Efficacy, safety, and lot-to-lot immunogenicity of an inactivated SARS-CoV-2 vaccine (BBV152): interim results of a randomised, double-blind, controlled, phase 3 trial.

BACKGROUND: We report the clinical efficacy against COVID-19 infection of BBV152, a whole virion inactivated SARS-CoV-2 vaccine formulated with a toll-like receptor 7/8 agonist molecule adsorbed to alum (Algel-IMDG) in Indian adults. METHODS: We did a randomised, double-blind, placebo-controlled, multicentre, phase 3 clinical trial in 25 Indian hospitals or medical clinics to evaluate the efficacy, safety, and immunological lot consistency of BBV152. Adults (age ≥18 years) who were healthy or had stable chronic medical conditions (not an immunocompromising condition or requiring treatment with immunosuppressive therapy) were randomised 1:1 with a computer-generated randomisation scheme (stratified for the presence or absence of chronic conditions) to receive two intramuscular doses of vaccine or placebo administered 4 weeks apart. Participants, investigators, study coordinators, study-related personnel, the sponsor, and nurses who administered the vaccines were masked to treatment group allocation; an unmasked contract research organisation and a masked expert adjudication panel assessed outcomes. The primary outcome was the efficacy of the BBV152 vaccine in preventing a first occurrence of laboratory-confirmed (RT-PCR-positive) symptomatic COVID-19 (any severity), occurring at least 14 days after the second dose in the per-protocol population. We also assessed safety and reactogenicity throughout the duration of the study in all participants who had received at least one dose of vaccine or placebo. This report contains interim results (data cutoff May 17, 2021) regarding immunogenicity and safety outcomes (captured on days 0 to 56) and efficacy results with a median of 99 days for the study population. The trial was registered on the Indian Clinical Trials Registry India, CTRI/2020/11/028976, and ClinicalTrials.gov, NCT04641481 (active, not recruiting). FINDINGS: Between Nov 16, 2020, and Jan 7, 2021, we recruited 25 798 participants who were randomly assigned to receive BBV152 or placebo; 24 419 received two doses of BBV152 (n=12 221) or placebo (n=12 198). Efficacy analysis was dependent on having 130 cases of symptomatic COVID-19, which occurred when 16 973 initially seronegative participants had at least 14 days follow-up after the second dose. 24 (0·3%) cases occurred among 8471 vaccine recipients and 106 (1·2%) among 8502 placebo recipients, giving an overall estimated vaccine efficacy of 77·8% (95% CI 65·2-86·4). In the safety population (n=25 753), 5959 adverse events occurred in 3194 participants. BBV152 was well tolerated; the same proportion of participants reported adverse events in the vaccine group (1597 [12·4%] of 12 879) and placebo group (1597 [12·4%] of 12 874), with no clinically significant differences in the distributions of solicited, unsolicited, or serious adverse events between the groups, and no cases of anaphylaxis or vaccine-related deaths. INTERPRETATION: BBV152 was highly efficacious against laboratory-confirmed symptomatic COVID-19 disease in adults. Vaccination was well tolerated with no safety concerns raised in this interim analysis. FUNDING: Bharat Biotech International and Indian Council of Medical Research.

Resilience level, its determinants and its effect on psychological well-being: A cross-sectional evaluation among school-going adolescents of Patna, Bihar, India.

BACKGROUND: Adolescents with higher resilience levels are reported to be less vulnerable to psychological illnesses. The study examined resilience level, its determinants and its effect on psychological well-being among school-going adolescents of Patna, Bihar, India. METHODS: Adopting cross-sectional design we examined resilience levels among the study participants reading in the sixth, seventh and eighth standards of selected schools of Patna district using the Child Youth Resilience Measure-Revised questionnaire during March 2021. Psychological well-being was assessed using Patient Health Questionnaire-4. Data of in total 468 enrolled participants were analysed using SPSS 22.0. RESULTS: The mean resilience score was observed to be 62.4 ± 8.8. In multiple linear regression analysis using backward method; increasing age (unstandardised beta [ß]: 0.564, standard error [SE]: 0.271, P: 0.038), male gender (ß: 2.753, SE: 0.775, P < 0.001), high per capita monthly family income (≥18 USD [median]) (ß: 1.829, SE: 0.743, P: 0.014), academic satisfaction (ß: 2.003, SE: 0.962, P: 0.038), no history of abuse (physical or mental) in the past 30 days (ß: 2.752, SE: 1.220, P: 0.025) and increasing self-esteem score (measured by Rosenberg Self-Esteem Scale) (ß: 0.808, SE: 0.098, P: < 0.001) were found to be positive determinants of the total resilience level. Resilience was found to be positively correlated with psychological well-being (spearman rho correlation co-efficient [ρ]: 0.363, P < 0.001). CONCLUSIONS: Abuse, academic satisfaction and self-esteem were the modifiable determinates of resilience that could be elucidated in this investigation. Resilience level positively influenced psychological well-being.

Effectiveness of COVID-19 vaccine in preventing infection and disease severity: a case-control study from an Eastern State of India.

