Does Cardiac Arrhythmia Predict Worse Outcome in Mild or Moderate Covid-19 Infection?

Covid-19 is a multisystem disease with the lungs being predominantly affected. Cardiac involvement is mostly seen as a rise in troponins, arrhythmias, and ventricular dysfunction. This study aimed to estimate the incidence of arrhythmias seen in Covid-19 infection and assess if arrhythmias predict worsening or mortality. Prospective observational study involving patients with mild to moderate Covid illness admitted in a tertiary care centre. Among the 85 patients (Mean age 45.8 + 14.1 years; 75.31% men), worsening of Covid-19 illness was seen in 29 (34.1%) patients. New onset arrhythmias were detected on Holter in 9 (10.5%) patients. Supraventricular tachycardia was seen in 7 (8.2%) patients of whom 6 showed worsening which was statistically significant (p-value-0.006). Risk factors associated with worsening on univariate analysis were male gender (OR [95%CI] = 6.93(1.49-32.31), p-value - 0.014), new onset supraventricular tachycardia (OR [95% CI] = 14.35 [1.64-125.94], p-value - 0.016) and D-dimer elevation (OR [95% CI] = 1.00(1.00-1.01), p-value - 0.02). On multivariate analysis D-dimer (OR [95% CI] = 1.00(1.00-1.01; p-value 0.046) and supraventricular arrhythmias (OR [95% CI] = 11.12 (1.22-101.14); p-value - 0.033) were independently associated with worsening. Covid-19 infection can lead to cardiac arrhythmias. The development of supraventricular tachycardia in patients with Covid-19 infection predicts higher morbidity and worsening.

Economic Evaluation Comparing Virtual Reality with Child Life Programming for Non-sedated Pediatric Medical Imaging: A Cost-Consequence Analysis.

INTRODUCTION: Effective preparation of children for hospital procedures, including non-sedated medical imaging, is an important clinical issue. This study aimed to assess the costs and consequences (effects) of preparing pediatric patients using two methods of delivering preparation for a scheduled magnetic resonance image (MRI)-virtual reality (VR-MRI) and a certified Child Life Program (CLP). METHODS: A cost-consequence analysis (CCA) was performed using a societal perspective in Canada. The CCA catalogs a wide range of costs and consequences of VR-MRI compared with a CLP. The evaluation uses data from a prior randomized clinical trial evaluating VR and a CLP in a simulated trial. The economic evaluation encompassed health-related effects, including anxiety, safety and adverse events, and non-health effects, including preparation time, displaced time from usual activities, workload capacity, patient-specific adaptation, administrative burden, and user-experience metrics. The costs have been categorized into hospital operational costs, travel costs, other patient costs, and societal costs. RESULTS: VR-MRI has similar benefits to the CLP in managing anxiety, safety and adverse events, as well as converting patients to non-sedated medical imaging. Preparation time and patient-specific adaptation are in favor of the CLP, while displaced time from usual activities, potential workload capacity, and administrative burden are in favor of VR-MRI. Both programs rank favorably in terms of user experience. The hospital operational costs ranged in Canadian dollars (CAN$) from CAN$32.07 for the CLP to between CAN$107.37 and CAN$129.73 for VR-MRI. Travel costs ranged from CAN$50.58 to CAN$2365.18 depending on travel distance for the CLP, and CAN$0 for VR-MRI. Other patient costs involved caregiver time off, and ranged from CAN$190.69 to CAN$$1144.16 for the CLP and CAN$47.67 for VR-MRI. The total cost for the CLP ranged from CAN$315.16 (CAN$277.91-$426.64) to CAN$3843.41 (CAN$3196.59-$4849.91) per patient depending on travel distance and amount of administrative support required, while VR-MRI preparation ranged from CAN$178.30 (CAN$178.20-$188.76) to CAN$283.85 (CAN$283.71-$298.40) per patient. For every instance where patient travel to visit a Certified Child Life Specialist (CCLS) onsite was replaced with VR-MRI, between CAN$119.01 and CAN$3364.62 total costs could be saved per patient. CONCLUSIONS: While it is neither feasible nor appropriate to replace all preparation with VR, using VR to reach children who cannot otherwise visit the CLP onsite could increase access to quality preparation, and using VR in place of the CLP where clinically indicated could reduce the overall costs for patients, the hospital, and society. Our CCA gives decision makers a cost analysis and the relevant effects of each preparation program so they can value the VR and CLP programs more broadly within the potential health and non-health outcomes of pediatric patients scheduled for MRI at their facilities.

