A randomized, controlled study to evaluate the safety and immunogenicity of a heterologous booster dose of an adjuvanted SARS CoV-2 recombinant spike protein vaccine in adults (preprint)

Background Due to waning immunity following primary immunization with Covid-19 vaccines, booster doses may be required. The present study assessed a heterologous booster of SII-NVX-CoV2373 (spike protein vaccine) in adults primed with viral vector and inactivated vaccines.Methods In this Phase 3, observer-blind, randomized, active controlled study, a total of 372 adults primed with ChAdOx1 nCoV-19 (n = 186) or BBV152 (n = 186) at least six months ago, were randomized to receive a booster of SII-NVX-CoV2373 or control vaccine. The control group received homologous booster of ChAdOx1 nCoV-19 or BBV152 depending upon the prime cohort. Anti-S IgG and neutralizing antibodies were assessed at baseline (day 1), day 29, day 91 and day 181 for immunogenicity assessments. Solicited reactions were collected for one week after vaccination. Unsolicited adverse events (AEs) were collected for 28 days while serious adverse events (SAE) and adverse events of special interest (AESI) were reported throughout the six-month study duration. (Identifier: CTRI/2022/04/042017)Results In both the ChAdOx1 nCoV-19 primed group and BBV152 primed group, 186 participants each received the study vaccines. In the ChAdOx1 nCoV-19 Prime cohort, at 28 days after the booster dose, there was a 3.9- to 5.1-fold-rise and 1.9- to 2.8-fold-rise in anti-S IgG and neutralizing antibody titres from the baseline in the SII-NVX-CoV2373 group and the ChAdOx1 nCoV-19 group, respectively. The same responses for the BBV152 prime cohort was 7.4- to 10.4-fold-rise and 1.5- to 2.5-fold-rise in the SII-NVX-CoV2373 group and the BBV152 group, respectively. There was 86.96% (95% CI 78.32, 93.07) to 94.57% (95% CI 87.77, 98.21) and 37.63% (95% CI 27.79, 48.28) to 79.57% (95% CI 69.95, 87.23) anti-S IgG and neutralizing antibody seroresponse (2-fold-rise from baseline) in the SII-NVX-CoV2373 group and ChAdOx1 nCoV-19 group, respectively. The same was 94.51% (95% CI 87.64, 98.19) to 98.90% (95% CI 94.03, 99.97) and 20.43% (95% CI 12.77, 30.05) to 74.19% (95% CI 64.08, 82.71) in the SII-NVX-CoV2373 group and BBV152 group, respectively. No SAE or AESI was caused by the study vaccines.Conclusion SII-NVX-CoV2373 showed a numerically higher boosting effect than homologous boosters in adults primed with ChAdOx1 nCoV-19 and BBV152. The vaccine was also safe and well tolerated.

A Phase 2/3 observer-blind, randomized, controlled study to determine the safety and immunogenicity of SARS-CoV-2 recombinant spike protein vaccine in Indian children and adolescents aged 2 to 17 years (preprint)

Background: A recombinant, adjuvanted COVID-19 vaccine, SII-NVX-CoV2373 was manufactured in India and evaluated in Indian children and adolescents to assess safety and immunogenicity. Methods: This was a Phase 2/3 observer-blind, randomized, controlled study in children and adolescents aged 2 to 17 years. Participants were randomly assigned in 3:1 ratio to receive two doses of SII-NVX-CoV2373 or placebo on day 1 and day 22. Solicited adverse events (AEs) were collected for 7 days after each vaccination. Unsolicited AEs were collected for 35 days following first dose and serious AEs (SAEs) and adverse events of special interest (AESI) were collected throughout the study. Anti S IgG and neutralizing antibodies against the SARS-CoV-2 were measured at baseline, day 22, day 36 and day 180. Variant immune responses were assessed in a subset of participants at baseline, day 36 and day 180. Primary objectives were to demonstrate non-inferiority of SII-NVX-CoV2373 in each pediatric age group (12 to 17 years and 2 to 11 years, separately) to that in adults in terms of ratio of titers of both anti-S IgG and neutralizing antibodies 14 days after the second dose (day 36). Non-inferiority was to be concluded if the lower bound of 95% CI of the ratio was >0.67. Results: A total of 920 children and adolescents (460 in each age cohort; 12 to 17 years and 2 to 11 years) were randomized and vaccinated. The demographic and baseline characteristics between the two groups were comparable in both age groups. After the second dose, there were more than 100-fold rise in anti-S IgG GMEUs and more than 84-fold rise in neutralizing antibodies GMTs from baseline in the participants who received SII-NVX-CoV2373. The GMTs in both age groups were non-inferior to those observed in Indian adults. The seroconversion rate was [≥] 98% (anti-S IgG) and [≥] 97.9% (neutralizing antibodies) in both age groups, respectively. Similar findings were seen in the baseline seronegative participants. SII-NVX-CoV2373 also showed robust responses against various variants of concern. Injection site pain, tenderness, swelling, erythema and fever, headache, malaise, fatigue, myalgia, arthralgia, nausea and vomiting were the common solicited adverse events which were transient and resolved without any sequelae. Throughout the study, only two causally unrelated SAEs and no AESI were reported. Conclusion: SII-NVX-CoV2373 has been found safe and well tolerated in children and adolescents of 2 to 17 years. The vaccine was highly immunogenic and the immune response was non-inferior to that in adults.

