RESUMEN
BACKGROUND: Current evidence regarding COVID-19 convalescent plasma (CCP) transfusion practices is limited and heterogeneous. We aimed to determine the impact of the use of CCP transfusion in patients with previous circulating neutralizing antibodies (nAbs) in COVID-19. METHODS: Prospective cohort including 102 patients with COVID-19 transfused with ABO compatible CCP on days 0-2 after enrollment. Clinical status of patients was assessed using the adapted World Health Organization (WHO) ordinal scale on days 0, 5, and 14. The nAbs titration was performed using the cytopathic effect-based virus neutralization test with SARS-CoV-2 (GenBank MT126808.1). The primary outcome was clinical improvement on day 14, defined as a reduction of at least two points on the adapted WHO ordinal scale. Secondary outcomes were the number of intensive care unit (ICU)-free days and the number of invasive mechanical ventilation-free days. RESULTS: Both nAbs of CCP units transfused (p < 0.001) and nAbs of patients before CCP transfusions (p = 0.028) were associated with clinical improvements by day 14. No significant associations between nAbs of patients or CCP units transfused were observed in the number of ICU or mechanical ventilation-free days. Administration of CCP units after 10 days of symptom onset resulted in a decrease in ICU-free days (p < 0.001) and mechanical ventilation-free days (p < 0.001). CONCLUSION: Transfusion of high titer nAbs CCP units may be a determinant in clinical strategies against COVID-19. We consider these data as useful parameters to guide future CCP transfusion practices.
Asunto(s)
Anticuerpos Neutralizantes/sangre , COVID-19/terapia , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Donantes de Sangre , COVID-19/sangre , COVID-19/inmunología , Estudios de Cohortes , Femenino , Humanos , Inmunización Pasiva/métodos , Masculino , Persona de Mediana Edad , SARS-CoV-2/inmunología , Sueroterapia para COVID-19RESUMEN
BACKGROUND: Blood groups and anti-A isohemagglutinin may be involved in susceptibility to SARS-CoV-2 infection. MATERIALS AND METHODS: We retrospectively studied 268 COVID-19 convalescent plasma donors and 162 COVID-19 inpatients (total 430 subjects, confirmed by RT-PCR) and 2,212 healthy volunteer first-time blood donors as a control group. These were further divided into two groups: those with anti-A (blood types O and B) and those without it (types A and AB). Titres of nucleoproteins, and neutralizing SARS-CoV-2 antibody were measured in the convalescent plasma donors and inpatients. Multivariate logistic regression and non-parametric tests were applied. RESULTS: Persons having types O or B showed less infection prevalence than those of types A or AB (OR = 0·62, 95% CI 0·50-0·78; P < 0·001), but there was no difference when COVID-19 inpatients were analysed. Immunoglobulins M, G and A were lower in COVID-19 subjects of types O or B group than those of A or AB (0·16 vs. 0·19; P = 0·03, 2·11 vs. 2·55; P = 0·02, 0·23 vs. 0·32; P = 0·03, respectively). CONCLUSION: In this retrospective cohort, COVID-19 individuals were less likely to belong to blood types O and B, and also had lower SARS-CoV-2 antibody titres than A and AB individuals. COVID-19 severity did not associate with the blood groups.
Asunto(s)
Sistema del Grupo Sanguíneo ABO/sangre , Anticuerpos Antivirales/sangre , COVID-19/sangre , COVID-19/terapia , Adulto , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , COVID-19/inmunología , Hemaglutininas/inmunología , Humanos , Inmunización Pasiva , Masculino , Persona de Mediana Edad , SARS-CoV-2/inmunología , Sueroterapia para COVID-19RESUMEN
Hereditary Xerocytosis (HX) is an autosomal dominantly inherited congenital hemolytic anemia associated with erythrocyte dehydration due to decreased intracellular potassium content resulting in increased mean corpuscular hemoglobin concentration. The affected members of HX families show compensated anemia with splenomegaly, hemosiderosis, and perinatal edema but are in large part transfusion independent. Functional studies show a link between mutations in mechanosensitive ion channel, encoded by PIEZO1 gene and the HX. We identified new PIEZO1 variants that are likely pathogenic in three phenotypically characterized multi-generational HX Brazilian families. Interestingly, one missense variant of the PIEZO1 gene identified, p.E2494V was associated in trans with the previously reported most frequent pathogenic duplication p.E2496ELE. The three-dimensional structure of the human protein modeled using structural coordinates of the mouse Piezo1 solved by cryo-electron microscopy (Cryo-ME) showed that the two identified variants, p.M2007L and p.T2014I, are localized to an important mechanosensitive transmembrane domain suggesting a conformational mechanism for altered channel's gating. The p.E2496ELE variant identified alters the extension of helix α1 bringing it much closer to the beam affecting the position of it structure at the end of the pore.
