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 >60years 44.8%, hypertension 44.1%, diabetes 39.6% and cardiovascular disease 18.9%. Median symptom duration was 5days (IQR 4-7) and oxygen saturation 95% (90%-97%). Total white cell count was 6.9x10(9)/L (5.0-9.8), neutrophils 79.2% (68.1%-88.2%), lymphocytes 15.8% (8.7%-25.5%) and creatinine 0.93mg/dL (0.78-1.22). Median (IQR) for biomarkers were hsCRP 6.9mg/dL (2.2-18.9), D-dimer 464ng/dL (201-982), IL-6 20.1ng/dL (6.5-60.4), LDH 284mg/dL (220-396) and ferritin 351mg/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.