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.

Analysis of predictors and outcomes of COVID-19 patients requiring ICU admission from COVID 19 (preprint)

BackgroundSevere Corona virus disease (COVID-19) is associated with high mortality. Although single centre intensive care units (ICU) have reported clinical characteristics and outcomes, no large scale multicentric study from India has been published. The present retrospective, multi-centre study was aimed to describe the predictors and outcomes of COVID-19 patients requiring ICU admission from COVID-19 Registry of Indian council of Medical Research (ICMR), India.MethodsProspectively collected data from multiple participating institutions was entered in the electronic National Clinical Registry of COVID 19. We enrolled patients aged>18 years with COVID-19 pneumonia requiring ICU admission between March 2020 and August 2021. Exclusion criteria were negative RT PCR, death within 24 hours of ICU admission, or patients with incomplete data in the registry Their demographic characteristics, laboratory variables, ICU severity indices, treatment strategies and outcomes were analysed.ResultsA total of 5865 patients, with mean age 56±15 years, with 3840/5865 (65.4%) men, were enrolled in the ICMR registry.. Overall mortality was 2535/5865 (43.5%). Non-survivors were older than survivors (58.2±15.4 years vs 53.6 ±14.7 years; P=0.001). Non-survivors had multiple comorbidities (n=1951, 52.9%) with hypertension (47.2%) and diabetes (45.6%) being the most common, higher creatinine (1.6 ± P=0.001, high D-dimer (1.56 vs 1.37, P=0.001), higher CT severity index (16.8±5.2 vs 13.5 ±5.47 ) compared to  survivors. Non survivors had longer hospital and ICU stay (P=0.001). On multivariate regression analysis, high NLR (HR 1.017, 95% CI 1.005- 1.029, P=0.001), high CRP (HR 1.008, 95% CI 1.006- 1.010, P=0.001), high D dimer ((HR 1.089, 95% CI 1.065- 1.113, P=0.001) were associated with mechanical ventilation while younger age, (HR 0.974, CI 0.965-0.983, p=0.001), high D dimer (HR-1.014, CI 1.001-1.027, P=0.035) and use of prophylactic LMWH (HR 0.647, CI 0.527-0.794, p=0.001) were independently associated with mortality. ConclusionIn this large retrospective study of 5865 critically ill COVID 19 patients admitted to ICU, overall mortality was 2535/5865 (43.5%). Age, high D dimer, CT Severity score and use of prophylactic LMWH were independently associated with mortality. 

BCG vaccination induces enhanced frequencies of memory T and B cells and dendritic cell subsets in elderly individuals (preprint)

Background BCG vaccination is known to induce innate immune memory, which confers protection against heterologous infections. However, the effect of BCG vaccination on the conventional innate and adaptive immune cells subsets is not well characterized. Methods We investigated the impact of BCG vaccination on the frequencies of T cell, B cell, monocyte and dendritic cell subsets as well as total antibody levels in a group of healthy elderly individuals (age 60-80 years) at one month post vaccination as part of our clinical study to examine the effect of BCG on COVID-19. Results Our results demonstrate that BCG vaccination induced enhanced frequencies of central and effector memory CD4+ T cells and diminished frequencies of naïve, transitional memory, stem cell memory CD4+ T cells and regulatory T cells. In addition, BCG vaccination induced enhanced frequencies of central, effector and terminal effector memory CD8+ T cells and diminished frequencies of naïve, transitional memory and stem cell memory CD8+T cells. BCG vaccination also induced enhanced frequencies of immature, classical and activated memory B cells and plasma cells and diminished frequencies of naïve and atypical memory B cells. While BCG vaccination did not induce significant alterations in monocytes subsets, it induced increased frequencies of myeloid and plasmacytoid DCs. Finally, BCG vaccination resulted in elevated levels of all antibody isotypes. Conclusions BCG vaccination was associated with enhanced innate and adaptive memory cell subsets, as well as total antibody levels in elderly individuals, suggesting its potential utility in SARS-Cov2 infection by enhancing heterologous immunity.