Biomarkers and Their Dynamic Changes Associated with Acute Respiratory Distress Syndrome, Acute Kidney Injury and Death in COVID-19: Prospective Cohort Study

Objectives: An exceptionally high mortality rate of SARS-CoV-2 pneumonia is due to complications such as acute respiratory distress syndrome (ARDS) and acute kidney injury (AKI). New prognostic markers for deterioration of lung function, increased mortality rate, and development of AKI are constantly emerging. Most of the research done so far is based on cross-sectional data collection, and there are few dynamic studies evaluating patients using serial samples. We focus on novel and well-described biomarkers and their dynamic changes over time. Leucine-rich Alpha-2 Glycoprotein (LRG) is a novel acute phase protein included in our study, which as a perspective serum biomarker, has been studied in autoimmune diseases, fetal infection, acute appendicitis in children and kidney disease.
Methods: In a single-centered prospective cohort study, 60 patients with laboratory-confirmed SARS-CoV-2 pneumonia were included. Twenty-one biomarkers were measured in serial blood and urine samples on the first and fifth day of admission. Delta values were calculated and compared between groups of various outcomes- death, worsening of ARDS, and AKI.
Results: An increase in ferritin levels during the first five days was associated with the progression of ARDS, increased mortality, and AKI development, compared to widely used markers such as lactates, IL-6, CRP, procalcitonin, and others. If ferritin levels did not decrease during the first five days of hospitalization, the RR of in-hospital death was 5.36 (95% CI 1.87 - 15.50). The best prognostic value for death was observed in the PaO2/FiO2 ratio measured of fifth day with AUC 0.944 (p<0.001). Serum LRG did not show any predictive value.
Conclusion: Increasing ferritin levels over the first five days of admission signal a poor outcome, and therefore, as an easy to use and universal marker, it should be taken into account in decision-making. Although serum LRG was not predictive, further studies are needed on its possible role in SARS-CoV-2 infection.