Effectiveness of corona virus disease-19 (COVID-19) vaccines used in India is unexplored and need to be substantiated. The present case-control study was planned to elicit the effectiveness of COVID-19 vaccines in preventing infection and disease severity in the general population of Bihar, India. This case-control study was conducted among people aged ≥45 years during April to June 2021. The cases were the COVID-19 patients admitted or visited All India Institute of Medical Sciences (AIIMS), Patna, Bihar, India, and were contacted directly. The controls were the individuals tested negative for severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) at the Virology laboratory, AIIMS-Patna and contacted telephonically for collection of relevant information. The vaccine effectiveness (VE) was calculated by using the formula (VE = 1 - odds ratio). The adjusted VE for partial and full vaccination were estimated to be 52.0% (95% confidence interval (CI) 39.0-63.0%) and 83.0% (95% CI 73.0-89.0%) respectively for preventing SARS CoV-2 infection. The sub-group analyses of the cases have shown that the length of hospital stays (LOS) (partially vaccinated: 9 days vs. unvaccinated: 12 days; P = 0.028) and the severity of the disease (fully vaccinated: 30.3% vs. partially vaccinated: 51.3% and unvaccinated: 54.1%; P = 0.035) were significantly low among vaccinated compared to unvaccinated individuals. To conclude, four out of every five fully vaccinated individuals are estimated to be protected from contracting SARS CoV-2 infection. Vaccination lowered LOS and chances of development of severe disease.

Acute Necrotizing Encephalitis as a Probable Association of COVID-19.

BACKGROUND: Meanwhile, over 50 lakh people have now been affected by coronavirus disease-2019 (COVID-19) across the globe. There are various reports on neurological manifestations of COVID-19, which have attracted broad attention. Acute necrotizing encephalopathy (ANE) is a rare complication of influenza and other viral infections and has been related to intracranial cytokine storm, which results in breach in blood-brain barrier leading to encephalitis like presentation. We report an unusual case of acute necrotizing encephalitis as a solitary presentation of COVID-19. CASE DESCRIPTION: We report a case of 35-year-old man from Bihar, presented to our emergency department in unconscious state, with high-grade fever and vomiting since last 5 days. Previous magnetic resonance imaging (MRI) brain showed a left parasellar-middle cranial fossa mass looks most likely like an invasive meningioma. Urgent noncontrast computed tomography scan (NCCT) brain showed that mass as well as hypodensities in both thalami and left caudate nucleus. As per our institutional protocol, clinical management of raised intracranial pressure was initiated. As there is no current evidence from any randomized control trails (RCTs) to recommend any specific treatment for suspected or confirmed patients with COVID-19 with acute necrotizing encephalitis. CONCLUSION: Our case highlights the importance of identifying encephalitis as a presenting sign of COVID-19 based on NCCT findings with normal cerebrospinal fluid (CSF) and normal chest X-ray (CXR) findings. HOW TO CITE THIS ARTICLE: Kumar N, Kumar S, Kumar A, Pati BK, Kumar A, Singh C, et al. Acute Necrotizing Encephalitis as a Probable Association of COVID-19. Indian J Crit Care Med 2020;24(10):991-994.

Effect of indoor residual spraying on sandfly abundance and incidence of visceral leishmaniasis in India, 2016-22: an interrupted time-series analysis and modelling study.

BACKGROUND: Efforts to eliminate visceral leishmaniasis in India mainly consist of early detection and treatment of cases and indoor residual spraying with insecticides to kill the phlebotomine sandfly Phlebotomus argentipes that transmits the causative Leishmania protozoa. In this modelling study, we aimed to estimate the effect of indoor residual spraying (IRS) on vector abundance and transmission of visceral leishmaniasis in India. METHODS: In this time-series analysis and modelling study, we assessed the effect of IRS on vector abundance by using indoor vector-abundance data (from 2016 to 2022) and IRS quality-assurance data (from 2017-20) from 50 villages in eight endemic blocks in India where IRS was implemented programmatically. To assess a potential dose-response relation between insecticide concentrations and changes in sandfly abundance, we examined the correlation between site-level insecticide concentrations and the site-level data for monthly sandfly abundances. We used mathematical modelling to link vector data to visceral leishmaniasis case numbers from the national Kala-Azar Management Information System registry (2013-21), and to predict the effect of IRS on numbers of averted cases and deaths. FINDINGS: IRS was estimated to reduce indoor sandfly abundance by 27% (95% CI 20-34). Concentrations of insecticides on walls were significantly-but weakly-associated with the degree of reduction in vector abundance, with a reduction of -0·0023 (95% CI -0·0040 to -0·0007) sandflies per mg/m2 insecticide (p=0·0057). Reported case numbers of visceral leishmaniasis were well explained by trends in vector abundance. Village-wide IRS in response to a newly detected case of visceral leishmaniasis was predicted to reduce disease incidence by 6-40% depending on the presumed reduction in vector abundance modelled. INTERPRETATION: Indoor residual spraying has substantially reduced sandfly abundance in India, which has contributed to reductions in visceral leishmaniasis and related deaths. To prevent the re-emergence of visceral leishmaniasis as a public health problem, surveillance of transmission and sandfly abundance is warranted. FUNDING: Bill & Melinda Gates Foundation. TRANSLATION: For the Hindi translation of the abstract see Supplementary Materials section.

