The world is facing Coronavirus Disease-2019 (COVID-19) pandemic, which is causing a large number of deaths and burden on intensive care facilities. It is caused by Severe Acute Respiratory Syndrome ...coronavirus-2 (SARS-CoV-2) originating in Wuhan, China. It has been seen that fewer children contract COVID-19 and among infected, children have less severe disease. Insights in pathophysiological mechanisms of less severity in children could be important for devising therapeutics for high-risk adults and elderly. Early closing of schools and day-care centers led to less frequent exposure and hence, lower infection rate in children. The expression of primary target receptor for SARS-CoV-2, i.e. angiotensin converting enzyme-2 (ACE-2), decreases with age. ACE-2 has lung protective effects by limiting angiotensin-2 mediated pulmonary capillary leak and inflammation. Severe COVID-19 disease is associated with high and persistent viral loads in adults. Children have strong innate immune response due to trained immunity (secondary to live-vaccines and frequent viral infections), leading to probably early control of infection at the site of entry. Adult patients show suppressed adaptive immunity and dysfunctional over-active innate immune response in severe infections, which is not seen in children. These could be related to immune-senescence in elderly. Excellent regeneration capacity of pediatric alveolar epithelium may be contributing to early recovery from COVID-19. Children, less frequently, have risk factors such as co-morbidities, smoking, and obesity. But young infants and children with pre-existing illnesses could be high risk groups and need careful monitoring. Studies describing immune-pathogenesis in COVID-19 are lacking in children and need urgent attention.
Abstract
Broadly neutralizing antibodies (bnAbs) develop in a subset of HIV-1 infected individuals over 2–3 years of infection. Infected infants develop plasma bnAbs frequently and as early as 1-year ...post-infection suggesting factors governing bnAb induction in infants are distinct from adults. Understanding viral characteristics in infected infants with early bnAb responses will provide key information about antigenic triggers driving B cell maturation pathways towards induction of bnAbs. Herein, we evaluate the presence of plasma bnAbs in a cohort of 51 HIV-1 clade-C infected infants and identify viral factors associated with early bnAb responses. Plasma bnAbs targeting V2-apex on the env are predominant in infant elite and broad neutralizers. Circulating viral variants in infant elite neutralizers are susceptible to V2-apex bnAbs. In infant elite neutralizers, multivariant infection is associated with plasma bnAbs targeting diverse autologous viruses. Our data provides information supportive of polyvalent vaccination approaches capable of inducing V2-apex bnAbs against HIV-1.
Hypothermia is a life-threatening condition where the temperature of the body drops below 35°C and is a key source of concern in Intensive Care Units (ICUs). Early identification can help to nudge ...clinical management to initiate early interventions. Despite its importance, very few studies have focused on the early prediction of hypothermia. In this study, we aim to monitor and predict Hypothermia (30 min-4 h) ahead of its onset using machine learning (ML) models developed on physiological vitals and to prospectively validate the best performing model in the pediatric ICU. We developed and evaluated ML algorithms for the early prediction of hypothermia in a pediatric ICU. Sepsis advanced forecasting engine ICU Database (SafeICU) data resource is an in-house ICU source of data built in the Pediatric ICU at the All-India Institute of Medical Science (AIIMS), New Delhi. Each time-stamp at 1-min resolution was labeled for the presence of hypothermia to construct a retrospective cohort of pediatric patients in the SafeICU data resource. The training set consisted of windows of the length of 4.2 h with a lead time of 30 min-4 h from the onset of hypothermia. A set of 3,835 hand-engineered time-series features were calculated to capture physiological features from the time series. Features selection using the Boruta algorithm was performed to select the most important predictors of hypothermia. A battery of models such as gradient boosting machine, random forest, AdaBoost, and support vector machine (SVM) was evaluated utilizing five-fold test sets. The best-performing model was prospectively validated. A total of 148 patients with 193 ICU stays were eligible for the model development cohort. Of 3,939 features, 726 were statistically significant in the Boruta analysis for the prediction of Hypothermia. The gradient boosting model performed best with an Area Under the Receiver Operating Characteristic curve (AUROC) of 85% (SD = 1.6) and a precision of 59.2% (SD = 8.8) for a 30-min lead time before the onset of Hypothermia onset. As expected, the model showed a decline in model performance at higher lead times, such as AUROC of 77.2% (SD = 2.3) and precision of 41.34% (SD = 4.8) for 4 h ahead of Hypothermia onset. Our GBM(gradient boosting machine) model produced equal and superior results for the prospective validation, where an AUROC of 79.8% and a precision of 53% for a 30-min lead time before the onset of Hypothermia whereas an AUROC of 69.6% and a precision of 38.52% for a (30 min-4 h) lead time prospective validation of Hypothermia. Therefore, this work establishes a pipeline termed
ThermoGnose
for predicting hypothermia, a major complication in pediatric ICUs.
