The most recent ESPEN guideline on nutritional support in critically ill patients
identifies 3 phases in the evolution of critically ill patients: the early acute phase
(formerly EBB Phase), characterized by endogenous energy production and activation of
autophagy that limits full caloric-protein intake; the late period of the acute phase,
when endogenous energy production has reduced to a basal level and autophagy is no longer
manifested, and the late or rehabilitation phase. The identification of each of these
moments is not based on precise elements. Despite this division into phases, there is no
clear evidence of metabolic behavior, especially in the second and third phases, when the
catabolic state gives way to anabolism.

Currently, monitoring catabolism is complicated since there is no available biomarker
with acceptable sensitivity and specificity. 3-methyl histidine and nitrogen balance are
not available in everyday life. As catabolism is not measured, its presence and severity
only become apparent when muscle loss and weakness set in.

Recently, Haines et al., analyzing a population of patients with persistent severe
disease, who are patients with prolonged hospitalization and with no resolution in the
ICU, showed that continued catabolism is their metabolic hallmark and was measured by the
urea/creatinine ratio persistently high.

The phases of severe illness could then be defined based on the UCR relationship. The
ratio must be high in the early acute and late acute phases and may be a marker of the
beginning of the late phase of recovery and anabolism.

Indirect calorimetry, the gold standard for determining energy expenditure energy, has
revealed in studies that it can be the marker of the beginning of the anabolic when
energy expenditure increases rapidly. This behavior of indirect calorimetry was observed
in COVID-19 but has also been demonstrated in other patient populations.

Although indirect calorimetry can represent a reliable measure for determining the
beginning of the anabolic phase, it is not a widely available measurement in ICUs, unlike
urea and creatinine measurements that are part of routine daily exams in ICUs.

The urea/creatinine ratio may be an efficient catabolism marker to guide nutritional
therapy in critically ill patients. Evidence to confirm this hypothesis can be obtained
by comparing the urea/creatinine ratio with indirect calorimetry, which is the gold
standard for evaluating energy expenditure and catabolism in these patients.

The primary objective will be to correlate the behavior of the urea/creatinine ratio with
the energetic expenditure measured by indirect calorimetry in patients with severe forms
of COVID-19 to identify the beginning of the anabolic phase that would be translated by a
reduction in UCR and an increase in energy expenditure in IC. Secondarily, correlate
other catabolism markers with calorimetry results. They are serum albumin, hemoglobin,
and C-reactive protein.