Interim results from comparison of immune responses elicited by an inactivated and a vectored SARS-CoV-2 vaccine in seronegative and seropositive participants in India (preprint)

Background There are limited global data on head-to-head comparisons of vaccine platforms assessing both humoral and cellular immune responses, stratified by pre-vaccination serostatus. The COVID-19 vaccination drive for the Indian population in the 18 to 45-year age-group began in April 2021 when seropositivity rates in the general population were rising due to the Delta wave in April-May 2021. Methods Between 30 June 2021 and 28 January 2022, we enrolled 691 participants in the 18-45 age group across 4 clinical sites in India. In this non-randomized and laboratory blinded study, participants received either two doses of Covaxin(R) 4 weeks apart or two doses of Covishield 12 weeks apart per the national vaccination policy. The primary outcome was the seroconversion rate and the geometric mean titer (GMT) of antibodies against the SARS-CoV-2 spike and nucleocapsid proteins. The secondary outcome was the frequency of cellular immune responses pre- and post-vaccination. Findings When compared to pre-vaccination baseline, both vaccines elicited statistically significant seroconversion and binding antibody levels in both seronegative and seropositive individuals. In the per-protocol cohort, Covishield elicited higher antibody responses than Covaxin(R) as measured by seroconversion rate (98.3% vs 74.4%, p<0.0001 in seronegative individuals; 91.7% vs 66.9%, p<0.0001 in seropositive individuals) as well as by anti-spike antibody levels against the ancestral strain (GMT 1272.1 vs 75.4 BAU/ml, p<0.0001 in seronegative individuals; 2089.07 vs 585.7 BAU/ml, p<0.0001 in seropositive individuals). Not all sites recruited at the same time, therefore site-specific immunogenicity was impacted by the timing of vaccination relative to the Delta and Omicron waves. Surrogate neutralizing antibody responses against variants-of-concern were higher in Covishield recipients than in Covaxin(R) recipients and in seropositive than in seronegative individuals after both vaccination and asymptomatic Omicron infection. T cell responses are reported from only one of the four site cohorts where the vaccination schedule preceded the Omicron wave. In seronegative individuals, Covishield elicited both CD4+ and CD8+ spike-specific cytokine-producing T cells whereas Covaxin(R) elicited mainly CD4+ spike-specific T cells. Neither vaccine showed significant post-vaccination expansion of spike-specific T cells in seropositive individuals. Interpretation Covishield elicited immune responses of higher magnitude and breadth than Covaxin(R) in both seronegative individuals and seropositive individuals, across cohorts representing the pre-vaccination immune history of the majority of the vaccinated Indian population.

Safety, feasibility and initial efficacy of an app-facilitated telerehabilitation (AFTER) programme for COVID-19 survivors: a pilot randomised study.

OBJECTIVES: Determine the safety, feasibility and initial efficacy of a multicomponent telerehabilitation programme for COVID-19 survivors. DESIGN: Pilot randomised feasibility study. SETTING: In-home telerehabilitation. PARTICIPANTS: 44 participants (21 female, mean age 52 years) discharged home following hospitalisation with COVID-19 (with and without intensive care unit (ICU) stay). INTERVENTIONS: Participants were block randomised 2:1 to receive 12 individual biobehaviourally informed, app-facilitated, multicomponent telerehabilitation sessions with a licenced physical therapist (n=29) or to a control group (n=15) consisting of education on exercise and COVID-19 recovery trajectory, physical activity and vitals monitoring, and weekly check-ins with study staff. Interventions were 100% remote and occurred over 12 weeks. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was feasibility, including safety and session adherence. Secondary outcomes included preliminary efficacy outcomes including tests of function and balance; patient-reported outcome measures; a cognitive assessment; and average daily step count. The 30 s chair stand test was the main secondary (efficacy) outcome. RESULTS: No adverse events (AEs) occurred during testing or in telerehabilitation sessions; 38% (11/29) of the intervention group compared with 60% (9/15) of the control group experienced an AE (p=0.21), most of which were minor, over the course of the 12-week study. 27 of 29 participants (93%; 95% CI 77% to 99%) receiving the intervention attended ≥75% of sessions. Both groups demonstrated clinically meaningful improvement in secondary outcomes with no statistically significant differences between groups. CONCLUSION: Fully remote telerehabilitation was safe, feasible, had high adherence for COVID-19 recovery, and may apply to other medically complex patients including those with barriers to access care. This pilot study was designed to evaluate feasibility; further efficacy evaluation is needed. TRIAL REGISTRATION NUMBER: NCT04663945.

