ABSTRACT Hepatitis C virus (HCV) infection is a significant cause of morbidity and mortality among hematopoietic stem cell transplant (HCT) recipients. In Brazil, its occurrence in HCT recipients remains undetermined. We now report on HCV prevalence in HCT recipients and its clinical consequences. The medical records of all HCT recipients seen at Hospital das Clinicas, Sao Paulo University Medical School, from January 2010 to January 2020 were reviewed to determine HCV serostatus. A retrospective analysis of medical charts was undertaken on all seropositive cases to determine HCV genotype, presence of liver fibrosis, co-infections with other viruses, previous treatments, and clinical evolution of liver pathology after HCT. Of the 1,293 HCT recipients included in the study, seven (0.54%) were HCV antibody-positive and five (0.39%) were also viremic for HCV-RNA. Four of these individuals had moderate to severe liver fibrosis (METAVIR F2/F3) and one was cirrhotic. Two of the viremic patients developed acute liver dysfunction following transplantation. All patients had their acute episode of liver dysfunction resolved with no further complications. Four of the viremic patients were treated for HCV infection with direct acting agents (DAA). Information regarding HCV treatment was lacking for one of the viremic HCV patients due to loss of follow up. Sustained anti-virologic responses were observed in three cases after the use of DAA. The detection of HCV in hematological adults undergoing HCT and its successful treatment with DAA highlight the necessity of testing for HCV both prior to and following transplantation.

ABSTRACT This study aimed to provide further insight into the evolutionary dynamics of SARS-CoV-2 by analyzing the case of a 40-year-old man who had previously undergone autologous hematopoietic stem cell transplantation due to a diffuse large B-cell lymphoma. He developed a persistent SARS-CoV-2 infection lasting at least 218 days and did not manifest a humoral immune response to the virus during this follow-up period. Whole-genome sequencing and viral cultures confirmed a persistent infection with a replication-positive virus that had undergone genetic variation for at least 196 days after symptom onset.

ABSTRACT Vaccination is a fundamental tool to prevent SARS-CoV-2 infection and to limit the COVID-19 pandemic. The emergence of SARS-CoV-2 variants with multiple mutations has raised serious concerns about the ability of neutralizing antibody responses elicited by prior vaccination to effectively combat these variants. The neutralizing capacity against the Gamma, Delta and Omicron variants of sera from individuals immunized with the CoronaVac vaccine remains incompletely determined. The present study evaluated 41 health care workers at the Faculdade de Medicina of the Universidade de Sao Paulo, in Sao Paulo, Brazil, naive to previous SARS- CoV-2 infection, who were vaccinated with two doses of the CoronaVac SARS-CoV-2 vaccine 28 days apart. Neutralizing antibody levels against the Gamma, Delta, and Omicron variants were measured at 32 and 186 days after the second vaccination. We also measured neutralizing antibodies against Omicron in 34 of these individuals following a subsequent booster immunization with the Pfizer vaccine. Quantification of neutralizing antibodies was performed using the Cytopathic Effect-based Virus Neutralization test. Neutralization antibody activity against the Gamma, Delta and Omicron variants was observed in 78.0%, 65.9% and 58.5% of serum samples, respectively, obtained at a mean of 32 days after the second immunization. This decreased to 17.1%, 24.4% and 2.4% of sera having activity against Delta, Gamma and Omicron, respectively, at 186 days post-vaccination. The median neutralizing antibody titers at 32 days were 1:40, 1:20 and 1:20 against Gamma, Delta and Omicron, respectively, and decreased to an undetectable median level against all variants at the later time. A booster immunization with the Pfizer vaccine elicited neutralizing antibodies against Omicron in 85% of subjects tested 60 days after vaccination. We conclude that two doses of the CoronaVac vaccine results in limited protection of short duration against the Gamma, Delta and Omicron SARS-CoV-2 variants. A booster dose with the Pfizer vaccine induced antibody neutralizing activity against Omicron in most patients which was measurable 60 days after the booster.

