Serial measurement of circulating calprotectin as a prognostic biomarker in COVID-19 patients in intensive care setting

Abstract

Objectives Circulating calprotectin (cCLP) has been shown to be a promising prognostic marker for COVID-19 severity. We aimed to investigate the prognostic value of serial measurements of cCLP in COVID-19 patients admitted to an intensive care unit (ICU). Methods From November 2020 to May 2021, patients with COVID-19, admitted at the ICU of the OLV Hospital, Aalst, Belgium, were prospectively included. For sixty-six (66) patients, blood samples were collected at admission and subsequently every 48 h during ICU stay. On every sample (total n=301), a cCLP (EliA™ Calprotectin 2, Phadia 200, Thermo Fisher Scientific; serum/plasma protocol (for Research Use Only, -RUO-) and C-reactive protein (CRP; cobas c501/c503, Roche Diagnostics) analysis were performed. Linear mixed models were used to associate biomarkers levels with mortality, need for mechanical ventilation, length of stay at ICU (LOS-ICU) and medication use (antibiotics, corticosteroids, antiviral and immune suppressant/modulatory drugs). Results Longitudinally higher levels of all biomarkers were associated with LOS-ICU and with the need for mechanical ventilation. Medication use and LOS-ICU were not associated with variations in cCLP and CRP levels. cCLP levels increased significantly during ICU hospitalization in the deceased group (n=21/66) but decreased in the non-deceased group (n=45/66). In contrast, CRP levels decreased non-significantly in both patient groups, although significantly longitudinally higher CRP levels were obtained in the deceased subgroup. Conclusions Serial measurements of cCLP provides prognostic information which can be useful to guide clinical management of COVID-19 patients in ICU setting.

Elevated level of circulating calprotectin correlates with severity and high mortality in patients with COVID‐19

“…Third, circulating calprotectin offers a clear kinetic advantage as the first indication of acute inflammation since it does not require de novo synthesis 60 . Moreover, compared with other more common biomarkers, calprotectin had the advantage that marker levels did not increase significantly during ICU due to potential bacterial infection and other influences 61 . Last but not least, given the encouraging results in treating inflammatory disorders, 62 S100A8/S100A9 inhibitors (e.g., paquinimod) may be a promising treatment option for severe or critically ill COVID‐19 individuals 63 …”

“…60 Moreover, compared with other more common biomarkers, calprotectin had the advantage that marker levels did not increase significantly during ICU due to potential bacterial infection and other influences. 61 Last but not least, given the encouraging results in treating inflammatory disorders, 62 S100A8/S100A9 inhibitors (e.g., paquinimod) may be a promising treatment option for severe or critically ill COVID-19 individuals. 63 Although there were multiple original studies evaluating the value of calprotectin in COVID-19 from the aspects of expression level, diagnostic, and prognostic value, their results were controversial.…”

Elevated Level of Circulating but Not Urine S100A8/A9 Identifies Poor COVID-19 Outcomes

“…11,24,39 However, this lack of variation may be advantageous, as routine biomarkers such as CRP and procalcitonin may be influenced by potential concomitant bacterial co-infection. 24 These conclusions are supported by previous studies that observed elevated S100A8/ A9 levels in severe COVID-19 patients occurring irrespective of concomitant bacterial co-infections. 9 Elevated S100A8/A9 urine and serum levels have been observed in patients with active lupus nephritis, and published studies have observed correlations between serum and urine S100A8/A9 levels in patients with Type II diabetes, suggesting that these levels may be related across different conditions.…”

“…While recent studies report the association of circulating S100A8/A9 levels with poor COVID-19 patient outcomes and demonstrate its ability to differentiate COVID-19 severity, these studies have only been conducted in non-U.S. patient cohorts and specifically analyzed samples collected from patients at the time of admission to emergency departments. ,,,,, We have previously observed 2-fold variations in serum S100A8/A9 levels in active tuberculosis patients in different geographical cohorts. , Therefore, the reported predictive capacities and threshold values of serum S100A8/A9 for the prognostication of COVID-19 patients from non-U.S. cohorts cannot be blindly applied to U.S. cohorts. Furthermore, investigations limited their exploration to the prognostic value of circulating S100A8/A9 levels and did not evaluate the utility of these levels in urine samples. ,,,,,,− …”

“…In contrast to published studies, we did not observe significant serum S100A8/A9 variation related to length of hospitalization or ventilation requirement. ,, However, this lack of variation may be advantageous, as routine biomarkers such as CRP and procalcitonin may be influenced by potential concomitant bacterial co-infection . These conclusions are supported by previous studies that observed elevated S100A8/A9 levels in severe COVID-19 patients occurring irrespective of concomitant bacterial co-infections …”