Endoplasmic Reticulum Stress in Elderly Patients with COVID-19: Potential of Melatonin Treatment

Yiang, Giou‐Teng; Wu, Chia‐Chao; Lu, Cheng Wei; Hu, Wan-Chung; Tsai, Yi-Ju; Huang, Yiao-Mien; Su, Wen‐Lin; Lu, Kuo‐Cheng

doi:10.3390/v15010156

Cited by 8 publications

(8 citation statements)

References 177 publications

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“…Taking this into account, our data may suggest a dysregulated T cell-mediated cellular homeostasis during COVID-19. It is reported that virus infection increases the ER stress which further enhances unfolded protein response (UPR) to neutralize the detrimental effect and restore ER homeostasis which is also evident in COVID-19 patients in activated CD4 + T cells ( 50 ). In concordance, we also found an enriched ER stress response in activated CD4 + T cells in COVID-19 positive individuals.…”

Section: Discussionmentioning

confidence: 99%

Dysregulated metal ion homeostasis underscores non-canonical function of CD8+ T cell during COVID-19

Khare,

Chattopadhyay,

Devi

et al. 2023

Front. Med.

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IntroductionSeveral efforts have been made to describe the complexity of T cell heterogeneity during the COVID-19 disease; however, there remain gaps in our understanding in terms of the granularity within.MethodsFor this attempt, we performed a single-cell transcriptomic analysis of 33 individuals (4 healthy, 16 COVID-19 positive patients, and 13 COVID-19 recovered individuals).ResultsWe found CD8+ T cell-biased lymphopenia in COVID-19 patients compared to healthy and recovered individuals. We also found an optimal Th1/Th2 ratio, indicating an effective immune response during COVID-19. Expansion of activated CD4+ T and NK T was detected in the COVID-19-positive individuals. Surprisingly, we found cellular and metal ion homeostasis pathways enriched in the COVID-19-positive individuals compared to the healthy and recovered in the CD8+ T cell populations (CD8+ TCM and CD8+ TEM) as well as activated CD4+ T cells.DiscussionIn summary, the COVID-19-positive individuals exhibit a dynamic T cell mediated response. This response may have a possible association with the dysregulation of non-canonical pathways, including housekeeping functions in addition to the conventional antiviral immune response mediated by the T cell subpopulation. These findings considerably extend our insights into the heterogeneity of T cell response during and post-SARS-CoV-2 infection.

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Section: Discussionmentioning

confidence: 99%

Dysregulated metal ion homeostasis underscores non-canonical function of CD8+ T cell during COVID-19

Khare,

Chattopadhyay,

Devi

et al. 2023

Front. Med.

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“…199 In relation to COVID-19, SARS-CoV-2 infections could potentially augment the production of reactive oxygen species and disturb the equilibrium of Ca 2+ via a UPR triggered by ER stress. 200 SGs are dynamic organelles that form when translation initiation is inhibited due to stress, have been the focus of previous studies. These studies suggested that mRNAs encoding signal sequences for ER targeting are less common in SGs, implying a potential protective role of ER localization against SG recruitment.…”

Section: Exploring the Hypothesis: Llps Of Sars-cov-2 Nucleocapsid Pr...mentioning

confidence: 99%

“…If this response is not effectively mitigated, it can culminate in cellular death 199 . In relation to COVID‐19, SARS‐CoV‐2 infections could potentially augment the production of reactive oxygen species and disturb the equilibrium of Ca 2+ via a UPR triggered by ER stress 200 …”

Section: Exploring the Hypothesis: Llps Of Sars‐cov‐2 Nucleocapsid Pr...mentioning

confidence: 99%

“…The virus causing COVID‐19 can create a range of cellular stresses, one of which is ER stress. Specifically, ER stress has been linked to the intensity of COVID‐19, 200 and SGs have been related to the pathological consequences of viral infections 201 . This could potentially instigate the creation of SGs via LLPS.…”

Section: Exploring the Hypothesis: Llps Of Sars‐cov‐2 Nucleocapsid Pr...mentioning

confidence: 99%

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Intrinsic factors behind long COVID: IV. Hypothetical roles of the SARS‐CoV‐2 nucleocapsid protein and its liquid–liquid phase separation

