Association between biomarkers and COVID-19 severity and mortality: a nationwide Danish cohort study

Abstract

Objective: To evaluate the association between common biomarkers, death and intensive care unit (ICU) admission in patients with COVID-19.

Design: Retrospective cohort study. From electronic national registry data, we used Cox analysis and bootstrapping to evaluate associations between baseline levels of biomarkers and standardised absolute risks of death/ICU admission, adjusted for age and gender.

Setting: All hospitals in Denmark.

Participants: 1310 patients aged ≥18 years admitted to hospital with COVID-19 from 27th of February to 1st of May 2020, with available biochemistry data.

Main outcome measures: A composite of death/ICU admission occurring within 30 days.

Results: Of the 1310 patients admitted to hospital (54.6% men; median age 73.6 years), 352 (26.9%) experienced the composite endpoint and 263 (20.1%) died. For the composite endpoint, the absolute risks for moderately and severely elevated C reactive protein (CRP) were significantly higher, 21.5% and 39.2%, respectively, compared with 5.0% for those with normal CRP. Moderately and severely elevated leucocytes were significantly higher, 34.5% and 46.6% risk, respectively, compared with 23.2% for those with normal leucocytes. Moderately and severely decreased estimated glomerular filtration rates (eGFR) were significantly higher, 41.5% and 45.9% risk, respectively, compared with 30.4% for those with normal/mildly decreased eGFR. Normal and elevated ureas were significantly higher, 22.3% and 40.6% risk, respectively, compared with 7.3% for those with low urea. Elevated D-dimer was significantly higher, 31.8% risk, compared with 17.5% for those with normal D-dimer. Moderately and severely elevated troponins were significantly higher, 27.7% and 57.3% risk, respectively, compared with 9.4% for those with normal troponin. Elevated procalcitonin was significantly higher, 52.1% risk, compared with 28.0% for those with normal procalcitonin.

Conclusion: In this nationwide study of patients admitted with COVID-19, elevated levels of CRP, leucocytes, procalcitonin, urea, troponins and D-dimer, and low levels of eGFR were associated with higher standardised absolute risk of death/ICU admission within 30 days.

Keywords: adult intensive & critical care; general medicine (see internal medicine); infectious diseases.

Figure 1

Flowchart of study cohort. ALAT, alanine aminotransferase; CRP, C reactive protein; eGFR, estimated glomerular filtration rate.

Figure 2

A 30-day absolute risk for the composite outcome of death or ICU admission, adjusted for age and gender. ALAT, alanine aminotransferase; CRP, C reactive protein; eGFR, estimated glomerular filtration rate; ICU, intensive care unit.

Figure 3

A 30-day absolute risk for the composite outcome of death or ICU admission, stratified by normal/elevated ranges, and adjusted for age and gender. ALAT, alanine aminotransferase; CRP, C reactive protein; eGFR, estimated glomerular filtration rate; ICU, intensive care unit.

Figure 4

A 30-day absolute risk for the composite outcome of death or ICU admission, adjusted for CRP level, age, gender, diabetes, chronic obstructive pulmonary disease, hypertension and ischaemic heart disease. CRP, C reactive protein; ICU, intensive care unit.