Abstract: Since May 2020, we have been conducting a comprehensive study to understand the natural history of SARS-CoV-2 infection in Rio de Janeiro, Brazil. Our focus has been on following families, systematically collecting respiratory tract swabs and blood samples, monitoring symptoms, and gathering data on vaccine status. This paper aims to describe the household cohort across five epidemic waves of SARS-CoV-2, providing an overview of the collected data and a description of the epidemiological, clinical, and immunological characteristics and incidence of SARS-CoV-2 infection. Our cohort includes 691 participants from 189 households. During the five epidemic waves, we detected 606 infections. The incidence density of SARS-CoV-2 infection ranged from 4 (Delta) to 56 (B.1.1.33) per 1,000 person-week, with a peak in wave B.1.1.33 in all age groups. The seroprevalence of SARS-CoV-2 antibodies (IgG anti spike protein) varied from 37%, in the pre-VoC period, to 99%, in the Omicron period, progressively increasing after each wave in a similar manner regardless of age. As we have monitored the cohort continuously since the beginning of the pandemic, we were able to collect data across different scenarios according to the predominant lineage in circulation. Via active monitoring of families, we were able to carry out an epidemiological surveillance on SARS-CoV-2, including its variants, persistence of symptoms, and changes in immunity over time in the population, contributing to knowledge of the natural history of SARS-CoV-2 infection.

Resumen: Desde mayo de 2020 se realiza un estudio exhaustivo con el fin de estimar el curso natural de la infección por SARS-CoV-2 en Río de Janeiro, Brasil. Se aplica un seguimiento a las familias en el cual se recolectan sistemáticamente muestras de sangre y de las vías respiratorias, se controlan los síntomas y se recogen datos sobre el estado de vacunación. Este artículo tiene como objetivo describir la cohorte de hogares durante cinco olas epidémicas de SARS-CoV-2, y proporcionar una visión general de los datos recopilados y una descripción de las características epidemiológicas, clínicas e inmunológicas, y de la incidencia de la infección por SARS-CoV-2. La cohorte incluyó a 691 participantes de 189 hogares. A lo largo de las cinco olas epidémicas, se detectaron 606 infecciones. La densidad de incidencia de la infección por SARS-CoV-2 varió de 4 (Delta) a 56 (B.1.1.33) por cada 1.000 personas por semana, y fue más alta en la ola B.1.1.33 en todos los grupos de edad. La seroprevalencia de anticuerpos contra el SARS-CoV-2 (proteína IgG antipico) varió del 37% en el período anti-VOC al 99% en el período Ómicron y aumentó ola tras ola de manera similar, independientemente de la edad de los participantes. El monitoreo continuo de la cohorte desde el comienzo de la pandemia permitió recopilar datos en diferentes escenarios según la cepa predominante en circulación. A partir del monitoreo activo de las familias, se realizó una vigilancia epidemiológica del SARS-CoV-2, sus variantes, la persistencia de los síntomas y los cambios en la inmunidad de la población a lo largo del tiempo, contribuyendo al conocimiento del curso natural de la infección por SARS-CoV-2.

Resumo: Desde maio de 2020, temos conduzido um estudo abrangente para entender a história natural da infecção por SARS-CoV-2 no Rio de Janeiro, Brasil. Nosso foco tem sido acompanhar as famílias das quais coletamos sistematicamente amostras de sangue e do trato respiratório, monitoramos os sintomas e reunimos dados sobre o status de vacinação. Este artigo tem como objetivo descrever a coorte de domicílios ao longo de cinco ondas epidêmicas de SARS-CoV-2, fornecendo uma visão geral dos dados coletados e uma descrição das características epidemiológicas, clínicas e imunológicas e da incidência da infecção por SARS-CoV-2. Nossa coorte inclui 691 participantes de 189 domicílios. Ao longo das cinco ondas epidêmicas, detectamos 606 infecções. A densidade de incidência da infecção por SARS-CoV-2 variou de 4 (Delta) a 56 (B.1.1.33) a cada 1.000 pessoas por semana e foi mais alta na onda B.1.1.33 em todas as faixas etárias. A soroprevalência de anticorpos contra o SARS-CoV-2 (proteína IgG anti-spike) variou de 37% no período pré-VoC a 99% no período Omicron e aumentou onda após onda de maneira semelhante, independentemente da idade dos participantes. Como monitoramos a coorte continuamente desde o início da pandemia, pudemos coletar dados em diferentes cenários, de acordo com a cepa predominante em circulação. Por meio do monitoramento ativo das famílias, conseguimos conduzir uma vigilância epidemiológica do SARS-CoV-2, de suas variantes, da persistência dos sintomas e das mudanças na imunidade da população ao longo do tempo, contribuindo para o conhecimento da história natural da infecção pelo SARS-CoV-2.