Tobacco Usage and Its Association With Mental Health Status of School-Going Adolescents Near Patna, Bihar: A Community-Based Cross-Sectional Study in Eastern India.

Background Of all the adolescents in India, 7.3% are suffering from some form of mental disorder. They frequently use tobacco to cope with these problems, but get stuck in a vicious cycle of deteriorating mental health. Our study aimed to determine the effect of tobacco on the mental health status of adolescents studying in the 9th to 12th standards in 10 high schools in urban and rural areas near Patna, Bihar. Methodology An analytical cross-sectional study was conducted among 360 school-going adolescents recruited using stratified random sampling. Selected adolescents were given the Indian Adolescent Health Questionnaire. The mental health status was calculated from the Strengths and Difficulties Questionnaire (SDQ) score. Information on sociodemographic characteristics and tobacco use was also obtained. Independent t-test, analysis of variance, and multiple linear regression analysis were used for predicting the significant factors. Significance was set at p-values <0.05. Results In this study, 40 (11.1%) adolescents had abnormal whereas 55 (15.3%) had borderline overall SDQ scores. The majority of those affected had peer problems (40%) and conduct problems (24.7%). All SDQ components of conduct (F = 2.94, p = 0.013), hyperactivity (F = 2.90, p = 0.014), emotional problems (F = 1.14, p = 0.001), and peer pressure (F = 3.06, p = 0.010), as well as the overall SDQ score (F = 5.74, p < 0.001), were significantly associated with increasing age. The adolescents attending rural schools (13.28 ± 5.22, p = 0.047) had significantly higher SDQ scores than those attending urban schools (12.08 ± 5.60). Hyperactivity scores were significantly higher in those studying in class 10 compared to other classes and in those attending rural rather than urban schools. Emotional problems score was significantly higher in 16-17-year-old students than in 14-15-year-old students, in females than in males, and in class 10 than in class 9 students. Only 24 (6.7%) adolescents had a history of tobacco consumption at least once which was significantly associated with the SDQ score (17.71 ± 5.69; t = 4.95, df = 358, p < 0.001). Around 79.4% of adolescents were exposed to passive smoking from close friends which deteriorated their overall mental health status (14.50 ± 5.99; F = 6.29, df = 2,357, p = 0.002). Those who had smoked for more than 10 days had significantly greater conduct problems and lesser pro-social behavior. Overall, 96.1% agreed that tobacco is harmful to health, and 76.1% had seen anti-smoking messages in the media. Female gender, increasing class and age, and history of smoking or chewing tobacco at least once also led to a significant increase in emotional problems. Age, area of the school, history of tobacco consumption, and exposure to cigarette smoke by either a close friend or male guardian had a significant impact on the conduct, hyperactivity, peer problems, and overall mental health status of school-going adolescents. Conclusions Predicting risk factors such as age, area of the school, and the history of tobacco consumption by self or by close friends is important for decision-making by school administration regarding counseling for mental health and preventing tobacco use.

Prevalence of acute low back pain with risk of long-term disability and its correlates among medical students: A cross-sectional study.

BACKGROUND: Low back pain (LBP) is responsible for the highest number of years lived with disability globally. There is a paucity of data regarding the same among medical students. So, this study was planned to estimate the prevalence of acute LBP having a high propensity to develop into chronic one as well as to determine associated correlates among medical students. MATERIALS AND METHODS: This cross-sectional study was conducted among 300 medical students at a tertiary hospital using an Acute Low Back Pain Screening Questionnaire (ALBPSQ) to identify individuals with LBP and having a high risk of developing a long-term disability. ALBPSQ is a 21-question-based biopsychosocial screening instrument for identifying patients at risk of chronicity. ALBPSQ scores have been found to be significantly associated with pain and functional disability. Descriptive statistics, bivariate analysis, and multiple binary logistic regression have been performed through SPSS-22 software. RESULTS: The prevalence of LBP having the propensity to develop into a long-term disability was found to be 14.3% (95% CI: 10.6-18.8). In bivariate analysis, higher age, no exercise, higher screen time, mental stress, studying in bed, abnormal posture, alcohol intake, tobacco use, positive family history, greater screen time per day, and more time spent in a sitting posture are significant with LBP. Stress ((adjusted odds ratio) AOR: 4.37, 95% CI: 1.79-10.68)), abnormally bent standing posture (AOR: 3.6, 95% CI: 1.3-10.6), and positive family of LBP (AOR: 3.6, 95% CI: 1.3-10.1) were found to be independent predictors of LBP among medical students. CONCLUSION: Among medical students, every 15 out of 100 have a low back problem with chances of long-term disability. These students require early intervention to avoid long-term disability. Abnormal stooping posture, psychological stress, and positive family history of low pain might independently lead to LBP.

Awareness of the Ayushman Bharat-Pradhan Mantri Jan Arogya Yojana in the Rural Community: A Cross-Sectional Study in Eastern India.