Eltayeb,

Al‐Sarraj,

Alharbi

et al. 2024

J of Cellular Biochemistry

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When the SARS‐CoV‐2 virus infects humans, it leads to a condition called COVID‐19 that has a wide spectrum of clinical manifestations, from no symptoms to acute respiratory distress syndrome. The virus initiates damage by attaching to the ACE‐2 protein on the surface of endothelial cells that line the blood vessels and using these cells as hosts for replication. Reactive oxygen species levels are increased during viral replication, which leads to oxidative stress. About three‐fifths (~60%) of the people who get infected with the virus eradicate it from their body after 28 days and recover their normal activity. However, a large fraction (~40%) of the people who are infected with the virus suffer from various symptoms (anosmia and/or ageusia, fatigue, cough, myalgia, cognitive impairment, insomnia, dyspnea, and tachycardia) beyond 12 weeks and are diagnosed with a syndrome called long COVID. Long‐term clinical studies in a group of people who contracted SARS‐CoV‐2 have been contrasted with a noninfected matched group of people. A subset of infected people can be distinguished by a set of cytokine markers to have persistent, low‐grade inflammation and often self‐report two or more bothersome symptoms. No medication can alleviate their symptoms efficiently. Coronavirus nucleocapsid proteins have been investigated extensively as potential drug targets due to their key roles in virus replication, among which is their ability to bind their respective genomic RNAs for incorporation into emerging virions. This review highlights basic studies of the nucleocapsid protein and its ability to undergo liquid–liquid phase separation. We hypothesize that this ability of the nucleocapsid protein for phase separation may contribute to long COVID. This hypothesis unlocks new investigation angles and could potentially open novel avenues for a better understanding of long COVID and treating this condition.

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“…Although this may be due to several causes, immunosenescence, genomic instability, telomeric attrition, and inflammasome formation could be involved in the increased pathophysiological responses to SARS-CoV-2 infection seen in elderly patients. Moreover, as oxidative damage is also known to be related to aging, such patients may be especially prone to ER stress [55].…”

Section: Cytopathic Effects On the Endoplasmic Reticulummentioning

confidence: 99%

From Cell to Symptoms: The Role of SARS-CoV-2 Cytopathic Effects in the Pathogenesis of COVID-19 and Long COVID

Gonzalez-Garcia¹,

Moreno²,

Peñate³

et al. 2023

Preprint

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Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) infection triggers various events from molecular to tissue level, which in turn is given by the intrinsic characteristics of each patient. Given the molecular diversity characteristic of each cellular phenotype, the possible cytopathic, tissue and clinical effects are difficult to predict, which determines the heterogeneity of COVID-19 symptoms. The purpose of this article is to provide a comprehensive review of the cytopathic effects of SARS-CoV-2 on various cell types, focusing on the development of COVID-19, which in turn may lead, in some patients, to a persistence of symptoms after recovery from the disease, a condition known as long COVID. We describe the molecular mechanisms underlying virus-host interactions, including alterations in protein expression, intracellular signaling pathways, and immune responses. In particular, the article highlights the potential impact of these cytopathies on cellular function and clinical outcomes, such as immune dysregulation, neuropsychiatric disorders, and organ damage. The article concludes by discussing future directions for research and implications for the management and treatment of COVID-19 and Long-COVID.

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Endoplasmic Reticulum Stress in Elderly Patients with COVID-19: Potential of Melatonin Treatment

Cited by 8 publications

References 177 publications

Dysregulated metal ion homeostasis underscores non-canonical function of CD8+ T cell during COVID-19

Dysregulated metal ion homeostasis underscores non-canonical function of CD8+ T cell during COVID-19

Intrinsic factors behind long COVID: IV. Hypothetical roles of the SARS‐CoV‐2 nucleocapsid protein and its liquid–liquid phase separation

From Cell to Symptoms: The Role of SARS-CoV-2 Cytopathic Effects in the Pathogenesis of COVID-19 and Long COVID

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