Asunto(s)
Anemia Hemolítica Congénita/genética , Hidropesía Fetal/genética , Canales Iónicos , Mutación Missense , Adolescente , Adulto , Sustitución de Aminoácidos , Animales , Niño , Femenino , Humanos , Recién Nacido , Canales Iónicos/química , Canales Iónicos/genética , Masculino , Ratones , Persona de Mediana Edad , Conformación Proteica en Hélice alfa , Dominios ProteicosRESUMEN
AIMS: Brazil ranks high in the number of coronavirus disease 19 (COVID-19) cases and the COVID-19 mortality rate. In this context, autopsies are important to confirm the disease, determine associated conditions, and study the pathophysiology of this novel disease. The aim of this study was to assess the systemic involvement of COVID-19. In order to follow biosafety recommendations, we used ultrasound-guided minimally invasive autopsy (MIA-US), and we present the results of 10 initial autopsies. METHODS AND RESULTS: We used MIA-US for tissue sampling of the lungs, liver, heart, kidneys, spleen, brain, skin, skeletal muscle and testis for histology, and reverse transcription polymerase chain reaction to detect severe acute respiratory syndrome coronavirus 2 RNA. All patients showed exudative/proliferative diffuse alveolar damage. There were intense pleomorphic cytopathic effects on the respiratory epithelium, including airway and alveolar cells. Fibrinous thrombi in alveolar arterioles were present in eight patients, and all patients showed a high density of alveolar megakaryocytes. Small thrombi were less frequently observed in the glomeruli, spleen, heart, dermis, testis, and liver sinusoids. The main systemic findings were associated with comorbidities, age, and sepsis, in addition to possible tissue damage due to the viral infection, such as myositis, dermatitis, myocarditis, and orchitis. CONCLUSIONS: MIA-US is safe and effective for the study of severe COVID-19. Our findings show that COVID-19 is a systemic disease causing major events in the lungs and with involvement of various organs and tissues. Pulmonary changes result from severe epithelial injury and microthrombotic vascular phenomena. These findings indicate that both epithelial and vascular injury should be addressed in therapeutic approaches.
Asunto(s)
Autopsia/métodos , COVID-19/patología , Adulto , Anciano , Anciano de 80 o más Años , Brasil , Femenino , Humanos , Masculino , Persona de Mediana Edad , SARS-CoV-2 , UltrasonografíaRESUMEN
Strongyloidiasis can occur without any symptoms or as a potentially fatal hyperinfection or disseminated infection, principally in immunosuppressed patients. Our study aimed to evaluate the application of conventional polymerase chain reaction (cPCR) and real-time PCR (qPCR). Polymerase chain reaction (PCR) and real-time PCR (qPCR) targeting the 18S rRNA gene for detection of Strongyloides stercoralis infection among transplant candidates were applied in stool samples obtained from 150 transplant candidates, preliminarily analyzed by parasitological methods. S. stercoralis larvae were visualized in 15/150 (10.0%) transplant candidates by parasitological methods. DNA from S. stercoralis was amplified in 26/150 (17.3%) and 49/150 (32.7%) stool samples of transplant candidates, using cPCR and qPCR, respectively. The results suggest that molecular methods, especially qPCR, should be used as an additional tool for diagnostic of S. stercoralis infection among transplant candidates.
Asunto(s)
ADN de Helmintos/aislamiento & purificación , Heces/parasitología , Análisis de Secuencia de ADN/métodos , Strongyloides stercoralis/aislamiento & purificación , Estrongiloidiasis/diagnóstico , Animales , Brasil/epidemiología , Genes de ARNr/genética , Humanos , Huésped Inmunocomprometido , Larva , Prevalencia , Reacción en Cadena en Tiempo Real de la Polimerasa , Sensibilidad y Especificidad , Strongyloides stercoralis/genética , Estrongiloidiasis/epidemiología , Estrongiloidiasis/inmunología , Estrongiloidiasis/parasitología , Trasplante/efectos adversosRESUMEN
BACKGROUND: The use of point-of-care testing (POCT) in different clinical applications is justified by the fact that the time to release the result is shortened, allowing the physician to define the diagnosis and most appropriate therapy in a shorter time. However, the negative aspects must also be highlighted and studied so that we can move forward with the use of these devices. These negative aspects include greater analytical imprecision compared to laboratory automation, the variability between different equipment from different manufacturers, the risk of inappropriate use, a low level of global regulation, higher costs compared with laboratory testing and cost ineffectiveness in terms of health care. Methods and. RESULTS: This review presents some clinical applications of POCT in different scenarios, such as for diabetes mellitus, infectious diseases, pediatrics, and chronic kidney disease, among others. CONCLUSIONS: We hope to see a global consensus on an acceptable quality standard for performing POCT that is adaptable, practical, and cost effective in primary care settings, ensuring patient safety, and minimizing the risk of harm.
