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.

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.

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.

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.

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.

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.

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.

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.

CAR T cell therapy: newer approaches to counter resistance and cost.

The genetically engineered Chimeric Antigen Receptor bearing T-cell (CAR T cell) therapy has been emerged as the new paradigm of cancer immunotherapy. However, recent studies have reported an increase in the number of relapsed haematological malignancies. This review provides newer insights into how the efficacy of CAR T cells might be increased by the application of new genome editing technologies, monitoring the complexity of tumor types and T cells sub-types. Next, tumor mutation burden along with tumormicroenvironment and epigenetic mechanisms of CAR T cell as well as tumor cell may play a vital role to tackle the cancer resistance mechanisms. These studies highlight the need to consider traditional cancer therapy in conjunction with CAR T cell therapy for relapsed or cases unresponsive to treatment. Of note, this therapy is highly expensive and requires multi-skill for successful implementation, which results in reduction of its accessibility/affordability to the patients. Here, we also propose a model for cost minimization of CAR T cell therapy by a collaboration of academia, hospitals and industry.