Prevalence and clinical consequences of Hepatitis C virus infection in patients undergoing hematopoietic stem cell transplantation.

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.

Prevalence and clinical consequences of Hepatitis C virus infection in patients undergoing hematopoietic stem cell transplantation

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.

Absence of neutralizing antibodies against the Omicron SARS-CoV-2 variant in convalescent sera from individuals infected with the ancestral SARS-CoV-2 virus or its Gamma variant.

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.

Lactobacilluscrispatus dominance in the vaginalmicrobiome reduces the occurrence of spontaneouspreterm birth in women with a short cervical length / Dominância de Lactobacillus crispatus no microbioma vaginal reduz a ocorrênciade parto prematuro espontâneo em mulheres com encurtamento do colo uterino

Introduction: The majority of pregnant women with a short cervix will deliver at term and, thus, may unnecessarily receive advanced monitoring and treatment. It is still necessary to define more accurately which sub-population of women with a short cervix is at elevated risk for early delivery. Objective: To determine if vaginal microbiome composition influenced the rate of spontaneous preterm birth in women with a short cervical length. Methods: In an exploratory, observational prospective study, vaginal secretions were obtained from 591 women at 21­24 week gestation. Vaginal microbiome composition was determined by analyzing the V1­V3 region of the bacterial 16S ribosomal RNA gene. Results: Lactobacillus crispatus was numerically dominant in the vagina in 41.7% of subjects, followed by L. iners in 32% and Gardnerella vaginalis in 12%. In women whose cervix was ≤25mm, the sensitivity to predict an spontaneous preterm birth was 11.8%. However, when L. crispatus was not the dominant vaginal bacterium, this sensitivity increased to 81.8%. Similarly, in women with a cervical length ≤30mm, the sensitivity to predict an spontaneous preterm birth increased from 21.7 to 78.3% when L. crispatus was not the dominant vaginal bacterium.In women with a prior spontaneous preterm birth and a cervix ≤25 or ≤30mm, L. crispatus dominance was also associated with a reduced rate of spontaneous preterm birth in the current pregnancy (p<0.001). Conclusion: In pregnant women with a cervix ≤25mm or ≤30mm, the risk for an spontaneous preterm birth is increased if L. crispatus is not dominant in the vagina.

Introdução: A maioria das mulheres grávidas com colo do útero curto dará à luz a termo e, portanto, pode receber desnecessariamente monitoramento e tratamento avançados. Permanece a necessidade de definir com mais precisão qual subpopulação de mulheres com colo do útero curto está em risco elevado de parto prematuro. Objetivo: Determinar se a composição do microbioma vaginal influenciou a taxa de parto prematuro espontâneo em mulheres com colo curto. Métodos: Em um estudo prospectivo exploratório observacional, os conteúdos vaginais foram obtidos de 591 mulheres com 21­24 semanas de gestação. A composição do microbioma vaginal foi determinada pela análise da região V1­V3 do gene de RNA ribossômico bacteriano 16S. Resultados: Lactobacilluscrispatus foi numericamente dominante na vagina em 41,7% dos indivíduos, seguido por L. iners em 32% e Gardnerella vaginalis em 12%. Em mulheres cujo colo do útero era <25 mm, a sensibilidade para prever uma taxa de parto prematuro espontâneo foi de 11,8%. No entanto, quando L. crispatus não era a bactéria vaginal dominante, essa sensibilidade aumentou para 81,8%. Da mesma forma, em mulheres com comprimento cervical <30 mm, a sensibilidade para prever uma taxa de parto prematuro espontâneo aumentou de 21,7 para 78,3% quando L. crispatus não era a bactéria vaginal dominante. Em mulheres com taxa de parto prematuro espontâneo anterior e colo do útero <25 ou <30 mm, a dominância de L. crispatus também foi associada a uma taxa reduzida de taxa de parto prematuro espontâneo na gravidez atual (p<0,001). Conclusão: Em mulheres grávidas com colo do útero <25 ou <30 mm, o risco de parto prematuro espontâneo é aumentado se L. crispatus não for dominante na vagina.

Absence of neutralizing antibodies against the Omicron SARS-CoV-2 variant in convalescent sera from individuals infected with the ancestral SARS-CoV-2 virus or its Gamma variant

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.

Impact on mortality of being seropositive for hepatitis C virus antibodies among blood donors in Brazil: A twenty-year study.