BBV152 is a whole-virion inactivated SARS-CoV-2 vaccine that has been deployed in India. The results of the phase 3 trial have shown clinical efficacy of BBV152. We aimed to evaluate the ...effectiveness of BBV152 against symptomatic RT-PCR-confirmed SARS-CoV-2 infection.
We conducted a test-negative, case-control study among employees of the All India Institute of Medical Sciences (a tertiary care hospital in New Delhi, India), who had symptoms suggestive of COVID-19 and had an RT-PCR test for SARS-CoV-2 during the peak of the second wave of the COVID-19 pandemic in India between April 15 and May 15, 2021. Cases (test-positives) and controls (test-negatives) were matched (1:1) on the basis of age and gender. The odds of vaccination with BBV152 were compared between cases and controls and adjusted for level of occupational exposure (to COVID-19), previous SARS-CoV-2 infection, and calendar time, using conditional logistic regression. The primary outcome was effectiveness of two doses of BBV152 (with the second dose received at least 14 days before testing) in reducing the odds of symptomatic RT-PCR-confirmed SARS-CoV-2 infection, expressed as (1 – odds ratio) × 100%.
Between April 15 and May 15, 2021, 3732 individuals had an RT-PCR test. Of these, 2714 symptomatic employees had data on vaccination status, and 1068 matched case-control pairs were available for analysis. The adjusted effectiveness of BBV152 against symptomatic COVID-19 after two doses administered at least 14 days before testing was 50% (95% CI 33–62; p<0·0001). The adjusted effectiveness of two doses administered at least 28 days before testing was 46% (95% CI 22–62) and administered at least 42 days before testing was 57% (21–76). After excluding participants with previous SARS-CoV-2 infections, the adjusted effectiveness of two doses administered at least 14 days before testing was 47% (95% CI 29–61).
This study shows the effectiveness of two doses of BBV152 against symptomatic COVID-19 in the context of a huge surge in cases, presumably dominated by the potentially immune-evasive delta (B.1.617.2) variant of SARS-CoV-2. Our findings support the ongoing roll-out of this vaccine to help control the spread of SARS-CoV-2, while continuing the emphasis on adherence to non-pharmacological measures.
None.
For the Hindi translation of the abstract see Supplementary Materials section.
Proactive detection of hemodynamic shock can prevent organ failure and save lives. Thermal imaging is a non-invasive, non-contact modality to capture body surface temperature with the potential to ...reveal underlying perfusion disturbance in shock. In this study, we automate early detection and prediction of shock using machine learning upon thermal images obtained in a pediatric intensive care unit of a tertiary care hospital. 539 images were recorded out of which 253 had concomitant measurement of continuous intra-arterial blood pressure, the gold standard for shock monitoring. Histogram of oriented gradient features were used for machine learning based region-of-interest segmentation that achieved 96% agreement with a human expert. The segmented center-to-periphery difference along with pulse rate was used in longitudinal prediction of shock at 0, 3, 6 and 12 hours using a generalized linear mixed-effects model. The model achieved a mean area under the receiver operating characteristic curve of 75% at 0 hours (classification), 77% at 3 hours (prediction) and 69% at 12 hours (prediction) respectively. Since hemodynamic shock associated with critical illness and infectious epidemics such as Dengue is often fatal, our model demonstrates an affordable, non-invasive, non-contact and tele-diagnostic decision support system for its reliable detection and prediction.
Many adults in India have received at least one dose of COVID-19 vaccine with or without a prior history SARS-CoV-2 infection. However, there is limited information on the effect of prior immunity on ...antibody response upon vaccination in India. As immunization of individuals continues, we aimed to assess whether pre-existing antibodies are further boosted by a single dose of BBV152, an inactivated SARS-CoV-2 vaccine, and, if these antibodies can neutralize SARS-CoV-2 Delta and Omicron variants. Here we show that natural infection during the second wave in 2021 led to generation of neutralizing antibodies against other lineages of SARS-CoV-2 including the Omicron variant, albeit at a significantly lower level for the latter. A single dose of BBV152 boosted antibody titers against the Delta and the Omicron variants but the antibody levels remained low against the Omicron variant. Boosting of antibodies showed negative correlation with baseline neutralizing antibody titers.
