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COVID-19 infection alters kynurenine and fatty acid metabolism, correlating with IL-6 levels and renal status.
Thomas, T, Stefanoni, D, Reisz, JA, Nemkov, T, Bertolone, L, Francis, RO, Hudson, KE, Zimring, JC, Hansen, KC, Hod, EA, et al
JCI insight. 2020;5(14)
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There is increasing urgency for the development of Covid-19 therapies. Treatments preventing infection and decreasing the amount of virus in the body have largely been unsuccessful and so the focus has turned to host biological pathways, which may be altered by Covid-19 infection. This observational study of forty-nine Covid-19 positive and negative individuals aimed to determine alterations in the hosts metabolism. The results showed that Covid-19 infection was associated with disrupted host inflammatory and immune pathways. Markers for kidney dysfunction were also increased alongside raised blood sugar levels and fatty acids in the blood. It was concluded that inflammatory markers may be an indicator for disease severity and a target for Covid-19 therapy. Dietary therapy could be used to target blood fatty acid changes brought about by Covid-19 infection. This study could be used by healthcare professionals to understand that inflammation is increased in Covid-19 patients and in lieu of approved therapies, dietary intervention may be of benefit.
Abstract
BACKGROUNDReprogramming of host metabolism supports viral pathogenesis by fueling viral proliferation, by providing, for example, free amino acids and fatty acids as building blocks.METHODSTo investigate metabolic effects of SARS-CoV-2 infection, we evaluated serum metabolites of patients with COVID-19 (n = 33; diagnosed by nucleic acid testing), as compared with COVID-19-negative controls (n = 16).RESULTSTargeted and untargeted metabolomics analyses identified altered tryptophan metabolism into the kynurenine pathway, which regulates inflammation and immunity. Indeed, these changes in tryptophan metabolism correlated with interleukin-6 (IL-6) levels. Widespread dysregulation of nitrogen metabolism was also seen in infected patients, with altered levels of most amino acids, along with increased markers of oxidant stress (e.g., methionine sulfoxide, cystine), proteolysis, and renal dysfunction (e.g., creatine, creatinine, polyamines). Increased circulating levels of glucose and free fatty acids were also observed, consistent with altered carbon homeostasis. Interestingly, metabolite levels in these pathways correlated with clinical laboratory markers of inflammation (i.e., IL-6 and C-reactive protein) and renal function (i.e., blood urea nitrogen).CONCLUSIONIn conclusion, this initial observational study identified amino acid and fatty acid metabolism as correlates of COVID-19, providing mechanistic insights, potential markers of clinical severity, and potential therapeutic targets.FUNDINGBoettcher Foundation Webb-Waring Biomedical Research Award; National Institute of General and Medical Sciences, NIH; and National Heart, Lung, and Blood Institute, NIH.
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Immediate and long-term consequences of COVID-19 infections for the development of neurological disease.
Heneka, MT, Golenbock, D, Latz, E, Morgan, D, Brown, R
Alzheimer's research & therapy. 2020;12(1):69
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Covid-19 may cause brain dysfunction evidenced by symptoms individuals experience once they have contracted the disease. Loss of smell, taste and confusion have all been reported by patients and a number of severe cases have reported incidences of stroke. These are all of concern, as Covid-19 can severely affect the elderly who ordinarily are the most likely to suffer from brain disorders. This small review paper of 27 studies stated that there are four possible ways in which Covid-19 may affect the brain, which put Covid-19 sufferers at an increased risk of long-term brain disorders. This was supported by findings, which showed one third of Covid-19 patients leave hospital with evidence of brain dysfunction. Inflammation was heavily reviewed by the authors as a possible causal factor. It was concluded that patients who survive Covid-19 infection are at an increased risk for developing brain disorders such as Alzheimer's disease, however it was acknowledged that further studies are required. Clinicians could use this study to understand the possible need for both short-term and long-term monitoring of brain function in individuals who have survived Covid-19, especially if they are elderly.
Abstract
Increasing evidence suggests that infection with Sars-CoV-2 causes neurological deficits in a substantial proportion of affected patients. While these symptoms arise acutely during the course of infection, less is known about the possible long-term consequences for the brain. Severely affected COVID-19 cases experience high levels of proinflammatory cytokines and acute respiratory dysfunction and often require assisted ventilation. All these factors have been suggested to cause cognitive decline. Pathogenetically, this may result from direct negative effects of the immune reaction, acceleration or aggravation of pre-existing cognitive deficits, or de novo induction of a neurodegenerative disease. This article summarizes the current understanding of neurological symptoms of COVID-19 and hypothesizes that affected patients may be at higher risk of developing cognitive decline after overcoming the primary COVID-19 infection. A structured prospective evaluation should analyze the likelihood, time course, and severity of cognitive impairment following the COVID-19 pandemic.