Resumo: Desde maio de 2020, temos conduzido um estudo abrangente para entender a história natural da infecção por SARS-CoV-2 no Rio de Janeiro, Brasil. Nosso foco tem sido acompanhar as famílias das quais coletamos sistematicamente amostras de sangue e do trato respiratório, monitoramos os sintomas e reunimos dados sobre o status de vacinação. Este artigo tem como objetivo descrever a coorte de domicílios ao longo de cinco ondas epidêmicas de SARS-CoV-2, fornecendo uma visão geral dos dados coletados e uma descrição das características epidemiológicas, clínicas e imunológicas e da incidência da infecção por SARS-CoV-2. Nossa coorte inclui 691 participantes de 189 domicílios. Ao longo das cinco ondas epidêmicas, detectamos 606 infecções. A densidade de incidência da infecção por SARS-CoV-2 variou de 4 (Delta) a 56 (B.1.1.33) a cada 1.000 pessoas por semana e foi mais alta na onda B.1.1.33 em todas as faixas etárias. A soroprevalência de anticorpos contra o SARS-CoV-2 (proteína IgG anti-spike) variou de 37% no período pré-VoC a 99% no período Omicron e aumentou onda após onda de maneira semelhante, independentemente da idade dos participantes. Como monitoramos a coorte continuamente desde o início da pandemia, pudemos coletar dados em diferentes cenários, de acordo com a cepa predominante em circulação. Por meio do monitoramento ativo das famílias, conseguimos conduzir uma vigilância epidemiológica do SARS-CoV-2, de suas variantes, da persistência dos sintomas e das mudanças na imunidade da população ao longo do tempo, contribuindo para o conhecimento da história natural da infecção pelo SARS-CoV-2. Resumo 2020 SARSCoV2 SARSCoV SARS CoV 2 SARS-CoV- Janeiro Brasil respiratório vacinação SARSCoV2, 2, epidemiológicas SARSCoV2. 2. 69 18 60 infecções Delta (Delta 5 B1133 B 1 33 (B.1.1.33 1000 000 1.00 B.1.1.3 etárias proteína antispike anti spike anti-spike 37 préVoC pré VoC 99 semelhante pandemia cenários circulação variantes tempo 202 SARS-CoV 6 B113 3 (B.1.1.3 100 00 1.0 B.1.1. 9 20 B11 (B.1.1. 10 0 1. B.1.1 B1 (B.1.1 B.1. (B.1. B.1 (B.1 B. (B. (B

Abstract: Since May 2020, we have been conducting a comprehensive study to understand the natural history of SARS-CoV-2 infection in Rio de Janeiro, Brazil. Our focus has been on following families, systematically collecting respiratory tract swabs and blood samples, monitoring symptoms, and gathering data on vaccine status. This paper aims to describe the household cohort across five epidemic waves of SARS-CoV-2, providing an overview of the collected data and a description of the epidemiological, clinical, and immunological characteristics and incidence of SARS-CoV-2 infection. Our cohort includes 691 participants from 189 households. During the five epidemic waves, we detected 606 infections. The incidence density of SARS-CoV-2 infection ranged from 4 (Delta) to 56 (B.1.1.33) per 1,000 person-week, with a peak in wave B.1.1.33 in all age groups. The seroprevalence of SARS-CoV-2 antibodies (IgG anti spike protein) varied from 37%, in the pre-VoC period, to 99%, in the Omicron period, progressively increasing after each wave in a similar manner regardless of age. As we have monitored the cohort continuously since the beginning of the pandemic, we were able to collect data across different scenarios according to the predominant lineage in circulation. Via active monitoring of families, we were able to carry out an epidemiological surveillance on SARS-CoV-2, including its variants, persistence of symptoms, and changes in immunity over time in the population, contributing to knowledge of the natural history of SARS-CoV-2 infection. Abstract 2020 SARSCoV2 SARSCoV SARS CoV 2 SARS-CoV- Janeiro Brazil families samples symptoms status SARSCoV2, 2, clinical 69 18 households 60 infections Delta (Delta 5 B1133 B 1 33 (B.1.1.33 1000 000 1,00 personweek, personweek person week, week person-week B.1.1.3 groups IgG protein 37 37% preVoC pre VoC period 99 99% pandemic circulation variants population 202 SARS-CoV 6 B113 3 (B.1.1.3 100 00 1,0 B.1.1. 9 20 B11 (B.1.1. 10 0 1, B.1.1 B1 (B.1.1 B.1. (B.1. B.1 (B.1 B. (B. (B

Resumen: Desde mayo de 2020 se realiza un estudio exhaustivo con el fin de estimar el curso natural de la infección por SARS-CoV-2 en Río de Janeiro, Brasil. Se aplica un seguimiento a las familias en el cual se recolectan sistemáticamente muestras de sangre y de las vías respiratorias, se controlan los síntomas y se recogen datos sobre el estado de vacunación. Este artículo tiene como objetivo describir la cohorte de hogares durante cinco olas epidémicas de SARS-CoV-2, y proporcionar una visión general de los datos recopilados y una descripción de las características epidemiológicas, clínicas e inmunológicas, y de la incidencia de la infección por SARS-CoV-2. La cohorte incluyó a 691 participantes de 189 hogares. A lo largo de las cinco olas epidémicas, se detectaron 606 infecciones. La densidad de incidencia de la infección por SARS-CoV-2 varió de 4 (Delta) a 56 (B.1.1.33) por cada 1.000 personas por semana, y fue más alta en la ola B.1.1.33 en todos los grupos de edad. La seroprevalencia de anticuerpos contra el SARS-CoV-2 (proteína IgG antipico) varió del 37% en el período anti-VOC al 99% en el período Ómicron y aumentó ola tras ola de manera similar, independientemente de la edad de los participantes. El monitoreo continuo de la cohorte desde el comienzo de la pandemia permitió recopilar datos en diferentes escenarios según la cepa predominante en circulación. A partir del monitoreo activo de las familias, se realizó una vigilancia epidemiológica del SARS-CoV-2, sus variantes, la persistencia de los síntomas y los cambios en la inmunidad de la población a lo largo del tiempo, contribuyendo al conocimiento del curso natural de la infección por SARS-CoV-2. Resumen 202 SARSCoV2 SARSCoV SARS CoV 2 SARS-CoV- Janeiro Brasil respiratorias vacunación SARSCoV2, 2, epidemiológicas inmunológicas SARSCoV2. 2. 69 18 60 infecciones Delta (Delta 5 B1133 B 1 33 (B.1.1.33 1000 000 1.00 semana B.1.1.3 proteína antipico 37 antiVOC anti VOC 99 similar circulación variantes tiempo 20 SARS-CoV 6 B113 3 (B.1.1.3 100 00 1.0 B.1.1. 9 B11 (B.1.1. 10 0 1. B.1.1 B1 (B.1.1 B.1. (B.1. B.1 (B.1 B. (B. (B