Dengue virus, a mosquito-borne flavivirus, is a causative agent for dengue infection, which manifests with symptoms ranging from mild fever to fatal dengue shock syndrome. The presence of four ...serotypes, against which immune cross-protection is short-lived and serotype cross-reactive antibodies that might enhance infection, pose a challenge to further investigate the role of virus and immune response in pathogenesis. We evaluated the viral and immunological factors that correlate with severe dengue disease in a cohort of pediatric dengue patients in New Delhi. Severe dengue disease was observed in both primary and secondary infections. Viral load had no association with disease severity but high viral load correlated with prolonged thrombocytopenia and delayed recovery. Severe dengue cases had low Th1 cytokines and a concurrent increase in the inflammatory mediators such as IL-6, IL-8 and IL-10. A transient increase in CD14+CD16+ intermediate monocytes was observed early in infection. Sorting of monocytes from dengue patient peripheral blood mononuclear cells revealed that it is the CD14+ cells, but not the CD16+ or the T or B cells, that were infected with dengue virus and were major producers of IL-10. Using the Boruta algorithm, reduced interferon-α levels and enhanced aforementioned pro-inflammatory cytokines were identified as some of the distinctive markers of severe dengue. Furthermore, the reduction in the levels of IL-8 and IL-10 were identified as the most significant markers of recovery from severe disease. Our results provide further insights into the immune response of children to primary and secondary dengue infection and help us to understand the complex interplay between the intrinsic factors in dengue pathogenesis.
There is increasing prevalence of both asthma and obesity in children globally in recent years. Various epidemiological studies link obesity as a risk factor for asthma and suggest a possible causal ...association. Obesity asthma phenotype is considered as distinct in view of greater severity and poor asthma control. Various mechanisms underlying this phenotype have been suggested including mechanical effects of obesity and systemic inflammation, but still the exact mechanism is unclear. Also, the comorbidities like gastroesophageal reflux disease (GERD) and sleep disordered breathing (SDB) lead to inflammation in airways and contribute to asthma obesity association. A better understanding of mechanisms by which obesity and GERD lead to inflammation in airways and increase the risk of asthma may provide insight towards targeted treatment approach of these patients.
Rationale
The extent of diaphragmatic atrophy and dysfunction in critically ill children from developing countries is not established.
Objectives
To estimate changes in ultrasound measurements of ...diaphragmatic thickness over the first week of mechanical ventilation. To assess magnitude and risk factors of diaphragmatic atrophy.
Methods
In an observational cohort study, children aged 1–18 years, requiring mechanical ventilation were included. Ultrasound measurements of diaphragmatic thickness at end‐expiration (DTe) and end‐inspiration (DTi), and diaphragmatic thickening fraction (DTF) were performed daily during the first week of admission, and pre‐ and post‐extubation. Diaphragmatic atrophy (%) and atrophy rate (rate of decline in DTe, % per day) were calculated.
Measurements and Main Results
Of 55 children (74.6% boys) enrolled, 20 (36.4%) died. Of 35 children with planned extubation, 5 (14.3%) required reintubation. Baseline median (interquartile range IQR) DTe, DTi, and DTF were 1.27 mm (1, 1.6), 1.76 mm (1.35, 2.10), and 33.75% (26.90, 44.60), respectively. There was a significant reduction in DTe over the first week of mechanical ventilation (p < .001), median (IQR) diaphragmatic atrophy and atrophy rate of 9.91% (5.26, 17.35) and 2.01% (1.08, 3.04) per day, respectively. Diaphragmatic atrophy rate was lower in pressure targeted ventilation (n = 44; 1.79% 1.03, 2.87) than volume targeted ventilation (n = 11; 3.10% 1.31, 5.49), p = .038. There was no difference in diaphragmatic parameters (atrophy rate, and peri‐extubation DTe and DTF) in extubation success versus failure.
Conclusions
The diaphragm undergoes progressive atrophy during the first week of mechanical ventilation in critically ill children. Future studies should evaluate ventilation strategies to reduce the diaphragmatic atrophy.
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