Background Ayushman Bharat-Pradhan Mantri Jan Arogya Yojana (AB-PMJAY) is one of the flagship programs intended to provide financial protection to people availing of secondary and tertiary level health care. It's been nearly three years since the implementation of AB-PMJAY in Bihar, yet the level of awareness, especially in rural communities, is unknown. So, this study was planned to explore the awareness and utilization of AB-PMJAY in the selected rural area of Bihar. Methodology This community-based cross-sectional study used a multistage sampling strategy to select 802 households within a radius of 5 Km from the rural health training centre, Naubatpur. A pre-tested, semi-structured questionnaire was used to collect the necessary data regarding awareness of AB-PMJAY. The association between category, occupation, education, age group, and ration card with the awareness of AB-PMJAY was assessed using Pearson's chi-square test. Results The awareness of the AB-PMJAY was 68.6% (95% CI: 65.30%-71.7%), while out of 459 eligible study participants, 362 (78.9%) were aware of the AB-PMJAY. Utilization of AB-PMJAY was only 1.3% among the eligible study participants. There was a statistical significance between the category of eligible study, ration card, and employment status with the awareness of the AB-PMJAY. Conclusion Every two out of three rural individuals and three out of every four eligible participants were aware of the AB-PMJAY scheme, while the level of utilization was found to be very low at 1.3%; hence, training of the healthcare workers at the grass-root level, like accredited social health activists (ASHA) and Anganwadi workers (AWW), should be done regularly to improve the connection in the community and for effective utilization of the Ayushman Bharat-PMJAY.

Household-level food insecurity and its correlates in rural Bihar: A cross-sectional study.

Introduction: Bihar has experienced high nutritional public health problem among children and women over the years. In this background, this study was planned to find the level of food insecurity and identify contributing factors in rural Bihar. Material and Methods: We conducted community-based cross-sectional study among 255 families residing in villages catered by RHTC, Naubatpur. A pretested semi-structured interview schedule and HFIAS were used. Result: A total of 27.8% of the 255 households were food insecure, of which 73.3% were severely food insecure. Kutcha houses, dispossession of agricultural land, and lower SES were found to be predictors. Conclusion: Around one in three families experienced food insecurity, and it was more among families residing in kutcha houses, without possession of agricultural land and belonging to lower socioeconomic status.

Molecular surveillance of insecticide resistance in Phlebotomus argentipes targeted by indoor residual spraying for visceral leishmaniasis elimination in India.

Molecular surveillance of resistance is an increasingly important part of vector borne disease control programmes that utilise insecticides. The visceral leishmaniasis (VL) elimination programme in India uses indoor residual spraying (IRS) with the pyrethroid, alpha-cypermethrin to control Phlebotomus argentipes the vector of Leishmania donovani, the causative agent of VL. Prior long-term use of DDT may have selected for knockdown resistance (kdr) mutants (1014F and S) at the shared DDT and pyrethroid target site, which are common in India and can also cause pyrethroid cross-resistance. We monitored the frequency of these marker mutations over five years from 2017-2021 in sentinel sites in eight districts of north-eastern India covered by IRS. Frequencies varied markedly among the districts, though finer scale variation, among villages within districts, was limited. A pronounced and highly significant increase in resistance-associated genotypes occurred between 2017 and 2018, but with relative stability thereafter, and some reversion toward more susceptible genotypes in 2021. Analyses linked IRS with mutant frequencies suggesting an advantage to more resistant genotypes, especially when pyrethroid was under-sprayed in IRS. However, this advantage did not translate into sustained allele frequency changes over the study period, potentially because of a relatively greater net advantage under field conditions for a wild-type/mutant genotype than projected from laboratory studies and/or high costs of the most resistant genotype. Further work is required to improve calibration of each 1014 genotype with resistance, preferably using operationally relevant measures. The lack of change in resistance mechanism over the span of the study period, coupled with available bioassay data suggesting susceptibility, suggests that resistance has yet to emerge despite intensive IRS. Nevertheless, the advantage of resistance-associated genotypes with IRS and under spraying, suggest that measures to continue monitoring and improvement of spray quality are vital, and consideration of future alternatives to pyrethroids for IRS would be advisable.

Comparison of the immunogenicity and safety of Euvichol-Plus with Shanchol in healthy Indian adults and children: an open-label, randomised, multicentre, non-inferiority, parallel-group, phase 3 trial.

