Recent Developments in the Understanding of Immunity, Pathogenesis and Management of COVID-19.

Coronaviruses represent a diverse family of enveloped positive-sense single stranded RNA viruses. COVID-19, caused by Severe Acute Respiratory Syndrome Coronavirus-2, is a highly contagious respiratory disease transmissible mainly via close contact and respiratory droplets which can result in severe, life-threatening respiratory pathologies. It is understood that glutathione, a naturally occurring antioxidant known for its role in immune response and cellular detoxification, is the target of various proinflammatory cytokines and transcription factors resulting in the infection, replication, and production of reactive oxygen species. This leads to more severe symptoms of COVID-19 and increased susceptibility to other illnesses such as tuberculosis. The emergence of vaccines against COVID-19, usage of monoclonal antibodies as treatments for infection, and implementation of pharmaceutical drugs have been effective methods for preventing and treating symptoms. However, with the mutating nature of the virus, other treatment modalities have been in research. With its role in antiviral defense and immune response, glutathione has been heavily explored in regard to COVID-19. Glutathione has demonstrated protective effects on inflammation and downregulation of reactive oxygen species, thereby resulting in less severe symptoms of COVID-19 infection and warranting the discussion of glutathione as a treatment mechanism.

Role of Microbiota-Gut-Brain Axis in Regulating Dopaminergic Signaling.

Dopamine is a neurotransmitter that plays a critical role both peripherally and centrally in vital functions such as cognition, reward, satiety, voluntary motor movements, pleasure, and motivation. Optimal dopamine bioavailability is essential for normal brain functioning and protection against the development of neurological diseases. Emerging evidence shows that gut microbiota have significant roles in maintaining adequate concentrations of dopamine via intricate, bidirectional communication known as the microbiota-gut-brain axis. The vagus nerve, immune system, hypothalamus-pituitary-adrenal axis, and microbial metabolites serve as important mediators of the reciprocal microbiota-gut-brain signaling. Furthermore, gut microbiota contain intrinsic enzymatic activity that is highly involved in dopamine metabolism, facilitating dopamine synthesis as well as its metabolite breakdown. This review examines the relationship between key genera of gut microbiota such as Prevotella, Bacteroides, Lactobacillus, Bifidobacterium, Clostridium,Enterococcus, and Ruminococcus and their effects on dopamine. The effects of gut dysbiosis on dopamine bioavailability and the subsequent impact on dopamine-related pathological conditions such as Parkinson's disease are also discussed. Understanding the role of gut microbiota in modulating dopamine activity and bioavailability both in the periphery and in the central nervous system can help identify new therapeutic targets as well as optimize available methods to prevent, delay, or restore dopaminergic deficits in neurologic and metabolic disorders.