as long-covid and long-haulers in recent publications. As the COVID-19 is a zoonotic infection and comes under a medically related disease, the term chronic covid syndrome (CCS) would be a more traditional way of symbolizing the so-called long-covid and long-haulers in COVID-19. Though the renaming of this chronic state of now well-recognized chronicity seen in COVID-19 would not affect its prognosis, this is much needed to recognize this entity with a more appropriate nomenclature as published work is making its way into databases like Google Scholar and PubMed. This article is protected by copyright. All rights reserved.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/jmv.26624

Chronic COVID Syndrome: Need for an appropriate medical terminology for Long-COVID and COVID Long-Haulers.

Amid our understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the mechanisms involved in the causation of acute-phase coronavirus disease (COVID-19), we have come across clinical cases that have been shown to run a protracted course of COVID-19 with complex clinical findings related to organ systems in general and the CNS in particular that deserve to be addressed in the COVID long-haulers, for which the more clinically-related term chronic COVID syndrome (CCS) has been coined recently. An in-depth understanding of the mechanism that forms the basis of CCS and neurological deficits in CCS is needed as this can help in determining the management of cases of neuro-COVID, which is emerging as a less lethal but more disabling disease state. This Viewpoint highlights this syndrome, the possible pathogenetic pathways involved, and the treatment approaches that can be taken to help manage COVID long-haulers in CCS.

Deleterious Outcomes in Long-Hauler COVID-19: The Effects of SARS-CoV-2 on the CNS in Chronic COVID Syndrome.

Coronavirus disease-2019 (COVID-19) was declared a global pandemic on 11 March 2020. Scientists and clinicians must acknowledge that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has the potential to attack the human body in multiple ways simultaneously and exploit any weaknesses of its host. A multipronged attack could potentially explain the severity and extensive variety of signs and symptoms observed in patients with COVID-19. Understanding the diverse tactics of this virus to infect the human body is both critical and incredibly complex. Although patients diagnosed with COVID-19 have primarily presented with pulmonary involvement, viral invasion, and injury to diverse end organs is also prevalent and well documented in these patients, but has been largely unheeded. Human organs known for angiotensin-converting enzyme 2 (ACE2) expression including the gastrointestinal tract, kidneys, heart, adrenals, brain, and testicles are examples of extra pulmonary tissues with confirmed invasion by SARS-CoV-2. Initial multiple organ involvement may present with vague signs and symptoms to alert health care professionals early in the course of COVID-19. Another example of an ongoing, yet neglected element of the syndromic features of COVID-19, are the reported findings of loss of smell, altered taste, ataxia, headache, dizziness, and loss of consciousness, which suggest a potential for neural involvement. In this review, we further deliberate on the neuroinvasive potential of SARS-CoV-2, the neurologic symptomology observed in COVID-19, the host-virus interaction, possible routes of SARS-CoV-2 to invade the central nervous system, other neurologic considerations for patients with COVID-19, and a collective call to action.

Abdul Mannan Baig

Papers

Evidence of the COVID-19 Virus Targeting the CNS: Tissue Distribution, Host–Virus Interaction, and Proposed Neurotropic Mechanisms

Neurological manifestations in COVID-19 caused by SARS-CoV-2.

Chronic COVID Syndrome: Need for an appropriate medical terminology for Long-COVID and COVID Long-Haulers.

Deleterious Outcomes in Long-Hauler COVID-19: The Effects of SARS-CoV-2 on the CNS in Chronic COVID Syndrome.

Potential neuroinvasive pathways of SARS-CoV-2: Deciphering the spectrum of neurological deficit seen in coronavirus disease-2019 (COVID-19).