Epidemiological investigation of the COVID-19 outbreak in Vellore district in South India using Geographic Information Surveillance (GIS) (preprint)

Objectives Geographical Information Surveillance (GIS) is an advanced digital technology tool that maps location-based data and helps in epidemiological modeling. We applied GIS to analyze patterns of spread and hotspots of COVID-19 cases in Vellore district in South India. Methods Laboratory-confirmed COVID-19 cases from the Vellore district and neighboring taluks from March 2020 to June 2021 were geo-coded and spatial maps were generated. Time trends exploring urban-rural burden with an age-sex distribution of cases and other variables were correlated with outcomes. Results A total of 45,401 cases of COVID-19 were detected with 20730 cases during the first wave and 24671 cases during the second wave. The overall incidence rates of COVID-19 were 462.8 and 588.6 per 100,000 populations during the first and second waves respectively. The pattern of spread revealed epicenters in densely populated urban areas with radial spread sparing rural areas in the first wave. The case fatality rate was 1.89% and 1.6% during the first and second waves that increased with advancing age. Conclusions Modern surveillance systems like GIS can accurately predict the trends and pattern of spread during future pandemics. A real-time mapping can help design risk mitigation strategies thereby preventing the spread to rural areas.

A Web-Based Risk-Reframing Intervention to Influence Early Childhood Educators' Attitudes and Supportive Behaviors Toward Outdoor Play: Protocol for the OutsidePlay Study Randomized Controlled Trial.

BACKGROUND: Early learning and childcare centers (ELCCs) can offer young children critical opportunities for quality outdoor play. There are multiple actual and perceived barriers to outdoor play at ELCCs, ranging from safety fears and lack of familiarity with supporting play outdoors to challenges around diverse perspectives on outdoor play among early childhood educators (ECEs), administrators, licensing officers, and parents. OBJECTIVE: Our study objective is to develop and evaluate a web-based intervention that influences ECEs' and ELCC administrators' perceptions and practices in support of children's outdoor play at ELCCs. METHODS: The development of the fully automated, open-access, web-based intervention was guided by the intervention mapping process. We first completed a needs assessment through focus groups of ECEs, ELCC administrators, and licensing officers. We identified key issues, needs, and challenges; opportunities to influence behavior change; and intervention outcomes and objectives. This enabled us to develop design objectives and identify features of the OutsidePlay web-based intervention that are central to addressing the issues, needs, and challenges of ECEs and ELCC administrators. We used social cognitive theory and behavior change techniques to select methods, applications, and technology to deliver the intervention. We will use a two-parallel-group randomized controlled trial (RCT) design to evaluate the efficacy of the intervention. We will recruit 324 ECEs and ELCC administrators through a variety of web-based means, including Facebook advertisements and mass emails through our partner networks. The RCT study will be a purely web-based trial where outcomes will be self-assessed through questionnaires. The RCT participants will be randomized into the intervention group or the control group. The control group participants will read the Position Statement on Active Outdoor Play. RESULTS: The primary outcome is increased tolerance of risk in children's play, as measured by the Teacher Tolerance of Risk in Play Scale. The secondary outcome is self-reported attainment of a self-developed behavior change goal. We will use mixed effects models to test the hypothesis that there will be a difference between the intervention and control groups with respect to tolerance of risk in children's play. Differences in goal attainment will be tested using logistic regression analysis. CONCLUSIONS: The OutsidePlay web-based intervention guides users through a personalized journey that is split into 3 chapters. An effective intervention that addresses the barriers to outdoor play in ELCC settings has the potential to improve children's access to outdoor play and support high-quality early childhood education. TRIAL REGISTRATION: ClinicalTrials.gov NCT04624932; https://clinicaltrials.gov/ct2/show/NCT04624932. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/31041.

Replicating Anatomical Teaching Specimens Using 3D Modeling Embedded Within a Multimodal e-Learning Course: Pre-Post Study Exploring the Impact on Medical Education During COVID-19.

