The possible entry of SARS‐CoV‐2 to reach the brain via cribriform plate (B) or after systemic circulatory dissemination following infection of the lung (C), in early or late phases of COVID‐19 may ...result in loss of involuntary control of breathing resulting in acute respiratory insufficiency requiring assisted ventilation (D) 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 COVID‐19. 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. 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 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 ...humans worldwide. As we are in the midst of an ongoing pandemic of COVID-19, scientists are struggling to understand how it resembles and differs from the severe acute respiratory syndrome coronavirus (SARS-CoV) at the genomic and transcriptomic level. In a short time following the outbreak, it has been shown that, similar to SARS-CoV, COVID-19 virus exploits the angiotensin-converting enzyme 2 (ACE2) receptor to gain entry inside the cells. This finding raises the curiosity of investigating the expression of ACE2 in neurological tissue and determining the possible contribution of neurological tissue damage to the morbidity and mortality caused by COIVD-19. Here, we investigate the density of the expression levels of ACE2 in the CNS, the host–virus interaction and relate it to the pathogenesis and complications seen in the recent cases resulting from the COVID-19 outbreak. Also, we debate the need for a model for staging COVID-19 based on neurological tissue involvement.
With the ongoing pandemic of coronavirus disease (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), our knowledge of the pathogenesis of COVID-19 is still in its ...infancy. Almost every aspect of the pathogen remains largely unknown, ranging from mechanisms involved in infection transmission, interplay with the human immune system, and covert mechanisms of end-organ damage. COVID-19 has manifested itself worldwide with a syndromic appearance that is dominated by respiratory dysregulations. While clinicians are focused on correcting respiratory homeostasis, echoing the original SARS, SARS-CoV-2 is also invading other end-organs, which may not exhibit overt clinical features. Nervous system involvement was not initially considered to play a significant role in patients with COVID-19. However, since this viewpoint was initially published, multiple studies have been released regarding the possible neurovirulence of SARS-CoV-2. In our previous viewpoint, we implored our colleagues to recognize the covert tactics of SARS-CoV-2 and emphasized that symptoms like anosmia, dysgeusia, ataxia, and altered mental status could be early signs of the neurotropic potential of this virus. The past few weeks, after the viewpoint surfaced, it was noticed that it has enabled clinicians and healthcare professionals to compute the neurovirulence associated with SARS-CoV-2 in COVID-19 patients, as evidenced by very recently reported studies.
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.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been established as a cause of severe alveolar damage and pneumonia in patients with advanced Coronavirus disease (COVID-19). The ...consolidation of lung parenchyma precipitates the alterations in blood gases in COVID-19 patients that are known to complicate and cause hypoxemic respiratory failure. With SARS-CoV-2 damaging multiple organs in COVID-19, including the central nervous system that regulates the breathing process, it is a daunting task to compute the extent to which the failure of the central regulation of the breathing process contributes to the mortality of COVID-19 affected patients. Emerging data on COVID-19 cases from hospitals and autopsies in the last few months have helped in the understanding of the pathogenesis of respiratory failures in COVID-19. Recent reports have provided overwhelming evidence of the occurrence of acute respiratory failures in COVID-19 due to neurotropism of the brainstem by SARS-CoV-2. In this review, a cascade of events that may follow the alterations in blood gases and possible neurological damage to the respiratory regulation centers in the central nervous system (CNS) in COVID-19 are related to the basic mechanism of respiratory regulation in order to understand the acute respiratory failure reported in this disease. Though a complex metabolic and respiratory dysregulation also occurs with infections caused by SARS-CoV-1 and MERS that are known to contribute toward deaths of the patients in the past, we highlight here the role of systemic dysregulation and the CNS respiratory regulation mechanisms in the causation of mortalities seen in COVID-19. The invasion of the CNS by SARS-CoV-2, as shown recently in areas like the brainstem that control the normal breathing process with nuclei like the pre-Bötzinger complex (pre-BÖTC), may explain why some of the patients with COVID-19, who have been reported to have recovered from pneumonia, could not be weaned from invasive mechanical ventilation and the occurrences of acute respiratory arrests seen in COVID-19. This debate is important for many reasons, one of which is the fact that permanent damage to the medullary respiratory centers by SARS-CoV-2 would not benefit from mechanical ventilators, as is possibly occurring during the management of COVID-19 patients.