ABSTRACT An immunocompromised patient was infected by the SARS-CoV-2 variant of interest named Zeta (P.2) in February 2021. More than one year later, he suffered from symptomatic COVID-19 and sequencing revealed the same variant, which accumulated 23 substitutions. This case illustrates intra-host evolution of a particular SARS-CoV-2 variant, highlighting the importance of genomic surveillance of immunocompromised patients. SARSCoV2 SARSCoV SARS CoV 2 SARS-CoV- P.2 P2 P (P.2 2021 later COVID19 COVID 19 COVID-1 substitutions intrahost intra host patients SARS-CoV P. (P. 202 COVID1 1 COVID- (P 20

RESUMO O Município do Rio de Janeiro (MRJ) estava entre as cidades com altas taxas de mortalidade ao longo da pandemia de Covid-19. Neste estudo, analisamos as taxas de incidência, de mortalidade e letalidade por Covid-19 nas áreas com predominância de Aglomerados Subnormais (ASN). Foram considerados todos os 36 bairros da Sub-Bacia do Canal do Cunha (SBCC) associadas às características demográficas, socioeconômicas e epidemiológicas, com estatística espacial de Moran. A taxa de incidência nos bairros da SBCC foi de 621,5/10.000 habitantes. Complexo do Alemão, Mangueira, e Maré tiveram maiores proporções de casos e mortes. A menor incidência (33,6/10.000 habitantes) e mortalidade (8,3/10.000 habitantes), mas com maior taxa de letalidade (24,7%) foi registrada no Complexo do Alemão. Foi observado correlação negativa entre a taxa de mortalidade e a proporção de habitantes nos bairros com ASN (rho= -0,433; p=0,023). Na estatística espacial, houve correlação inversa para a incidência da Covid-19 (índice Moran, -0,155863; p=0,02). Conclui-se que incidência e mortalidade nas áreas de ASN estão significativamente relacionadas com as estruturas sociodemográficas, demandando o reforço dos sistemas de vigilância e de controle da Covid-19 em territórios de favelas. As recomendações não farmacológicas e a Atenção Primária à Saúde em favelas desempenham relevante papel na redução da transmissão, mortalidade e iniquidades em saúde.

ABSTRACT Along COVID-19 pandemics, Rio de Janeiro (MRJ) has figured among the Brazilian cities with the highest mortality rates. In this study, we explored COVID-19 incidence and mortality in areas with a predominance of subnormal population clusters (SNC) in MRJ. We analyzed 36 neighborhoods of Canal do Cunha Sub-basin (CCSB) and the associations between demographic, socioeconomic, and epidemiological features, and the cumulative incidence, mortality, and lethality rates, and Moran’s spatial statistics were performed. The incidence rate in CCSB neighborhoods was 621.5/10,000 inhabitants. Complexo do Alemão, Mangueira, and Maré had the highest proportions of cases and deaths. And the lowest incidence (33.6/10,000 inhabitants), mortality (8.3/10,000 inhabitants), but with the highest lethality rate (24.7%) was recorded in Complexo do Alemão. There was a negative correlation between mortality and the proportion of inhabitants in neighborhoods with ASN (rho= -0.433; p=0.023). In spatial statistics, there was an inverse correlation for the incidence (Moran index, -0.155863; p=0.02). It is concluded that incidence and mortality in SNC areas are significantly related to their sociodemographic structures, highlighting the need to strengthen the surveillance and control systems of COVID-19 in slums territories. Non-pharmacological recommendations and suitable Primary Health Care in slums areas play a relevant role in reducing viral transmission, mortality, and health inequities.

