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 latest articles are related to COVID-19 and Alzheimer Diseases.
Title: Inflammation at the crossroads of COVID-19, cognitive deficits and depression
Authors: Natalia M. Lyra e Silva, Fernanda G.Q. Barros-Aragão, Fernanda G. De Felice, Sergio T. Ferreira
Type: Review Article
●COVID-19 is frequently associated with acute or persistent neurological impacts.
●COVID-19 survivors may be at increased risk for cognitive and mood disorders.
●Dementia and neuropsychiatric disorders appear to be risk factors for COVID-19 complications.
●Inflammation links COVID-19, Alzheimer's disease and depression.
Acute neurological alterations have been associated with SARS-CoV-2 infection. Additionally, it is becoming clear that coronavirus disease 2019 (COVID-19) survivors may experience long-term neurological abnormalities, including cognitive deficits and mood alterations. The mechanisms underlying acute and long-term impacts of COVID-19 in the brain are being actively investigated. Due to the heterogeneous manifestations of neurological outcomes, it is possible that different mechanisms operate following SARS-CoV-2 infection, which may include direct brain infection by SARS-CoV-2, mechanisms resulting from hyperinflammatory systemic disease, or a combination of both. Inflammation is a core feature of COVID-19, and both central and systemic inflammation are known to lead to acute and persistent neurological alterations in other diseases. Here, we review evidence indicating that COVID-19 is associated with neuroinflammation, along with blood-brain barrier dysfunction. Similar neuroinflammatory signatures have been associated with Alzheimer's disease and major depressive disorder. Current evidence demonstrates that patients with pre-existing cognitive and neuropsychiatric deficits show worse outcomes upon infection by SARS-CoV-2 and, conversely, COVID-19 survivors may be at increased risk of developing dementia and mood disorders. Considering the high prevalence of COVID-19 patients that recovered from infection in the world and the alarming projections for the prevalence of dementia and depression, investigation of possible molecular similarities between those diseases may shed light on mechanisms leading to long-term neurological abnormalities in COVID-19 survivors.
Access this article: https://doi.org/10.1016/j.neuropharm.2022.109023
Title: Trained immunity in viral infections, Alzheimer's disease and multiple sclerosis: A convergence in type I interferon signalling and IFNβ-1a
Authors: George D. Vavougios, Theodore Mavridis, Artemios Artemiadis, Karen A. Krogfelt, Georgios Hadjigeorgiou
●Type I interferon responses a perturbed in neurodegenerative disease and infection.
●IFNβ etiologically restores canonical Type I interferon signalling in viral infection.
●IFNβ-1α ameliorates neuroinflammation and cognitive decline in multiple sclerosis.
●IFNβ-1α has shown efficacy in modulating hyperinflammation in COVID-19.
●IFNβ-1α repositioning may be efficacious in Type I interferon signalling-driven cognitive decline.
Type I interferon (IFN-I) signalling represents a major target for modulation in a virus' bid for latency. IFN-I perturbations are also present in such as Alzheimer's disease (AD) and multiple sclerosis (MS), where viral infections are known to increase symptomatic burden. IFN-I modulation such as via IFNβ-1a, an established MS treatment, has been researched to a limited extent to both AD and COVID-19. In this mini review, we present emerging research on trained immunity as a pathogenetic basis for Alzheimer's disease and the emerging context for IFNβ-1a repositioning, via mechanisms shared with multiple sclerosis and induced by viral infections.
