ABSTRACT
Background Booster vaccines providing protection against emergent SARS-CoV-2 variants are needed. In an international phase 3 study, we evaluated booster vaccines containing prototype (D614) and/or Beta (B.1.351) variant recombinant spike proteins and AS03 adjuvant (CoV2 preS dTM-AS03). Methods Adults, primed 4-10 months earlier with mRNA (BNT162b2, mRNA-1273]), adenovirus-vectored (Ad26.CoV2.S, ChAdOx1nCoV-19) or adjuvanted protein (CoV2 preS dTM-AS03 [D614]) vaccines and stratified by age (18-55 and [≥]56 years), were boosted with monovalent (MV) D614 (5[≥]g, n=1285), MV (B.1351) (5g, n=707) or bivalent (BiV) (2.5[≥]g D614 plus 2.5[≥]g B.1.351, n=625) CoV2 preS dTM-AS03. SARS-CoV-2-naive adults (controls, n=479) received a primary series (two injections, 21 days apart) of CoV2 preS dTM-AS03 containing 10g D614. Antibodies to D614G, B.1.351 and Omicron BA.2 and BA.1 variants were evaluated using validated pseudovirus (lentivirus) neutralization (PsVN) assay. D614G or B.1.351 PsVN titers 14 days (D15) post-booster were compared with pre-booster (D1) titers in BNT162b2-primed participants (18-55 years old) and controls (D36), for each booster formulation (co-primary objectives). Safety was evaluated throughout the trial. Results of a planned interim analysis are presented. Results Among BNT162b2-primed adults (18-55 years old), PsVN titers against D614G or B.1.351 were significantly higher post-booster than anti-D614G titers post-primary vaccination in controls, for all booster formulations, with an anti-D614G GMT ratio (98.3% CI) of 2.16 (1.69; 2.75) for MV(D614), an anti-B.1.351 ratio of 1.96 (1.54; 2.50) for MV (B.1.351) and anti-D614G and anti-B.1.351 ratios of 2.34 (1.84; 2.96) and 1.39 (1.09; 1.77), respectively, for BiV. All booster formulations elicited cross-neutralizing antibodies against Omicron BA.2 across vaccine priming subgroups and against Omicron BA.1 (evaluated in BNT162b2-primed participants). Similar patterns in antibody responses were observed for participants aged [≥]56 years. No safety concerns were identified. Conclusion CoV2 preS dTM-AS03 boosters demonstrated acceptable safety and elicited robust neutralizing antibodies against multiple variants, regardless of priming vaccine. ClinicalTrials.gov: NCT04762680
ABSTRACT
Background: In April 2020, deaths directly attributable to COVID-19 in the United Kingdom (UK) exceeded 40,000. Although a number of studies have examined the association between demographic and morbidity variables and outcomes of COVID-19, few have evaluated the additional predictive value of admission blood results and clinical observations. Methods: Adults admitted to Northwick Park Hospital (London, UK) between 12th March and 15th April 2020 with laboratory-confirmed COVID-19 were retrospectively identified. Demographic descriptors, comorbidities, blood tests and clinical observations were collected. The primary outcome was death. Secondary outcomes were the need for ventilatory support. Time-dependent associations were explored using Cox proportional hazards modelling. Censoring was performed on 13th May 2020, ensuring a minimum of 28 days follow-up. Findings: The study cohort consisted of 981 patients. During the study period, 354 (36.0%) patients died. Age (adjusted hazard ratio (aHR) 1.53), respiratory disease (aHR 1.37), immunosuppression (aHR 2.23), higher respiratory rate (aHR 1.28), hypoxia (aHR 1.36), Glasgow Coma Score <15 (aHR 1.92), higher urea levels (aHR 2.67), higher alkaline phosphatase (aHR 2.53), higher CRP (aHR 1.15), higher lactate levels (aHR 2.67), lower platelet counts (aHR 0.77) and pulmonary infiltrates on chest radiograph (aHR 1.89) were all associated with increased mortality. Sex and ethnicity were not associated with mortality. Interpretation: Mortality rates from COVID-19 are high among hospitalised patients. This study identifies a number of characteristics associated with a higher risk of mortality. These important data will aid clinical risk stratification and provide direction for further research. Funding: This project did not receive funding. Declaration of Interests: The authors declare no competing interests.Ethics Approval Statement: This study had National Research Ethics approval (REC 20/NW/0218, IRAS 282630).