RESUMEN
Background: SOBERANA-02 is a COVID-19 conjugate vaccine (recombinant RBD conjugated to tetanus toxoid). Phases 1/2 clinical trials demonstrated high immunogenicity, promoting neutralising IgG and specific T-cell response. A third heterologous dose of SOBERANA-Plus (RBD-dimer) further increased neutralising antibodies. The aim of this study is to evaluate the safety and efficacy of two immunisation regimes: two doses of SOBERANA-02 and a heterologous three-dose combination with SOBERANA-Plus added to it. Methods: From March 8th to June 24th, 2021 we conducted in Havana, Cuba a multicentre randomised, double-blind, placebo-controlled, phase-3 trial evaluating a two doses SOBERANA-02 scheme and a heterologous scheme with one dose SOBERANA-Plus added to it (RPCEC00000354). Participants 19-80 years were randomly assigned to receiving 28 days apart either the two or three dose scheme or placebo. The main endpoint was vaccine efficacy in preventing the occurrence of RT-PCR confirmed symptomatic COVID-19 at least 14 days after the second or third dose in the per-protocol population. We also assessed efficacy against severe disease and, in all participants receiving at least one vaccine/placebo dose, safety for 28 days after each dose. Findings: We included 44,031 participants (52.0% female, 48.0% male; median age 50 years, range 19-80 years; 7.0% black, 24.0% mixed-race, 59.0% white) in a context of initial Beta VOC predominance, with this variant being partially replaced by Delta near the trial's end. Vaccine efficacy in the heterologous combination was 92.0% (95%CI 80.4-96.7) against symptomatic disease. There were no severe COVID-19 cases in the vaccine group against 6 in the placebo group. Two doses of SOBERANA-02 was 69.7% (95%CI 56.5-78.9) and 74.9% (95%CI 33.7-90.5) efficacious against symptomatic and severe COVID-19, respectively. The occurrence of serious and severe adverse events (AE) was very rare and equally distributed between placebo and vaccine groups. Solicited AEs were slightly more frequent in the vaccine group but predominantly local and mostly mild and transient. Interpretation: Our results indicate that the straightforward to manufacture SOBERANA vaccines are efficacious in a context of Beta and Delta VOC circulation, have a favourable safety profile, and may represent an attractive option for use in COVID-19 vaccination programmes. Funding: This study received funds from the National Fund for Science and Technology (FONCI-CITMA-Cuba, contract 2020-20) of the Ministry of Science, Technology and Environment of Cuba.
RESUMEN
. Introducción: Con los primeros casos de COVID-19 en Cuba era necesario el reconocimiento temprano de los pacientes con riesgo de evolucionar hacia formas graves de la enfermedad. Objetivo: Describir el comportamiento clínico de la COVID-19 en pacientes hospitalizados en el Instituto de Medicina Tropical "Pedro Kourí" e identificar factores asociados a la gravedad. Métodos: Se presentaron los primeros 73 casos de COVID-19 hospitalizados en el Instituto de Medicina Tropical Pedro Kourí desde el 11 de marzo al 5 mayo de 2020. Los pacientes se clasificaron en dos grupos: graves y con enfermedad ligera. Se compararon variables clínicas, demográficas, de laboratorio e imagenológicas en el momento del ingreso, y su posible asociación con la gravedad de la enfermedad. Resultados: Hubo siete pacientes graves (9,6 por ciento), cinco fallecieron. La edad > 60 años, tener más de una comorbilidad, hipertensión arterial y asma bronquial, fueron más frecuentes en pacientes graves. La fiebre más de seis días (p= 0,00), disnea (p= 0,00), presencia de estertores húmedos (p= 0,00), frecuencia respiratoria > 24/min (p= 0,00) y valores de linfocitos < 0,8 x109/L (p= 0,00), de ferritina > 500µg/L (p =0,00), proteína C reactiva ( 10μg/L (p= 0,01) y LDH ( 500 U/L (p= 0,01) se relacionaron con la gravedad. El 18,2 por ciento de las radiografías de tórax mostró alteraciones, con predominio de focos de condensación inflamatoria bilateral. Las complicaciones más frecuentes fueron: distrés respiratorio, choque, sepsis bacteriana y afecciones cardíacas. Conclusiones: Existen características clínicas y de laboratorio, identificables al ingreso, que están relacionadas con la gravedad de la enfermedad; lo que puede ser útil para la estratificación del riesgo y el manejo adecuado de los pacientes(AU)
Introduction: Upon appearance of the first COVID-19 cases in Cuba, early identification of patients at risk of developing severe forms of the disease became a necessity. Objective: Describe the clinical behavior of COVID-19 in patients admitted to Pedro Kourí Tropical Medicine Institute and identify factors associated to severity. Methods: A presentation was made of the first 73 COVID-19 cases admitted to Pedro Kourí Tropical Medicine Institute from 11 March to 5 May 2020. The patients were divided into two groups: severe and mild disease. A comparison was made of clinical, demographic, laboratory and imaging variables at admission, and their possible association to disease severity. Results: Seven patients (9.6%) were critically ill; five died. Age > 60 years, more than one comorbidity, arterial hypertension and bronchial asthma were more common among critical patients. Fever for more than six days (p= 0.00), dyspnea (p= 0.00), presence of humid stertors (p= 0.00), respiratory rate > 24/min (p= 0.00) and lymphocytes < 0.8 x109/l (p= 0.00), ferritin > 500 µg/L (p =0.00), C-reactive protein 10 μg/l (p= 0.01) and LDH 500 U/l (p= 0.01) were related to disease severity. 18.2 percent of the chest radiographs showed alterations, with a predominance of bilateral foci of inflammatory condensation. The most common complications were respiratory distress, shock, bacterial sepsis and heart disorders. Conclusions: Some clinical and laboratory characteristics identifiable at admission may be associated to disease severity, which makes them useful for risk stratification and the appropriate management of patients(AU)