Abstract Objectives: The aim of the present study was to evaluate if neutralizing antibody responses induced by infection with the SARS-CoV-2 strain that was dominant at the beginning of the pandemic or by the Gamma variant was effective against the Omicron variant. Methods: Convalescent sera from 109 individuals, never exposed to a SARS-CoV-2 vaccine, who had mild or moderate symptoms not requiring hospitalization following either a documented SARS-CoV-2 ancestral strain infection or a Gamma variant infection, were assayed for in vitro neutralizing antibody activity against their original strains and the Omicron variant. Results: Following an infection with the ancestral strain, 56 (93.3%), 45 (77.6%) and 1 (1.7%) serum sample were positive for neutralizing antibodies against the ancestral, Gamma variant, and Omicron variant, respectively. After infection with the Gamma variant, 43 (87.8%) and 2 (4.1%) sera were positive for neutralizing antibodies against the Gamma and Omicron variants, respectively. Conclusions: Neutralizing antibodies generated following mild or moderate infection with the SARS-CoV-2 ancestral strain or the Gamma variant are not protective against the Omicron variant. HIGHLIGHTS Individuals previously infected with SARS-CoV-2 ancestral strain do not develop neutralizing antibodies against the Omicron variant. Omicron variant escapes immune response after SARS CoV-2 previous infection with the SARS CoV-2 Gamma variant. Individuals previously infected with SARS-CoV-2 ancestral strain or with SARS-CoV-2 Gamma variant will likely have little protection if subsequently exposed to the Omicron variant.

ABSTRACT Mobile phones (MPs) have become an important work tool around the world including in hospitals. We evaluated whether SARS-CoV-2 can remain on the surface of MPs of first-line healthcare workers (HCW) and also the knowledge of HCWs about SARS-CoV-2 cross-transmission and conceptions on the virus survival on the MPs of HCWs. A cross-sectional study was conducted in the COVID-19 Intensive Care Unit of a teaching hospital. An educational campaign was carried out on cross-transmission of SARS-CoV-2, and its permanence in fomites, in addition to the proper use and disinfection of MPs. Herewith an electronic questionnaire was applied including queried conceptions about hand hygiene and care with MP before and after the pandemic. The MPs were swabbed with a nylon FLOQ Swab™, in an attempt to increase the recovery of SARS-CoV-2. All MP swab samples were subjected to SARS-CoV-2 RT-PCR; RT-PCR positive samples were subjected to viral culture in Vero cells (ATCC® CCL-81™). Fifty-one MPs were swabbed and a questionnaire on hand hygiene and the use and disinfection of MP was applied after an educational campaign. Most HCWs increased adherence to hand hygiene and MP disinfection during the pandemic. Fifty-one MP swabs were collected and two were positive by RT-PCR (4%), with Cycle threshold (Ct ) values of 34-36, however, the cultures of these samples were negative. Although most HCWs believed in the importance of cross-transmission and increased adherence to hand hygiene and disinfection of MP during the pandemic, SARS-CoV-2 RNA was detected in MPs. Our results suggest the need for a universal policy in infection control guidelines on how to care for electronic devices in hospital settings.