Background: Considering the cholera menace in India and to seek licensure of the oral cholera vaccine (OCV), Euvichol-Plus, we conducted a clinical trial to compare the immunogenicity and safety of Euvichol-Plus with Shanchol in healthy Indian adults and children. Methods: This phase 3, open-label, multicentre, randomised, non-inferiority, parallel-group, comparative study was conducted at seven sites across India involving 416 healthy adults (aged ≥18-60 years) and children (aged ≥1 to <18 years). Healthy individuals who agreed to participate through a voluntary written informed consent form along with oral or written assent (for children aged 7-18 years) were included. No assent was required for those <7 years, as consent was given by the legally acceptable representatives (LAR). Participants were randomised 1:1 to receive two doses of either Euvichol-Plus or Shanchol orally, 14 days apart. The first dose (1.5 ml) was administered on visit 1, and the second dose at 2 weeks after the first dose during visit 2. Participants were followed up telephonically for 3 consecutive days after each visit and returned for final assessment at 2 weeks after the second dose (visit 3). Blood samples were collected for immunogenicity assessment, and safety analyses were done during all the visits. The primary immunogenicity endpoint was the percentage of participants with ≥4-fold increase in anti-Vibrio cholerae (V. cholerae) O1 Ogawa and O1 Inaba (vibriocidal) antibody titres at 2 weeks after the second dose as compared to baseline titres prior to dosing. The secondary immunogenicity endpoints included the percentage of participants with ≥4-fold increase in anti-V. cholerae O139 antibody titres at 2 weeks after the second dose as compared to baseline titres, and geometric mean titres (GMT) and geometric mean ratios (GMR) as measured by anti-V. cholerae O1 Ogawa, O1 Inaba, and O139 antibody titres at 2 weeks after the second dose as compared to baseline titres. The safety endpoints included assessment of solicited, unsolicited adverse events (AEs), and serious adverse events (SAEs). The clinical trial was registered with the Clinical Trials Registry of India (CTRI/2021/08/035344). Findings: The study was performed in two age cohorts: cohort 1 (aged ≥18-60 years, 208 participants [104 in Euvichol-Plus group and 104 in Shanchol group]), and cohort 2 (aged ≥1 to <18 years, 208 participants [104 in Euvichol-Plus group and 104 in Shanchol group]). A total of 414 participants (Euvichol-Plus: 206 and Shanchol: 208) who completed the study (intention-to-treat and per-protocol set) were analysed to compare the vibriocidal titre as an index for immunogenicity. At 2 weeks after the second dose, the percentage of participants in the Euvichol-Plus group who reported a ≥4-fold increase in anti-V. cholerae antibody titres were 68.93% (O1 Ogawa) [95% CI 62.13%-75.18%], 66.02% (O1 Inaba) [95% CI 59.11%-72.46%], and 59.71% (O139) [95% CI 52.67%-66.47%] as compared to 63.94% (O1 Ogawa) [95% CI 57.01%-70.47%], 65.87% (O1 Inaba) [95% CI 58.99%-72.28%], and 56.25% (O139) [95% CI 49.22%-63.10%] in the Shanchol group. The lower limit of 95% CI for treatment difference for all the antibody titres was ≥10% (non-inferiority margin), demonstrating that Euvichol-Plus was non-inferior to Shanchol. The post-vaccination GMT (Day 14 and 28) were more than the pre-vaccination GMT for all three serotypes in both groups. The GMR obtained for Euvichol-Plus over Shanchol for O1 Ogawa, O1 Inaba, and O139 serotypes was >1, indicating non-inferiority of Euvichol-Plus to Shanchol. The safety cohort included 416 participants. Headache was the most common solicited AE, whereas cold and cough were the most common unsolicited AEs in both groups. Interpretation: Euvichol-Plus appears to be non-inferior to Shanchol in terms of immunogenicity and safety in healthy Indian adults and children. Funding: Techinvention Lifecare Private Limited, Mumbai, India.

Immunogenicity and safety of Biological E's CORBEVAX™ vaccine compared to COVISHIELD™ (ChAdOx1 nCoV-19) vaccine studied in a phase-3, single blind, multicentre, randomized clinical trial.

Optimum formulation of Biological-E's protein subunit CORBEVAX™ vaccine was selected in phase-1 and -2 studies and found to be safe and immunogenic in healthy adult population. This is a phase-3 prospective, single-blinded, randomized, active controlled study conducted at 18 sites across India in 18-80 year-old subjects. This study has two groups; (i) immunogenicity-group, participants randomized either to CORBEVAX™ (n = 319) or COVISHIELD™ arms (n = 320). (ii) Safety-group containing single CORBEVAX™ arm (n = 1500) and randomization is not applicable. Healthy adults without a history of COVID-19 vaccination or SARS-CoV-2 infection were enrolled into immunogenicity arm and subjects seronegative to SARS-CoV-2 infection were enrolled into the safety arm. The safety profile of CORBEVAX™ vaccine was comparable to the comparator vaccine COVISHIELD™. Majority of reported AEs were mild in nature in both arms. The CORBEVAX™ to COVISHIELD™ GMT-ratios at day-42 time-point were 1·15 and 1·56 and the lower limit of the 95% confidence interval for the GMT-ratios was determined as 1·02 and 1·27 against Ancestral and Delta strains of SARS-COV-2 respectively. Both COVISHIELD™ and CORBEVAX™ vaccines showed comparable seroconversion post-vaccination against anti-RBD-IgG response. The subjects in CORBEVAX™ cohort also exhibited higher interferon-gamma secreting PBMC's post-stimulation with SARS-COV-2 RBD-peptides than subjects in COVISHIELD™ cohort.

