Dietetic-Led Nutrition Interventions in Patients with COVID-19 during Intensive Care and Ward-Based Rehabilitation: A Single-Center Observational Study.

BACKGROUND: In this study, a report of dietitian-led nutrition interventions for patients with COVID-19 during ICU and ward-based rehabilitation is provided. As knowledge of COVID-19 and its medical treatments evolved through the course of the pandemic, dietetic-led interventions were compared between surge 1 (S1) and surge 2 (S2). METHODS: A prospective observational study was conducted of patients admitted to the ICU service in a large academic hospital (London, UK). Clinical and nutrition data were collected during the first surge (March-June 2020; n = 200) and the second surge (November 2020-March 2021; n = 253) of COVID-19. RESULTS: A total of 453 patients were recruited. All required individualized dietetic-led interventions during ICU admission as the ICU nutrition protocol did not meet nutritional needs. Feed adjustments for deranged renal function (p = 0.001) and propofol calories (p = 0.001) were more common in S1, whereas adjustment for gastrointestinal dysfunction was more common in S2 (p = 0.001). One-third of all patients were malnourished on ICU admission, and all lost weight in ICU, with a mean (SD) total percentage loss of 8.8% (6.9%). Further weight loss was prevented over the remaining hospital stay with continued dietetic-led interventions. CONCLUSIONS: COVID-19 patients have complex nutritional needs due to malnutrition on admission and ongoing weight loss. Disease complexity and evolving nature of medical management required multifaceted dietetic-led nutritional strategies, which differed between surges.

Cytoplasmic serine hydroxymethyltransferase mediates competition between folate-dependent deoxyribonucleotide and S-adenosylmethionine biosyntheses.

Folate-dependent one-carbon metabolism is required for the synthesis of purines and thymidylate and for the remethylation of homocysteine to methionine. Methionine is subsequently adenylated to S-adenosylmethionine (SAM), a cofactor that methylates DNA, RNA, proteins, and many metabolites. Previous experimental and theoretical modeling studies have indicated that folate cofactors are limiting for cytoplasmic folate-dependent reactions and that the synthesis of DNA precursors competes with SAM synthesis. Each of these studies concluded that SAM synthesis has a higher metabolic priority than dTMP synthesis. The influence of cytoplasmic serine hydroxymethyltransferase (cSHMT) on this competition was examined in MCF-7 cells. Increases in cSHMT expression inhibit SAM concentrations by two proposed mechanisms: (1) cSHMT-catalyzed serine synthesis competes with the enzyme methylenetetrahydrofolate reductase for methylenetetrahydrofolate in a glycine-dependent manner, and (2) cSHMT, a high affinity 5-methyltetrahydrofolate-binding protein, sequesters this cofactor and inhibits methionine synthesis in a glycine-independent manner. Stable isotope tracer studies indicate that cSHMT plays an important role in mediating the flux of one-carbon units between dTMP and SAM syntheses. We conclude that cSHMT has three important functions in the cytoplasm: (1) it preferentially supplies one-carbon units for thymidylate biosynthesis, (2) it depletes methylenetetrahydrofolate pools for SAM synthesis by synthesizing serine, and (3) it sequesters 5-methyltetrahydrofolate and inhibits SAM synthesis. These results indicate that cSHMT is a metabolic switch that, when activated, gives dTMP synthesis higher metabolic priority than SAM synthesis.