INTRODUCTION: Hepatitis C virus (HCV) infection is a major health problem associated with considerable risk of mortality in different regions of the world. The purpose of this study was to investigate the contribution of HCV infection on all-cause and liver-related mortality, in a large cohort of blood donors in Brazil. METHODS: This is a retrospective cohort study of blood donors from 1994 to 2013, at Fundação Pró-Sangue-Hemocentro de São Paulo (FPS). This cohort included 2,892 and 5,784 HCV antibody seropositive and seronegative donors, respectively. Records from the FPS database and the Mortality Information System (SIM: a national database in Brazil) were linked through a probabilistic record linkage (RL). Mortality outcomes were defined based on ICD-10 (10th International Statistical Classification of Diseases and Related Health Problems) codes listed as the cause of death on the death certificate. Hazard ratios (HRs) were estimated for outcomes using Cox multiple regression models. RESULTS: When all causes of death were considered, RL identified 209 deaths (7.2%) among seropositive blood donors and 190 (3.3%) among seronegative blood donors. Donors seropositive for HCV infection had a 2.5 times higher risk of death due to all causes (95% CI: 1.76-2.62; p<0.001). When only liver-related causes of death were considered, RL identified 73 deaths among seropositive blood donors and only 6 among seronegative blood donors. Donors seropositive for HCV infection had a 23.4 times higher risk of death due to liver related causes (95% CI: 10.2-53.9; p<0.001). Donors seropositive for HCV had a 29.5 (95%CI: 3.9-221.7), 2.8 (95% CI: 1.4-5.5) and a 1.9 (95% CI: 1.2-3.0) times higher risk of death due to hepatocellular carcinoma, infection or trauma, respectively, compared to seronegative donors. CONCLUSIONS: All-cause and liver-related mortality rate was increased among blood donors seropositive for HCV compared with the mortality rate among seronegative blood donors. Our data confirms HCV as a relevant cause of death in Brazil and also suggest that interventions directed at following patients even after access to specific drug treatment are urgent and necessary.

Mannose-binding lectin gene polymorphism and risk factors for cardiovascular disease in postmenopausal women.

BACKGROUND: Inflammatory responses may be altered in postmenopausal women and predispose to cardiovascular disease (CVD). Genetic factors can also influence susceptibility to CVD. Mannose-binding lectin (MBL) is a component of the innate immune system and an activator of the complement cascade. We evaluated the association of genetic polymorphism of MBL (MBL2) on risk factors for CVD in postmenopausal women. METHODS: In this cross-sectional study, 311 Brazilian women (age ≥45 years and amenorrhea ≥12 months) were included. EXCLUSION CRITERIA: presence of previous or current CVD, insulin dependent diabetes, chronic kidney disease, autoimmune diseases and cancer. Clinical, anthropometric and biochemical assessments were performed to evaluate the cardiovascular risk factors. DNA was extracted from buccal cell and polymorphisms at codons 54 and 57 in the MBL2 were determined by polymerase chain reaction (PCR). For statistical analysis, the chi-square and logistic regression (odds ratio, OR) were used. RESULTS: The presence of the polymorphic allele for codon 54 was found in 25.8% of women (A/B=22.6%, B/B=3.2%) and for codon 57 in 12.2% (A/C=10.8%, C/C=1.4%). The polymorphism at codon 54 was significantly associated with the presence of hypertension (OR 0.55, 95% CI 0.31-0.99, p=0.044) and insulin resistance assessed by HOMA-IR (OR 0.46, 95% CI 0.24-0.91, p=0.025). No significant associations were observed between the polymorphism at codon 57 with risk factors for CVD. CONCLUSION: In postmenopausal women, the polymorphism at codon 54 of the MBL2 was associated with lower risk for hypertension and insulin resistance that are important risk factors for CVD.

Evaluation of clinical and inflammatory markers of subclinical carotid atherosclerosis in postmenopausal women.

OBJECTIVE: This study aims to evaluate clinical and inflammatory markers of subclinical carotid atherosclerosis (ATS) in asymptomatic postmenopausal women. METHODS: This cross-sectional study included 268 Brazilian women (aged ≥45 y and amenorrhea ≥12 mo). Subclinical ATS was defined as increased carotid intima-media thickness (>1.0 mm) and/or the presence of plaques evaluated by carotid duplex ultrasound. Inflammatory markers included C-reactive protein (CRP), as well as heat shock protein (HSP) 60 and HSP70 and their antibodies. Pearson's correlation and stepwise logistic regression were used for statistical analysis. RESULTS: Among the women studied, 45.9% (123 of 268) had a diagnosis of ATS, and 54.1% (145 of 268) had normal carotid ultrasound scans (controls). Women with ATS were older (56.6 vs 52.5 y), and their time since menopause was longer (6.0 vs 4.0 y). In addition, higher prevalences of metabolic syndrome (39.0% vs 25.5%), hypertension (52.0% vs 30.3%), and diabetes (11.4% vs 4.8%), and elevated circulating levels of CRP and HSP60, were observed in women with ATS compared with controls (P < 0.05). Intima-media thickness was positively correlated with anti-HSP70 antibodies (r = 0.110, P = 0.049) and CRP (r = 0.167, P = 0.009). ATS risk increased with age at menopause (odds ratio [OR], 1.18; 95% CI, 1.10-1.26), time since menopause (OR, 1.12; 95% CI, 1.02-1.14), and glucose of 100 mg/dL or higher (OR, 2.17; 95% CI, 1.12-4.20). Serum HSP70 levels (OR, 0.71; 95% CI, 0.47-0.98) were associated with a lower ATS risk (P < 0.05). CONCLUSIONS: In postmenopausal women, age, menopause status, and hyperglycemia are associated with a higher prevalence of ATS, whereas elevated serum HSP70 is associated with a lower prevalence of ATS.