Asunto(s)
Sistemas de Atención de Punto/normas , Pruebas en el Punto de Atención/normas , Enfermedades Transmisibles/diagnóstico , Enfermedades Transmisibles/terapia , Análisis Costo-Beneficio , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/terapia , Humanos , Sistemas de Atención de Punto/economía , Sistemas de Atención de Punto/estadística & datos numéricos , Pruebas en el Punto de Atención/economía , Pruebas en el Punto de Atención/estadística & datos numéricos , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/terapiaRESUMEN
Point-of-Care Testing (POCT) has been highlighted in the health care sector in recent decades. On the other hand, due to its low demand, POCT is at a disadvantage compared to conventional equipment, since its cost is inversely proportional to the volume of use. In addition, for the implementation of POCT to succeed, it is essential to rely on the work of a multidisciplinary team. The awareness of health professionals of the importance of each step is perhaps the critical success factor. The trend towards the continuous advancement of the use of POCT and the great potential of its contributions reinforce the need to implement quality management tools, including performance indicators, to ensure their results. This review presents some advantages and disadvantages concerning POCT and the real need to use it. A worldwide call for the availability of easy-to-use health technologies that are increasingly closer to the final user is one of the main reasons for this focus.
Asunto(s)
Técnicas de Laboratorio Clínico/normas , Guías como Asunto/normas , Sistemas de Atención de Punto/normas , Pruebas en el Punto de Atención/normas , Técnicas de Laboratorio Clínico/economía , Técnicas de Laboratorio Clínico/métodos , Análisis Costo-Beneficio , Humanos , Sistemas de Atención de Punto/economía , Pruebas en el Punto de Atención/economía , Reproducibilidad de los ResultadosRESUMEN
We detected Zika virus in breast milk of a woman in Brazil infected with the virus during the 36th week of pregnancy. Virus was detected 33 days after onset of signs and symptoms and 9 days after delivery. No abnormalities were found during fetal assessment or after birth of the infant.
Asunto(s)
Leche Humana/virología , Complicaciones Infecciosas del Embarazo/diagnóstico , Complicaciones Infecciosas del Embarazo/virología , Infección por el Virus Zika/diagnóstico , Infección por el Virus Zika/virología , Virus Zika , Adulto , Brasil , Femenino , Humanos , Lactante , Reacción en Cadena de la Polimerasa , Embarazo , Complicaciones Infecciosas del Embarazo/epidemiología , Resultado del Embarazo , ARN Viral , Carga Viral , Infección por el Virus Zika/epidemiologíaRESUMEN
South America is considered to have a low prevalence of hepatitis B virus (HBV) infection, although areas with a relatively high prevalence have been identified in northern Brazil. Few epidemiological studies of populations at risk of HBV infection are available for this region. Given this, in the present study, we investigated the prevalence of HBV and the factors associated with infection among illicit drug users (DUs) in the Marajó Archipelago, northern Brazil. In this cross-sectional study, we collected samples and epidemiological information from DUs in 11 municipalities of the Marajó Archipelago. The diagnosis was established by ELISA and real-time PCR; and genotyping was done by multiplex real-time PCR. Statistical modeling was based on simple and multiple logistical regressions with the Hosmer-Lemeshow test. The mean age of the 466 DUs was 28.4 years, and most were male. The most-consumed illicit drugs were crack cocaine and marijuana. In all, 171 DUs were exposed to HBV, with genotypes A, D and F being identified. The factors associated with higher frequencies of HBV infection were (i) male gender, (ii) age above 35 years, (iii) anti-HIV positivity, (iv) tattoos, (v) the use of injected drugs, (vi) the use of illicit drugs for more than 3 years, (vii) sexual relations without protection, (viii) sexual relations with another DU, and (ix) more than 10 sexual partners in the past 24 months. In summary, this study provides important insights into the dynamics of HBV infection among DUs in the Marajó Archipelago. We hope that these findings will contribute to the development of strategies, actions and public health policies aimed at preventing and controlling this viral infection more effectively.
