Catabolic Phase of COVID-19 and Its Association With Outcome

Urinary nitrogen excretion in patients with COVID-19 should be monitored to determine the amount of protein intake these patients require.

Individuals who did not survive COVID-19 had a more prolonged and seemingly more pronounced catabolic state than those who survived, according to a study published in Clinical Nutrition.

In patients critically ill with COVID-19, the onset of inflammation is usually accompanied by a state of hypercatabolism that results in skeletal muscle wasting, which in turn contributes to organ failure and increased mortality risk. The intensity and duration of catabolic phase in COVID-19 can differ between patients. Investigators therefore assessed the temporal trajectories of nitrogen balance (NBAL) in critically ill patients with COVID-19.

Patients admitted to the intensive care unit (ICU) at a single center in France from January 2020 to May 2021 with COVID-19 pneumonia were included in this retrospective observational study. Data was collected prospectively at admission and during the stay. Investigators compared the time course of NBAL according to outcome. The effect of non-negative NBAL on ICU death was assessed at days 3, 5, 7, 10, and 14.

This study has the main advantage of being one of the first in COVID patients to report multiple serial NBAL determinations to examine overall protein balance.

In total, 99 patients were included in the study. Among those who survived and those who did not, a similar negative NBAL was observed at day 3 (-16.4 g/d [-26.5 to -3.3] and -17.3 g/d [-22.2 to -3.8], respectively; P =.54). Over time, the trajectories of NBAL differed between those who survived and those who did not (P =.01), with the balance increasing over time for survivors and decreasing from days 2 to 6 in those who did not survive, after which it slowly increased up to day 14. A non-negative NBAL at days 5 and 7 was protective from death, and administration of higher protein amounts was associated with higher NBAL.

More specifically, the investigators found:

  • a high protein catabolism level in the first 10 days after ICU admission (but less marked after day 3) among those who survived COVID-19;
  • an association between inflammation and negative NBAL at day 3, suggesting that inflammation is a key determinant of protein loss in these patients;
  • a more positive NBAL among those who survived their illness;
  • an association between increased protein intake and improved NBAL, with a higher increase in NBAL associated with protein intakes higher than 1.2 g/kg/day and a neutral NBAL achieved when protein intakes were 2 g/kg and 1.64 g/kg at days 3 and 7;
  • a more negative NBAL among patients who were obese, who went through a more severe catabolic phase;
  • differing time trajectories for NBAL among those who survived COVID-19 and those who did not, especially in patients who were older, female, and not obese; and
  • an apparent association between minimizing negative nitrogen imbalance and improved patient outcomes.

The study was limited by its observational, retrospective design and use of only a single center. Moreover, due to a significant reduction of participants with NBAL measurements between day 7 and 14, the second week trajectories should be interpreted with caution. Additionally, the link between NBAL and inflammation relies solely upon hospital admission data.

“This study has the main advantage of being one of the first in COVID patients to report multiple serial NBAL determinations to examine overall protein balance,” said study authors. “Our study underlines the need for monitoring both urinary nitrogen excretion and energy expenditure to individualize nutritional needs in COVID-19 patients,” the researchers concluded. “Whether catabolism and nitrogen losses can be reversed by enhanced individualized nutritional support, and whether this improves outcome, remain to be investigated,” they added.


Dupuis C, Bret A, Janer A, et al. Association of NBAL trajectories with clinical outcomes in critically ill COVID-19 patients: A retrospective cohort study. Clin Nutr. Published online September 6, 2022. doi:10.1016/j.clnu.2022.08.023