A cross-sectional study on the role of hematological and inflammatory biomarkers as predictor of mortality at the time of admission among COVID-19 patients

Whole world experienced COVID-19 pandemic with more than 155 million cases and >3.4 million deaths. Vasculitis and immune system activation plays a critical role in pathogenesis, especially in severely ill and non-survivors COVID-19 patients. Aims and Objectives: The aim of the study was to establish the role of hematological indices and inflammatory biomarker as predictors of mortality among non-survivor and survivor COVID-19 cases at the time of admission. Materials and Methods: The cross-sectional study was conducted at a dedicated COVID-19 referral hospital from July 2020 to August 2020, among 300 real time-polymerase chain reaction confirmed COVID-19 cases. Demographic, clinical, comorbidity, laboratory investigation, and outcome data were collected from patient's medical record. Outcome variables -- discharged (survived) or death (non-survived) were considered for comparison of various hematological indices and inflammatory biomarkers. Data are represented as median, IQR (Q1-Q3) and difference between median and proportions were calculated by Mann--Whitney U-test and χ² test. A predictive power of laboratory parameters between survivors and non-survivors was evaluated using receiver operant curve (ROC) analysis and area under the ROC curve (AUC). Results: The median age of non-survivors was significantly higher than survivors. Hypertension was significantly associated with non-survivors. Hematological parameters such as total leukocyte count, absolute neutrophil count, Neutrophil: Lymphocyte ratio were significantly increased with lymphocytopenia (P=0.001), and Inflammatory biomarkers such as C-reactive protein (CRP), lactate dehydrogenase, D-dimer, ferritin, procalcitonin, and NT-Pro BNP, all were significantly increased in non-survivors patients (P=0.001). CRP and neutrophil lymphocyte ratio (NLR) showed "Good" predictive value for mortality with cutoff value of 74.0 mg/l (AUC=0.841, Sensitivity=80.4%, Specificity=73.0%) and 5.65 (AUC=0.805, Sensitivity=76.1%, Specificity=73.0%), respectively. Pro-BNP showed "Fair" predictive value for mortality with cutoff value of 330.5 pg/ml (AUC=0.726, Sensitivity=73.9%, Specificity=58.2%). Conclusion: We suggest that CRP, NLR, and Pro-BNP can be used as a screening tool to predict mortality in COVID-19 patients for timely intervention to save valuable life, especially when sensitivity toward severity of COVID-19 among medical health professionals and general public is on decline. [ABSTRACT FROM AUTHOR] Copyright of Asian Journal of Medical Sciences is the property of Manipal Colleges of Medical Sciences and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Anti-cytokine Therapy in Hospitalized Patients with COVID-19: The Jury is Out.

How to cite this article: Garg SK. Anti-cytokine Therapy in Hospitalized Patients with COVID-19: The Jury is Out. Indian J Crit Care Med 2022;26(10):1069-1071.

Analysis of Chitinase-3-Like Protein 1, IL-1-Alpha, and IL-6 as Novel Inflammatory Biomarkers for COVID-19.

The aim of our study was to investigate the potential role of IL-1-alpha, IL-6, and chitinase 3-like protein-1 (CHI3L1) as potential biomarkers for COVID-19. Sixty adult SARS Cov-2 PCR-positive patients (22 mild, 25 moderate, and 13 severe) and 50 healthy controls were included in this study. The serum levels of CHI3L1, IL-1-alpha, and IL-6 for all study participants were measured by protein-specific ELISAs. Mean serum CHI3L1 levels in patients with severe disease (7,185.5 ± 1,109.4) were significantly higher than in the moderate (3,977.4 ± 1,260.3), mild (1,379.5 ± 598.8), and control (329.5 ± 128.4) groups (P = 0.001). There was no difference in IL-1-alpha levels between the patient and control groups (P = 0.083). IL-6 levels differed significantly, being lowest in the control group (35.9 ± 13.7), 89.1 ± 23.4 in the mild group, 156.2 ± 29.6 in the moderate group, and the highest in the severe group (214.9 ± 28.1) (P = 0.001). A strong significant correlation was found between disease severity and serum IL-6 and CHI3L1 values (r = 0.894 and r = 0.905, respectively, and P < 0.001 for both). Serum CHI3L1 and IL-6 levels exhibited a linear correlation with the clinical course of COVID-19 infection. These results indicate that inhibitors of IL-6 and/or CHI3L1 may provide useful treatments for COVID-19.

