Development of the India COVID-19 vaccine tracker.

COVID-19 was declared a pandemic by the World Health Organization (WHO) on March 11, 2020. Since then, efforts were initiated to develop safe and effective vaccines. Till date, 11 vaccines have been included in the WHO's emergency use list. The emergence and spread of variant strains of SARS-CoV-2 has altered the disease transmission dynamics, thus creating a need for continuously monitoring the real-world effectiveness of various vaccines and assessing their overall impact on disease control. To achieve this goal, the Indian Council of Medical Research (ICMR) along with the Ministry of Health and Family Welfare, Government of India, took the lead to develop the India COVID-19 Vaccination Tracker by synergizing three different public health databases: National COVID-19 testing database, CoWIN vaccination database and the COVID-19 India portal. A Vaccine Data Analytics Committee (VDAC) was constituted to advise on various modalities of the proposed tracker. The VDAC reviewed the data related to COVID-19 testing, vaccination and patient outcomes available in the three databases and selected relevant data points for inclusion in the tracker, following which databases were integrated, using common identifiers, wherever feasible. Multiple data filters were applied to retrieve information of all individuals ≥18 yr who died after the acquisition of COVID-19 infection with or without vaccination, irrespective of the time between vaccination and test positivity. Vaccine effectiveness (VE) against the reduction of mortality and hospitalizations was initially assessed. As compared to the hospitalization data, mortality reporting was found to be much better in terms of correctness and completeness. Therefore, hospitalization data were not considered for analysis and presentation in the vaccine tracker. The vaccine tracker thus depicts VE against mortality, calculated by a cohort approach using person-time analysis. Incidence of COVID-19 deaths among one- and two-dose vaccine recipients was compared with that among unvaccinated groups, to estimate the rate ratios (RRs). VE was estimated as 96.6 and 97.5 per cent, with one and two doses of the vaccines, respectively, during the period of reporting. The India COVID-19 Vaccination Tracker was officially launched on September 9, 2021. The high VE against mortality, as demonstrated by the tracker, has helped aid in allaying vaccine hesitancy, augmenting and maintaining the momentum of India's COVID-19 vaccination drive.

Mathematical model and interpretation of crowding effects on SARS-CoV-2 using Atangana-Baleanu fractional operator

The novel coronavirus disease (COVID-19) outbreak, which infects a normal person through droplets of infected person and has its route via mouth, eyes, nose, or hands is caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Coronavirus causes severe infections that include acute respiratory distress syndrome, acute lung injury, and various others. SARS-CoV-2 infection activates innate and adaptive immune responses, but uncontrolled, inflammatory, and impaired responses lead to harmful tissue damage. Crowding is the major factor involved in the increasing trend in COVID-19 cases. Modeling of this effect will help in predicting the effects of overcrowding on the overall population. In this chapter, we define a model depicting the crowding effects of SARS-CoV-2 virus and examine the existence and uniqueness of the results involving Atangana-Baleanu fractional operator using a fixed-point method. We then interpret the model explaining its significance. © 2022 Elsevier Inc. All rights reserved.

Initial Immunomodulation and Outcome of Children with Multisystem Inflammatory Syndrome Related to COVID-19: A Multisite Study from India.

OBJECTIVE: To determine the outcomes in children with MIS-C receiving different immunomodulatory treatment. METHODS: In this multicentric, retrospective cohort study, data regarding treatment and outcomes of children meeting the WHO case definition for MIS-C, were collected. The primary composite outcome was the requirement of vasoactive/inotropic support on day 2 or beyond or need of mechanical ventilation on day 2 or beyond after initiation of immunomodulatory treatment or death during hospitalization in the treatment groups. Logistic regression and propensity score matching analyses were used to compare the outcomes in different treatment arms based on the initial immunomodulation, i.e., IVIG alone, IVIG plus steroids, and steroids alone. RESULTS: The data of 368 children (diagnosed between April 2020 and June 2021) meeting the WHO case definition for MIS-C, were analyzed. Of the 368 subjects, 28 received IVIG alone, 82 received steroids alone, 237 received IVIG and steroids, and 21 did not receive any immunomodulation. One hundred fifty-six (42.39%) children had the primary outcome. On logistic regression analysis, the treatment group was not associated with the primary outcome; only the children with shock at diagnosis had higher odds for the occurrence of the outcome [OR (95% CI): 11.4 (5.19-25.0), p < 0.001]. On propensity score matching analysis, the primary outcome was comparable in steroid (n = 45), and IVIG plus steroid (n = 84) groups (p = 0.515). CONCLUSION: While no significant difference was observed in the frequency of occurrence of the primary outcome in different treatment groups, data from adequately powered RCTs are required for definitive recommendations.

Effectiveness of an inactivated virus-based SARS-CoV-2 vaccine, BBV152, in India: a test-negative, case-control study.

BACKGROUND: 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. METHODS: 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%. FINDINGS: 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). INTERPRETATION: 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. FUNDING: None. TRANSLATION: For the Hindi translation of the abstract see Supplementary Materials section.

