Snehil Kumar

Bio: Snehil Kumar is an academic researcher from Christian Medical College & Hospital. The author has contributed to research in topics: Medicine & Breast milk. The author has an hindex of 1, co-authored 8 publications receiving 8 citations.

Factors associated with mortality among moderate and severe patients with COVID-19 in India: a secondary analysis of a randomised controlled trial.

Abstract: Objective Large data on the clinical characteristics and outcome of COVID-19 in the Indian population are scarce. We analysed the factors associated with mortality in a cohort of moderately and severely ill patients with COVID-19 enrolled in a randomised trial on convalescent plasma. Design Secondary analysis of data from a Phase II, Open Label, Randomized Controlled Trial to Assess the Safety and Efficacy of Convalescent Plasma to Limit COVID-19 Associated Complications in Moderate Disease. Setting 39 public and private hospitals across India during the study period from 22 April to 14 July 2020. Participants Of the 464 patients recruited, two were lost to follow-up, nine withdrew consent and two patients did not receive the intervention after randomisation. The cohort of 451 participants with known outcome at 28 days was analysed. Primary outcome measure Factors associated with all-cause mortality at 28 days after enrolment. Results The mean (SD) age was 51±12.4 years; 76.7% were males. Admission Sequential Organ Failure Assessment score was 2.4±1.1. Non-invasive ventilation, invasive ventilation and vasopressor therapy were required in 98.9%, 8.4% and 4.0%, respectively. The 28-day mortality was 14.4%. Median time from symptom onset to hospital admission was similar in survivors (4 days; IQR 3–7) and non-survivors (4 days; IQR 3–6). Patients with two or more comorbidities had 2.25 (95% CI 1.18 to 4.29, p=0.014) times risk of death. When compared with survivors, admission interleukin-6 levels were higher (p 10 (9.97, 3.65–27.13, p 1.0 mg/L (2.50, 1.14–5.48, p=0.022), ferritin ≥500 ng/mL (2.67, 1.44–4.96, p=0.002) and lactate dehydrogenase ≥450 IU/L (2.96, 1.60–5.45, p=0.001) were significantly associated with death. Conclusion In this cohort of moderately and severely ill patients with COVID-19, severity of illness, underlying comorbidities and elevated levels of inflammatory markers were significantly associated with death. Trial registration number CTRI/2020/04/024775.

Plasma Von Willebrand Factor Levels Predict Survival in COVID-19 Patients Across the Entire Spectrum of Disease Severity.

Abstract: Background: Characterization of reticulo-endothelial activation in COVID-19 may guide treatment. Objectives: To assess reticulo-endothelial activation and its correlation with disease severity and death in patients across the entire spectrum of COVID-19 severity. Methods: Consecutive hospitalized COVID-19 patients were studied, with similar number of patients in each disease severity category. Baseline serum ferritin, sCD163 (macrophage activation markers) and plasma von Willebrand factor (VWF) antigen (endothelial activation marker) levels were studied. Clinical parameters and plasma D-dimer levels were also studied. The study parameters were correlated with COVID-19 severity and survival. Results: The 143 patients (104 males [80%], age 54 [42 – 65] years, median [inter-quartile range]) presented 4 (3—7) days after symptom onset. Thirty-four patients had mild disease, 36 had moderate disease, 36 had severe disease and 37 had critical disease at baseline. With increasing COVID-19 severity, ferritin, sCD163, VWF and D-dimer levels significantly increased at baseline, however, 139 patients had normal sCD163 levels. Of the reticulo-endothelial markers, VWF level independently correlated with COVID-19 severity and with survival. VWF level > 332.6 units/dl correlated with COVID-19 severity (odds ratio [OR]: 2.77 [95% confidence interval (C.I): 1.1 – 6.99], p value: 0.031) and in-hospital death (OR [95% CI]: 29.28 [5.2 – 165], p value < 0.001). Conclusions: Reticulo-endothelial activation markers increased incrementally with worsening COVID-19 severity. Baseline endothelial activation marker (VWF), and not macrophage activation markers, independently correlated with COVID-19 severity and death.

Do red cell alloantibodies continue to challenge breast fed babies

Abstract: Background Newborns have limited specific immune capability at birth, owing to delayed and constrained development of adaptive immunity. To supplement this period the mother passively transfers antibodies to the child either transplacentally or through breast milk. When maternal alloimmunisation occurs through foreign or fetal red cell surface antigens, stimulating the production of immunoglobulin G (IgG) antibodies, these IgG antibodies can cross the placenta and cause haemolytic disease of the fetus and the newborn. Objective We present two case reports of a neonate and an infant in whom IgG red cell alloantibodies were transferred through maternal breast milk. Methods Maternal serum, baby's serum and expressed breast milk samples were tested for the presence of red cell alloantibodies using gel card. Antibody screening, antibody identifications and titres alongside monospecific direct antiglobulin test, IgG subtypes were performed using the standard methods. Results In the first case, a 6-month-old child was incidentally found to have positive antibody screen. Anti-KELL1 was identified, which was also present in maternal serum and breast milk. The second neonate was evaluated for haemolysis and was found to have anti-D. Anti-D was also detected in the maternal serum and breast milk. Both babies did not have any sensitising events. The first baby was asymptomatic, but the second baby had ongoing haemolysis until 1 month. Conclusion We report that maternal anti-KELL1 and anti-D antibodies were present in breast milk and were capable of being transferred to a feeding child. Our case report also raises interesting and unanswered immunologic fundamentals that should be considered in neonates with unexplained anaemia or delayed and persistent haemolysis.

