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Background: Multiple vaccine candidates against COVID-19 are currently being evaluated. We evaluate the safety and immunogenicity protein of a novel SARS-CoV-2 virus receptor-binding domain (RBD) vaccine. Methods: A phase 1-2, randomised, double-blind, placebo-controlled trial was carried out in "Saturnino Lora" Hospital, Santiago de Cuba, Cuba. Subjects (healthy or those with controlled chronic diseases) aged between 19 and 80 years, who gave written informed consent were eligible. Subjects were randomly assigned (1:1:1, in blocks) to three groups: placebo, 25 µg and 50 µg RBD vaccine (Abdala). The product was administered intramuscularly, 0·5 mL in the deltoid region. During the first phase, two immunization schedules were studied: 0-14-28 days (short) and 0-28-56 days (long). In phase 2, only the short schedule was evaluated. The organoleptic characteristics and presentations of vaccine and placebo were identical. All participants (subjects, clinical researchers, statisticians, laboratory technicians, and monitors) remained masked during the study period. The main endpoints were safety and the proportion of subjects with seroconversion of anti-RBD IgG antibodies, analysed by intention to treat and per protocol, respectively. The trial is registered with the Cuban Public Registry of Clinical Trials, RPCEC00000346. Findings: Between Dec 7, 2020, and Feb 9, 2021, 792 subjects were included; 132 (66 in each vaccination schedule, divided into 22 for each group) in phase 1, and 660 (220 in each group plus 66 from the short scheme of phase 1) in phase 2. The product was well tolerated. No severe adverse events were reported. During phase 1, the incidence of adverse events in the 25 µg, 50 µg, and placebo arms for the short schedule were 6/22 (27·3%), 6/22 (27·3%), 3/22 (13·6%), respectively, and for the long schedule were 8/22 (36·4%), 9/22 (40·9%), 4/22 (18·2%), respectively. In phase 2, adverse reactions were reported by 53/242 (21·9%), 75/242 (31·0%) and 41/242 (16·9%) participants in the 25 µg, 50 µg, and placebo group, respectively. Adverse reactions were minimal, mostly mild, and from the injection site, which resolved in the first 24-48 hours. In phase 1, seroconversion at day 56 was seen in 95·2% of the participants (20/21) in the 50 µg group, 81% (17/21) in the 25 µg group, and none in the placebo group (0/22). For the long schedule, seroconversion at day 70 was seen in 100% of the participants (21/21) in the 50 µg group, 94·7% (18/19) in the 25 µg group, and none in the placebo group (0/22). In phase 2, seroconversion of anti-RBD IgG antibodies at day 56 was seen in 89·2% of the participants in the 50 µg group (214/240; 95% CI 84·5-92·82), 77·7% in the 25 µg group (185/238; 72·0-82·9) and 4·6% in the placebo group (11/239; 2·3-8·1). Compared with the placebo arm, the differences in the proportion of participants with seroconversion were 73·1% (95% CI 66·8-79·5) and 84·6% (79·4-89·7) in the 25 µg and 50 µg groups, respectively. The seroconversion rate in the 50 µg group was significantly higher than in the 25 µg group (p=0·0012). Interpretation: The Abdala vaccine was safe, well tolerated, and induced humoral immune responses against SARS-CoV-2. These results, in the context of the emergency COVID-19 pandemic, support the 50 µg dose, applied in a 0-14-28 days schedule, for further clinical trials to confirm vaccine efficacy. Funding: Centre for Genetic Engineering and Biotechnology (CIGB), Havana, Cuba.
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RESUMEN Introducción: La modulación autonómica cardiovascular puede ser considerada como una herramienta útil en la determinación del estado fisiológico de la interacción entre los sistemas nervioso autónomo y cardiovascular. Objetivo: Determinar las diferencias en los parámetros lineales del balance autonómico basal entre estudiantes de medicina y atletas juveniles de béisbol. Método: Se realizó un estudio analítico de tipo transversal en el Laboratorio de Ciencias Básicas Biomédicas de la Facultad Nº. 1 de la Universidad de Ciencias Médicas de Santiago de Cuba. Universo y muestra de 36 individuos (Grupo 1: 18 atletas juveniles de béisbol de alto rendimiento, Grupo 2: 18 estudiantes de medicina). Los datos fueron recolectados mediante de polígrafo PowerLab de 8 canales, y fueron procesados usando el software Kubios® versión 3.0.4 Premium. Resultados: Existieron diferencias significativas en los valores de pNN50 (p=0,009), índice de estrés (stress index [p=0,044]), y en los índices parasimpático (p=0,005) y simpático (p=0,001) entre estudiantes y atletas. La capacidad discriminatoria del índice parasimpático para asociarse con la mejor forma física de los atletas fue buena (área bajo la curva 0,784). El punto de corte óptimo por encima del cual el índice parasimpático se asocia al grupo de los atletas, quedó establecido en 0,57. Conclusiones: El índice parasimpático se asoció con el grupo de atletas, lo que evidencia el predominio vagal en la modulación de la actividad cardíaca en los sujetos de este grupo.
ABSTRACT Introduction: Cardiovascular autonomic modulation can be considered a useful tool in determining the physiological state of the interaction between the autonomic nervous system and the cardiovascular system. Objective: To determine the differences in linear parameters of the basal autonomic balance between medical students and young baseball players. Method: A cross-sectional analytical study was carried out in the Biomedical Basic Sciences Laboratory, Faculty No.1, of the Universidad de Ciencias Médicas in Santiago de Cuba. The population and sample consisted of 36 individuals (Group 1: 18 high-performance young baseball athletes, Group 2: 18 medical students). Data was collected using an 8-channel PowerLab polygraph and it was processed using the Kubios® Software version 3.0.4 Premium. Results: There were significant differences in the values between students and athletes: pNN50 (p=0.009), stress index (p=0.044) and in parasympathetic (p=0.005) and sympathetic (p=0.001) indexes. The discriminatory ability of the parasympathetic index to be associated with the best physical fitness of the athletes was good (area under the curve 0.784). The optimum cut-off point above which the parasympathetic index is associated with the group of athletes was set at 0.57. Conclusions: The parasympathetic index was associated with the group of athletes, showing the vagal predominance in the modulation of cardiac activity in the individuals belonging to this group.