Prevalence of psychological outcomes and its associated factors in healthcare personnel working during COVID-19 outbreak in India.

Background: Care of COVID-19 patients has been shown to affect the mental health of healthcare personnel (HCP), however, there is little data reflecting psychological health of HCP in India. Aims: The present study was undertaken to assess the prevalence of psychological outcomes and its association with various sociodemographic and occupational factors among the HCP in India. Methodology: A cross-sectional, online survey, using snowball sampling method was conducted between June 1, 2020, and June 22, 2020. The HCP working in COVID-19 designated hospitals across India were invited to participate. Patient Health Questionnaire-4 and 19-item stress-related questionnaire were used to evaluate symptoms of overall anxiety, depression, COVID-19 infection specific anxiety, exhaustion, and workload. Results: In this cross-sectional study with 2334 HCP from 27 states and 7 union territories of India; 17.9% of participants had depression, 18.7% had overall anxiety, 26.5% had exhaustion, 30.3% reported heavy workload, and 25.4% had COVID-19 infection-specific anxiety, respectively. The HCP working in states with higher caseload was a common risk factor for overall anxiety (odds ratio [OR], 1.7; P < 0.001), depression (OR, 1.6; P < 0.001), COVID-19 infection-specific anxiety (OR, 2.5; P < 0.001), exhaustion (OR, 3.1; P < 0.001), and heavy workload (OR, 2.6; P < 0.001). Nurses were more at risk for depression (OR, 2.2; P < 0.001), anxiety specific to COVID-19 infection (OR, 1.3; P = 0.034), and heavy workload (OR, 2.9; P < 0.001); while doctors were more at risk for overall anxiety (OR, 2.0; P = 0.001) and exhaustion (OR, 3.1; P < 0.001). Conclusions: Frontline workers, specifically nurses and doctors, and those working in states with high COVID-19 caseload are more at risk for adverse psychological outcomes. The relatively less prevalence compared with other countries, is perhaps a reflection of measures undertaken, including early lockdown, ensuring better all-round preparedness and social norms.

Suspend or amend? Randomized controlled trial on neuropsychological rehabilitation for epilepsy: A COVID-19 impact.

COVID-19 caused devastating effects of human loss and suffering along with disruption in clinical research, forcing reconceptualization and modification of studies. This paper attempts to outline the steps followed and detail the modifications undertaken to deal with the impacts of the pandemic on the first ongoing randomized controlled trial on effectiveness of neuropsychological rehabilitation in adult patients with drug-resistant epilepsy in India. All modifications were based on evolving guidelines and circumstantial context and were planned, reviewed and approved by important stakeholders. Results obtained from the trial need to be interpreted and analysed within this context. These modifications have implications for wider outreach of neuropsychology services in India.

Randomized controlled trial on neuropsychological rehabilitation for patients with drug refractory epilepsy: Challenges, adaptations & findings

Purpose: Reviews of neuropsychological rehabilitation literature in epilepsy outnumber the original studies with one Randomized Controlled Trial (RCT) reported till date. A home-based neuropsychological rehabilitation program was developed for patients with Drug Refractory Epilepsy (DRE) [Post-Operative (PO) & Not Cleared for Surgery (NCS)]. The COVID-19 pandemic posed challenges of follow-up and tele- assessment. Adaptations were made to the ongoing study and solutions were found based on available literature and focus group discussions with experts in the field of neuropsychology and epileptology. The efficacy was studied. Method: 27 consenting adults with DRE were recruited in a single blind RCT (CTRI/2019/10/021777) with 14 patients in the Intervention (IG) (PO = 13, NCS = 1), and 13 in the Treatment As Usual (TAU) (PO = 11, NCS = 2) groups. They were of any gender, aged 18-45 years diagnosed with DRE atleast 1 year back, with minimum primary level of education, IQ > 80, having an available primary caregiver. At 3 months, reasons for non-compliance to rehabilitation due to COVID-19 were noted and a booster session was given. Pre-post neuropsychological assessment included Auditory Verbal Learning Test and Everyday Memory Questionnaire (EMQ). All follow-ups were done through tele-assessment at 6 months and coded for validity on a 3-point scale. The 6-week neuropsychological rehabilitation program included psychoeducation, compensatory training and cognitive retraining aimed at improving memory. The booster session focused on internal and external aids. Result: Themes of non-compliance included 1) Non-availability of time due to shift to virtual work/study 2) Increased household work. Mann-Whitney test of the absolute differences of the test scores (follow-up score- baseline score) between two groups revealed significant differences in immediate recall (P = 0.002), delayed recall (p <0.001), long term retention (P = 0.024), patient reported EMQ (p <0.001) and caregiver reported EMQ (p <0.001) with IG showing improvement. Conclusions: Despite challenges of the pandemic, efficacy of the rehabilitation was observed.

