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

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.

Greater Covid-19 Severity and Mortality in Hospitalized Patients in Second (Delta Variant) Wave Compared to the First: Single Centre Prospective Study in India (preprint)

Background & ObjectiveCovid-19 pandemic has led to multiple waves secondary to mutations in SARS-CoV-2 and emergence of variants of concern (VOC). Clinical characteristics of delta (B.1.617.2) VOC are not well reported. To compare demographic, clinical and laboratory features and outcomes in the second Covid-19 wave in India (delta VOC) with the previous wave we performed a registry-based study. MethodsSuccessive SARS-CoV-2 reverse transcriptase-polymerase chain reaction (RT-PCR) confirmed Covid-19 patients presenting to our Advanced Covid Care hospital were prospectively recruited. In the first phase (wave) from March-December 2020, 1395 of 7476 (18.7%) suspected patients tested positive and 863 (61.89%) hospitalized, while in second wave from January-July 2021 out of 1641 confirmed cases out of 8680 (19.4%) suspected 388 (23.6%) were hospitalized. Details of clinical and laboratory features at admission to hospital, management and outcomes in the two waves have been compared. ResultsIn both cohorts, majority were men and 20% less than 40 years. Prevalence of hypertension, diabetes and cardiovascular diseases was more than 20%. Second wave patients had similar pre-hospitalization symptom duration but had significantly greater cough, fever and shortness of breath and lower SpO2 at presentation with greater lymphopenia, C-reactive proteins, interleukin-6, ferritin, lactic dehydrogenase and transaminases. In the second vs first wave patients, requirement of supplementary oxygen (47.9% vs 34.3%), prone positioning (89.2 vs 38.6%), high flow nasal oxygen(15.7 vs 9.1%), non-invasive ventilation (14.4 vs 9.5%), invasive ventilation (16.2 vs 9.5%), steroids (94.1 vs 85.9%), remdesivir (91.2 vs 76.0%) and anticoagulants (94.3 vs 76.0%) was greater (p<0.001). Median (IQR) length of stay [8 (6-10) vs 7 (5-10) days] as well as ICU stay [9 (5-13) vs 6 (2-10) days] was more in second wave (p<0.001). In-hospital deaths occurred in 173 patients (13.9%) and were significantly more in the second wave, 75 (19.3%), compared to the first, 98 (11.5%); unadjusted odds ratio (95% CI) 1.84 (1.32-2.55) which did not change significantly with adjustment for age and sex (2.03, 1.44-2.86), and age, sex and comorbidities (2.09, 1.47-2.95). Greater disease severity at presentation was associated with mortality in both the waves. ConclusionsCovid-19 patients hospitalized during the second wave of the epidemic (delta variant) had more severe disease with greater dyspnea, hypoxia, hematological and biochemical abnormalities compared to first wave patients. They had greater length of stay in intensive care unit, oxygen requirement, non-invasive and invasive ventilatory support. The in-hospital mortality in the second wave was double of the first.