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Data science has been an invaluable part of the COVID-19 pandemic response with multiple applications, ranging from tracking viral evolution to understanding the effectiveness of interventions. Asymptomatic breakthrough infections have been a major problem during the ongoing surge of Delta variant globally. Serological discrimination of vaccine response from infection has so far been limited to Spike protein vaccines used in the higher-income regions. Here, we show for the first time how statistical and machine learning (ML) approaches can discriminate SARS-CoV-2 infection from immune response to an inactivated whole virion vaccine (BBV152, Covaxin, India), thereby permitting real-world vaccine effectiveness assessments from cohort-based serosurveys in Asia and Africa where such vaccines are commonly used. Briefly, we accessed serial data on Anti-S and Anti-NC antibody concentration values, along with age, sex, number of doses, and number of days since the last vaccine dose for 1823 Covaxin recipients. An ensemble ML model, incorporating a consensus clustering approach alongside the support vector machine (SVM) model, was built on 1063 samples where reliable qualifying data existed, and then applied to the entire dataset. Of 1448 self-reported negative subjects, 724 were classified as infected. Since the vaccine contains wild-type virus and the antibodies induced will neutralize wild type much better than Delta variant, we determined the relative ability of a random subset of such samples to neutralize Delta versus wild type strain. In 100 of 156 samples, where ML prediction differed from self-reported uninfected status, Delta variant, was neutralized more effectively than the wild type, which cannot happen without infection. The fraction rose to 71.8% (28 of 39) in subjects predicted to be infected during the surge, which is concordant with the percentage of sequences classified as Delta (75.6%-80.2%) over the same period.
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To understand the spread of SARS-CoV2, in August and September 2020, the Council of Scientific and Industrial Research (India), conducted a sero-survey across its constituent laboratories and centers across India. Of 10,427 volunteers, 1058 (10.14%) tested positive for SARS CoV2 anti-nucleocapsid (anti-NC) antibodies; 95% with surrogate neutralization activity. Three-fourth recalled no symptoms. Repeat serology tests at 3 (n=346) and 6 (n=35) months confirmed stability of antibody response and neutralization potential. Local sero-positivity was higher in densely populated cities and was inversely correlated with a 30 day change in regional test positivity rates (TPR). Regional seropositivity above 10% was associated with declining TPR. Personal factors associated with higher odds of sero-positivity were high-exposure work (Odds Ratio, 95% CI, p value; 2{middle dot}23, 1{middle dot}92-2{middle dot}59, 6{middle dot}5E-26), use of public transport (1{middle dot}79, 1{middle dot}43-2{middle dot}24, 2{middle dot}8E-06), not smoking (1{middle dot}52, 1{middle dot}16-1{middle dot}99, 0{middle dot}02), non-vegetarian diet (1{middle dot}67, 1{middle dot}41-1{middle dot}99, 3{middle dot}0E-08), and B blood group (1{middle dot}36,1{middle dot}15-1{middle dot}61, 0{middle dot}001). Impact StatementWidespread asymptomatic and undetected SARS-CoV2 infection affected more than a 100 million Indians by September 2020. Declining new cases thereafter may be due to persisting humoral immunity amongst sub-communities with high exposure. FundingCouncil of Scientific and Industrial Research, India (CSIR)
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BACKGROUND: The aim of this study was to investigate the early onset effects of diabetes on pro-angiogenic signaling pathway, total number of bone marrow cells, organs (pancreas and kidney) damage and the reversal effect of diabetes by combinatorial treatment of curcumin and bone marrow transplantation in streptozotocin (STZ) induced diabetic mice. METHODS: In the present study, Streptozotocin induced diabetic mice were transplanted with bone marrow cells (2 × 10(6) ) followed by the administration of curcumin (80 mg/kg bodyweight). Effect of diabetes on the different organs was studied by H&E, Western blotting and immunofluorescence using vascular endothelial growth factor (VEGF), platelet/endothelial cell adhesion molecule (PECAM), insulin, Caspase-9 and Caspase-3 antibodies. RESULTS: The effect of diabetes results in the reduction of the total cell number and viability of the bone marrow cells, organ degeneration and lower VEGF/PECAM expression. However, transplantation with normal bone marrow cells significantly reduced the blood glucose levels (above normal range) and initiated the organ regeneration via the VEGF/PECAM mediated manner. Curcumin treatment further reduced the blood glucose level (near normal); and accelerated the organ regeneration, enhanced VEGF/PECAM expression and decreased caspase expression level in the organs. Curcumin also had a protective role against the glucotoxicity test performed on the bone marrow cells. CONCLUSION: This study suggests that bone marrow transplantation and curcumin administration is an effective treatment in reversing the early onset effects of diabetes via the VEGF/PECAM signaling pathway.
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Trasplante de Médula Ósea , Curcumina/farmacología , Diabetes Mellitus Experimental/prevención & control , Animales , Glucemia/metabolismo , Masculino , Ratones , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Dengue infection is endemic in many parts of India, including the state of Uttar Pradesh. This study describes the changing clinical picture of dengue viral infections observed by us in children admittedto a teaching hospital in Lucknow, India.A total of 139 children with suspected dengue were admitted during this period, of which 124 couldbe tested by dengue IgM capture ELISA and 102 were positive. However, only 80 of these 102 patientscould be followed up. Average age was 5.9 (±3.1) years and 87.5% of them were from rural areas. Themale:female ratio was 1.6:1. Seizures were observed in 45% cases, altered sensorium in 53.7%, vomitingin 41.2%, haemorrhage in 38.8%, skin rash in 37.5%, abdominal pain in 25%, headache in 18.8% andjaundice in 2% cases. Gastrointestinal tract was the commonest site of bleeding. On examination,edema was present in 47.5% cases, hepatomegaly in 62.5%, splenomegaly in 60.0% and hypotensionin 10.0% cases. The investigations revealed a low platelet count of less than 100000/mm3 in 60.3%cases. Mean liver enzyme levels were mildly raised. Definitions of WHO criteria for DHF were presentin only 18 (22.5%) cases. Mean total duration of fever in survivors was 14.9±7.3 days. The overall fatality rate in hospital was 5.0%.The results indicated a significant proportion of children presented with little-described features ofencephalopathy, edema, splenomegaly and prolonged fever rather than the typical dengue presentation.These features were not noted during the past epidemics and in previous years.