Clinical efficacy of eucaloric ketogenic nutrition in the COVID-19 cytokine storm: A retrospective analysis of mortality and intensive care unit admission.

OBJECTIVES: Our primary objective was to explore the effect of a eucaloric ketogenic diet (EKD) on mortality, admission to the intensive care unit, and need for non-invasive ventilation in hospitalized patients with COronaVIrus Disease 19 (COVID-19), in comparison to a eucaloric standard diet. Secondary objectives were verification of the safety and feasibility of the diet and its effects on inflammatory parameters, particularly interleukin-6. METHODS: The study is a retrospective analysis of 34 patients fed with an EKD in comparison to 68 patients fed with a eucaloric standard diet, selected and matched using propensity scores 1:2 to avoid the confounding effect of interfering variables. Our hypothesis was that an EKD would reduce mortality, admission to the intensive care unit, and need for non-invasive ventilation in patients with COVID-19. RESULTS: The preliminary multivariate analysis showed a statistically significant difference in survival (P = 0.046) and need for the intensive care unit (P = 0.049) for the EKD compared with a eucaloric standard diet. Even considering the EKD start day as a time-dependent variable, the results maintain a positive trend for application of the diet, and it is not possible to reject the null hypothesis (P < 0.05). Interleukin-6 concentrations between t0 and t7 (7 d after the beginning of the diet) in the ketogenic nutrition group show a trend that is almost significant (P = 0.062). The EKD was safe and no adverse events were observed. CONCLUSIONS: These results show a possible therapeutic role of an EKD in the clinical management of COVID-19. Currently, a prospective controlled randomized trial is running to confirm these preliminary data.

Clinical Efficacy of Eucaloric Ketogenic Nutrition in the COVID-19 Cytokine Storm: a Retrospective Analysis of Mortality and ICU Admission (preprint)

Background: Some patients affected by COVID-19 present a life-threatening hyperinflammatory state known as cytokine storm syndrome (CSS) associated with a high mortality rate. Our hypothesis is that a eucaloric ketogenic diet (EKD) may be a safe and efficacious treatment option to reduce CSS and consequently to reduce the need for CPAP, ICU admission and COVID-19 mortality.Aim of the study: The primary objective is to explore the effect of an EKD on mortality, admission to the ICU and the need for NIV in hospitalized patients with COVID-19 in comparison to a eucaloric standard diet (ESD). The secondary objectives are to collect data about the safety and feasibility of an EKD during hospitalization and to evaluate the effect of the diet on biological and inflammatory parameters, particularly interleukin-6 (IL-6).Patients and methods: The study is a retrospective explorative analysis of 34 patients fed with an EKD during hospitalization for COVID-19 in comparison to 68 patients fed an ESD selected and matched using propensity score one-to-two to avoid the confounding effect of interfering variables.Results: A trend of reduced 30-day mortality (HR 0.416, 95% CI 0.122 – 1.413, P = 0.160) and a trend regarding the need for ICU admission (HR 0.357, 95% CI 0.045 – 2.847, P = 0.331) were observed in subjects treated with the EKD compared to patients fed with the standard diet. No significantly different risks in the need for CPAP (HR 0.968, CI 0.289 – 3.242, P = 0.958 for EKD) or the composite endpoint (HR 0.674, CI 0.233 – 1.949, P = 0.446 for EKD) were detectable between the two groups of dietary patterns.Furthermore, IL-6 concentrations between t 0 and t 7 (seven days after the beginning of the diet) in the ketogenic nutrition group showed a median difference of -26.0 ȵg/mL and a mean difference of -164 ȵg/mL (data from 23 of the 34 pairs) compared to controls, with a trend toward significance (P = 0.062). EKD was safe and no adverse events were observed in patients fed an EKD.Discussion and conclusions: These preliminary data on the clinical results for mortality, need for ICU admission and the effect on the IL-6 concentration during EKD feeding, collected in a retrospective way during the most aggressive period of the COVID-19 pandemic, suggest a favorable role of this dietary treatment in COVID-19 clinical management. The EKD was safe and well accepted by patients during hospitalization and seems to be an interesting tool in controlling COVID-19 CSS. The results of the prospective controlled randomized trial, currently underway with a large number of subjects, are necessary to confirm these preliminary data.