Asunto(s)
Consumidores de Drogas , Virus de la Hepatitis B/clasificación , Virus de la Hepatitis B/genética , Hepatitis B/epidemiología , Hepatitis B/virología , Trastornos Relacionados con Sustancias/complicaciones , Adulto , Distribución por Edad , Brasil/epidemiología , Ensayo de Inmunoadsorción Enzimática , Femenino , Técnicas de Genotipaje , Virus de la Hepatitis B/aislamiento & purificación , Humanos , Drogas Ilícitas , Masculino , Reacción en Cadena de la Polimerasa , Factores de Riesgo , Distribución por SexoAsunto(s)
COVID-19/transmisión , Sangre Fetal/virología , Transmisión Vertical de Enfermedad Infecciosa , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , SARS-CoV-2/aislamiento & purificación , Adulto , COVID-19/virología , Femenino , Humanos , Recién Nacido , Masculino , Embarazo , Complicaciones Infecciosas del Embarazo , SARS-CoV-2/genéticaRESUMEN
Hepatitis C virus (HCV) infection affects approximately 3 % of the world population. HCV targets hepatic tissue, and most infected patients develop a chronic infection. Currently, studies have demonstrated an association between HCV-RNA replication and miR-122, the most abundant microRNA in the liver. Our aim was to evaluate liver and serum expression of miR-122 in patients infected with HCV genotypes 1 and 3, and to identify possible associations between miR-122 expression and lipid profiles, HCV viral load, apolipoproteins and liver enzymes. MicroRNAs were isolated from blood and liver tissue, and miR-122 expression was quantified by real-time PCR. HCV viral load was quantified by real-time PCR and HCV genotype, and serum biomarkers were obtained from medical report. The levels of miR-122 were higher in liver than those in blood from individuals infected with HCV genotypes 1 and 3 (p < 0.0001). The tissue levels of miR-122 were higher in subjects infected with HCV genotype 3 (6.22-fold, p < 0.001). A positive correlation was observed between the blood and hepatic levels of miR-122 in patients infected with HCV genotype 1 (r = 0.302, p = 0.026); in these patients, an inverse correlation was observed between serum apolipoprotein A-II (ApoA-II) levels and the blood (r = -0.330; p = 0.014) and hepatic (r = -0.311; p = 0.020) levels of miR-122. In patients infected with HCV genotype 3, there was a positive correlation between the hepatic miR-122 and the high-density lipoprotein-HDL (r = 0.412, p = 0.036) and insulin (r = 0.478, p = 0.044). Lipid metabolism proteins and miR-122 expression levels have different relations in HCV-3- and HCV-1-infected patients.
Asunto(s)
Regulación de la Expresión Génica , Genotipo , Hepacivirus/genética , Hepatitis C/genética , Hepatitis C/virología , Hígado/metabolismo , Hígado/virología , MicroARNs/genética , Adulto , Biomarcadores , Biopsia , Femenino , Hepatitis C/metabolismo , Hepatitis C Crónica/genética , Hepatitis C Crónica/metabolismo , Hepatitis C Crónica/virología , Humanos , Metabolismo de los Lípidos , Hígado/patología , Cirrosis Hepática/etiología , Cirrosis Hepática/patología , Pruebas de Función Hepática , Masculino , MicroARNs/sangre , Persona de Mediana Edad , Carga ViralAsunto(s)
COVID-19 , COVID-19/terapia , Convalecencia , Humanos , Inmunización Pasiva , Plasma , SARS-CoV-2 , Sueroterapia para COVID-19RESUMEN
The hepatitis E virus is a major etiological agent of chronic hepatitis in immunosuppressed individuals. Seroprevalence in the liver transplantation setting varies according to the seroprevalence of the general population in different countries. This was a prospective cohort study of liver transplant recipients in southeastern Brazil. Recipients were systematically followed for one year, with the objective of determining the prevalence, incidence, and natural history of HEV infection in this population. We included 107 liver transplant recipients and 83 deceased donors. Positivity for anti-HEV IgG was detected in 10.2% of the recipients and in 9.7% of the donors. None of the patients tested positive for HEV RNA at baseline or during follow-up. There were no episodes of reactivation or seroconversion, even in cases of serological donor-recipient mismatch or in recipients with acute hepatitis. Acute and chronic HEV infections seem to be rare events in the region studied. That could be attributable to social, economic, and environmental factors. Our data indicate that, among liver transplant recipients, hepatitis E should be investigated only when there are elevated levels of transaminases with no defined cause, as part of the differential diagnosis of seronegative hepatitis after transplantation.