OBJECTIVES: In this preliminary study we investigated cellular and humoral immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens in blood samples from 14 recovered coronavirus disease 2019 (COVID-19) patients and compared them to those in samples from 12 uninfected/unvaccinated volunteers. METHODS: Cellular immunity was assessed by intracellular detection of IFN-γ in CD3+ T lymphocytes after stimulation with SARS-CoV-2 spike (S1), nucleocapsid (NC), or receptor-binding domain (RBD) recombinant proteins or overlapping peptide pools covering the sequence of SARS-CoV-2 spike, membrane and nucleocapsid regions. The humoral response was examined by ELISAs and/or chemiluminescence assays for the presence of serum IgG antibodies directed to SARS-CoV-2 proteins. RESULTS: We observed differences between humoral and cellular immune profiles in response to stimulation with the same proteins. Assays of IgG antibodies directed to SARS-CoV-2 NC, RBD and S1/S2 recombinant proteins were able to differentiate convalescent from uninfected/unvaccinated groups. Cellular immune responses to SARS-CoV-2 protein stimuli did not exhibit a specific response, as T cells from both individuals with no history of contact with SARS-CoV-2 and from recovered donors were able to produce IFN-γ. CONCLUSIONS: Determination of the cellular immune response to stimulation with a pool of SARS-CoV-2 peptides but not with SARS-CoV-2 proteins is able to distinguish convalescent individuals from unexposed individuals. Regarding the humoral immune response, the screening for serum IgG antibodies directed to SARS-CoV-2 proteins has been shown to be specific for the response of recovered individuals.

Abstract INTRODUCTION: HBV and HIV have identical transmission routes. The aim of this study was to determine the prevalence of HBV in HIV patients and to detect the presence of occult HBV infection. METHODS: All samples were tested for serology markers and using qPCR. RESULTS: This study included 232 individuals, out of which 36.6% presented with HBV markers and 11.8% presented with HBsAg or HBV-DNA, including 3 patients that showed OBI. CONCLUSIONS: We observed a high prevalence of HBV among HIV patients. In addition, the results suggest that OBI can occur in patients with serological profiles that are indicative of past infection. Therefore, the application of molecular tests may enable the identification of infections that are not evident solely based on serology.

ABSTRACT Introduction and aim: Hepatitis C is a key challenge to public health in Brazil. The objective of this paper was to describe the Brazilian strategy for hepatitis C to meet the 2030 elimination goal proposed by World Health Organization (WHO). Methods: A mathematical modeling approach was used to estimate the current HCV-infected Brazilian population, and to evaluate the relative costs of two different scenarios to address HCV disease burden in Brazil: (1) if no further changes are made to the HCV treatment program in Brazil; (2) where the WHO targets for 2030 elimination are met through diagnosis and treatment efforts peaking before 2024. Results: An anti-HCV prevalence of 0.53% was calculated for the total population. It was estimated that the number of HCV-RNA+ individuals in Brazil in 2017 was 632,000 (0.31% of the population). Scale-up of treatment and diagnosis over time will be necessary in order to achieve WHO targets beginning in 2018. Direct costs (diagnostic, treatment and healthcare costs) are projected to increase significantly during the scale-up of treatment and diagnosis in the initial years of the intervention scenario, but then fall below the base case on an annual basis by 2025-2036, once HCV is eliminated, due to health sectors savings from the prevention of HCV liver-related morbidity and mortality. Conclusion: Achieving the WHO targets is technically feasible in Brazil with a scale-up of treatment and diagnosis over time, beginning in 2018. However, elimination of hepatitis C requires policy changes to substantially scale-up prevention, screening and treatment of HCV, together with public health advocacy to raise awareness among affected populations and healthcare providers.

ABSTRACT Zika virus (ZIKV) clinical presentation and frequency/duration of shedding need further clarification. Symptomatic ZIKV-infected individuals identified in two hospitals in Sao Paulo State, Brazil, were investigated regarding clinical characteristics, shedding in body fluids, and serodynamics. Ninety-four of 235 symptomatic patients (Site A: 58%; Site B: 16%) had Real-Time PCR-confirmed ZIKV infection; fever, headache and gastrointestinal symptoms were less frequent, and rash was more frequent compared to ZIKV-negative patients. Real-Time PCR in serum had worse performance compared to plasma, while urine had the highest sensitivity. Shedding in genital fluids and saliva was rare. IgM positivity was the highest <14 days after the symptoms onset (86%), decreasing >28 days (24%); IgG positivity increased >14 days (96%) remaining positive in 94% of patients >28 days. ZIKV prevalence varied importantly in two neighboring cities during the same transmission season. Urine Real-Time PCR can improve diagnostic sensitivity; serum testing is less useful. Accurate serological tests are needed to improve diagnosis and surveillance.

