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Investigating Ketone Bodies as Immunometabolic Countermeasures against Respiratory Viral Infections.

ABSTRACT: Respiratory viral infections remain a scourge, with seasonal influenza infecting millions and killing many thousands annually and viral pandemics, such as COVID-19, recurring every decade. Age, cardiovascular disease, and diabetes mellitus are risk factors for severe disease and death from viral infection. Immunometabolic therapies for these populations hold promise to reduce the risks of death and disability. Such interventions have pleiotropic effects that might not only target the virus itself but also enhance supportive care to reduce cardiopulmonary complications, improve cognitive resilience, and facilitate functional recovery. Ketone bodies are endogenous metabolites that maintain cellular energy but also feature drug-like signaling activities that affect immune activity, metabolism, and epigenetics. Here, we provide an overview of ketone body biology relevant to respiratory viral infection, focusing on influenza A and severe acute respiratory syndrome (SARS)-CoV-2, and discuss the opportunities, risks, and research gaps in the study of exogenous ketone bodies as novel immunometabolic interventions in these diseases.

SUBMITTER: Stubbs BJ

PROVIDER: S-EPMC7362813 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Investigating Ketone Bodies as Immunometabolic Countermeasures against Respiratory Viral Infections.

Stubbs Brianna J BJ Koutnik Andrew P AP Goldberg Emily L EL Upadhyay Vaibhav V Turnbaugh Peter J PJ Verdin Eric E Newman John C JC

Med (New York, N.Y.) 20200715 1

Respiratory viral infections remain a scourge, with seasonal influenza infecting millions and killing many thousands annually and viral pandemics, such as COVID-19, recurring every decade. Age, cardiovascular disease, and diabetes mellitus are risk factors for severe disease and death from viral infection. Immunometabolic therapies for these populations hold promise to reduce the risks of death and disability. Such interventions have pleiotropic effects that might not only target the virus itsel ...[more]

PMID: 32838361

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Project description:BackgroundIn this large-scale cluster-randomized controlled trial (cRCT) we sought to assess the effectiveness of facemasks against viral respiratory infections.Methods and resultsOver three consecutive Hajj seasons (2013, 2014, 2015) pilgrims' tents in Makkah were allocated to 'facemask' or 'no facemask' group. Fifty facemasks were offered to participants in intervention tents, to be worn over four days, and none were offered to participants in control tents. All participants recorded facemask use and respiratory symptoms in health diaries. Nasal swabs were collected from the symptomatic for virus detection by reverse transcription polymerase chain reaction. Clinical symptoms and laboratory results were analyzed by 'intention- to-treat' and 'per-protocol'. A total of 7687 adult participants from 318 tents were randomized: 3864 from 149 tents to the intervention group, and 3823 from 169 tents to the control group. Participants were aged 18 to 95 (median 34, mean 37) years, with a male to female ratio of 1:1.2. Overall, respiratory viruses were detected in 277 of 650 (43%) nasal/pharyngeal swabs collected from symptomatic pilgrims. Common viruses were rhinovirus (35.1%), influenza (4.5%) and parainfluenza (1.7%). In the intervention arm, respectively 954 (24.7%) and 1842 (47.7%) participants used facemasks daily and intermittently, while in the control arm, respectively 546 (14.3%) and 1334 (34.9%) used facemasks daily and intermittently. By intention-to-treat analysis, facemask use did not seem to be effective against laboratory-confirmed viral respiratory infections (odds ratio [OR], 1.4; 95% confidence interval [CI], 0.9 to 2.1, p = 0.18) nor against clinical respiratory infection (OR, 1.1; 95% CI, 0.9 to 1.4, p = 0.40). Similarly, in a per-protocol analysis, facemask use did not seem to be effective against laboratory-confirmed viral respiratory infections (OR 1.2, 95% CI 0.9-1.7, p = 0.26) nor against clinical respiratory infection (OR 1.3, 95% CI 1.0-1.8, p = 0.06).ConclusionThis trial was unable to provide conclusive evidence on facemask efficacy against viral respiratory infections most likely due to poor adherence to protocol.

