RESUMO
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Gamma variant of concern has spread rapidly across Brazil since late 2020, causing substantial infection and death waves. Here we used individual-level patient records after hospitalization with suspected or confirmed coronavirus disease 2019 (COVID-19) between 20 January 2020 and 26 July 2021 to document temporary, sweeping shocks in hospital fatality rates that followed the spread of Gamma across 14 state capitals, during which typically more than half of hospitalized patients aged 70 years and older died. We show that such extensive shocks in COVID-19 in-hospital fatality rates also existed before the detection of Gamma. Using a Bayesian fatality rate model, we found that the geographic and temporal fluctuations in Brazil's COVID-19 in-hospital fatality rates were primarily associated with geographic inequities and shortages in healthcare capacity. We estimate that approximately half of the COVID-19 deaths in hospitals in the 14 cities could have been avoided without pre-pandemic geographic inequities and without pandemic healthcare pressure. Our results suggest that investments in healthcare resources, healthcare optimization and pandemic preparedness are critical to minimize population-wide mortality and morbidity caused by highly transmissible and deadly pathogens such as SARS-CoV-2, especially in low- and middle-income countries.
Assuntos
COVID-19 , Idoso , Idoso de 80 Anos ou mais , Teorema de Bayes , Brasil/epidemiologia , COVID-19/epidemiologia , Hospitais , Humanos , SARS-CoV-2RESUMO
The emergence and global dissemination of Severe Acute Respiratory Syndrome virus 2 (SARS-CoV-2) variants of concern (VOCs) have been described as the main factor driving the Coronavirus Disease 2019 pandemic. In Brazil, the Gamma variant dominated the epidemiological scenario during the first period of 2021. Many Brazilian regions detected the Delta variant after its first description and documented its spread. To monitor the introduction and spread of VOC Delta, we performed Polymerase Chain Reaction (PCR) genotyping and genome sequencing in ten regional sentinel units from June to October 2021 in the State of Minas Gerais (MG). We documented the introduction and spread of Delta, comprising 70 per cent of the cases 8 weeks later. Comparing the viral loads of the Gamma and Delta dominance periods, we provide additional evidence that the latter is more transmissible. The spread and dominance of Delta did not culminate in the increase in cases and deaths, suggesting that the vaccination may have restrained the epidemic growth. Analysis of 224 novel Delta genomes revealed that Rio de Janeiro state was the primary source for disseminating this variant in the state of MG. We present the establishment of Delta, providing evidence of its enhanced transmissibility and showing that this variant shift did not aggravate the epidemiological scenario in a high immunity setting.
RESUMO
The emergence of diverse lineages harboring mutations with functional significance and potentially enhanced transmissibility imposes an increased difficulty on the containment of the SARS-CoV-2 pandemic [...].
Assuntos
COVID-19/epidemiologia , COVID-19/virologia , SARS-CoV-2/genética , Brasil/epidemiologia , COVID-19/transmissão , Genoma Viral/genética , Humanos , Mutação , Filogenia , Filogeografia , SARS-CoV-2/classificaçãoRESUMO
The SARS-CoV-2 Gamma variant spread rapidly across Brazil, causing substantial infection and death waves. We use individual-level patient records following hospitalisation with suspected or confirmed COVID-19 to document the extensive shocks in hospital fatality rates that followed Gamma's spread across 14 state capitals, and in which more than half of hospitalised patients died over sustained time periods. We show that extensive fluctuations in COVID-19 in-hospital fatality rates also existed prior to Gamma's detection, and were largely transient after Gamma's detection, subsiding with hospital demand. Using a Bayesian fatality rate model, we find that the geographic and temporal fluctuations in Brazil's COVID-19 in-hospital fatality rates are primarily associated with geographic inequities and shortages in healthcare capacity. We project that approximately half of Brazil's COVID-19 deaths in hospitals could have been avoided without pre-pandemic geographic inequities and without pandemic healthcare pressure. Our results suggest that investments in healthcare resources, healthcare optimization, and pandemic preparedness are critical to minimize population wide mortality and morbidity caused by highly transmissible and deadly pathogens such as SARS-CoV-2, especially in low- and middle-income countries. NOTE: The following manuscript has appeared as 'Report 46 - Factors driving extensive spatial and temporal fluctuations in COVID-19 fatality rates in Brazilian hospitals' at https://spiral.imperial.ac.uk:8443/handle/10044/1/91875 . ONE SENTENCE SUMMARY: COVID-19 in-hospital fatality rates fluctuate dramatically in Brazil, and these fluctuations are primarily associated with geographic inequities and shortages in healthcare capacity.
RESUMO
Zika virus (ZIKV) infection during pregnancy can cause a set of severe abnormalities in the fetus known as congenital Zika syndrome (CZS). Experiments with animal models and in vitro systems have substantially contributed to our understanding of the pathophysiology of ZIKV infection. Here, to investigate the molecular basis of CZS in humans, we used a systems biology approach to integrate transcriptomic, proteomic, and genomic data from the postmortem brains of neonates with CZS. We observed that collagens were greatly reduced in expression in CZS brains at both the RNA and protein levels and that neonates with CZS had several single-nucleotide polymorphisms in collagen-encoding genes that are associated with osteogenesis imperfecta and arthrogryposis. These findings were validated by immunohistochemistry and comparative analysis of collagen abundance in ZIKV-infected and uninfected samples. In addition, we showed a ZIKV-dependent increase in the expression of cell adhesion factors that are essential for neurite outgrowth and axon guidance, findings that are consistent with the neuronal migration defects observed in CZS. Together, these findings provide insights into the underlying molecular alterations in the ZIKV-infected brain and reveal host genes associated with CZS susceptibility.
Assuntos
Encéfalo , Colágeno , Matriz Extracelular , Polimorfismo de Nucleotídeo Único , Infecção por Zika virus , Zika virus , Encéfalo/metabolismo , Encéfalo/patologia , Colágeno/genética , Colágeno/metabolismo , Matriz Extracelular/genética , Matriz Extracelular/metabolismo , Feminino , Humanos , Recém-Nascido , Masculino , Síndrome , Infecção por Zika virus/congênito , Infecção por Zika virus/genética , Infecção por Zika virus/metabolismo , Infecção por Zika virus/patologiaRESUMO
A infecção pelo vírus zika (ZIKV) durante a gravidez pode causar um conjunto de anormalidades graves no feto, conhecidas como síndrome congênita do zika (CZS). Experimentos com modelos animais e sistemas in vitro contribuíram substancialmente para a nossa compreensão da fisiopatologia da infecção pelo ZIKV. Aqui, para investigar a base molecular da CZS em humanos, usamos uma abordagem de biologia de sistemas para integrar dados transcriptômicos, proteômicos e genômicos dos cérebros post-mortem de neonatos com CZS. Observamos que os colágenos foram bastante reduzidos em expressão nos cérebros de CZS nos níveis de RNA e de proteínas e que os neonatos com CZS tinham vários polimorfismos de nucleotídeo único em genes que codificam colágeno que estão associados à osteogênese imperfeita e à artrogripose. Esses achados foram validados por imuno-histoquímica e análise comparativa da abundância de colágeno em amostras infectadas e não infectadas por ZIKV. Além disso, mostramos um aumento dependente de ZIKV na expressão de fatores de adesão celular que são essenciais para o crescimento de neurites e a orientação do axônio, achados consistentes com os defeitos de migração neuronal observados na CZS. Juntos, esses achados fornecem informações sobre as alterações moleculares subjacentes no cérebro infectado pelo ZIKV e revelam genes hospedeiros associados à suscetibilidade à CZS.