RESUMEN
Background: NVX-CoV2373, a Covid-19 vaccine was developed in the USA with â¼90% efficacy. The same vaccine is manufactured in India after technology transfer (called as SII-NVX-CoV2373), was evaluated in this phase 2/3 immuno-bridging study. Methods: This was an observer-blind, randomised, phase 2/3 study in 1600 adults. In phase 2, 200 participants were randomized 3:1 to SII-NVX-CoV2373 or placebo. In phase 3, 1400 participants were randomized 3:1 to SII-NVX-CoV2373 or NVX-CoV2373 (940 safety cohort and 460 immunogenicity cohort). Two doses of study products (SII-NVX-CoV2373, NVX-CoV2373 or placebo) were given 3 weeks apart. Primary objectives were to demonstrate non-inferiority of SII-NVX-CoV2373 to NVX-CoV2373 in terms of geometric mean ELISA units (GMEU) ratio of anti-S IgG antibodies 14 days after the second dose (day 36) and to determine the incidence of causally related serious adverse events (SAEs) through 180 days after the first dose. Anti-S IgG response was assessed using an Enzyme-Linked Immunosorbent Assay (ELISA) and neutralizing antibodies (nAb) were assessed by a microneutralization assay using wild type SARS CoV-2 in participants from the immunogenicity cohort at baseline, day 22, day 36 and day 180. Cell mediated immune (CMI) response was assessed in a subset of 28 participants from immunogenicity cohort by ELISpot assay at baseline, day 36 and day 180. The total follow-up was for 6 months. Trial registration: CTRI/2021/02/031554. Findings: Total 1596 participants (200 in Phase 2 and 1396 in Phase 3) received the first dose. SII-NVX-CoV2373 was found non-inferior to NVX-CoV2373 (anti-S IgG antibodies GMEU ratio 0.91; 95% CI: 0.79, 1.06). At day 36, there was more than 58-fold rise in anti-S IgG and nAb titers compared to baseline in both the groups. On day 180 visit, these antibody titers declined to levels slightly lower than those after the first dose (13-22 fold-rise above baseline). Incidence of unsolicited and solicited AEs was similar between the SII-NVX-CoV2373 and NVX-CoV2373 groups. No adverse event of special interest (AESI) was reported. No causally related SAE was reported. Interpretation: SII-NVX-CoV2373 induced a non-inferior immune response compared to NVX-CoV2373 and has acceptable safety profile. Funding: SIIPL, Indian Council of Medical Research, Novavax.
RESUMEN
BACKGROUND: In the ongoing COVID-19 pandemic, an increased incidence of ROCM was noted in India among those infected with COVID. We determined risk factors for rhino-orbito-cerebral mucormycosis (ROCM) post Coronavirus disease 2019 (COVID-19) among those never and ever hospitalized for COVID-19 separately through a multicentric, hospital-based, unmatched case-control study across India. METHODS: We defined cases and controls as those with and without post-COVID ROCM, respectively. We compared their socio-demographics, co-morbidities, steroid use, glycaemic status, and practices. We calculated crude and adjusted odds ratio (AOR) with 95% confidence intervals (CI) through logistic regression. The covariates with a p-value for crude OR of less than 0·20 were considered for the regression model. RESULTS: Among hospitalised, we recruited 267 cases and 256 controls and 116 cases and 231 controls among never hospitalised. Risk factors (AOR; 95% CI) for post-COVID ROCM among the hospitalised were age 45-59 years (2·1; 1·4 to 3·1), having diabetes mellitus (4·9; 3·4 to 7·1), elevated plasma glucose (6·4; 2·4 to 17·2), steroid use (3·2; 2 to 5·2) and frequent nasal washing (4·8; 1·4 to 17). Among those never hospitalised, age ≥ 60 years (6·6; 3·3 to 13·3), having diabetes mellitus (6·7; 3·8 to 11·6), elevated plasma glucose (13·7; 2·2 to 84), steroid use (9·8; 5·8 to 16·6), and cloth facemask use (2·6; 1·5 to 4·5) were associated with increased risk of post-COVID ROCM. CONCLUSIONS: Hyperglycemia, irrespective of having diabetes mellitus and steroid use, was associated with an increased risk of ROCM independent of COVID-19 hospitalisation. Rational steroid usage and glucose monitoring may reduce the risk of post-COVID.