RESUMO O Município do Rio de Janeiro (MRJ) estava entre as cidades com altas taxas de mortalidade ao longo da pandemia de Covid-19. Neste estudo, analisamos as taxas de incidência, de mortalidade e letalidade por Covid-19 nas áreas com predominância de Aglomerados Subnormais (ASN). Foram considerados todos os 36 bairros da Sub-Bacia do Canal do Cunha (SBCC) associadas às características demográficas, socioeconômicas e epidemiológicas, com estatística espacial de Moran. A taxa de incidência nos bairros da SBCC foi de 621,5/10.000 habitantes. Complexo do Alemão, Mangueira, e Maré tiveram maiores proporções de casos e mortes. A menor incidência (33,6/10.000 habitantes) e mortalidade (8,3/10.000 habitantes), mas com maior taxa de letalidade (24,7%) foi registrada no Complexo do Alemão. Foi observado correlação negativa entre a taxa de mortalidade e a proporção de habitantes nos bairros com ASN (rho= -0,433; p=0,023). Na estatística espacial, houve correlação inversa para a incidência da Covid-19 (índice Moran, -0,155863; p=0,02). Conclui-se que incidência e mortalidade nas áreas de ASN estão significativamente relacionadas com as estruturas sociodemográficas, demandando o reforço dos sistemas de vigilância e de controle da Covid-19 em territórios de favelas. As recomendações não farmacológicas e a Atenção Primária à Saúde em favelas desempenham relevante papel na redução da transmissão, mortalidade e iniquidades em saúde.

ABSTRACT Along COVID-19 pandemics, Rio de Janeiro (MRJ) has figured among the Brazilian cities with the highest mortality rates. In this study, we explored COVID-19 incidence and mortality in areas with a predominance of subnormal population clusters (SNC) in MRJ. We analyzed 36 neighborhoods of Canal do Cunha Sub-basin (CCSB) and the associations between demographic, socioeconomic, and epidemiological features, and the cumulative incidence, mortality, and lethality rates, and Moran’s spatial statistics were performed. The incidence rate in CCSB neighborhoods was 621.5/10,000 inhabitants. Complexo do Alemão, Mangueira, and Maré had the highest proportions of cases and deaths. And the lowest incidence (33.6/10,000 inhabitants), mortality (8.3/10,000 inhabitants), but with the highest lethality rate (24.7%) was recorded in Complexo do Alemão. There was a negative correlation between mortality and the proportion of inhabitants in neighborhoods with ASN (rho= -0.433; p=0.023). In spatial statistics, there was an inverse correlation for the incidence (Moran index, -0.155863; p=0.02). It is concluded that incidence and mortality in SNC areas are significantly related to their sociodemographic structures, highlighting the need to strengthen the surveillance and control systems of COVID-19 in slums territories. Non-pharmacological recommendations and suitable Primary Health Care in slums areas play a relevant role in reducing viral transmission, mortality, and health inequities.

BACKGROUND The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has become a major concern contributing to increased morbidity and mortality worldwide. OBJECTIVES Here we describe the replacement of the Gamma variant of concern (VOC) with Delta in the western Brazilian Amazon. METHODS In this study, we analysed 540 SARS-CoV-2 positive samples determined by qualitative real-time RT-PCR selected in the state of Rondônia between June and December 2021. The positive cohort was sequenced through next-generation sequencing (NGS) and each sample was quantified using real-time RT-qPCR, the whole genome sequence was obtained, SARS-CoV-2 lineages were classified using the system Pango and the maximum likelihood (ML) method was used to conduct phylogenetic analyses. FINDINGS A total of 540 high-quality genomes were obtained, where the Delta VOC showed the highest prevalence making up 72%, with strain AY.43 being the most abundant, while the Gamma VOC was present in 28%, where the P.1 strain was the most frequent. In this study population, only 32.96% (178/540) had completed the vaccination schedule. MAIN CONCLUSIONS This study highlighted the presence of Gamma and Delta variants of SARS-CoV-2 in RO. Furthermore, we observed the replacement of the Gamma VOC with the Delta VOC and its lineages. SARSCoV2 SARSCoV SARS CoV (SARS-CoV-2 worldwide (VOC Amazon 54 SARS-CoV- realtime real time RTPCR RT PCR 2021 nextgeneration next generation NGS (NGS RTqPCR, RTqPCR qPCR, qPCR RT-qPCR obtained ML (ML analyses highquality high quality 72 72% AY43 AY 43 AY.4 abundant 28 28% P1 P 1 P. frequent population 3296 32 96 32.96 178/540 178540 178 (178/540 schedule RO Furthermore (SARS-CoV- 5 SARS-CoV 202 7 AY4 4 AY. 329 3 9 32.9 178/54 17854 17 (178/54 (SARS-CoV 20 32. 178/5 1785 (178/5 178/ (178/ (178 (17 (1 (

The objective of this study was to analyze the COVID-19 incidence of and mortality in a population from a territorial area with a predominance of neighborhoods with slum areas (subnormal settlements), and its relationship with contextual variables. We analyzed 36 neighborhoods of the Canal do Cunha Sub-basin that presented 30,008 deaths by COVID-19 until February 5, 2021. Cumulative incidence, cumulative mortality, and cumulative lethality rates were considered as dependent variables. Contextual variables included patient neighborhood; proportion of ASN by neighborhoods, percentage of black and brown people, age group; income ratio, and sanitation indices. The variables were analyzed descriptively, bivariately by Spearman correlation, and Moran's spatial statistics were performed. The Complexo do Alemão, Mangueira, and Maré neighborhoods had the highest proportions of cases and deaths from COVI-19. The percentage of infection in the 20 to 29, 30 to 39, and 40 to 49 age groups were 13.6%, 21.5%, and 20.1%, respectively. In the 70 to 79 age group was 7.3% of the total COVID-19 cases, and 26.7% deaths and 34.2% lethality rate. When added the records of black and brown people with those without records for color/race there was significant positive moderate correlation between the cumulative incidence rate and mortality rate (rho = 0.383; p=0.048 and rho= 0.3176; p= 0.0106). The global and local Moran's spatial statistical evaluation allowed to verify intermediate and medium priority areas that need to strengthen the surveillance and control system of COVID-19. The epidemiological situation of an area with a high percentage of slum areas showed that mortality by COVID-19 in black and brown people is related to demographic aspects and that there is low notification of cases and deaths attributed to COVID-19 in residents of areas with slums.

