Table 2.

Studies on the efficacy of KD/ketone bodies in SARS-CoV-2 on biological material from patients with COVID-19.

	Study Material/Quantity of Samples	Evaluation	Intervention/ Measurement	Results	Bibliography
1	Serum from patients with moderate COVID-19 or ARDS due to COVID-19/n = 155	Evaluation of the relationship between infection-induced metabolic changes and host immune responses in severe lung infections	Cultured human TCD4+/ E ketone ester BHB (d -β-hydroxybutyrate-(R)-1,3-butanediol monoester) added at days 0, 1, and 2 in an amount of 5 mM BHB (6 days of culture)	-in the peripheral blood of patients with moderate to severe COVID-19, low concentrations of BHB irrespective of calorie intake and blood glucose levels -BHB resulted in improved mitochondrial function, and fatty acid and amino acid oxidation; reduced glycolysis in CD4 + T lymphocytes -cultures of human TH1 CD4 + lymphocytes with BHB showed an increase in the number of CD4+ cells and IFNy production, and a decrease in PD-1 (programmed death receptor 1) expression	Karagiannis et al. [116]
2	Immune cells from patients with COVID-19; disease severity >IV0 and respiratory failure/n = 9/20	Evaluation of the efficacy of metabolic reprogramming of CD8 + T cells by ketone bodies in overcoming immune paralysis in patients with COVID-19	Peripheral blood mononuclear cells (PBMCs) from COVID-19 patients. Incubation with BHB, D/L-beta-hydroxybutyrate with a final concentration of 10 mM	-significant increase in granzyme B-expressing CD8 + lymphocytes and increased granzyme B expression per cell, -profound enhancement of CD8 + immune capacity -significantly increased secretion of the T lymphocyte cytokines CD8 + IFNγ, TNFα, perforin, and granzyme B -markedly increased cell lysis capacity of CD8 + T lymphocytes -CD8 + T lymphocytes showed significantly higher basal and maximal respiratory chain activity and better spare respiratory capacity -a tendency towards increased mitochondrial mass in CD8 + T cells -significantly increased mitochondrial ROS but cellular ROS levels remained unchanged	Hirschberger et al. [143]
3	DNA methylation levels of ACE2 from data sets generated by hybridization of subcutaneous (n = 32), visceral (n = 32) adipose tissue, and leukocyte samples (n = 34).	Evaluation of ACE2 methylation levels in different depots of adipose tissue and leukocytes in obesity	DNA methylation levels of ACE2. Data were compared based on degree of obesity and after 4–6 months of weight loss following weight loss therapy based on VLCKD vs. HCD vs. bariatric surgery	-decreased levels of ACE2 methylation and increased ACE2 mRNA expression in visceral adipose tissue and leukocytes in obese patients after VLCKD	Izquierdo et al. [125]
4	Simulated Kbhb antibody produced using in vitro chemical modification from a commercially obtained human serum antibody	Investigating the immunomodulatory mechanisms of β-hydroxybutyrate	Antibody solution with addition of free β-hydroxybutyrate	Kbhb did not affect the binding capacity of B38 to the S-protein of COVID-19 virus, indicating that the chemically modified antibody retained its original antigen-binding activity	Li et al. [144]

VLCKD—very low-calorie ketogenic diet, HCD—balanced hypocaloric diet, BHB—beta-hydroxybutyrate, ARDS—acute respiratory distress syndrome, ACE2—angiotensin-converting enzyme type 2, IFNy—interferon gamma, TNFα—tumor necrosis factor α, ROS—reactive oxygen species, Kbhb -.