RESUMO Objetivo: Analisar o padrão de distribuição espacial dos casos de hepatite causada pelo vírus B (HBV) e a mortalidade atribuída a esse agravo em todo o território nacional, nos anos de 2005, 2016 e 2017. Métodos : Trata-se de um estudo ecológico de análise espacial, utilizando dados do Sistema de Informação de Agravos de Notificação e do Sistema Nacional de Mortalidade. Analisaram-se as taxas de detecção e mortalidade de HBV. A análise espacial no período de 2005 a 2017 foi realizada por meio do Índice Global de Moran para os dados globais e dos Indicadores Locais de Associação Espacial (Lisa) para os 5.564 municípios do país. Resultados : A região Norte destaca-se pelas maiores taxas de detecção e mortalidade de HBV do país. O Índice Global de Moran revelou uma correlação espacial dos casos de HBV no Brasil, e o Lisa Map evidenciou a presença de bolsões (tipo high-high), principalmente na região Norte e também em alguns municípios de Santa Catarina, Paraná, Rio Grande do Sul, Espírito Santo, São Paulo e Rio de Janeiro. Conclusão : A análise espacial do padrão de distribuição do HBV no Brasil revela áreas com grande concentração de casos, particularmente no Norte do país e em outros pontos distribuídos pelo território nacional. Esses dados reforçam a urgência de ações de intervenção relativas a prevenção, diagnóstico e tratamento da hepatite B.

ABSTRACT Objective: To analyze the pattern of spatial distribution of hepatitis B virus (HBV) cases and the mortality attributed to this disease throughout the Brazilian territory, in 2005, 2016 and 2017. Methods: This is an ecological study of spatial analysis, using data from the Information System for Notifiable Diseases and the Brazilian Mortality Information System. HBV detection and mortality rates were analyzed. The spatial analysis from 2005 to 2017 was held through the Global Moran’s Index (I) for global data and the Local Indicators of Spatial Association (LISA) for the 5,564 municipalities of the country. Results: The North region stands out with the highest HBV detection and mortality rates in the country. The Global Moran’s I showed a spatial correlation of HBV cases in Brazil, and the LISA Map evidenced the presence of hotspots or spatial clusters (high-high type), mainly in the North region and also in some municipalities of Santa Catarina, Paraná, Rio Grande do Sul, Espírito Santo, São Paulo and Rio de Janeiro. Conclusion: The spatial analysis of the HBV distribution pattern in Brazil shows areas with a large concentration of cases, particularly in the North of the country and in other points distributed throughout the national territory. These data reinforce the urgency of intervention actions related to prevention, diagnosis and treatment of hepatitis B.

RESUMO Objetivo: Analisar o padrão de distribuição espacial dos casos de hepatite causada pelo vírus B (HBV) e a mortalidade atribuída a esse agravo em todo o território nacional, nos anos de 2005, 2016 e 2017. Métodos : Trata-se de um estudo ecológico de análise espacial, utilizando dados do Sistema de Informação de Agravos de Notificação e do Sistema Nacional de Mortalidade. Analisaram-se as taxas de detecção e mortalidade de HBV. A análise espacial no período de 2005 a 2017 foi realizada por meio do Índice Global de Moran para os dados globais e dos Indicadores Locais de Associação Espacial (Lisa) para os 5.564 municípios do país. Resultados : A região Norte destaca-se pelas maiores taxas de detecção e mortalidade de HBV do país. O Índice Global de Moran revelou uma correlação espacial dos casos de HBV no Brasil, e o Lisa Map evidenciou a presença de bolsões (tipo high-high), principalmente na região Norte e também em alguns municípios de Santa Catarina, Paraná, Rio Grande do Sul, Espírito Santo, São Paulo e Rio de Janeiro. Conclusão : A análise espacial do padrão de distribuição do HBV no Brasil revela áreas com grande concentração de casos, particularmente no Norte do país e em outros pontos distribuídos pelo território nacional. Esses dados reforçam a urgência de ações de intervenção relativas a prevenção, diagnóstico e tratamento da hepatite B.