A comparative analysis of COVID-19 mortality rate across the globe: an extensive analysis of the associated factors

Background: The vast variation in COVID 19 mortality across the globe draws attention to potential risk factors other than the patient characteristics that determine COVID-19 mortality, this study aimed to analyze and apply evidence-based explanation for the impact offactors associated with COVID-19-related mortality. Subjects dan Method: This was a cross sectional study of global database for wide set of factors associated with COVID-19 mortality, ranging from disease related co-morbidities, socioeconomic factors, healthcare capacity and government policy and interventions. Data for population, total cases, total COVID mortality, tests done, and GDP per capita were extracted from the worldometers database. Datasets for health expenditure by government, hospital beds, rural population, prevalence of smoking, prevalence of overweight population, deaths due to communicable disease and incidence of malaria were extracted from the World Bank website. Prevalence of diabetes was retrieved from the indexmundi rankings. The average population age, 60+ population, delay in lockdown, population density and BCG data were also included for analysis. The COVID-19 mortality per million and its associated factors were retrieved for 56 countries across the globe. Quantitative analysis was done at the global as well as continent level. All the countries included in the study were categorized continent and region wise for comparative analysis determining the correlation between COVID 19 mortality and the aforementioned factors.

A comparative analysis of COVID-19 mortality rate across the globe: An extensive analysis of the associated factors (preprint)

BackgroundThe vast variation in COVID 19 mortality across the globe draws attention to potential risk factors other than the patient characteristics that determine COVID-19 mortality. Subjects and MethodsWe have quantified and analyzed one of the broadest set of clinical factors associated with COVID-19-related death, ranging from disease related co-morbities, socioeconomic factors, healthcare capacity and government policy and interventions. Data for population, total cases, total COVID mortality, tests done, and GDP per capita were extracted from the worldometers database. Datasets for health expenditure by government, hospital beds, rural population, prevalence of smoking, prevalence of overweight population, deaths due to communicable disease and incidence of malaria were extracted from the World Bank website. Prevalence of diabetes was retrieved from the indexmundi rankings. The average population age, 60+ population, delay in lockdown, population density and BCG data were also included for analysis. The COVID-19 mortality per million and its associated factors were retrieved for 56 countries across the globe. Quantitative analysis was done at the global as well as continent level. All the countries included in the study were categorized continent and region wise for comparative analysis determining the correlation between COVID 19 mortality and the aforementioned factors. ResultsThere was significant association found between mortality per million and 60+ population of country, average age, prevalence of diabetes mellitus, and case fatality rate with correlation and p value (p) of 0.422 (p 0.009), 0.386 (p 0.0186), -0.384 (p 0.019) and 0.753 (p 0.000) respectively at 95% CI. ConclusionThe study observations will serve as a evidence based management strategy for generating predictive model for COVID-19 infection and mortality rate.

Molecular Analyses of Over Hundred Sixty Clinical Isolates of SARS-CoV-2: Insights on Likely Origin, Evolution and Spread, and Possible Intervention (preprint)

We are witnessing the severe third outbreak mediated by coronaviruses affecting global public health with unprecedented economic consequences. A better understanding of its phylogenetics, exploration of sequence features and mutational changes could unveil its genealogy to gain insights into the mechanism of transmission and development of possible interventions. Our comparative genomic analyses of >160 isolates of SARS-CoV-2 reveal phylogenetic kinship with other coronaviruses and emergence of evolutionary divergence in clinical isolates. t-SNE-based clustering revealed different clades but no continent specific clusters. Amino acid substitutions at RBD of spike protein provide possible reasons for rapid transmission. Few proteins specific to SARS-CoV-2 were identified which could have implications as therapeutic targets and diagnostic biomarkers. Virtual screening identified repurposed drugs, known nutraceuticals, for specific interventions. These phylogenetic observations reveal the ancestry and computational studies reveal the emergency measures to interject this emerging pathogen that pose threat to whole of mankind.