Asunto(s)
Virus de la Hepatitis E , Hepatitis E , Trasplante de Hígado , Humanos , Virus de la Hepatitis E/genética , Trasplante de Hígado/efectos adversos , Estudios Prospectivos , Brasil/epidemiología , Estudios Seroepidemiológicos , Reinfección , ARN Viral/genética , Estudios de Cohortes , Anticuerpos Antihepatitis , Infección PersistenteRESUMEN
BACKGROUND: The quasispecies composition of Hepatitis C virus (HCV) could have important implications with regard to viral persistence and response to interferon-based therapy. The complete NS5A was analyzed to evaluate whether the composition of NS5A quasispecies of HCV 1a/1b is related to responsiveness to combined interferon pegylated (PEG-IFN) and ribavirin therapy. METHODS: Viral RNA was isolated from serum samples collected before, during and after treatment from virological sustained responder (SVR), non-responder (NR) and the end-of-treatment responder patients (ETR). NS5A region was amplified, cloned and sequenced. Six hundred and ninety full-length NS5A sequences were analyzed. RESULTS: This study provides evidence that lower nucleotide diversity of the NS5A region pre-therapy is associated with viral clearance. Analysis of samples of NRs and the ETRs time points showed that genetic diversity of populations tend to decrease over time. Post-therapy population of ETRs presented higher genetic distance from baseline probably due to the bottleneck phenomenon observed for those patients in the end of treatment. The viral effective population of those patients also showed a strong decrease after therapy. Otherwise, NRs demonstrated a continuous variation or stability of effective populations and genetic diversity over time that did not seem to be related to therapy. Phylogenetic relationships concerning complete NS5A sequences obtained from patients did not demonstrate clustering associated with specific response patterns. However, distinctive clustering of pre/post-therapy sequences was observed. In addition, the evolution of quasispecies over time was subjected to purifying or relaxed purifying selection. Codons 157 (P03), 182 and 440 (P42), 62 and 404 (P44) were found to be under positive selective pressure but it failed to be related to the therapy. CONCLUSION: These results confirm the hypothesis that a relationship exists between NS5A heterogeneity and response to therapy in patients infected with chronic hepatitis C.
Asunto(s)
Antivirales/uso terapéutico , Hepacivirus/efectos de los fármacos , Hepatitis C Crónica/virología , Adulto , Secuencia de Aminoácidos , Análisis por Conglomerados , Evolución Molecular , Femenino , Hepacivirus/clasificación , Hepacivirus/genética , Hepatitis C Crónica/sangre , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Modelos Biológicos , Datos de Secuencia Molecular , Mutación , Filogenia , ARN Viral/sangre , Alineación de Secuencia , Análisis de Secuencia de ARN , Proteínas no Estructurales Virales/genéticaRESUMEN
Background: Symptomatic patients with COVID-19 typically have a high SARS-CoV-2 viral load in their saliva. Procedures to reduce the viral load in their oral cavity are important for mitigating the viral transmission. Methods: This randomized clinical trial investigated the impact of two mouthwashes (0.075% cetylpyridinium chloride plus 0.28% zinc lactate (CPC+Zn) (n = 32), and 0.075% cetylpyridinium chloride (CPC) (n = 31)) on the viral load of SARS-CoV-2 in saliva when compared to the distilled water negative control (n = 32). Saliva was collected before (T0) and after (5 min, T1; 30 min, T2; and 60 min, T3) the intervention. Viral load in saliva was measured by qRT-PCR assays. The data in both groups was normalized for T0 and Negative Control, resulting in fold change values. Results: CPC+Zn oral solution reduced the viral load in saliva by 6.34-fold at T1, 3.6-fold at T2 and 1.9-fold at T3. Rinsing with the CPC mouthwash reduced the viral load in saliva by 2.5-fold at T1, 1.9-fold at T2 and 2.0-fold at T3. Conclusion: CPC+Zn mouthwash or with the CPC mouthwash reduced the viral load in saliva of COVID-19 patients immediately after rinsing. These reductions extended up to 60 min.
