Assessing the best time interval between doses in a two-dose vaccination regimen to reduce the number of deaths in an ongoing epidemic of SARS-CoV-2.

The SARS-CoV-2 pandemic is a major concern all over the world and, as vaccines became available at the end of 2020, optimal vaccination strategies were subjected to intense investigation. Considering their critical role in reducing disease burden, the increasing demand outpacing production, and that most currently approved vaccines follow a two-dose regimen, the cost-effectiveness of delaying the second dose to increment the coverage of the population receiving the first dose is often debated. Finding the best solution is complex due to the trade-off between vaccinating more people with lower level of protection and guaranteeing higher protection to a fewer number of individuals. Here we present a novel extended age-structured SEIR mathematical model that includes a two-dose vaccination schedule with a between-doses delay modelled through delay differential equations and linear optimization of vaccination rates. By maintaining the minimum stock of vaccines under a given production rate, we evaluate the dose interval that minimizes the number of deaths. We found that the best strategy depends on an interplay between the vaccine production rate and the relative efficacy of the first dose. In the scenario of low first-dose efficacy, it is always better to vaccinate the second dose as soon as possible, while for high first-dose efficacy, the best strategy of time window depends on the production rate and also on second-dose efficacy provided by each type of vaccine. We also found that the rate of spread of the infection does not affect significantly the thresholds of the best window, but is an important factor in the absolute number of total deaths. These conclusions point to the need to carefully take into account both vaccine characteristics and roll-out speed to optimize the outcome of vaccination strategies.

Model-based estimation of transmissibility and reinfection of SARS-CoV-2 P.1 variant.

Background: The SARS-CoV-2 variant of concern (VOC) P.1 (Gamma variant) emerged in the Amazonas State, Brazil, in November 2020. The epidemiological consequences of its mutations have not been widely studied, despite detection of P.1 in 36 countries, with local transmission in at least 5 countries. A range of mutations are seen in P.1, ten of them in the spike protein. It shares mutations with VOCs previously detected in the United Kingdom (B.1.1.7, Alpha variant) and South Africa (B.1.351, Beta variant). Methods: We estimated the transmissibility and reinfection of P.1 using a model-based approach, fitting data from the national health surveillance of hospitalized individuals and frequency of the P.1 variant in Manaus from December-2020 to February-2021. Results: Here we estimate that the new variant is about 2.6 times more transmissible (95% Confidence Interval: 2.4-2.8) than previous circulating variant(s). Manaus already had a high prevalence of individuals previously affected by the SARS-CoV-2 virus and our fitted model attributed 28% of Manaus cases in the period to reinfections by P.1, confirming the importance of reinfection by this variant. This value is in line with estimates from blood donors samples in Manaus city. Conclusions: Our estimates rank P.1 as one of the most transmissible among the SARS-CoV-2 VOCs currently identified, and potentially as transmissible as the posteriorly detected VOC B.1.617.2 (Delta variant), posing a serious threat and requiring measures to control its global spread.

Brazil in the face of new SARS-CoV-2 variants: emergencies and challenges in public health.

This article discusses the epidemic situation of Covid-19 in Brazil, in the face of the emergence of a new strain called P.1, which is more transmissible and may be associated with reinfection. Given the collapse of hospital care in Manaus in January 2021 and the results of three recent preprints, each that reports increased transmissibility of the P.1 variant, we propose some urgent measures. Genomic surveillance based on multi-step diagnostics, starting with RT-PCR type tests and up to sequencing, should be established. Efforts to identify reinfections associated with this variant and the update of its definition in protocols should be prioritized, and studies on the efficacy of currently available vaccines in Brazil concerning the new variant should be conducted. We also propose improving the Brazilian health surveillance system such that genomic surveillance is coordinated and thereby better able to respond to future emergencies in a more timely fashion. We call on the public agents involved in health surveillance to share data and information regarding the epidemic in a clear, fast and transparent way. Finally, we propose a greater engagement in inter-institutional cooperation of all those involved in the response and production of knowledge about the pandemic in our country.

Brazil in the face of new SARS-CoV-2 variants: emergencies and challenges in public health / O Brasil perante as novas variantes de SARS-CoV-2: emergências e desafios em saúde pública

ABSTRACT: This article discusses the epidemic situation of Covid-19 in Brazil, in the face of the emergence of a new strain called P.1, which is more transmissible and may be associated with reinfection. Given the collapse of hospital care in Manaus in January 2021 and the results of three recent preprints, each that reports increased transmissibility of the P.1 variant, we propose some urgent measures. Genomic surveillance based on multi-step diagnostics, starting with RT-PCR type tests and up to sequencing, should be established. Efforts to identify reinfections associated with this variant and the update of its definition in protocols should be prioritized, and studies on the efficacy of currently available vaccines in Brazil concerning the new variant should be conducted. We also propose improving the Brazilian health surveillance system such that genomic surveillance is coordinated and thereby better able to respond to future emergencies in a more timely fashion. We call on the public agents involved in health surveillance to share data and information regarding the epidemic in a clear, fast and transparent way. Finally, we propose a greater engagement in inter-institutional cooperation of all those involved in the response and production of knowledge about the pandemic in our country.

RESUMO: Este artigo discute a situação epidêmica da COVID-19 no Brasil diante do aparecimento de uma nova linhagem, chamada P.1, mais transmissível e com possível reinfecção associada. Tendo em vista o colapso do atendimento hospitalar em Manaus em janeiro de 2021 e os resultados de três preprints recentes, dos quais todos encontraram maior transmissibilidade da variante P.1, propomos algumas ações urgentes: o estabelecimento de uma vigilância genômica baseada em diagnóstico em múltiplos passos, iniciando com os testes do tipo transcrição reversa seguida de reação em cadeia da polimerase (RT-PCR) até o sequenciamento; um esforço imediato na identificação de reinfecções associadas à nova variante, com a atualização dos protocolos de definição; e estudos sobre a eficácia das vacinas disponíveis no Brasil na vigência da nova variante. Propomos, ademais, o aprimoramento do sistema de vigilância em saúde brasileiro para que seja articulado com a vigilância genômica, de forma a responder mais oportunamente a emergências futuras. Chamamos os agentes públicos implicados na vigilância em saúde para que compartilhem dados e informações referentes à epidemia de forma clara, rápida e transparente. Finalmente propomos maior engajamento na cooperação interinstitucional de todos os envolvidos na resposta e produção de conhecimento sobre a pandemia em nosso país.