Serum calprotectin can indicate current and future severity ofCOVID‐19

Abstract

Background Predictive and prognostic biomarkers to guide 2019 novel coronavirus disease (COVID‐19) are critically evolving. Dysregulated immune responses are the pivotal cause of severity mainly mediated by neutrophil activation. Thus, we evaluated the association of calprotectin, neutrophil secretory protein, and other mediators of inflammation with the severity and outcomes of COVID‐19. Methods This two‐center prospective study focused on PCR‐proven COVID‐19 patients (n = 76) with different clinical presentations and SARS‐CoV‐2 negative control subjects (n = 24). Serum calprotectin (SC) was compared with IL‐6 and other laboratory parameters. Results Median levels of SC were significantly higher in COVID‐19 patients in comparison to the control group (3760 vs. 2100 ng/ml, p < 0.0001). Elevated SC was significantly respective of disease severity (3760 ng/ml in mild up to 5700 ng/ml in severe cases, p < 0.0001). Moreover, the significant positive and negative correlations of SC with disease severity and oxygenation status indicated disease progression and respiratory worsening, respectively. It was found that SC was high in severe patients during hospitalization and significantly declined to normal after recovery. The logistic analysis identified the independent predictive power of SC for respiratory status or clinical severity. Indeed, SC behaved as a better discriminator for both outcomes, as it exhibited the largest area under the curve (receiver operating curve analysis), with the highest specificity and sensitivity when the predictive value of inflammatory biomarkers was compared. Conclusion Calprotectin can be used as a reliable prognostic tool to predict the poor clinical outcomes of COVID‐19 patients.

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

“…Since there was no sufficient data of serum or plasma calprotectin, six others studies were also considered ineligible for this meta‐analysis. Finally, 15 studies 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 involving 2753 patients were included in the quantitative analysis. Among the 15 studies, 11 24 , 26 , 27 , 28 , 29 , 31 , 32 , 33 , 34 , 35 , 38 assessed the diagnostic value of calprotectin, five 25 , 31 , 34 , 35 , 36 reported the mortality and eight 24 , 27 , 29 , 30 , 32 , 35 , 36 , 37 presented the level of calprotectin.…”

“…Finally, 15 studies 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 involving 2753 patients were included in the quantitative analysis. Among the 15 studies, 11 24 , 26 , 27 , 28 , 29 , 31 , 32 , 33 , 34 , 35 , 38 assessed the diagnostic value of calprotectin, five 25 , 31 , 34 , 35 , 36 reported the mortality and eight 24 , 27 , 29 , 30 , 32 , 35 , 36 , 37 presented the level of calprotectin. The methods used to detect calprotectin in all 15 studies were enzyme‐linked immunosorbent assay (ELISA), chemiluminescent immunoassay, turbidimetric assay, and quantitative reverse‐transcription polymerase chain reaction (RT‐qPCR).…”

Alterations in gut immunological barrier in SARS-CoV-2 infection and their prognostic potential

“…This finding possibly suggests that the increase in fecal calprotectin associated with SARS-CoV-2 infection is due in part to chemotaxis of immune cells into to the gastrointestinal tract and hypoxic intestinal damage rather than intestinal inflammation and destruction of enterocytes ( 29 , 30 ). In addition, the role of serum calprotectin was also investigated and was found to be an effective marker for predicting the future status of SARS-CoV-2-infected individuals ( 31 ). The strong correlation of serum calprotectin with poor clinical outcomes highlights the potential value of this marker in identifying COVID-19 patients at high risk for disease progression ( 31 ).…”

“…In addition, the role of serum calprotectin was also investigated and was found to be an effective marker for predicting the future status of SARS-CoV-2-infected individuals ( 31 ). The strong correlation of serum calprotectin with poor clinical outcomes highlights the potential value of this marker in identifying COVID-19 patients at high risk for disease progression ( 31 ).…”

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

“…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. ,,,,,,− …”