Diverse immunopathological manifestations and immunogenomic predispositions in COVID-19: summarizing the evidence

The COVID-19 pandemic has caused immense damage to most nations of the world, both in terms of loss of human lives, as well as, socio-economic attributes. The immunopathogenesis of the responsible pathogen, SARS-CoV-2, has been a focal point and researchers have succeeded in deciphering the multi-organ tropism of the virus along with its different routes of infection. The hallmark feature of the SARS-CoV-2 disease pathogenesis is the high rates of transmission and the susceptibility of a vulnerable group with systemic co-morbidities. Also, genetic components of the host, as well as mutant variants of the virus have further complicated the development of appropriate treatment strategies and preventive measures. The virus is aptly able to modulate the host immune system and mediate immune-dysregulation in terms of cytokine or chemokine production leading to a heightened inflammatory response. In the current review, we have summarized the present research on SARS-CoV-2 from the angles of host genetic polymorphism, genetic variants of the virus, and how these affect the high transmission, disease susceptibility, and tissue tropism in multiple organs of the human body

Vitamin D and Alzheimer’s Disease: Neurocognition to Therapeutics

Alzheimer’s disease (AD), the major cause of dementia worldwide, is characterized by progressive loss of memory and cognition. The sporadic form of AD accounts for nearly 90% of the patients developing this disease. The last century has witnessed significant research to identify various mechanisms and risk factors contributing to the complex etiopathogenesis of AD by analyzing postmortem AD brains and experimenting with animal and cell culture based models. However, the treatment strategies, as of now, are only symptomatic. Accumulating evidences suggested a significant association between vitamin D deficiency, dementia, and AD. This review encompasses the beneficial role of vitamin D in neurocognition and optimal brain health along with epidemiological evidence of the high prevalence of hypovitaminosis D among aged and AD population. Moreover, disrupted signaling, altered utilization of vitamin D, and polymorphisms of several related genes including vitamin D receptor (VDR) also predispose to AD or AD-like neurodegeneration. This review explores the relationship between this gene-environmental influence and long term vitamin D deficiency as a risk factor for development of sporadic AD along with the role and rationale of therapeutic trials with vitamin D. It is, therefore, urgently warranted to further establish the role of this potentially neuroprotective vitamin in preventing and halting progressive neurodegeneration in AD patients

Oxidative Stress, Neuroinflammation, and NADPH Oxidase: Implications in the Pathogenesis and Treatment of Alzheimer’s Disease

NADPH oxidase as an important source of intracellular reactive oxygen species (ROS) has gained enormous importance over the years, and the detailed structures of all the isoenzymes of the NADPH oxidase family and their regulation have been well explored. The enzyme has been implicated in a variety of diseases including neurodegenerative diseases. The present brief review examines the body of evidence that links NADPH oxidase with the genesis and progression of Alzheimer’s disease (AD). In short, evidence suggests that microglial activation and inflammatory response in the AD brain is associated with increased production of ROS by microglial NADPH oxidase. Along with other inflammatory mediators, ROS take part in neuronal degeneration and enhance the microglial activation process. The review also evaluates the current state of NADPH oxidase inhibitors as potential disease-modifying agents for AD

Vitamin D and immuno-pathology of COVID-19: many interactions but uncertain therapeutic benefits

Introduction: COVID-19 pandemic has caused huge loss of human lives and extensive socio-economic damages. The immuno-pathology of this disease is neither clearly understood, nor there are effective drugs for severe cases of COVID-19. Repurposing of available drugs for the treatment of COVID-19 is imperative. Areas Covered: This review has gathered the evidence from PubMed, Google Scholar, WHO, and other reliable websites on COVID-19 and summarized the existing knowledge of the immuno-pathology of COVID-19. We elucidated how vitamin D through its diverse actions on immune effector cells, epithelial cells, or rennin-angiotensin-aldosterone system could have a modulatory role on the pathogenic mechanisms of COVID-19. The epidemiological evidence associating vitamin D deficiency with the severity and incidence of COVID-19 is also presented. However, the evidence of clinical benefit to patients of COVID-19 from randomized controlled trials with vitamin D has not come as yet. Expert opinion: It is now established that fatality of COVID-19 is primarily determined by hyperactivation of the host's innate immune system in response to SARS-CoV-2 invasion, and thus the research on the immuno-modulatory and other roles of vitamin D against viral infections should be pursued vigorously. This would be also useful for future pandemics caused by other novel viruses