Serum glucose-regulated protein 78 (GRP78) levels in COVID-19-associated mucormycosis: results of a case-control study

Background In experimental models, the expression of glucose-regulated protein 78 (GRP78) in endothelial cells played a role in the pathogenesis of mucormycosis. However, the role of GRP78 in COVID-19-associated mucormycosis (CAM) has not been studied. We hypothesized that serum GRP78 levels are elevated in subjects with CAM. Objective To compare the serum GRP78 levels in subjects with CAM and COVID-19 controls without mucormycosis. Design And Setting We performed a hospital-based, case-control study between 1 April 2021 and 31 May 2021. Participants We enrolled 24 subjects each of CAM and COVID-19 subjects without mucormycosis. We also measured serum GRP78 levels in ten healthy controls. Exposure The primary exposure studied was serum GRP78 concentration, estimated using a commercially available ELISA kit in stored serum samples. Results We found the mean +/- standard deviation (SD) serum GRP78 levels significantly higher (p = 0.0001) among the CAM (374.3 +/- 127.3 pg/ mL) than the COVID-19 (246.4 +/- 67.0 pg/mL) controls. The proportion of subjects with an abnormal GRP78 level (> mean [184.8 pg/mL] plus two SD [23.2 pg/mL] of GRP78 from healthy participants) was 87.5% and 45.8% in the CAM group and COVID-19 controls, respectively. Serum GRP78 level was independently associated with CAM (odds ratio 1.011; 95% confidence interval [1.002-1.019]) after adjusting for diabetes mellitus and hypoxemia during acute COVID-19. Conclusion Serum GRP78 levels were significantly higher in CAM than in COVID-19 controls. Further studies are required to the role of GRP78 in the pathogenesis of CAM.

Automated summary

This study compared the serum levels of glucose-regulated protein 78 (GRP78) in subjects with COVID-19-associated mucormycosis (CAM) and COVID-19 controls without mucormycosis. The results showed that the serum levels of GRP78 were significantly higher in CAM subjects than in COVID-19 controls. The study suggests that GRP78 may play a role in the pathogenesis of CAM.