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Objective To estimate the effectiveness of a two dose vaccine schedule (mRNA-1273, BNT162b2, and BBIBP-CorV) against SARS-CoV-2 infection and covid-19 related death and short term waning of immunity in children (3-11 years old) and adolescents (12-17 years old) during periods of delta and omicron variant predominance in Argentina. Design Test negative, case-control study. Setting Database of the National Surveillance System and the Nominalized Federal Vaccination Registry of Argentina. Participants 844 460 c hildren and adolescents without previous SARS-CoV-2 infection eligible to receive primary vaccination schedule who were tested for SARS-CoV-2 by polymerase chain reaction or rapid antigen test from September 2021 to April 2022. After matching with their corresponding controls, 139 321 (60.3%) of 231 181 cases remained for analysis. Exposures Two dose mRNA-1273, BNT162b2, and BBIBP-CorV vaccination schedule. Main outcome measures SARS-CoV-2 infection and covid-19 related death. Conditional logistic regression was used to estimate the odds of SARS-CoV-2 infection among two dose vaccinated and unvaccinated participants. Vaccine effectiveness was estimated as (1–odds ratio)×100%. Results Estimated vaccine effectiveness against SARS-CoV-2 infection was 61.2% (95% confidence interval 56.4% to 65.5%) in children and 66.8% (63.9% to 69.5%) in adolescents during the delta dominant period and 15.9% (13.2% to 18.6%) and 26.0% (23.2% to 28.8%), respectively, when omicron was dominant. Vaccine effectiveness declined over time, especially during the omicron period, from 37.6% (34.2% to 40.8%) at 15-30 days after vaccination to 2.0% (1.8% to 5.6%) after ≥60 days in children and from 55.8% (52.4% to 59.0%) to 12.4% (8.6% to 16.1%) in adolescents. Vaccine effectiveness against death related to SARS-CoV-2 infection during omicron predominance was 66.9% (6.4% to 89.8%) in children and 97.6% (81.0% to 99.7%) in adolescents. Conclusions Vaccine effectiveness in preventing mortality remained high in children and adolescents regardless of the circulating variant. Vaccine effectiveness in preventing SARS-CoV-2 infection in the short term after vaccination was lower during omicron predominance and decreasing sharply over time. Trial registration National Registry of Health Research IS003720.

Introducción: se busca cuantificar los retornos de la inversión asociados a una intervención en el sistema público de salud de un municipio de la Provincia de Buenos Aires, Argentina, consistente en el fortalecimiento de la estrategia denominada Eliminación de la Transmisión Maternoinfantil de la Infección por VIH, Sífilis, enfermedad de Chagas Congénita e Infección Perinatal por Hepatitis B (ETMI-PLUS). Metodología: el estudio (cuantitativo) se basa en la metodología de Retorno Social de la Inversión (RSI). Se establecieron definiciones ad-hoc para la medición de los retornos sobre la base de los datos disponibles provenientes de diversas fuentes: información primaria de la Secretaría de Salud del MAB; tasas de transmisión congénita de cada enfermedad notificados al Sistema Nacional de Vigilancia de Salud; presupuestos detallados de los recursos asignados al proyecto por parte de la Fundación Mundo Sano y costos de tratamientos e insumos de nomencladores oficiales. Resultados: por cada peso invertido para reforzar la ETMI-PLUS en el MAB, se obtuvo un retorno de casi 4 pesos, gracias a las mejoras en la eliminación vertical de las cuatro enfermedades y al descenso de las complicaciones cardiacas en las mujeres embarazadas diagnosticadas con chagas y tratadas oportunamente. Conclusiones: estos resultados sugieren la existencia de una relación retorno-inversión favorable, analizada bajo una perspectiva conservadora, ya que, se incluyen exclusivamente los ahorros para el sistema de salud y se excluyen otras dimensiones de los retornos vinculadas con las mejoras en los resultados alcanzados.

Several vaccines have been found effective against COVID-19, usually administered in homologous regimens, with the same vaccine used for the prime and boost doses. However, recent studies have demonstrated improved protection via heterologous mix-and-match COVID-19 vaccine combinations, and a direct comparison among these regimens is needed to identify the best employment strategies. Here, we show a single-cohort comparison of changes to the humoral and cellular immune compartments following five different COVID-19 vaccines spanning three technologies (adenoviral, mRNA and inactivated vaccines). These vaccines were administered in a combinatorial fashion, resulting in sixteen different homologous and heterologous regimens. SARS-CoV-2-targeting antibody titres were highest when the boost dose consisted of mRNA-1273, independent of the vaccine used for priming. Priming with BBIBP-CorV induced less class-switching among spike-binding memory B cells and the highest antigen-specific T cell responses in heterologous combinations. These were generally more immunogenic in terms of specific antibodies and cellular responses compared to homologous regimens. Finally, single-cell analysis of 754 samples revealed specific B and T cell signatures of the vaccination regimens, indicating distinctive differences in the immune responses. These data provide new insights on the immunological effects of COVID-19 vaccine combinations and a framework for the design of improved vaccination strategies for other pathogens and cancer.