Access this article: https://doi.org/10.1016/j.bbadis.2022.166430
Title: Infection and inflammation: New perspectives on Alzheimer's disease
Authors: Heather E. Whitson, Carol Colton, Joseph El Khoury, David Gate, Alison Goate, Michael T. Heneka, Rima Kaddurah-Daouk, Robyn S. Klein, Mari L. Shinohara, Sangram Sisodia, Serena S. Spudich, Beth Stevens, Rudolph Tanzi, Jenny P. Ting, Gwenn Garden
Type: Review Article
●The hypothesis that infectious agents could trigger Alzheimer's disease was proposed more than a century ago
●Genomic and transcriptomic studies, functional assays, and new animal and cell models are dissecting the roles of microglia and other innate immune cells in AD, and microbe exposure is considered here as one potential trigger for immune activation
●Changes in brain metabolism and gut-brain communication are influenced by microbes and may contribute to Alzheimer's pathology and cognitive decline
●Studies are investigating how age dependent responses to the microbiome or to other bacterial, fungal or viral pathogens including SARS-CoV-2, could lead to neurodegeneration in Alzheimer's disease
Neuroinflammation has been recognized as a component of Alzheimer's Disease (AD) pathology since the original descriptions by Alois Alzheimer and a role for infections in AD pathogenesis has long been hypothesized. More recently, this hypothesis has gained strength as human genetics and experimental data suggest key roles for inflammatory cells in AD pathogenesis. To review this topic, Duke/University of North Carolina (Duke/UNC) Alzheimer's Disease Research Center hosted a virtual symposium: “Infection and Inflammation: New Perspectives on Alzheimer's Disease (AD).” Participants considered current evidence for and against the hypothesis that AD could be caused or exacerbated by infection or commensal microbes. Discussion focused on connecting microglial transcriptional states to functional states, mouse models that better mimic human immunity, the potential involvement of inflammasome signaling, metabolic alterations, self-reactive T cells, gut microbes and fungal infections, and lessons learned from Covid-19 patients with neurologic symptoms. The content presented in the symposium, and major topics raised in discussions are reviewed in this summary of the proceedings.
Access this article: https://doi.org/10.1016/j.bbih.2022.100462
Title: Racial and ethnic disparities in cardiometabolic disease and COVID-19 outcomes in White, Black/African American, and Latinx populations: Physiological underpinnings
Authors: Kanokwan Bunsawat, Gregory J. Grosicki, Soolim Jeong, Austin T. Robinson
Type: Review Article
Coronavirus disease 2019 (COVID-19) is a highly contagious respiratory illness caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that began spreading globally in late 2019. While most cases of COVID-19 present with mild to moderate symptoms, COVID-19 was the third leading cause of mortality in the United States in 2020 and 2021. Though COVID-19 affects individuals of all races and ethnicities, non-Hispanic Black and Hispanic/Latinx populations are facing an inequitable burden of COVID-19 characterized by an increased risk for hospitalization and mortality. Importantly, non-Hispanic Black and Hispanic/Latinx adults have also faced a greater risk of non-COVID-19-related mortality (e.g., from cardiovascular disease/CVD) during the pandemic. Contributors to the racial disparities in morbidity and mortality during the pandemic are multi-factorial as we discuss in our companion article on social determinants of health. However, profound racial variation in the prevalence of CVD and metabolic diseases may serve as a key driver of worse COVID-19-related and non-COVID-19-related health outcomes among racial and ethnic minority groups. Within this review, we provide data emphasizing the inequitable burden of CVD and metabolic diseases among non-Hispanic Black and Hispanic/Latinx populations. We also discuss the pathophysiology of these conditions, with a focus on how aberrant physiological alterations in the context of CVD and metabolic diseases manifest to increase susceptibility to severe COVID-19.
Access this article: https://doi.org/10.1016/j.pcad.2022.04.005
Title: COVID-19 and retinal degenerative diseases: Promising link "Kaempferol"
Authors: Arman Firoz, Priti Talwar
Type: Review Article
Coronavirus disease (COVID-19) outbreak has caused unprecedented global disruption since 2020. Approximately 238 million people are affected worldwide where the elderly succumb to mortality. Post-COVID syndrome and its side effects have popped up with several health hazards, such as macular degeneration and vision loss. It thus necessitates better medical care and management of our dietary practices. Natural flavonoids have been included in traditional medicine and have also been used safely against COVID-19 and several other diseases. Kaempferol is an essential flavonoid that has been demonstrated to influence several vital cellular signaling pathways involved in apoptosis, angiogenesis, inflammation, and autophagy. In this review, we emphasize the plausible regulatory effects of Kaempferol on hallmarks of COVID-19 and macular degeneration.
Access this article: https://doi.org/10.1016/j.coph.2022.102231