Table 2.
Overview of studies on calprotectin in COVID-19 patients
| Study | COVID-19 | Mild | Moderate | Severe | Survivor | Non-survivor | ICU | Non-ICU | Controls | Survival Kaplan Meier |
ICU | MV vs. non-MV | Method for calprotectin | Sample matrix | Comments/Key findings |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| de Guadiana Romualdo et al. [37] |
66 | N/R | N/A | N/A | 58 | 8 | N/ R |
N/A | AUC = 0.801 (0.691–0.894) OR 13.3 (1.53–116) |
Yes | N/R | Particle enhanced turbidimetric immunoassay (PETIA, GenyianAS, Norway |
Blood (not specified further) | Discrimination between death/survival | |
| Chen et al. [34] | 121 | N/R | N/A | N/A | 83 | 36 | 40 | 81 | N/A | HR 13.32 AUC = 0.875 Sen/Spe 83.3/83.5 c/o 6284 |
AUC = 0.860 Sen/Spe 85.0/82.7 c/o 6195 |
N/R | Human S100A8/S100A9 Heterodimer DuoSet ELISA (DY8226-05, R&D Systems) | Serum (processed within 24 hours) | Discrimination between ICU/non-ICU and death/survival |
| Shi et al. [35] | 172* | N/R | N/A | N/A | N/A | N/A | N/A | N/A | 50# | N/R | N/R | AUC = 0.794 | Human S100A8/S100A9 Heterodimer DuoSet ELISA (DY8226-05, R&D Systems) |
Plasma/serum (stability study in supplement) |
Discrimination between patients in need of MV vs. no MV Monitoring |
| Silvin et al. [33] | 86 | 27 | 16 | 43 | 76 | 10 | N/R | N/R | 72$ | N/R | N/R | N/R | R-plex Human Calprotectin Antibody Set (Meso Scale Discovery, ref: F21YB-3 + MESO QuickPlex SQ120 reader + MSD’s Discovery Workbench 4.0). Average of duplicates | EDTA plasma | Discovery work revealed calprotectin Controls + Mild vs. Moderate + severe AUC = 0.959 |
| Sohn et al. [36] | 28 | 20 | N/A | 8 | N/A | N/A | N/A | N/A | 20# | N/R | N/R | N/R | N/A, Gene expression of S100A8 and S100A9 |
N/A | Gene expression of S100A8 and S100A9 Link between TLR4 and inflammation in COVID-19 |
| Wu et al. [145] | N/R | N/R | N/A | 9 | N/A | 9 | 9 | N/A | N/A | N/R | N/R | N/R | Gene expression |
Lung tissue | Low virus load, high calprotectin expression Also other S100 proteins overexpressed |
| Shu et al. [136] | 120 | 40 | N/A | 40 | 80 | 40 | 40 | N/R | N/R | N/R | Gene expression/ELISA CUSABIO (Cat#CSB-E12149h) | EDTA Plasma | Combination with CRP, CETP accurately identifies severe COVID-19 | ||
| Shaath et al. [137] | 8 | 3 | N/A | 5 | N/A | N/A | N/A | N/A | 2 | N/R | N/R | N/R | Single cell analysis | N/A | |
| Bauer et al. [138] | 19 | N/R | N/R | N/R | 17 | 2 | 8 | 11 | N/A | AUC = 0.85 (0.54–1.00) | AUC = 0.70 (0.42–0.99) |
turbidimetric method, Gentian AS, Norway | Serum, centrifuged within 30 min | Predictor of multi-organ failure | |
| Kaya et al. [134] | 80 | N/A | N/A | N/A | N/A | N/A | 38 | 42 | N/A | N/R | AUC = 0.64 (0.52–0.76) | ELISA (Elabscience, Bioassay Technology Laboratory, China) |
Serum | Associated with ICU requirement (p = 0.031) | |
| Ren et al. [135] | 171 | N/A | 122 | 134 | N/A | N/A | N/A | N/A | 25 | N/R | N?R | N?R | Single cell analysis | blood | Calprotectin highly upregulated in severe COVID-19 immune cells |
| Abers et al. [139] | 175 | 30 | 145 | 142 | 33 | N/A | N/A | 60 | N/R | N/R | N/R | Custom multiplex assay (R&D Systems) | Serum/plasma | Slope of ± 40% excepted between serum and plasma Calprotectin as one of the most significant predictors of severity |
Abbreviations: AUC = area under the curve; c/o = cutoff; CETP = Cholesteryl ester transfer protein; HI = healthy individuals; ICU = intensive care unit; N/R = not reported; OR = odds ratio; S100A8 and S100A9 = components of calprotectin complex; MV = mechanical ventilation; Sen = sensitivity; Spe = specificity; TLR = toll-like receptor # healthy controls, $ disease controls, * Room air oxygen = 41, noninvasive supplement oxygen = 71, mechanical ventilation = 60