Optical Coherence Tomography Angiography Analysis of Vessel Density Indices in Early Post-COVID-19 Patients.

Purpose: A hypercoagulable state has been reported to cause potential sight-threatening ischemia in patients suffering from Coronavirus disease 2019 (COVID-19). This study aimed to determine whether vessel density (VD), as measured by optical coherence tomography angiography (OCT-A), has insights into retinal and choriocapillaris vascular changes in patients affected by SARS-CoV-2 infection. Methods: Hundred and fifty two patients positive for SARS-CoV-2 infection were enrolled in this observational, retrospective, controlled study. A control group of 60 healthy subjects was selected for statistical comparisons. Raw OCT and OCT-A data were exported and 3D datasets were analyzed to determine VD. Results: Hundred and forty eyes (92.1%) were included for final analysis. The VD of the superficial capillary plexus (SCP) did not differ between the two groups. The mean VD of the deep capillary plexus (DCP) and the choriocapillaris (CC) was significantly lower in the foveal sector of the COVID-19 group compared to healthy controls. Within the post-COVID-19 group, the lowest DCP and CC foveal VD values were recorded in patients treated with antiviral therapy; no differences were observed among COVID-19 patients with other comorbidities (hypertension, diabetes, thyroid disease) or taking antiplatelet therapy. DCP and CC foveal VD were significantly lower in patients hospitalized in an intensive care unit (ICU) than asymptomatic patients. Conclusion: Foveal vessel density at the level of DCP and CC was reduced in post-COVID-19 patients. Further studies evaluating these changes over time will be needed to corroborate the hypothesis of a microvascular retinal impairment in individuals who have recently recovered from SARS-CoV-2 infection.

Inflammatory Markers as Early Predictors of Disease Severity in COVID-19 Patients Admitted to Intensive Care Units: A Retrospective Observational Analysis.

Background: In pandemic situations, it is essential that the limited resources are used judiciously to achieve most benefits. Prediction of the disease severity at the earliest will help in better allocation, thus, positively affecting prognosis and treatment. Aim and objective: To investigate patient characteristics and specific biomarkers as possible early predictors of disease severity of SARS-COV-2 infection. Materials and methods: Retrospective single-centric observational study conducted at 70-bedded intensive care unit of tertiary care hospital at Haryana, India. 100 consecutive RT-PCR positive coronavirus disease-2019 (COVID-19) adult patients. Demographics, acute physiology and chronic health evaluation II (Apache-II) score, and Inflammatory markers were compared with respect to oxygenation defect (PaO2/FiO2 ratio: <300 or ≥300 mm Hg), need of invasive ventilation, ICU length of stay and 28-day mortality. Findings: Mean age was significantly more in lower PF ratio group (58.01 ± 15.33 vs 50.97 ± 13.78, p = 0.023) whereas sex ratio was comparable among patients in two groups. Significantly, higher APACHE-II score (p ≤0.001) and presence of hypertension (43.54% vs 23.68%; p = 0·045) in low PF ratio group along with higher C-reactive protein (171.78 ± 124.45 vs 101.52 ± 88.70), IL-6 (173.51 vs 53.18) and ferritin (1677.60 ± 2271.13 vs 643.54 ± 718.68) levels. Procalcitonin, lactate dehydrogenase, and creatine phosphokinase (CPK) levels were not significant. Interpretation: Age and APACHE II score and among laboratory parameters CRP, ferritin, and IL-6 levels were significantly higher in low PF ratio group, patients requiring invasive ventilation and in mortality group. Use of this triad (CRP, ferritin, and IL-6 levels) at admission may predict the disease severity early in the course. Addition of APACHE-II may further improve the accuracy of the score. How to cite this article: Gupta D, Jain A, Chauhan M, Dewan S. Inflammatory Markers as Early Predictors of Disease Severity in COVID-19 Patients Admitted to Intensive Care Units: A Retrospective Observational Analysis. Indian J Crit Care Med 2022;26(4):482-486.

