Biomarkers and outcomes in hospitalised patients with COVID-19: a prospective registry.

Objectives: To determine association of biomarkers-high-sensitivity C reactive protein (hsCRP), D-dimer, interleukin-6 (IL-6), lactic dehydrogenase (LDH), ferritin and neutrophil-lymphocyte ratio (NLR)-at hospitalisation with outcomes in COVID-19.

Design And Setting: Tertiary-care hospital based prospective registry.

Participants: Successive virologically confirmed patients with COVID-19 hospitalised from April 2020 to July 2021 were prospectively recruited. Details of clinical presentation, investigations, management and outcomes were obtained.

Primary And Secondary Outcome Measures: All biomarkers were divided into tertiles to determine associations with clinical features and outcomes. Primary outcome was all-cause deaths and secondary outcome was oxygen requirement, non-invasive and invasive ventilation, dialysis, duration of stay in ICU and hospital. Numerical data are presented in median and interquartile range (IQR 25-75). Univariate and multivariate (age, sex, risk factors, comorbidities, treatments) ORs and 95% CIs were calculated.

Results: 3036 virologically confirmed patients with COVID-19 were detected and 1251 hospitalised. Men were 70.0%, aged >60 years 44.8%, hypertension 44.1%, diabetes 39.6% and cardiovascular disease 18.9%. Median symptom duration was 5 days (IQR 4-7) and oxygen saturation 95% (90%-97%). Total white cell count was 6.9×10/L (5.0-9.8), neutrophils 79.2% (68.1%-88.2%), lymphocytes 15.8% (8.7%-25.5%) and creatinine 0.93 mg/dL (0.78-1.22). Median (IQR) for biomarkers were hsCRP 6.9 mg/dL (2.2-18.9), D-dimer 464 ng/dL (201-982), IL-6 20.1 ng/dL (6.5-60.4), LDH 284 mg/dL (220-396) and ferritin 351 mg/dL (159-676). Oxygen support at admission was in 38.6%, subsequent non-invasive or invasive ventilatory support in 11.0% and 11.6%, and haemodialysis in 38 (3.1%). 173 (13.9%) patients died and 15 (1.2%) transferred to hospice care. For each biomarker, compared with the first, those in the second and third tertiles had more clinical and laboratory abnormalities, and oxygen, ventilatory and dialysis support. Multivariate-adjusted ORs (95% CI) for deaths in second and third versus first tertiles, respectively, were hsCRP 2.24 (1.11 to 4.50) and 12.56 (6.76 to 23.35); D-dimer 3.44 (1.59 to 7.44) and 14.42 (7.09 to 29.30); IL-6 2.56 (1.13 to 5.10) and 10.85 (5.82 to 20.22); ferritin 2.88 (1.49 to 5.58) and 8.19 (4.41 to 15.20); LDH 1.75 (0.81 to 3.75) and 9.29 (4.75 to 18.14); and NLR 3.47 (1.68 to 7.14) and 17.71 (9.12 to 34.39) (p<0.001).

Conclusion: High levels of biomarkers-hsCRP, D-dimer, IL-6, LDH, ferritin and NLR-in COVID-19 are associated with more severe illness and higher in-hospital mortality. NLR, a widely available investigation, provides information similar to more expensive biomarkers.