Immunogenicity of SARS-CoV-2 vaccines BBV152 (COVAXIN®) and ChAdOx1 nCoV-19 (COVISHIELD™) in seronegative and seropositive individuals in India: a multicentre, nonrandomised observational study.

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 age group 18-45 years began in April 2021 when seropositivity rates in the general population were rising due to the delta wave of COVID-19 pandemic during April-May 2021. Methods: Between June 30, 2021, and Jan 28, 2022, we enrolled 691 participants in the age group 18-45 years across four clinical sites in India. In this non-randomised and laboratory blinded study, participants received either two doses of Covaxin® (4 weeks apart) or two doses of Covishield™ (12 weeks apart) as per the national vaccination policy. The primary outcome was the seroconversion rate and the geometric mean titre (GMT) of antibodies against the SARS-CoV-2 spike and nucleocapsid proteins post two doses. 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® 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 binding antibody units/ml [BAU/ml], p < 0.0001 in seronegative individuals; 2089.07 vs 585.7 BAU/ml, p < 0.0001 in seropositive individuals). As participants at all clinical sites were not recruited at the same time, site-specific immunogenicity was impacted by the timing of vaccination relative to the delta and omicron waves. Surrogate neutralising antibody responses against variants-of-concern including delta and omicron was higher in Covishield™ recipients than in Covaxin® recipients; and in seropositive than in seronegative individuals after both vaccination and asymptomatic infection (omicron variant). 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® 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® in both seronegative individuals and seropositive individuals, across cohorts representing the pre-vaccination immune history of most of the vaccinated Indian population. Funding: Corporate social responsibility (CSR) funding from Hindustan Unilever Limited (HUL) and Unilever India Pvt. Ltd. (UIPL).

Genomic surveillance reveals early detection and transition of delta to omicron lineages of SARS-CoV-2 variants in wastewater treatment plants of Pune, India.

The COVID-19 pandemic has emphasized the urgency for rapid public health surveillance methods to detect and monitor the transmission of infectious diseases. The wastewater-based epidemiology (WBE) has emerged as a promising tool for proactive analysis and quantification of infectious pathogens within a population before clinical cases emerge. In the present study, we aimed to assess the trend and dynamics of SARS-CoV-2 variants using a longitudinal approach. Our objective included early detection and monitoring of these variants to enhance our understanding of their prevalence and potential impact. To achieve our goals, we conducted real-time quantitative polymerase chain reaction (RT-qPCR) and Illumina sequencing on 442 wastewater (WW) samples collected from 10 sewage treatment plants (STPs) in Pune city, India, spanning from November 2021 to April 2022. Our comprehensive analysis identified 426 distinct lineages representing 17 highly transmissible variants of SARS-CoV-2. Notably, fragments of Omicron variant were detected in WW samples prior to its first clinical detection in Botswana. Furthermore, we observed highly contagious sub-lineages of the Omicron variant, including BA.1 (~28%), BA.1.X (1.0-72%), BA.2 (1.0-18%), BA.2.X (1.0-97.4%) BA.2.12 (0.8-0.25%), BA.2.38 (0.8-1.0%), BA.2.75 (0.01-0.02%), BA.3 (0.09-6.3%), BA.4 (0.24-0.29%), and XBB (0.01-21.83%), with varying prevalence rates. Overall, the present study demonstrated the practicality of WBE in the early detection of SARS-CoV-2 variants, which could help track future outbreaks of SARS-CoV-2. Such approaches could be implicated in monitoring infectious agents before they appear in clinical cases.

A tale of two waves: Delineating diverse genomic and transmission landscapes driving the COVID-19 pandemic in Pune, India.

BACKGROUND: Modern response to pandemics, critical for effective public health measures, is shaped by the availability and integration of diverse epidemiological outbreak data. Tracking variants of concern (VOC) is integral to understanding the evolution of SARS-CoV-2 in space and time, both at the local level and global context. This potentially generates actionable information when integrated with epidemiological outbreak data. METHODS: A city-wide network of researchers, clinicians, and pathology diagnostic laboratories was formed for genome surveillance of COVID-19 in Pune, India. The genomic landscapes of 10,496 sequenced samples of SARS-CoV-2 driving peaks of infection in Pune between December-2020 to March-2022, were determined. As a modern response to the pandemic, a "band of five" outbreak data analytics approach was used. This integrated the genomic data (Band 1) of the virus through molecular phylogenetics with key outbreak data including sample collection dates and case numbers (Band 2), demographics like age and gender (Band 3-4), and geospatial mapping (Band 5). RESULTS: The transmission dynamics of VOCs in 10,496 sequenced samples identified B.1.617.2 (Delta) and BA(x) (Omicron formerly known as B.1.1.529) variants as drivers of the second and third peaks of infection in Pune. Spike Protein mutational profiling during pre and post-Omicron VOCs indicated differential rank ordering of high-frequency mutations in specific domains that increased the charge and binding properties of the protein. Time-resolved phylogenetic analysis of Omicron sub-lineages identified a highly divergent BA.1 from Pune in addition to recombinant X lineages, XZ, XQ, and XM. CONCLUSIONS: The band of five outbreak data analytics approach, which integrates five different types of data, highlights the importance of a strong surveillance system with high-quality meta-data for understanding the spatiotemporal evolution of the SARS-CoV-2 genome in Pune. These findings have important implications for pandemic preparedness and could be critical tools for understanding and responding to future outbreaks.

Cardiovascular disease and menopause.

AIM: The aim of the study was to study the abnormalities in the cardiovascular profile in postmenopausal Indian women and to compare the same with the cardiovascular profile of pre menopausal Indian women belonging to the same age group; taken as controls. The goal was to throw some light on the cardiovascular risk in postmenopausal women of the Indian population as this population is thought to be at higher risk than their western counterparts and significant studies of the same kind in this population have been few. MATERIALS AND METHODS: A cross-sectional comparative study on 100 women who were either postmenopausal or premenopausal and were between the age group of 40 to 55 years was carried out over a period of ten months at our hospital. The variations in the cardiovascular profile between both groups were studied. All the women were subjected to a detailed history, thorough examination, investigations and imaging studies. RESULTS: The evaluation revealed that Coronary Artery Disease (CAD), hypertension, abnormal Body Mass Index (BMI) and abnormal Waist Hip Ratio (WHR) were significantly higher in the postmenopausal group as compared to the premenopausal group. The post menopausal women had significantly higher prevalence of abnormal lipid profiles as compared to their premenopausal counterparts. The postmenopausal women with a normal lipid profile also had increased prevalence of CAD and SAHT, which emphasizes the non-lipid cardiovascular benefits of estrogen. CONCLUSION: Thus, we can conclude that cardiovascular disease was more common in postmenopausal women of age group 40-55 years as compared to those not yet achieved menopause in a population of western Indian women. And this risk was significantly associated with central obesity, an abnormal lipid profile and the postmenopausal state in itself.