Aims: 

SARS-CoV-2 lead to the COVID-19 pandemic causing tremendous numbers of deaths and a heavy burden for national healthcare systems continuing to the present day. The aim of this study was to investigate whether bioactive adrenomedullin (bio-ADM) and interleukin-6 (IL-6) are related to acute kidney injury (AKI) and severe illness in COVID-19 patients.

Methods:

In this prospective observational study 208 patients admitted to the emergency department (ED) with respiratory symptoms were included and divided into a COVID-19 cohort (n=153) and a non-COVID cohort (n=55). Blood samples were collected from each patient at admission. Bio-ADM and IL-6, as well as routinely measured markers like creatinine, NT-proBNP and hsTnT were evaluated regarding the endpoints AKI (COVID-19: n= 22 patients, non-COVID: n= 14 patients) and critical illness - defined as a composite endpoint of admission to intensive care unit (ICU) and/or in-hospital death (COVID-19: n= 26 patients, non-COVID: n= 8 patients).

Results:

168 patients were hospitalized (128 COVID-19 and 40 non-COVID-patients). While IL-6 was significantly higher (p=0.017) in the non-COVID cohort, bioADM did not significantly differ between COVID-19 patients and non-COVID-patients (p=n.s.).

Bio-ADM and IL-6 were significantly elevated in COVID-19 patients with AKI compared to COVID-19 patients without AKI (each p<0.001). Regarding ROC analysis IL-6 and bioADM had the largest AUC (0.84 and 0.81) in the COVID-19 cohort compared to hsTnT, NT-proBNP, creatinine and dpp3 (0.80, 0.76, 0.75 and 0.70; each p<0.05). In the non-COVID cohort bio-ADM was also significantly increased in AKI patients (p<0.05), showing an AUC of 0.73, whereas IL-6 was not significantly elevated (p=n.s.).

Furthermore, bio-ADM and IL-6 were significantly elevated in COVID-19 patients reaching the composite endpoint critical illness compared to other COVID-19 patients (each p<0.001). Regarding ROC analysis IL-6 and bioADM showed an AUC of 0.89 and 0.83 for COVID-19 patients, being larger than  hsTnT, dpp3, NT-proBNP and creatinine (0.80, 0.80, 0.75 and 0.65; each p<0.05). Concerning patients with respiratory infection other than COVID-19, IL-6 (AUC 0.88) and bio-ADM (AUC 0.87) were also significantly elevated in those reaching the composite endpoint (each p<0.001).

In the multivariable logistic model bio-ADM and IL-6 presented as independent significant predictors regarding both endpoints AKI and critical illness in COVID-19 patients (as well as creatinine regarding AKI; each p <0.05), opposite to leukocytes, CRP and dpp3 (each p=n.s.).

Conclusion: 

Bio-ADM and IL-6 are associated with acute kidney injury and critical illness in patients with COVID-19. Therefore, both biomarkers may be potential tools in risk stratification in COVID-19 patients at presentation in the ED. These associations were less pronounced in non-COVID-19 patients.