RNA-extraction-free diagnostic method to detect SARS-CoV-2: An assessment from two States, India

With increasing demand for large numbers of testing during COVID-19 pandemic, came alternative protocols with shortened turn-around time. We evaluated the performance of such a protocol wherein 1138 consecutive clinic attendees were enrolled;584 and 554 respectively from two independent study sites in the cities of Pune and Kolkata. Paired nasopharyngeal and oropharyngeal swabs were tested by using both reference and index methods in blinded fashion. Prior to conducting RT-PCR, swabs collected in viral transport medium (VTM) were processed for RNA extraction (reference method) and swabs collected in dry tube without VTM were incubated in Tris-EDTA-Proteinase K buffer for 30 minutes and heat inactivated at 98oC for 6 minutes (index method). Overall sensitivity and specificity of the index method were 78.9% (95% CI 71% to 86%) and 99 % (95% CI 98% to 99.6%) respectively. Agreement between the index and reference method was 96.8 % (k = 0.83, SE=0.030). The reference method exhibited enhanced detection of viral genes (E, N and RdRP) with lower Ct values compared to the index method. The index method can be used for detecting SARS-CoV-2 infection with appropriately chosen primer-probe set and heat treatment approach in pressing time;low sensitivity constrains its potential wider use. © 2021 Cambridge University Press. All rights reserved.

Impact of metabolic and cardiovascular disease on COVID-19 mortality: A systematic review and meta-analysis.

BACKGROUND AND AIMS: This meta-analysis aims to highlight the impact of cardio-metabolic comorbidities on COVID-19 severity and mortality. METHODS: A thorough search on major online databases was done for studies describing the clinical outcomes of COVID-19 patients. We used random-effects model to compute pooled estimates for critical or fatal disease. RESULTS: A total of 20,475 patients from 33 eligible studies were included. Maximum risk of development of critical or fatal COVID-19 disease was seen in patients with underlying cardiovascular disease [OR: 3.44, 95% CI: 2.65-4.48] followed by chronic lung disease, hypertension and diabetes mellitus. Of the total cases, 64% had one of the four comorbidities with the most prevalent being hypertension with a pooled prevalence of 27%. CONCLUSIONS: Presence of comorbidities like cardiovascular disease, chronic lung disease, hypertension and diabetes mellitus led to a higher risk of development of critical or fatal COVID-19 disease, with maximum risk seen with underlying cardiovascular disease.

Awake prone positioning in non-intubated patients for the management of hypoxemia in COVID-19: A systematic review and meta-analysis

Coronavirus disease-2019 (COVID-19) may lead to hypoxemia, requiring intensive care in many patients. Awake prone positioning (PP) is reported to improve oxygenation and is a relatively safe modality. We performed a systematic review of the literature to evaluate the available evidence and performed meta-analysis of the effect of awake PP in non-intubated patients on improvement in oxygenation and reducing the need for intubation. We searched the PubMed and EMBASE databases to identify studies using awake PP as a therapeutic strategy in the management of COVID-19. Studies were included if they reported respiratory outcomes and included five or more subjects. The quality of individual studies was assessed by the Qualsyst tool. A meta-analysis was performed to estimate the proportion of patients requiring intubation. The degree of improvement in oxygenation parameters (PaO2: FiO2 or PaO2 or SpO2) was also calculated. Sixteen studies (seven prospective trials, three before-after studies, six retrospective series) were selected for review. The pooled proportion of patients who required mechanical ventilation was 0.25 (95% confidence interval (CI) 0.16-0.34). There was a significant improvement in PaO2: FiO2 ratio, PaO2, and SpO2 during awake PP. To conclude, there is limited evidence to support the efficacy of awake PP for the management of hypoxemia in COVID-19. Further RCTs are required to study the impact of awake PP on key parameters like avoidance of mechanical ventilation, length of stay, and mortality.

TB infection and BCG vaccination: are we protected from COVID-19?

OBJECTIVES: The incidence of emerging coronavirus disease 2019 (COVID-19) disease is variable across the different parts of the world. Apart from travel patterns, other factors determining this difference may include host immune response. The aim of this study was to assess the effect of tuberculosis (TB) endemicity and Bacille Calmette-Guerin (BCG) coverage on COVID-19. STUDY DESIGN: This was a cross-sectional study. METHODS: We reviewed available data regarding TB incidence, BCG coverage (as per the World Health Organization), and COVID-19 incidence of 174 countries. We divided the countries into four cohorts depending on annual TB incidence and BCG coverage. RESULTS: Countries with high TB incidence had lower COVID-19 than countries with low TB incidence. Similarly, countries with high BCG coverage had lower incidence of COVID-19, suggesting some protective mechanisms in TB-endemic areas. However, the ecological differences and different testing strategies between countries could not be accounted for in this analysis. CONCLUSION: Higher TB incidence and BCG coverage were found to be associated with lesser incidence of COVID-19. This outcome paves the way for further research into pathogenesis and immune response in COVID-19.