BACKGROUND: The COVID-19 pandemic has had significant effects on anatomy education. During the pandemic, students have had no access to cadavers, which has been the principal method of learning anatomy. We created and tested a customized congenital heart disease e-learning course for medical students that contained interactive 3D models of anonymized pediatric congenital heart defects. OBJECTIVE: The aim of this study is to assess whether a multimodal e-learning course contributed to learning outcomes in a cohort of first-year undergraduate medical students studying congenital heart diseases. The secondary aim is to assess student attitudes and experiences associated with multimodal e-learning. METHODS: The pre-post study design involved 290 first-year undergraduate medical students. Recruitment was conducted by course instructors. Data were collected before and after using the course. The primary outcome was knowledge acquisition (test scores). The secondary outcomes included attitudes and experiences, time to complete the modules, and browser metadata. RESULTS: A total of 141 students were included in the final analysis. Students' knowledge significantly improved by an average of 44.6% (63/141) when using the course (SD 1.7%; Z=-10.287; P<.001). Most students (108/122, 88.3%) were highly motivated to learn with the course, and most (114/122, 93.5%) reported positive experiences with the course. There was a strong correlation between attitudes and experiences, which was statistically significant (rs=0.687; P<.001; n=122). No relationships were found between the change in test scores and attitudes (P=.70) or experiences (P=.47). Students most frequently completed the e-learning course with Chrome (109/141, 77.3%) and on Apple macOS (86/141, 61%) or Windows 10 (52/141, 36.9%). Most students (117/141, 83%) had devices with high-definition screens. Most students (83/141, 58.9%) completed the course in <3 hours. CONCLUSIONS: Multimodal e-learning could be a viable solution in improving learning outcomes and experiences for undergraduate medical students who do not have access to cadavers. Future research should focus on validating long-term learning outcomes.

Reconstructing the COVID-19 epidemic in Delhi, India: infection attack rate and reporting of deaths (preprint)

India reported over 10 million COVID-19 cases and 149,000 deaths in 2020. To estimate exposure and the potential for further spread, we used a SARS-CoV-2 transmission model fit to seroprevalence data from three serosurveys in Delhi and the time-series of reported deaths to reconstruct the epidemic. The cumulative proportion of the population estimated infected was 48.7% (95% CrI 22.1% - 76.8%) by end-September 2020. Using an age-adjusted overall infection fatality ratio (IFR) based on age-specific estimates from mostly high-income countries (HICs), we estimate that 15.0% (95% CrI 9.3% - 34.0%) of COVID-19 deaths were reported. This indicates either under-reporting of COVID-19 deaths and/or a lower age-specific IFR in India compared with HICs. Despite the high attack rate of SARS-CoV-2, a third wave occurred in late 2020, suggesting that herd immunity was not yet reached. Future dynamics will strongly depend on the duration of immunity and protection against new variants.

The time to begin plans for COVID-19 eradication is now

After the world recovers from the pandemic of SARS-CoV-2, it is most likely to stabilise as endemic and seasonal, deserving/demanding control efforts perpetually in all countries, unless it can be eradicated. The risk of mortality is high among those above 65 years and those with chronic "lifestyle" diseases. Endemic circulation will, therefore, take a heavy toll on life annually. Eradication is an extreme form of control, eliminating the disease permanently and globally. Effective vaccines are expected in the near future. As the pandemic abates, herd immunity will be very high, enabling early eradication by additional build-up of a vaccine-induced herd immunity. Public memory of the pandemic will be fresh, which will assist in social mobilisation and fund raising towards eradication. If time is lost, the infection is likely to become non-eradicable as domestic/farmed animals may become fresh reservoirs. Resolve to eradicate and designing its road-map must be made at the earliest. © 2020 Center for Health in Mission. All rights reserved.

Community prevalence of antibodies to SARS-CoV-2 and correlates of protective immunity in five localities in an Indian metropolitan city (preprint)