ABSTRACT Objective: To analyze the pattern of spatial distribution of hepatitis B virus (HBV) cases and the mortality attributed to this disease throughout the Brazilian territory, in 2005, 2016 and 2017. Methods: This is an ecological study of spatial analysis, using data from the Information System for Notifiable Diseases and the Brazilian Mortality Information System. HBV detection and mortality rates were analyzed. The spatial analysis from 2005 to 2017 was held through the Global Moran’s Index (I) for global data and the Local Indicators of Spatial Association (LISA) for the 5,564 municipalities of the country. Results: The North region stands out with the highest HBV detection and mortality rates in the country. The Global Moran’s I showed a spatial correlation of HBV cases in Brazil, and the LISA Map evidenced the presence of hotspots or spatial clusters (high-high type), mainly in the North region and also in some municipalities of Santa Catarina, Paraná, Rio Grande do Sul, Espírito Santo, São Paulo and Rio de Janeiro. Conclusion: The spatial analysis of the HBV distribution pattern in Brazil shows areas with a large concentration of cases, particularly in the North of the country and in other points distributed throughout the national territory. These data reinforce the urgency of intervention actions related to prevention, diagnosis and treatment of hepatitis B.

OBJECTIVES: Our objective was to analyze, in a population treated for hepatitis C infection at a tertiary care treatment unit, the prevalence of comorbidities and extrahepatic manifestations, the range and degree of the clinical complexity and the associations between advanced liver disease and clinical variables. METHODS: Medical records from chronically infected hepatitis C patients seen at a dedicated treatment facility for complex cases in the Infectious Diseases Division of Hospital das Clínicas in Brazil were analyzed. Clinical complexity was defined as the presence of one or more of the following conditions: advanced liver disease (Metavir score F3 or F4 and/or clinical manifestations or ultrasound/endoscopy findings consistent with cirrhosis) or hepatocellular carcinoma and/or 3 or more extrahepatic manifestations and/or comorbidities concomitantly. RESULTS: Among the 1574 patients analyzed, only 41% met the definition of being clinically complex. Cirrhosis or hepatocarcinoma was identified in 22.2% and 1.8% of patients, respectively. According to multiple logistic regression analysis, male sex (p=0.007), age>40 years (p<0.001) and the presence of metabolic syndrome (p=0.008) were independently associated with advanced liver disease. CONCLUSION: The majority of patients did not meet the criteria for admittance to this specialized tertiary service, reinforcing the need to reevaluate public health policies. Enhanced utilization of existing basic and intermediate complexity units for the management of less complex hepatitis C cases could improve care and lower costs.

Abstract INTRODUCTION: Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) have identical transmission routes, explaining the high prevalence of coinfections. The main aim of this study was to detect fluctuations in serological HCV levels in HIV patients. METHODS: We analyzed samples of 147 patients who attended an outpatient service that supports HIV/AIDS patients in São Paulo city. We also recruited 22 HCV-monoinfected patients who attended the Instituto Adolfo Lutz Laboratory in São Paulo city, to compare the test results. Serological testing of the blood samples was performed for the detection of HCV antibodies. The samples were then analyzed using real-time PCR for RNA viral quantification and sequencing. RESULTS We found that 13.6% of the study population was coinfected with HIV and HCV. In 20% of coinfected patients, fluctuations in serology results were detected in samples collected during the follow-up. No changes in anti-HCV serological markers were observed in HCV-monoinfected patients. An HCV viral load was detected in 9,5% of the samples collected from HIV patients. CONCLUSIONS: Our findings provide important clinical data to public health professionals and highlight the importance of periodic monitoring of HCV/HIV coinfected patients.