Evaluation of hematological, coagulation and inflammatory biomarker's role in predicting the severity of disease in patients with COVID-19, admitted in designated COVID-19 hospital of central India.

BACKGROUND: COVID-19 is a pandemic viral disease that has affected the Indian population very badly with more than 8.46 million cases and > 0.125 million deaths. AIM: Primary objective of the study is to establish the role of hematological, coagulation and inflammatory biomarkers in early identification of clinically severe covid-19 cases. MATERIALS AND METHODS: This study was conducted from July 2020 to August 2020 at a dedicated COVID-19 referral hospital in central India. Only RT-PCR confirmed COVID-19 positive 300 cases admitted in the hospital were included in this study. Based on the clinical assessment, patients were categorised as mild, moderate, and severe groups as per ICMR guidelines. Blood samples of all cases were tested for haematological, coagulation and inflammatory biomarkers and mean values were compared among the three groups of patients. RESULTS: 46% patients belonged to >60 years of age group. Hematological parameters like total leukocyte count, absolute neutrophil count, Neutrophil: Lymphocyte ratio, Platelet: Lymphocyte ratio significantly increased with lymphocytopenia (P=0.001). Coagulation profile(D-dimer and PT) and inflammatory biomarkers like CRP, LDH, ferritin, procalcitonin and NT- Pro BNP, all were significantly increased with severity of patients(p=0.001). ROC plotted for all the parameters between severe v/s non-severe cases showed that CRP, LDH and D-dimer had a good discriminative precision with AUC >0.8. CONCLUSION: We suggest that biochemical markers like CRP, LDH and D-dimer can be used as a screening tool to differentiate severe patients from non-severe patients of Covid-19 disease in order to identify severe disease at early stage for optimal utilization of resources & reducing further morbidity & mortality.

Interleukin-6, procalcitonin and neutrophil-to-lymphocyte ratio: Potential immune-inflammatory parameters to identify severe and fatal forms of COVID-19.

Accumulating evidence supports that the viral-induced hyper-inflammatory immune response plays a central role in COVID-19 pathogenesis. It might be involved in the progression to acute respiratory distress syndrome (ARDS), multi-organ failure leading to death. In this study, we aimed to evaluate the prognostic value of the immune-inflammatory biomarkers in COVID-19, then determine optimal thresholds for assessing severe and fatal forms of this disease.153 patients with confirmed COVID-19 were included in this study, and classified into non-severe and severe groups. Plasmatic levels of interleukin 6 (IL6), C-reactive protein (CRP), soluble-IL2 receptor (IL2Rα), procalcitonin (PCT) and ferritin were measured using chemiluminescence assay. Complete blood count was performed by Convergys 3X® hematology analyzer. Our results demonstrated that the peripheral blood levels of IL6, PCT, CRP, ferritin, IL2Rα, white blood cell count (WBC), neutrophil count (NEU), neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (d-NLR) were significantly higher in severe forms of COVID-19. The ROC curve analysis showed that IL6 was the most accurate inflammatory biomarker. The calculated cutoff of IL6 (42 pg/ml) could correctly classify > 90% of patients regarding their risk of severity (area under ROC curve (AUROC) = 0.972) and the threshold value of 83 pg/ml was highly predictive of the progression to death (AUROC = 0.94, OR = 184) after a median of 3 days. Besides, IL-6 was positively correlated with other inflammatory markers and the kinetic analysis highlighted its value for monitoring COVID-19 patients. PCT and NLR had also a high prognostic relevance to assess severe forms of COVID-19 with corresponding AUROC of 0.856, 0.831 respectively. Furthermore the cut-off values of PCT (0.16 ng/ml) and NLR (7.4) allowed to predict mortality with high accuracy (se = 96.3%, sp = 70.5%,OR = 61.2)' (se = 75%, sp = 84%, OR = 14.6).The levels of these parameters were not influenced by corticosteroid treatment, which make them potential prognostic markers when patients are already undergoing steroid therapy.