BackgroundCurrent testing guidelines for COVID-19 substantially underestimates the spread of SARS-CoV-2 in dense urban populations. Granular estimates of infection are important for understanding population-level immunity. We examined seroprevalence of anti-SARS-CoV-2 antibodies in Pune city in India and its implication for protective immunity. MethodsSeroprevalence was estimated during July 20-August 5, 2020 from 1659 randomly selected individuals recruited from five administrative Pune sub-wards (combined population 366,984). Prevalence of anti-SARS-CoV-2 spike protein antibodies were estimated and along with correlates of virus neutralisation. FindingsSeropositivity was extensive (51{middle dot}3%; 95%CI 39{middle dot}9-62{middle dot}4) but varied widely in the five localities tested, ranging from 35{middle dot}8% to 66{middle dot}4%. Seropositivity was higher in crowded living conditions in the slums (OR 1{middle dot}91), and was lower in those 65 years or older (OR 0{middle dot}59). The infection-fatality ratio was estimated at 0.28%. Post survey, COVID-19 incidence was lower in areas noted to have higher seroprevalence. Substantial virus-neutralising activity was observed in seropositive individuals, but with considerable heterogeneity in the immune response and possible age-dependent diversity in the antibody repertoire. InterpretationDespite crowded living conditions having facilitated widespread transmission, the variability in seroprevalence in localities that are in geographical proximity indicates a heterogenous spread of infection. Declining infection rates in areas with high seropositivity suggest population-level protection and is supported by substantial neutralising activity in asymptomatically infected individuals. The heterogeneity in antibody levels and neutralisation capacity indicates the existence of immunological sub-groups of functional interest. FundingPersistent Foundation, Pune, India RESEARCH IN CONTEXTO_ST_ABSEvidence before this studyC_ST_ABSWe searched the literature (upto 2 Nov 2020), using the terms "seroprevalence", "serosurveillance", "seroepidemiology", "immune response", "seroconversion" and "SARS-CoV-2," without any article type restrictions, and selected only population- or community-level seroprevalence studies for collecting background information. The survey of literature indicated that community serosurveys for SARS-CoV-2 in LICs and LMICs have been limited and have largely reported correlations of seroprevalence with demographic factors. There are no reports of protective immunity-associated characteristics in community surveillance settings from LMIC/LICs. In fact, such studies from the global North are also limited. The existing evidence thus lacks granular details critical to understand community-level heterogeneities, and provides limited epidemiological data without meaningful immunobiological correlates. Added value of this studyThis is the first systematic study (at the time of submission) from a LMIC reporting community SARS-CoV-2 sero-surveillance of high granularity alongside estimation of correlates of immune protection. We estimated seroprevalence as well as serological correlates of protection in a cross-sectional cohort of 1659 asymptomatic participants from five small urban localities in the metropolitan city of Pune, India. IgG seroprevalence was determined against the receptor-binding-domain (RBD) of the SARS-CoV-2 spike protein, to aid correlation with immune protection since RBD is the predominant target for neutralising antibodies. Large subsets of the sera were also tested for surrogate neutralisation as well as live SARS-CoV-2 virus neutralisation, data not so far reported in community sero-surveillance studies. We identified substantial locality-specific variations in seropositivity levels and infection fatality rates (IFRs), highlighting heterogeneities of infection behaviour even in dense, urban populations often lost in more global analyses. Notably, the incidence of new infections after the sero-sampling period revealed a strong negative association with seropositivity, indicating potential modification of transmission by community immunity. While RBD-specific antibody levels expectedly showed broad correlation with neutralisation capacities, 30% of individuals showed significant departures from this correlation, again underlining significant immune response heterogeneities. Implications of all the available evidenceHigh seroprevalence in the dense urban localities of the study site, despite a protracted and stringent lockdown, provides a realistic account on transmission dynamics crucial for public health policies in LMICs. Micro-geographic variability within locales, dominated by sub-optimal living conditions, needs to be acknowledged and used to develop measures designed for people in such socio-economic contexts. The heterogeneity of correlation between RBD seropositivity and neutralising capacity, as well as the complex association with age encountered in this study open up a plethora of research questions into epitope dominance and affinity variations in anti-viral antibodies in asymptomatic infection.

Covid-19 mortality trends and reporting comparing india and italy

During the early phase of the coronavirus pandemic, Italy had a high infection burden and death rate while India appeared much less affected. By 22 May, Italy and India had 3,770 and 86 infections/million population with mortality rates of 14.24% and 3.03%, respectively. There was speculation about hidden advantages to India leading to a false sense of security. These differences are readily explained by the time and frequency of virus importations and the differences of the age profile of Italy and India. © 2020 Economic and Political Weekly. All rights reserved.

Pooling RT-PCR or NGS samples has the potential to cost-effectively generate estimates of COVID-19 prevalence in resource limited environments (preprint)

Background: COVID-19 originated in China and has quickly spread worldwide causing a pandemic. Countries need rapid data on the prevalence of the virus in communities to enable rapid containment. However, the equipment, human and laboratory resources required for conducting individual RT-PCR is prohibitive. One technique to reduce the number of tests required is the pooling of samples for analysis by RT-PCR prior to testing. Methods: We conducted a mathematical analysis of pooling strategies for infection rate classification using group testing and for the identification of individuals by testing pooled clusters of samples. Findings: On the basis of the proposed pooled testing strategy we calculate the probability of false alarm, the probability of detection, and the average number of tests required as a function of the pool size. We find that when the sample size is 256, with a maximum pool size of 64, with only 7.3 tests on the average, we can distinguish between prevalences of 1% and 5% with a probability of detection of 95% and probability of false alarm of 4%. Interpretation: The pooling of RT-PCR samples is a cost-effective technique for providing much-needed course-grained data on the prevalence of COVID-19. This is a powerful tool in providing countries with information that can facilitate a response to the pandemic that is evidence-based and saves the most lives possible with the resources available.