Is there any role of intermittent fasting in the prevention and improving clinical outcomes of COVID-19?: intersection between inflammation, mTOR pathway, autophagy and calorie restriction

Abstract

The coronavirus disease 2019 (COVID-19) pandemic is provoking a global public health crisis. Even though the academic world is intensively pursuing new therapies, there is still no ''game changer'' in the management of COVID 19. The Mammalian Target of Rapamycin (mTOR) is an ancient signaling system that has been proposed as a molecular tool used by coronaviruses and other RNA and DNA viruses in order to replicate and persist in the host cell. In recent years, Intermittent Fasting (IF), a practice consisting on a strict calorie restriction during a prolonged period of time during the day, has gained popularity due to its potential benefits in multiple health systems and in regulating inflammation. IF inhibits the mTOR pathway which is similar to the effects of Rapamycin in some animal models. mTOR inhibition and promotion of autophagy could potentially be the link between the possible direct benefits of IF in COVID-19 due to the interruption of the viral cycle (protein synthesis). Besides, IF has shown to be a strong anti-inflammatory in multiple prior studies, and may play a role in attenuating COVID -19 severity. This review hypothesizes the possible intersection between viral, immunological, and metabolic pathways related to mTOR and the potential mechanisms through which IF may improve clinical outcomes. Future prospective randomized controlled clinical trials to evaluate intermittent fasting (IF) regimens in order to prevent and treat moderate to severe forms of COVID-19 in humans are needed.

Association of periodic fasting with lower severity of COVID-19 outcomes in the SARS-CoV-2 prevaccine era: an observational cohort from the INSPIRE registry

“…This may occur as fasting prevents or treats morbidities13–15 32 33 that increase the risk of severe COVID-19 outcomes, such as CAD, MI, HF and diabetes 19 20. A variety of mechanisms may be involved in the long-term prevention and treatment of those diseases (which mechanisms are beyond the scope of this study),4 6 16–18 26 30–37 and, as a preventive health practice, periodic fasting may indirectly prevent severe COVID-19 by its long-term impacts on those disease mechanisms and comorbidities 25 26 38…”

Association of Periodic Fasting with Lower Severity of COVID-19 Outcomes in the SARS-CoV-2 Pre-Vaccine Era: An Observational Cohort from the INSPIRE Registry

“…(19,20) A variety of mechanisms may be involved in the long-term prevention and treatment of those diseases (which mechanisms are beyond the scope of this study),(4,6,16-18,26,30-35) and, as a preventive health practice, periodic fasting may indirectly prevent severe COVID-19 by its long-term impacts on those disease mechanisms and comorbidities. (25,26,36)…”

“…This may occur as fasting prevents or treats morbidities(13)(14)(15)30,31) that increase the risk of severe COVID-19 outcomes, such as CAD, MI, HF, and diabetes (19,20). A variety of mechanisms may be involved in the long-term prevention and treatment of those diseases (which mechanisms are beyond the scope of this study),(4,6,16-18,26,30- 35) and, as a preventive health practice, periodic fasting may indirectly prevent severe COVID-19 by its long-term impacts on those disease mechanisms and comorbidities (25,26,36). Finally, a periodic fasting lifestyle may condition the body by elevating basal levels of key physiological parameters in preparation for insults such as infection.…”

Role of senescence in the chronic health consequences of COVID-19

“…158,159 IF and CR mimic Rapamycin by inhibiting the mTOR pathway and promoting autophagy. 160,161 Future work is needed to explore IF, CR, and autophagy inducers, as these interventions might help protect against COVID-19. 160,161 Exercise can help reduce risk factors in older adults for COVID-19, including frailty and chronic disease.…”

“…160,161 Future work is needed to explore IF, CR, and autophagy inducers, as these interventions might help protect against COVID-19. 160,161 Exercise can help reduce risk factors in older adults for COVID-19, including frailty and chronic disease. 162,163 Furthermore, exercise has immunoregulatory effects on both the innate and adaptive immune systems, which help in fighting against viral infections.…”