Objetivo desse estudo foi analisar a incidência e mortalidade por COVID-19 em população de área territorial com predominância de bairros com áreas de favelas (aglomerados subnormais), e sua relação com variáveis contextuais. Foram analisados 36 bairros da Sub-bacia do Canal do Cunha que apresentaram 30.008 óbitos por COVID-19 até o dia 05 de fevereiro de 2021. Considerou-se como variáveis dependentes as taxas de incidência acumulada, mortalidade acumulada e letalidade acumulada. Entre as variáveis contextuais, foram incluídas bairro do paciente; proporção de ASN por bairros, percentual de pretos e pardos, faixa etária; razão de renda, e índices de saneamento. As variáveis foram analisadas de forma descritiva, bivariada pela correlação de Spearman e utilizado a estatística espacial de Moran. Os bairros Complexo do Alemão, Mangueira e Maré foram que apresentaram as maiores proporções de casos e óbitos por COVI-19. O percentual de infecção nas faixas de 20 a 29 anos, 30 a 39 anos e 40 a 49 anos foram de 13,6%, 21.5% e 20,1%, respectivamente. Na faixa etária entre 70 e 79 anos foi 7,3% do total de casos de COVID-19, e 26,7% nbsp;de óbitos e 34,2% taxa de letalidade. Quando somado os registros de pessoas pretas e parda com os sem registro para cor/raça houve correlação moderada positiva significativa entre a taxa de incidência acumulada e a taxa de mortalidade nbsp;(rho = 0,383; p=0,048 e rho= 0,3176; p=0,0106). A avaliação estatística espacial global e local de Moran permitiu verificar áreas de prioridade intermediárias e médias que necessitam reforçar o sistema de vigilância e controle da COVID-19. A situação epidemiológica de área com grande percentual de áreas favelas mostrou que a mortalidade por COVID-19 em pessoas pretas e pardas está relacionada a aspectos demográficos e que ocorre baixa notificação de casos e de óbitos atribuídas ao COVID-19 em moradores de áreas com favelas.

BACKGROUND The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.33-derived lineage named N.9 was described recently in Brazil and it’s considered a potential variant of interest (VOI) due to the presence of E484K substitution at the receptor-binding domain (RBD) of the Spike (S) protein. OBJECTIVE To describe the first detection of variant N.9 in Rio de Janeiro State. METHODS SARS-CoV-2 N.9 was confirmed by quantitative reverse transcription polymerase chain reaction (qRT-PCR), whole-genome sequencing and phylogenetic analysis. FINDINGS Here, we report two SARS-CoV-2 N.9 lineage strains in Rio de Janeiro. One of them had only the E484K substitution of the six N.9 lineage-defining mutations. Other three strains pre-defined as N.9 have the same genomic profile. These four strains are grouped within the B.1.1.33 lineage and basal to the N.9 lineage in our phylogenetic analysis, and we call them “N.9-like/B.1.1.33 + E484K”. MAIN CONCLUSIONS The phylogenetic analysis shows four independent introductions of N.9 in the state of Rio de Janeiro in October and December 2020, January and March 2021. SARS-CoV-2 N.9 dissemination in the Rio de Janeiro could have been limited by the emergence and dominance of other variants, mainly by the lineage P.2 VOI Zeta that emerged in the same period and co-circulated with N.9, as observed in the neighboring State of São Paulo.

BACKGROUND The coronaviruses (CoVs) called the attention of the world for causing outbreaks of severe acute respiratory syndrome (SARS-CoV), in Asia in 2002-03, and respiratory disease in the Middle East (MERS-CoV), in 2012. In December 2019, yet again a new coronavirus (SARS-CoV-2) first identified in Wuhan, China, was associated with a severe respiratory infection, known today as COVID-19. This new virus quickly spread throughout China and 30 additional countries. As result, the World Health Organization (WHO) elevated the status of the COVID-19 outbreak from emergency of international concern to pandemic on March 11, 2020. The impact of COVID-19 on public health and economy fueled a worldwide race to approve therapeutic and prophylactic agents, but so far, there are no specific antiviral drugs or vaccines available. In current scenario, the development of in vitro systems for viral mass production and for testing antiviral and vaccine candidates proves to be an urgent matter. OBJECTIVE The objective of this paper is study the biology of SARS-CoV-2 in Vero-E6 cells at the ultrastructural level. METHODS In this study, we documented, by transmission electron microscopy and real-time reverse transcription polymerase chain reaction (RT-PCR), the infection of Vero-E6 cells with SARS-CoV-2 samples isolated from Brazilian patients. FINDINGS The infected cells presented cytopathic effects and SARS-CoV-2 particles were observed attached to the cell surface and inside cytoplasmic vesicles. The entry of the virus into cells occurred through the endocytic pathway or by fusion of the viral envelope with the cell membrane. Assembled nucleocapsids were verified inside rough endoplasmic reticulum cisterns (RER). Viral maturation seemed to occur by budding of viral particles from the RER into smooth membrane vesicles. MAIN CONCLUSIONS Therefore, the susceptibility of Vero-E6 cells to SARS-CoV-2 infection and the viral pathway inside the cells were demonstrated by ultrastructural analysis.