Phase III Pivotal comparative clinical trial of intranasal (iNCOVACC) and intramuscular COVID 19 vaccine (Covaxin®).

One of the most preferable characteristics for a COVID-19 vaccine candidate is the ability to reduce transmission and infection of SARS-CoV-2, in addition to disease prevention. Unlike intramuscular vaccines, intranasal COVID-19 vaccines may offer this by generating mucosal immunity. In this open-label, randomised, multicentre, phase 3 clinical trial (CTRI/2022/02/40065; ClinicalTrials.gov: NCT05522335), healthy adults were randomised to receive two doses, 28 days apart, of either intranasal adenoviral vectored SARS-CoV-2 vaccine (BBV154) or licensed intramuscular vaccine, Covaxin®. Between April 16 and June 4, 2022, we enrolled 3160 subjects of whom, 2971 received 2 doses of BBV154 and 161 received Covaxin. On Day 42, 14 days after the second dose, BBV154 induced significant serum neutralization antibody titers against the ancestral (Wuhan) virus, which met the pre-defined superiority criterion for BBV154 over Covaxin®. Further, both vaccines showed cross protection against Omicron BA.5 variant. Salivary IgA titers were found to be higher in BBV154. In addition, extensive evaluation of T cell immunity revealed comparable responses in both cohorts due to prior infection. However, BBV154 showed significantly more ancestral specific IgA-secreting plasmablasts, post vaccination, whereas Covaxin recipients showed significant Omicron specific IgA-secreting plasmablasts only at day 42. Both vaccines were well tolerated. Overall reported solicited reactions were 6.9% and 25.5% and unsolicited reactions were 1.2% and 3.1% in BBV154 and Covaxin® participants respectively.

Awareness and Readiness To Implement the Pradhan Mantri Jan Arogya Yojana: A Cross-Sectional Study Among Healthcare Workers of a Tertiary Care Hospital in Eastern India.

Background The Indian government announced "Ayushman Bharat" for a New India 2022 during the 2018-19 parliament budget sessions, which includes the national health protection scheme presently known as "Pradhan Mantri Jan Arogya Yojana (PMJAY)" to facilitate access to secondary and tertiary healthcare services. This study aimed to see how well healthcare workers (HCWs) understood the PMJAY and how prepared they were to administer it. Materials and methods With an anticipated sample size of 411, this hospital-based analytical, cross-sectional study was done among treating faculty, resident doctors, and nursing officers as study participants. Participants completed a self-administered, pre-tested, semi-structured questionnaire to determine their level of awareness and readiness to adopt PMJAY. SPSS Version 22 software (SPSS Inc., Chicago, IL, USA) was used to analyze the data. Results The overall mean (SD) awareness score and mean readiness score among HCWs were found to be 5.52 (1.82) and 18.49 (4.5), respectively. There was a significantly high awareness score among doctors compared to nursing officers. The relation between awareness score and readiness score showed a weak positive significant correlation (r=0.174, p=0.001). The linear regression model demonstrated an increase of 0.432 units in readiness for every unit increase in awareness score. Conclusion The doctor's mean awareness score was little over half of the maximum attainable score. Faculty members were more aware of the scheme than the residents and nursing officers. The readiness to implement PMJAY improves as the awareness grows. Frequent workshops on PMJAY for stakeholders are required for better readiness.

An Epidemiological Investigation to evaluate the link between hypovitaminosis D and COVID-19.

Background: The COVID-19 pandemic has become a global threat, with an inexplicable course of action and suboptimal response to the multitudes of therapies being tried. Vitamin D's pleiotropic effects (immunomodulatory, anti-inflammatory, and antiviral) have lately received considerable attention in the scientific community, and it has been shown to be helpful in the defense against viral respiratory infections. Aim: To find out the association between vitamin D and COVID-19. Methods: Overall, 360 (156 COVID-19 +ve and 204 COVID-19 -ve) subjects were investigated in this hospital-based case-control study. The study participants were taken from the COVID-19 wards and Flu clinic of a dedicated COVID hospital between August 1 and September 15, 2020. The demographics and clinical data including alcohol and smoking history along with serum vitamin D levels were recorded. Binary logistic regression analysis was performed to assess the association between age, gender, alcohol intake, smoking history, vitamin D status, and COVID-19. Results: There was no significant difference in the mean vitamin D levels between cases and controls. Bivariate analysis of predictors and COVID-19 revealed that predictors such as advanced age, BMI, alcohol intake, smoking habit, diabetes, hypertension, and vitamin D deficiency were significantly associated with COVID-19. Conclusions: This study showed that serum vitamin D status might be able to reduce the impact of COVID-19, although more studies are required to establish clear causality.

Evaluation of safety and immunogenicity of receptor-binding domain-based COVID-19 vaccine (Corbevax) to select the optimum formulation in open-label, multicentre, and randomised phase-1/2 and phase-2 clinical trials.

