Biomarkers and Outcomes in Hospitalized Covid-19 Patients: A Prospective Registry (preprint)

ABSTRACT

ABSTRACT 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 hospital admission with clinical features and outcomes in Covid-19. Methods: Successive virologically confirmed Covid-19 patients hospitalized from April 2020 to July 2021 were recruited in a prospective registry. Details of clinical presentation, investigations, management and outcomes were recorded. All the biomarkers were divided into tertiles to determine associations with clinical features and outcomes. Numerical data are presented in median and interquartile range (IQR 25-75). Univariate and multivariate (age, sex, risk factor, comorbidity adjusted) odds ratio (OR) and 95% confidence intervals (CI) were calculated to determine association of deaths with each biomarker. Results: We identified 3036 virologically confirmed Covid-19 patients during the study period, 1215 were hospitalized and included in the present study. Men were 70.0%, aged >60y 44.8%, hypertension 44.8% diabetes 39.6% and cardiovascular disease 18.9%. Median symptom duration was 5 days (IQR 4-7) and SpO2 95% (90-97). Total white cell count was 6.9x103/micro-litre, (5.0-9.8), neutrophils 79.2% (68.1-88.2) and lymphocytes 15.8% (8.7-25.5). Medians (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%, and non-invasive or invasive ventilatory support in 11.0% and 11.6% respectively. 173 (13.9%) patients died and 15 (1.2%) transferred to hospice care. For each biomarker, those in the second and third tertiles, compared to the first, had worse clinical and laboratory abnormalities, and greater oxygen and ventilatory support. Multivariate adjusted OR (95% CI) for deaths in second and third vs first tertiles, respectively, were for hsCRP 2.29(1.14-4.60) and 13.39(7.23-24.80); D-dimer 3.26(1.31-7.05) and 13.89(6.87-28.27); IL-6 2.61(1.31-5.18) and 10.96(5.88-20.43); ferritin 3.19(1.66-6.11) and 9.13(4.97-16.78); LDH 1.85(0.87-3.97) and 10.51(5.41-20.41); and NLR 3.34(1.62-6.89) and 17.52(9.03-34.00) (p<0.001). Conclusions: In Covid-19, high levels of biomarkers- hsCRP, D-dimer, IL-6, LDH, ferritin and NLR are associated with more severe illness and significantly greater in-hospital mortality. NLR, a simple, widely available and inexpensive investigation provides prognostic information similar to the more expensive biomarkers.