This study presents preliminary results from a sewage-based surveillance to monitor the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the municipality of Niterói, State of Rio de Janeiro, Brazil. By using ultracentrifugation method associated to quantitative reverse transcription polymerase chain reaction (RT-qPCR) we detected SARS-CoV-2 in 41.6% (5/12) of raw sewage samples obtained from sewage treatment plants and sewers network in the city. This pioneer study carried out in Brazil aims to subsidise information for health surveillance concerning the viral circulation in different areas of the city and, revealed the insertion and importance of environmental virology in health public policies.

Coronavirus disease 2019 (COVID-19) surveillance, in Brazil, initiated shortly after its description, in China. Our aim was to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and additional pathogens in samples from the initial phase of the outbreak in Brazil, from late February to late March. From 707 samples analysed, 29 (4.1%) were SARS-CoV-2 positive. Fever and cough were their most prevalent symptoms. Co-detection of rhinovirus was observed in 2 (6.9%) cases. Additional pathogens were identified in 66.1% of the SARS-CoV-2 negative cases, mainly rhinovirus and influenza A(H1N1)pdm09. Thus, we emphasise the importance of differential diagnosis in COVID-19 suspected cases.

BACKGROUND Field testing required to license the combined measles, mumps, and rubella (MMR) vaccine must take into account the current recommendation of the vaccine in Brazil: first dose at 12 months and second dose at 15 months of age in combination with a varicella vaccine. OBJECTIVES This study aimed to evaluate the clinical consistency, immunogenicity, and reactogenicity of three batches of MMR vaccine prepared with active pharmaceutical ingredients (API) from Bio-Manguinhos, Fiocruz (MMR-Bio), and compare it to a vaccine (MMR produced by GlaxoSmithKline) with different API. METHODS This was a phase III, randomised, double-blind, non-inferiority study of the MMR-Bio administered in infants immunised at health care units in Pará, Brazil, from February 2015 to January 2016. Antibody levels were titrated by immunoenzymatic assays. Adverse events were recorded in diaries. FINDINGS Seropositivity levels after MMR-Bio were 97.6% for measles, 84.7% for mumps, and 98.0% for rubella. After the MMRV vaccine, seroconversion rates and GMT increased substantially for mumps. In contrast, approximately 35% of the children had no detectable antibodies to varicella. Systemic adverse events were more frequent than local events. CONCLUSION The demonstration of batch consistency and non-inferiority of the Bio-MMR vaccine completed the technology transfer. This is a significant technological achievement with implications for immunisation programs.

Resumo: Internacionalmente, observa-se um incremento no uso das internações por condições sensíveis à atenção primária (ICSAP) como indicador de efetividade da atenção primária à saúde. Este artigo analisa as iniquidades étnico-raciais nas internações por causas em menores de cinco anos no Brasil e regiões, com ênfase nas ICSAP e nas infecções respiratórias agudas (IRA). Com dados do Sistema de Informações Hospitalares do Sistema Único de Saúde (SIH/SUS), 2009-2014, calcularam-se proporções por causas, taxas e razões de taxas de ICSAP ajustadas por sexo e idade após a imputação múltipla de dados faltantes de cor/raça. As principais causas de internação foram doenças do aparelho respiratório (37,4%) e infecciosas e parasitárias (19,3%), sendo as crianças indígenas as mais acometidas. As taxas brutas de ICSAP (por 1.000) foram mais elevadas em indígenas (97,3; IC95%: 95,3-99,2), seguidas das pardas (40,0; IC95%: 39,8-40,1), e as menores foram nas amarelas (14,8; IC95%: 14,1-15,5). As maiores razões de taxas ajustadas de ICSAP foram registradas entre crianças de cor/raça indígena e branca - 5,7 (IC95%: 3,9-8,4) no país, atingindo 5,9 (IC95%: 5,0-7,1) e 18,5 (IC95%: 16,5-20,7) no Norte e Centro-oeste, respectivamente. As IRA permanecem como importantes causas de hospitalização em crianças no Brasil. Foram observadas alarmantes iniquidades étnico-raciais nas taxas de ICSAP, com situação de desvantagem para indígenas. São necessárias melhorias nas condições de vida, saneamento e subsistência, bem como garantia de acesso oportuno e qualificado à atenção primária à saúde das populações mais vulneráveis, com destaque para os indígenas no Norte e no Centro-oeste, a fim de minimizar iniquidades em saúde e fazer cumprir as diretrizes do SUS e da Constituição do Brasil.