Diagnostic utility of flow cytometry based coated-platelets assay as a biomarker to predict thrombotic or hemorrhagic phenotype in acute stroke.

Abstract: BACKGROUND Coated-platelets are sub-population of platelets "coated" with highly procoagulant proteins and phosphatidylserine that sustains thrombin generation. They are produced upon dual agonist stimulation by collagen and thrombin. This study was conducted to assess if there was any difference in the levels of coated-platelets in patients with primary intracranial hemorrhage (PICH) and ischemic stroke due to large artery atherosclerosis (LAA) as compared to healthy controls, and to see if coated-platelet levels had any influence on the hemorrhagic transformation (HT) of ischemic stroke. METHODS Coated-platelet levels were determined by flow cytometry using fluorescently tagged Annexin V antibody to identify phosphatidylserine exposed on the surface of platelets activated by dual agonists (convulxin and thrombin) in cross-sectional cohort of 75 patients with stroke and 34 controls. RESULTS Patients with PICH (n = 35) had significantly lower coated-platelets than the controls (adjusted mean ± SE, 21.0 ± 1.9% vs. 36.1 ± 1.7%, p < 0.001), while patients with LAA (n = 30) had significantly higher coated-platelets than controls (adjusted mean ± SE, 51.9 ± 1.5% vs. 36.1 ± 1.7%, p < 0.001). Patients with subsequent HT of ischemic stroke (n = 10) had significantly lower coated-platelet levels at admission compared to those without HT (adjusted mean ± SE, 18.1 ± 2.6% vs. 51.9 ± 1.5%, p < 0.001). CONCLUSIONS Coated-platelet levels are significantly different in patients with hemorrhagic and ischemic stroke as compared with controls. Lower levels of coated-platelets measured by flow cytometry may be earliest predictor of subsequent HT in patients with ischemic stroke even before the radiological changes suggestive of HT are visualized.

Ankylosing spondylitis in West Africans - evidence for a non-HLA-B27 protective effect

Abstract: Objective - To determine the prevalence of ankylosing spondylitis in the Fula ethnic group in The Gambia, and relate the disease prevalence to the B27 frequency and subtype distribution of that population. Methods - 215 first degree relatives of 48 B27 positive Fula twin pairs, and 900 adult Fula males were screened for ankylosing spondylitis by clinical and, where appropriate, radiographic means. The B27 prevalence was determined by PCR/sequence specific oligonucleotides on finger prick samples from 100 unrelated Fula, and B27 subtype distribution by SSCP on unrelated B27 positive individuals. This data were then compared with the prevalence of ankylosing spondylitis among B27 positive Caucasians. Results - No case of ankylosing spondylitis was seen. Six per cent of Fula are B27 positive, of which 32% are B*2703 and 68% B*2705. Assuming the penetrance of ankylosing spondylitis in B27 positive Fula is the same as in B27 positive Caucasians, the probability of not observing any cases of ankylosing spondylitis among the Fula examined is remote (P = 6.7 x 10-6). Similarly, the chance of not seeing any cases among those expected to be either B*2705 or B*2703 was small (P = 3.2 x 10-4 for B*2705, and P = 0.02 for B*2703). Conclusions - The risk of developing ankylosing spondylitis in B27 positive Fula is lower than in B27 positive Caucasians. This is not explained by the B27 subtype distribution among Fula, and suggests the presence of some non-B27 protective factor reducing the prevalence of ankylosing spondylitis in this population.

Robust hemostatic bandages based on nanoclay electrospun membranes.

Abstract: Death from acute hemorrhage is a major problem in military conflicts, traffic accidents, and surgical procedures, et al. Achieving rapid effective hemostasis for pre-hospital care is essential to save lives in massive bleeding. An ideal hemostasis material should have those features such as safe, efficient, convenient, economical, which remains challenging and most of them cannot be achieved at the same time. In this work, we report a rapid effective nanoclay-based hemostatic membranes with nanoclay particles incorporate into polyvinylpyrrolidone (PVP) electrospun fibers. The nanoclay electrospun membrane (NEM) with 60 wt% kaolinite (KEM1.5) shows better and faster hemostatic performance in vitro and in vivo with good biocompatibility compared with most other NEMs and clay-based hemostats, benefiting from its enriched hemostatic functional sites, robust fluffy framework, and hydrophilic surface. The robust hemostatic bandages based on nanoclay electrospun membrane is an effective candidate hemostat in practical application. Rapid, easy and effective haemostasis is needed to reduce the loss of life from traumatic haemorrhage. Here, the authors report on the creation of polymer-nanoclay electrospun membranes and demonstrate haemostatic effects showing superior effects to other clay based haemostats.

COVID-19 and biomarkers of thrombosis: focus on von Willebrand factor and extracellular vesicles.

Abstract: COVID-19, caused by the SARS-CoV-2 virus, is responsible for a pandemic of unparalleled portion over the past century. While the acute phase of infection causes significant morbidity and mortality, post-acute sequelae that can affect essentially any organ system is rapidly taking on an equally large part of the overall impact on human health, quality of life, attempts to return to normalcy and the global economy. Herein, we summarize the potential role of von Willebrand Factor and extracellular vesicles toward understanding the pathophysiology, clinical presentation, duration of illness, diagnostic approach and management of COVID-19 and its sequelae.