Project description:With the global over 60-year-old population predicted to more than double over the next 35 years, caring for this aging population has become a major global healthcare challenge. In 2016 there were over 1 million deaths in >70 year olds due to lower respiratory tract infections; 13-31% of these have been reported to be caused by viruses. Since then, there has been a global COVID-19 pandemic, which has caused over 2.3 million deaths so far; increased age has been shown to be the biggest risk factor for morbidity and mortality. Thus, the burden of respiratory viral infections in the elderly is becoming an increasing unmet clinical need. Particular challenges are faced due to the interplay of a variety of factors including complex multimorbidities, decreased physiological reserve and an aging immune system. Moreover, their atypical presentation of symptoms may lead to delayed necessary care, prescription of additional drugs and prolonged hospital stay. This leads to morbidity and mortality and further nosocomial spread. Clinicians currently have limited access to sensitive detection methods. Furthermore, a lack of effective antiviral treatments means there is little incentive to diagnose and record specific non-COVID-19 viral infections. To meet this unmet clinical need, it is first essential to fully understand the burden of respiratory viruses in the elderly. Doing this through prospective screening research studies for all respiratory viruses will help guide preventative policies and clinical trials for emerging therapeutics. The implementation of multiplex point-of-care diagnostics as a mainstay in all healthcare settings will be essential to understand the burden of respiratory viruses, diagnose patients and monitor outbreaks. The further development of novel targeted vaccinations as well as anti-viral therapeutics and new ways to augment the aging immune system is now also essential.The reviews of this paper are available via the supplemental material section.

Project description:BackgroundThe goals of the National Action Plan on Antimicrobial Resistance (AMR) of Japan include "implementing appropriate infection prevention and control" and "appropriate use of antimicrobials," which are relevant to healthcare facilities. Specifically, linking efforts between existing infection control teams and antimicrobial stewardship programs was suggested to be important. Previous studies reported that human resources, such as full-time equivalents of infection control practitioners, were related to improvements in antimicrobial stewardship.MethodsWe posted questionnaires to all teaching hospitals (n = 1017) regarding hospital countermeasures against AMR and infections. To evaluate changes over time, surveys were conducted twice (1st survey: Nov 2016, 2nd survey: Feb 2018). A latent transition analysis (LTA) was performed to identify latent statuses, which refer to underlying subgroups of hospitals, and effects of the number of members in infection control teams per bed on being in the better statuses.ResultsThe number of valid responses was 678 (response rate, 66.7%) for the 1st survey and 559 (55.0%) for the 2nd survey. More than 99% of participating hospitals had infection control teams, with differences in activity among hospitals. Roughly 70% had their own intervention criteria for antibiotics therapies, whereas only about 60 and 50% had criteria established for the use of anti-methicillin-resistant Staphylococcus aureus antibiotics and broad-spectrum antibiotics, respectively. Only 50 and 40% of hospitals conducted surveillance of catheter-associated urinary tract infections and ventilator-associated pneumonia, respectively. Less than 50% of hospitals used maximal barrier precautions for central line catheter insertion. The LTA identified five latent statuses. The membership probability of the most favorable status in the 2nd study period was slightly increased from the 1st study period (23.6 to 25.3%). However, the increase in the least favorable status was higher (26.3 to 31.8%). Results of the LTA did not support a relationship between increasing the number of infection control practitioners per bed, which is reportedly related to improvements in antimicrobial stewardship, and being in more favorable latent statuses.ConclusionsOur results suggest the need for more comprehensive antimicrobial stewardship programs and increased surveillance activities for healthcare-associated infections to improve antimicrobial stewardship and infection control in hospitals.

Dataset Information

Investigating Ketone Bodies as Immunometabolic Countermeasures against Respiratory Viral Infections.

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Investigating Ketone Bodies as Immunometabolic Countermeasures against Respiratory Viral Infections.

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