ABSTRACT
Background There are limited global data on head-to-head comparisons of vaccine platforms assessing both humoral and cellular immune responses, stratified by pre-vaccination serostatus. The COVID-19 vaccination drive for the Indian population in the 18 to 45-year age-group began in April 2021 when seropositivity rates in the general population were rising due to the Delta wave in April-May 2021. Methods Between 30 June 2021 and 28 January 2022, we enrolled 691 participants in the 18-45 age group across 4 clinical sites in India. In this non-randomized and laboratory blinded study, participants received either two doses of Covaxin(R) 4 weeks apart or two doses of Covishield 12 weeks apart per the national vaccination policy. The primary outcome was the seroconversion rate and the geometric mean titer (GMT) of antibodies against the SARS-CoV-2 spike and nucleocapsid proteins. The secondary outcome was the frequency of cellular immune responses pre- and post-vaccination. Findings When compared to pre-vaccination baseline, both vaccines elicited statistically significant seroconversion and binding antibody levels in both seronegative and seropositive individuals. In the per-protocol cohort, Covishield elicited higher antibody responses than Covaxin(R) as measured by seroconversion rate (98.3% vs 74.4%, p<0.0001 in seronegative individuals; 91.7% vs 66.9%, p<0.0001 in seropositive individuals) as well as by anti-spike antibody levels against the ancestral strain (GMT 1272.1 vs 75.4 BAU/ml, p<0.0001 in seronegative individuals; 2089.07 vs 585.7 BAU/ml, p<0.0001 in seropositive individuals). Not all sites recruited at the same time, therefore site-specific immunogenicity was impacted by the timing of vaccination relative to the Delta and Omicron waves. Surrogate neutralizing antibody responses against variants-of-concern were higher in Covishield recipients than in Covaxin(R) recipients and in seropositive than in seronegative individuals after both vaccination and asymptomatic Omicron infection. T cell responses are reported from only one of the four site cohorts where the vaccination schedule preceded the Omicron wave. In seronegative individuals, Covishield elicited both CD4+ and CD8+ spike-specific cytokine-producing T cells whereas Covaxin(R) elicited mainly CD4+ spike-specific T cells. Neither vaccine showed significant post-vaccination expansion of spike-specific T cells in seropositive individuals. Interpretation Covishield elicited immune responses of higher magnitude and breadth than Covaxin(R) in both seronegative individuals and seropositive individuals, across cohorts representing the pre-vaccination immune history of the majority of the vaccinated Indian population.
Subject(s)
COVID-19ABSTRACT
The modern response to pandemics, critical for effective public health measures, is shaped by the availability and integration of diverse epidemiological outbreak data. Genomic surveillance has come to the forefront during the coronavirus disease 2019 (COVID-19) pandemic at both local and global scales to identify variants of concern. Tracking variants of concern (VOC) is integral to understanding the evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in space and time. Combining phylogenetics with epidemiological data like case incidence, spatial spread, and transmission dynamics generates actionable information. Here we discuss the genome surveillance done in Pune, India, through sequencing 10,496 samples from infected individuals and integrating them with multiple heterogeneous outbreak data. The rise and fall of VOCs along with shifting transmission dynamics in the time interval of December 2020 to March 2022 was identified. Population-based estimates of the proportion of circulating variants indicated the second and third peak of infection in Pune to be driven by VOCs Kappa (B.1.617.1), Delta (B.1.617.2), and Omicron (B.1.1.529) respectively. Integrating single nucleotide polymorphism changes across all sequenced genomes identified C (Cytosine) > T (Thymine) and G (Guanine) > T (Thymine) substitutions to dominate with higher rates of adaptive evolution in Spike (S), RNA-dependent RNA polymerase (RdRp), and Nucleocapsid (N) genes. Spike Protein mutational profiling during and pre-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 specific recombinant X lineages, XZ, XQ, and XM. BA.1 from Pune was found to be highly divergent by global sequence alignment and hierarchical clustering. Our ''band of five'' outbreak data analytics which includes the integration of five heterogeneous data types indicates that a strong surveillance system with comprehensive high-quality metadata was critical to understand the spatiotemporal evolution of the SARS-CoV-2 genome in Pune. We anticipate the use of such integrated workflows to be critical for pandemic preparedness in the future.
Subject(s)
Coronavirus Infections , COVID-19ABSTRACT
Background: The SARS-CoV-2 Delta variant (B.1.617.2) was first detected in India in late 2020 and soon became the predominant lineage owing to its high transmissibility. Over time, the virus has acquired mutations and has evolved into many new sub-lineages. AY.4 is one such sub-lineage that grew in frequency globally. Therefore, we aimed to compare the severity of infection due to Delta sub-lineages to Delta infections in Pune, Maharashtra, India. Material and Methods: Whole-genome sequencing and analysis of 255 SARS-CoV-2 positive samples, collected between 1st August to 1st September 2021, by BJ Government Medical College, Pune, was carried out at the Indian Institute of Science Education and Research (IISER), Pune and the Council of Scientific and Industrial Research-Institute of Genomics and Integrative Biology (CSIR-IGIB), New Delhi. Individual-level data on these patients were collected from ICMR COVID-19 Data Portal. Additional information regarding the presence of any symptoms, comorbidities, hospitalization, international travel history within 14 days and vaccination status was collected by telephonic interview with each patient by the BJGMC Sequencing Team.
ABSTRACT
With more than 140 million people infected globally and 3 million deaths, the COVID 19 pandemic has left a lasting impact. A modern response to a pandemic of such proportions needs to focus on exploiting all available data to inform the response in real-time and allow evidence-based decision-making. The intermittent lockdowns in the last 13 months have created economic adversity to prevent anticipated large-scale mortality and relax the lockdowns have been an attempt at recovering and balancing economic needs and public health realities. This article is a comprehensive case study of the outbreak in the city limits of Pune, Maharashtra, India, to understand the evolution of the disease and transmission dynamics starting from the first case on March 9, 2020. A unique collaborative effort between the Pune Municipal Corporation (PMC), a government entity, and the Pune knowledge Cluster (PKC) allowed us to layout a context for outbreak response and intervention. We report here how access to granular data for a metropolitan city with pockets of very high-density populations will help analyze, in real-time, the dynamics of the pandemic and forecasts for better management and control of SARS-CoV-2. Outbreak data analytics resulted in a real-time data visualization dashboard for accurate information dissemination for public access on the epidemic's progress. As government agencies craft testing and vaccination policies and implement intervention strategies to mitigate a second wave, our case study underscores the criticality of data quality and analytics to decode community transmission of COVID-19.