Abstract: There has been a global increase in hospital admissions for primary care-sensitive conditions (PCSCs) as an indicator of effectiveness in primary health care. This article analyzes ethnic and racial inequalities in cause-related hospitalizations in under-five children in Brazil as a whole and the country’s five major geographic regions, with an emphasis on PCSCs and acute respiratory infections (ARIs). Using data from the Hospital Information Systems of the Brazilian Unified National Health System (SIH/SUS), 2009-2014, the authors calculated proportions, rates, and rate ratios for PCSCs, adjusted by sex and age after multiple imputation of missing data on color/race. The principal causes of hospitalization were respiratory tract infections (37.4%) and infectious and parasitic diseases (19.3%), and indigenous children were proportionally the most affected. Crude PCSC rates (per 1,000) were highest in indigenous children (97.3; 95%CI: 95.3-99.2), followed by brown or mixed-raced children (40.0; 95%CI: 39.8-40.1), while the lowest rates were in Asiandescendant children (14.8; 95%CI: 14.1-15.5). The highest adjusted rate ratios for PCSCs were seen among indigenous children compared to white children - 5.7 (95%CI: 3.9-8.4) for Brazil as a whole, reaching 5.9 (95%CI: 5.0-7.1) and 18.5 (95%CI: 16.5-20.7) in the North and Central, respectively, compared to white children. ARIs remained as important causes of pediatric hospitalizations in Brazil. Alarming ethnic and racial inequalities were observed in PCSCs, with indigenous children at a disadvantage. Improvements are needed in living conditions, sanitation, and subsistence, as well as guaranteed timely access to high-quality primary health care in the more vulnerable population groups, especially the indigenous peoples of the North and Central, in order to mitigate the health inequalities and meet the guidelines of the SUS and the Brazilian Constitution.

Resumen: Internacionalmente, se observa un incremento en las hospitalizaciones por condiciones sensibles a la atención primaria (ICSAP), como un indicador de efectividad de la atención primaria a la salud. Este artículo analiza las inequidades étnico-raciales en las hospitalizaciones por causas evitables em menores de cinco años en Brasil y sus regiones, con énfasis en las ICSAP y en las infecciones respiratorias agudas (IRA). Con datos del Sistema de Informaciones Hospitalarias del Sistema Único de Salud (SIH/SUS), 2009-2014, se calcularon porcentajes por causas, tasas y razones de tasas de ICSAP ajustadas por sexo y edad, tras la imputación múltiple de datos faltantes de color/raza. Las principales causas de hospitalización fueron enfermedades del aparato respiratório (37,4%) e infecciosas y parasitarias (19,3%), siendo los niños indígenas los más afectados. Las tasas brutas de ICSAP (por 1.000) fueron más elevadas en indígenas (97,3; IC95%: 95,3-99,2), seguidas de las mulatos/mestizos (40,0; IC95%: 39,8-40,1), mientras que las menores fueron en las de origen asiática (14,8; IC95%: 14,1-15,5). Las mayores razones de tasas ajustadas de ICSAP fueron en los niños indígenas comparados a los niños de color/raza blanca - 5,7 (IC95%: 3,9-8,4) en el país, alcanzando 5,9 (IC95%: 5,0-7,1) y 18,5 (IC95%: 16,5-20,7) en el Norte y Centro-oeste, respectivamente, en comparación con El color/raza blanca. Las IRA permanecen como importantes causas de hospitalización en niños em Brasil. Se observaron alarmantes inequidades étnico-raciales en las tasas de ICSAP, con situación de desventaja para los indígenas. Se necesitan mejoras en las condiciones de vida, saneamiento y subsistencia, así como la garantía de un acceso oportuno y cualificado a la atención primaria a La salud de las poblaciones más vulnerables, destacando los indígenas en el Norte y Centro-oeste, a fin de minimizar inequidades en salud y hacer cumplir las directrices del SUS y de la Constitución de Brasil.

Resumo: Internacionalmente, observa-se um incremento no uso das internações por condições sensíveis à atenção primária (ICSAP) como indicador de efetividade da atenção primária à saúde. Este artigo analisa as iniquidades étnico-raciais nas internações por causas em menores de cinco anos no Brasil e regiões, com ênfase nas ICSAP e nas infecções respiratórias agudas (IRA). Com dados do Sistema de Informações Hospitalares do Sistema Único de Saúde (SIH/SUS), 2009-2014, calcularam-se proporções por causas, taxas e razões de taxas de ICSAP ajustadas por sexo e idade após a imputação múltipla de dados faltantes de cor/raça. As principais causas de internação foram doenças do aparelho respiratório (37,4%) e infecciosas e parasitárias (19,3%), sendo as crianças indígenas as mais acometidas. As taxas brutas de ICSAP (por 1.000) foram mais elevadas em indígenas (97,3; IC95%: 95,3-99,2), seguidas das pardas (40,0; IC95%: 39,8-40,1), e as menores foram nas amarelas (14,8; IC95%: 14,1-15,5). As maiores razões de taxas ajustadas de ICSAP foram registradas entre crianças de cor/raça indígena e branca - 5,7 (IC95%: 3,9-8,4) no país, atingindo 5,9 (IC95%: 5,0-7,1) e 18,5 (IC95%: 16,5-20,7) no Norte e Centro-oeste, respectivamente. As IRA permanecem como importantes causas de hospitalização em crianças no Brasil. Foram observadas alarmantes iniquidades étnico-raciais nas taxas de ICSAP, com situação de desvantagem para indígenas. São necessárias melhorias nas condições de vida, saneamento e subsistência, bem como garantia de acesso oportuno e qualificado à atenção primária à saúde das populações mais vulneráveis, com destaque para os indígenas no Norte e no Centro-oeste, a fim de minimizar iniquidades em saúde e fazer cumprir as diretrizes do SUS e da Constituição do Brasil.