After almost a year of COVID‐19, the chronic long‐COVID syndrome has been recognized as an entity in 2021. The patients with the long‐COVID are presenting with ominous neurological deficits that with ...time are becoming persistent and are causing disabilities in the affected individuals. The mechanisms underlying the neurological syndrome in long‐COVID have remained obscure and need to be actively researched to find a resolution for the patients with long‐COVID. Here, the factors like site of viral load, the differential immune response, neurodegenerative changes, and inflammation as possible causative factors are debated to understand and investigate the pathogenesis of neuro‐COVID in long‐COVID syndrome.
The SARS‐CoV‐2 viral loads in nose are now known to reach the brain via cribriform plate. If the neurons in the CNS experience cellular degeneration due to SARS‐COV‐2, it is expected that patient with Long‐COVID syndrome would exhibit neurological deficits.
Neurological features have now been reported very frequently in the ongoing COVID‐19 pandemic caused by SARS‐CoV‐2. The neurological deficits associated features are observed in both acute and ...chronic stages of COVID‐19 and they appear to overlap with wide‐ranging symptoms that can be attributed to being of non‐neural origins, thus obscuring the definitive diagnosis of neuro‐COVID. The pathogenetic factors acting in concert to cause neuronal injury are now emerging, with SARS‐CoV‐2 directly affecting the brain coupled with the neuroinflammatory factors have been implicated in the causation of disabilities in acute COVID‐19 and patients with Long‐COVID syndrome. As the differentiation between a neural origin and other organ‐based causation of a particular neurological feature is of prognostic significance, it implores a course of action to this covert, yet important neurological challenge.
Spinal cord microglia plays a crucial role in the pathogenesis of neuropathic pain. However, the mechanisms underlying spinal microglial activation during neuropathic pain remain incompletely ...determined. Here, we investigated the role of Pellino1 (Peli1) and its interplay with spinal microglial activation in neuropathic pain.
In this study, we examined the effects of Peli1 on pain hypersensitivity and spinal microglial activation after chronic constriction injury (CCI) of the sciatic nerve in mice. The molecular mechanisms involved in Peli1-mediated hyperalgesia were determined by western blot, immunofluorescence, quantitative polymerase chain reaction (qPCR), and enzyme-linked immunosorbent assay (ELISA). We utilized immunoprecipitation to examine the ubiquitination of tumor necrosis factor receptor-associated factor 6 (TRAF6) following CCI. In addition, we explored the effect of Peli1 on BV2 microglial cells in response to lipopolysaccharide (LPS) challenge.
We found that CCI induced a significant increase in the levels of Peli1, which was present in the great majority of microglia in the spinal dorsal horn. Our results showed that spinal Peli1 contributed to the induction and maintenance of CCI-induced neuropathic pain. The biochemical data revealed that CCI-induced Peli1 in the spinal cord significantly increased mitogen-activated protein kinase (MAPK) phosphorylation, activated nuclear factor kappa B (NF-κB), and enhanced the production of proinflammatory cytokines, accompanied by spinal microglial activation. Peli1 additionally was able to promote K63-linked ubiquitination of TRAF6 in the ipsilateral spinal cord following CCI. Furthermore, we demonstrated that Peli1 in microglial cells significantly enhanced inflammatory reactions after LPS treatment.
These results suggest that the upregulation of spinal Peli1 is essential for the pathogenesis of neuropathic pain via Peli1-dependent mobilization of spinal cord microglia, activation of MAPK/NF-κB signaling, and production of proinflammatory cytokines. Modulation of Peli1 may serve as a potential approach for the treatment of neuropathic pain.
Peer-to-peer (P2P) energy trading facilitates both consumers and prosumers to exchange energy without depending on an intermediate medium. This system makes the energy market more decentralized than ...before, which generates new opportunities in energy-trading enhancements. In recent years, P2P energy trading has emerged as a method for managing renewable energy sources in distribution networks. Studies have focused on creating pricing mechanisms for P2P energy trading, but most of them only consider energy prices. This is because of a lack of understanding of the pricing mechanisms in P2P energy trading. This paper provides a comprehensive overview of pricing mechanisms for energy and network service prices in P2P energy trading, based on the recent advancements in P2P. It suggests that pricing methodology can be categorized by trading process in two categories, namely energy pricing and network service pricing (NSP). Within these categories, network service pricing can be used to identify financial conflicts, and the relationship between energy and network service pricing can be determined by examining interactions within the trading process. This review can provide useful insights for creating a P2P energy market in distribution networks. This review work provides suggestions and future directions for further development in P2P pricing mechanisms.
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