BACKGROUND: We assessed the efficacy of a receptor-binding domain (RBD)-based protein subunit COVID-19 vaccine. METHODS: A randomised Phase-1/2 trial followed by a Phase-2 trial were conducted to assess the safety and immunogenicity of the COVID-19 vaccine Corbevax and select to an optimum formulation. Healthy adults (n=460) without COVID-19 vaccination or SARS-CoV-2 infection in the Phase-1/2 study were randomly divided into four vaccine formulation groups. FINDINGS: A low incidence of adverse events was reported post-vaccination. All formulations showed similar profiles of humoral and cellular immune responses that were associated with the content of CpG1018 adjuvant in the vaccine. In the Phase-2 study, 750 µg of CpG1018 showed significant improvement (> 4-fold increase from baseline) in immune responses, including the titres of anti-RBD IgG and neutralising antibody (nAb), and cellular immune responses, while maintaining the safety profile. Antibodies persisted consistently for 12 months after the second dose of vaccine. INTERPRETATIONS: Corbevax (two-dose schedule with 28 days of interval between doses) was well tolerated with no observed safety concerns. Previous observations from efficacy studies by Moderna and AstraZeneca and the correlation between nAb titres post-vaccination and a human convalescent serum panel showed that Corbevax induced significantly high nAb titres. These studies were prospectively registered with the Clinical Trial Registry of India (CTRI/2021/06/034014 and CTRI/2020/11/029032). FUNDING: Bill & Melinda Gates Foundation, BIRAC-Division of Department of Biotechnology, Govt of India, and the Coalition for Epidemic Preparedness Innovations funded this study.

Immunogenicity and reactogenicity of an inactivated SARS-CoV-2 vaccine (BBV152) in children aged 2-18 years: interim data from an open-label, non-randomised, age de-escalation phase 2/3 study.

BACKGROUND: Despite having milder symptoms than adults, children are still susceptible to and can transmit SARS-CoV-2. Vaccination across all age groups is therefore necessary to curtail the pandemic. Among the available COVID-19 vaccine platforms, an inactivated vaccine platform has the advantage of excellent safety profile across all age groups; hence, we conducted an age de-escalation study to assess the safety, reactogenicity, and immunogenicity of an inactivated COVID-19 vaccine, BBV152 (COVAXIN; Bharat Biotech International, Hyderabad, India), in children aged 2-18 years. METHODS: In this phase 2/3 open-label, non-randomised, multicentre study done in six hospitals in India, healthy children (male or female) aged 2-18 years were eligible for inclusion into the study. Children who had positive SARS-CoV-2 nucleic acid and serology tests at baseline, or any history of previous SARS-CoV-2 infection, or with known immunosuppressive condition were excluded. Children were sequentially enrolled into one of three groups (>12 to ≤18 years [group 1], >6 to 12 years [group 2], or ≥2 to 6 years [group 3]) and administered with adult formulation of BBV152 as two 0·5 mL intramuscular doses on days 0 and 28. Co-primary endpoints were solicited adverse events for 7 days post-vaccination and neutralising antibody titres on day 56, 28 days after the second dose. Immunogenicity endpoints were compared with Biodefense and Emerging Infections, Research Resources Repository (BEI) reference serum samples and from adults who received two doses of BBV152 in the same schedule in a previously reported phase 2 study. The trial is registered with the Clinical Trials Registry, India (CTRI/2021/05/033752) and ClinicalTrials.gov (NCT04918797). FINDINGS: From May 27, 2021, to July 10, 2021, we enrolled 526 children sequentially into groups 1 (n=176), 2 (n=175), and 3 (n=175). Vaccination was well tolerated, with no differences in reactogenicity between the three age groups, and no serious adverse events, deaths, or withdrawals due to an adverse event. Local reactions mainly consisted of mild injection site pain in 46 (26%) of 176 participants in group 1, 61 (35%) of 175 in group 2, and 39 (22%) of 175 in group 3 after dose 1; and 39 (22%) of 176 in group 1, 43 of 175 (25%) in group 2, and 14 of 175 (8%) in group 3 after dose 2; there were no cases of severe pain and few reports of other local reactions. After dose 1, the most frequent solicited systemic adverse event was mild-to-moderate fever, reported in eight (5%) of 176 participants in group 1, 17 (10%) of 175 in group 2, and 22 (13%) of 175 in group 3. No case of severe fever was reported, and rates of all fever were all 4% or less after dose 2. Geometric mean titres (GMTs) of microneutralisation antibodies at day 56 in groups 1 (138·8 [95% CI 111·0-173·6]), 2 (137·4 [99·1-167·5]), and 3 (197·6 [176·4-221·4]) were similar to titres in vaccinated adults (160·1 [135·8-188·8]) and with BEI reference serum samples (103·3 [50·3-202·1]). Similar results were obtained using the plaque reduction neutralisation test (PRNT), in which 166 (95%) of 175 participants in group 1, 165 (98%) of 168 in group 2, and 169 (98%) of 172 in group 3 seroconverted at day 56. The GMT ratio of PRNT titres in children and adults was 1·76 (95% CI 1·32-2·33), indicating a superior response in children compared with adults. INTERPRETATION: BBV152 was well tolerated in children aged 2-18 years, and induced higher neutralising antibody responses than those observed in adults, in whom the efficacy (ie, the prevention or decrease in the severity of COVID-19 infection) has been demonstrated. FUNDING: Bharat Biotech International.