Abstract: There has been a global increase in hospital admissions for primary care-sensitive conditions (PCSCs) as an indicator of effectiveness in primary health care. This article analyzes ethnic and racial inequalities in cause-related hospitalizations in under-five children in Brazil as a whole and the country’s five major geographic regions, with an emphasis on PCSCs and acute respiratory infections (ARIs). Using data from the Hospital Information Systems of the Brazilian Unified National Health System (SIH/SUS), 2009-2014, the authors calculated proportions, rates, and rate ratios for PCSCs, adjusted by sex and age after multiple imputation of missing data on color/race. The principal causes of hospitalization were respiratory tract infections (37.4%) and infectious and parasitic diseases (19.3%), and indigenous children were proportionally the most affected. Crude PCSC rates (per 1,000) were highest in indigenous children (97.3; 95%CI: 95.3-99.2), followed by brown or mixed-raced children (40.0; 95%CI: 39.8-40.1), while the lowest rates were in Asiandescendant children (14.8; 95%CI: 14.1-15.5). The highest adjusted rate ratios for PCSCs were seen among indigenous children compared to white children - 5.7 (95%CI: 3.9-8.4) for Brazil as a whole, reaching 5.9 (95%CI: 5.0-7.1) and 18.5 (95%CI: 16.5-20.7) in the North and Central, respectively, compared to white children. ARIs remained as important causes of pediatric hospitalizations in Brazil. Alarming ethnic and racial inequalities were observed in PCSCs, with indigenous children at a disadvantage. Improvements are needed in living conditions, sanitation, and subsistence, as well as guaranteed timely access to high-quality primary health care in the more vulnerable population groups, especially the indigenous peoples of the North and Central, in order to mitigate the health inequalities and meet the guidelines of the SUS and the Brazilian Constitution.

Resumen: Internacionalmente, se observa un incremento en las hospitalizaciones por condiciones sensibles a la atención primaria (ICSAP), como un indicador de efectividad de la atención primaria a la salud. Este artículo analiza las inequidades étnico-raciales en las hospitalizaciones por causas evitables em menores de cinco años en Brasil y sus regiones, con énfasis en las ICSAP y en las infecciones respiratorias agudas (IRA). Con datos del Sistema de Informaciones Hospitalarias del Sistema Único de Salud (SIH/SUS), 2009-2014, se calcularon porcentajes por causas, tasas y razones de tasas de ICSAP ajustadas por sexo y edad, tras la imputación múltiple de datos faltantes de color/raza. Las principales causas de hospitalización fueron enfermedades del aparato respiratório (37,4%) e infecciosas y parasitarias (19,3%), siendo los niños indígenas los más afectados. Las tasas brutas de ICSAP (por 1.000) fueron más elevadas en indígenas (97,3; IC95%: 95,3-99,2), seguidas de las mulatos/mestizos (40,0; IC95%: 39,8-40,1), mientras que las menores fueron en las de origen asiática (14,8; IC95%: 14,1-15,5). Las mayores razones de tasas ajustadas de ICSAP fueron en los niños indígenas comparados a los niños de color/raza blanca - 5,7 (IC95%: 3,9-8,4) en el país, alcanzando 5,9 (IC95%: 5,0-7,1) y 18,5 (IC95%: 16,5-20,7) en el Norte y Centro-oeste, respectivamente, en comparación con El color/raza blanca. Las IRA permanecen como importantes causas de hospitalización en niños em Brasil. Se observaron alarmantes inequidades étnico-raciales en las tasas de ICSAP, con situación de desventaja para los indígenas. Se necesitan mejoras en las condiciones de vida, saneamiento y subsistencia, así como la garantía de un acceso oportuno y cualificado a la atención primaria a La salud de las poblaciones más vulnerables, destacando los indígenas en el Norte y Centro-oeste, a fin de minimizar inequidades en salud y hacer cumplir las directrices del SUS y de la Constitución de Brasil.

ABSTRACT Objectives: The role of viral co-detection in children with severe acute respiratory infection is not clear. We described the viral detection profile and its association with clinical characteristics in children admitted to the Pediatric Intensive Care Unit (PICU) during the 2009 influenza A(H1N1) pandemic. Method: Longitudinal observational retrospective study, with patients aged 0–18 years, admitted to 11 PICUs in Rio de Janeiro, with suspected H1N1 infection, from June to November, 2009. The results of respiratory samples which were sent to the Laboratory of Fiocruz/RJ and clinical data extracted from specific forms were analyzed. Results: Of 71 samples, 38% tested positive for H1N1 virus. Of the 63 samples tested for other viruses, 58 were positive: influenza H1N1 (43.1% of positive samples), rhinovirus/enterovirus (41.4%), respiratory syncytial vírus (12.1%), human metapneumovirus (12.1%), adenovirus (6.9%), and bocavirus (3.5%). Viral codetection occured in 22.4% of the cases. H1N1-positive patients were of a higher median age, had higher frequency of fever, cough and tachypnea, and decreased leukometry when compared to H1N1-negative patients. There was no difference in relation to severity outcomes (number of organic dysfunctions, use of mechanical ventilation or amines, hospital/PICU length of stay or death). Comparing the groups with mono-detection and co-dection of any virus, no difference was found regarding the association with any clinical variable. Conclusions: Other viruses can be implicated in SARI in children. The role of viral codetection has not yet been completely elucidated.