Persistence of immunity and impact of third dose of inactivated COVID-19 vaccine against emerging variants.

This is a comprehensive report on immunogenicity of COVAXIN® booster dose against ancestral and Variants of Concern (VOCs) up to 12 months. It is well known that neutralizing antibodies induced by COVID-19 vaccines wane within 6 months of vaccination leading to questions on the effectiveness of two-dose vaccination against breakthrough infections. Therefore, we assessed the persistence of immunogenicity up to 6 months after a two or three-dose with BBV152 and the safety of a booster dose in an ongoing phase 2, double-blind, randomized controlled trial (ClinicalTrials.gov: NCT04471519). We report persistence of humoral and cell mediated immunity up to 12 months of vaccination, despite decline in the magnitude of antibody titers. Administration of a third dose of BBV152 increased neutralization titers against both homologous (D614G) and heterologous strains (Alpha, Beta, Delta, Delta Plus and Omicron) with a slight increase in B cell memory responses. Thus, seronversion rate remain high in boosted recipients compared to non-booster, even after 6 months, post third dose against variants. No serious adverse events observed, except pain at the injection site, itching and redness. Hence, these results indicate that a booster dose of BBV152 is safe and necessary to ensure persistent immunity to minimize breakthrough infections of COVID-19, due to newly emerging variants.Trial registration: Registered with the Clinical Trials Registry (India) No. CTRI/2021/04/032942, dated 19/04/2021 and on Clinicaltrials.gov: NCT04471519.

Pattern of Tobacco Use and Perceived Risk of COVID-19 Following Tobacco Use among the COVID-19 Patients of a Tertiary Health Care Institution in Eastern India.

BACKGROUND: COVID-19 presented an unprecedented situation in which behavioural factors including tobacco use were believed to increase the risk of morbidity and mortality. The objective of the present study was to find the tobacco use pattern among the COVID-19 patients and the perceived risk of developing severe COVID-19 following tobacco use. METHODS: This hospital-based, cross-sectional, analytical study was conducted among 300 COVID-19 patients at the All India Institute of Medical Sciences (AIIMS), Patna, India, during November and December 2020 using a semi-structured, pretested questionnaire. Descriptive and univariate analyses were performed using statistical software and the results were presented as proportion and percentage. FINDINGS: About 27% and 16% of the COVID-19 patients were ever and current tobacco users, respectively. Quit attempts were found to have increased during the COVID-19 pandemic. A majority (65%) of current tobacco users had reduced their amount of tobacco use. Nearly 2 in every 3 patients perceived high risk of developing severe COVID-19 following tobacco use. Perceived risk was significantly higher among tobacco non-users, patients who were aware of the ill health effects of tobacco use, and patients who had noticed anti-tobacco messages or had been advised to quit tobacco. Among the current tobacco users, a significantly higher proportion of patients who perceived high risk of developing severe COVID-19 following tobacco use had made quit attempts or had reduced tobacco consumption during the pandemic (76.7% vs. 40%; P = 0.032). CONCLUSION: A high proportion of COVID-19 patients believed that tobacco use aggravated the COVID-19 condition. Increased quit attempts and reduction in tobacco consumption during this pandemic is a positive sign for tobacco control.

Tobacco use pattern and quitting behaviour among healthcare professionals during the COVID-19 pandemic: Insights from a pan India online survey.

BACKGROUND: Healthcare professionals (HCPs) have a definite role in tobacco control and can help immensely by setting examples. The current study aimed to study the tobacco use pattern and quitting behaviour among HCPs of India during the COVID-19 pandemic. METHODS: We addressed the research objective using a cross-sectional, anonymous online survey using 'google form" among 687 HCPs of India during December 2020. Descriptive and inferential statistics were performed using SPSS. RESULTS: Overall, 32.6% of the HCPs were ever tobacco user while 23.4% and 16.9% were current and daily tobacco user. During the COVID-19 pandemic, 51.7% and 43.1% of HCPs cut down the frequency and amount of tobacco use respectively while for 24.1% COVID-19 pandemic exerted no effect on their tobacco use. Presence of vulnerable population at home [ adjusted odds ratio (AOR): 17.5 (95% confidence interval (CI): 3.3-92.2)], ever tobacco quit attempt [AOR: 13.5 (95% CI:2.7-67.7)] and history of COVID-19 disease [AOR: 5.1 (95% CI:1.3-20.7)] significantly determined reduced tobacco use (60.3%) during the pandemic. Similarly, reduced tobacco use during the pandemic [AOR: 4.8 (95% CI:1.7-13.5)] and perception of both smoking and smokeless tobacco form to be harmful for COVID-19 [AOR: 4.8 (95% CI:1.7-13.5)] were the independent correlates of tobacco quit attempt (50.0%) during the pandemic. CONCLUSION: Tobacco use was quite rampant among the HCPs with every fourth and sixth being a current and daily tobacco user respectively. During the COVID-19 pandemic three in every five HCPs surveyed reduced tobacco use while every second HCP made a quit attempt.