Asunto(s)
Antiinfecciosos Locales , COVID-19 , Humanos , Cetilpiridinio , Antisépticos Bucales , Saliva , SARS-CoV-2 , Carga ViralRESUMEN
Hepatitis E virus (HEV) is an emerging zoonotic pathogen associated with relevant public health issues. The aim of this study was to investigate HEV presence in free-living capybaras inhabiting urban parks in São Paulo state, Brazil. Molecular characterization of HEV positive samples was undertaken to elucidate the genetic diversity of the virus in these animals. A total of 337 fecal samples were screened for HEV using RT-qPCR and further confirmed by conventional nested RT-PCR. HEV genotype and subtype were determined using Sanger and next-generation sequencing. HEV was detected in one specimen (0.3%) and assigned as HEV-3f. The IAL-HEV_921 HEV-3f strain showed a close relationship to European swine, wild boar and human strains (90.7-93.2% nt), suggesting an interspecies transmission. Molecular epidemiology of HEV is poorly investigated in Brazil; subtype 3f has been reported in swine. This is the first report of HEV detected in capybara stool samples worldwide.
Asunto(s)
Virus de la Hepatitis E , Humanos , Animales , Porcinos , Brasil/epidemiología , Virus de la Hepatitis E/genética , Roedores , Heces , GenotipoRESUMEN
BACKGROUND: Hepatitis B virus (HBV) infection is one of the most prevalent viral infections in humans and represents a serious public health problem. In Colombia, our group reported recently the presence of subgenotypes F3, A2 and genotype G in Bogotá. The aim of this study was to characterize the HBV genotypes circulating in Quibdó, the largest Afro-descendant community in Colombia. Sixty HBsAg-positive samples were studied. A fragment of 1306 bp (S/POL) was amplified by nested PCR. Positive samples to S/POL fragment were submitted to PCR amplification of the HBV complete genome. FINDINGS: The distribution of HBV genotypes was: A1 (52.17%), E (39.13%), D3 (4.3%) and F3/A1 (4.3%). An HBV recombinant strain subgenotype F3/A1 was found for the first time. CONCLUSIONS: This study is the first analysis of complete HBV genome sequences from Afro-Colombian population. It was found an important presence of HBV/A1 and HBV/E genotypes. A new recombinant strain of HBV genotype F3/A1 was reported in this population. This fact may be correlated with the introduction of these genotypes in the times of slavery.
Asunto(s)
Variación Genética , Genoma Viral/genética , Virus de la Hepatitis B/clasificación , Hepatitis B/virología , Filogenia , África/etnología , Secuencia de Bases , Teorema de Bayes , Colombia/epidemiología , ADN Viral/química , ADN Viral/genética , Genotipo , Hepatitis B/etnología , Antígenos de Superficie de la Hepatitis B/inmunología , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/aislamiento & purificación , Humanos , Epidemiología Molecular , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , Análisis de Secuencia de ADNRESUMEN
BACKGROUND: Multi-organ damage is a common feature of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, going beyond the initially observed severe pneumonia. Evidence that the testis is also compromised is growing. OBJECTIVE: To describe the pathological findings in testes from fatal cases of COVID-19, including the detection of viral particles and antigens, and inflammatory cell subsets. MATERIALS AND METHODS: Postmortem testicular samples were obtained by percutaneous puncture from 11 deceased men and examined by reverse-transcription polymerase chain reaction (RT-PCR) for RNA detection and by light and electron microscopy (EM) for SARS-CoV-2. Immunohistochemistry (IHC) for the SARS-CoV-2 N-protein and lymphocytic and histiocytic markers was also performed. RESULTS: Eight patients had mild interstitial orchitis, composed mainly of CD68+ and TCD8+ cells. Fibrin thrombi were detected in five cases. All cases presented congestion, interstitial edema, thickening of the tubular basal membrane, decreased Leydig and Sertoli cells with reduced spermatogenesis, and strong expression of vascular cell adhesion molecule (VCAM) in vessels. IHC detected SARS-Cov-2 antigen in Leydig cells, Sertoli cells, spermatogonia, and fibroblasts in all cases. EM detected viral particles in the cytoplasm of fibroblasts, endothelium, Sertoli and Leydig cells, spermatids, and epithelial cells of the rete testis in four cases, while RT-PCR detected SARS-CoV-2 RNA in three cases. DISCUSSION AND CONCLUSION: The COVID-19-associated testicular lesion revealed a combination of orchitis, vascular changes, basal membrane thickening, Leydig and Sertoli cell scarcity, and reduced spermatogenesis associated with SARS-CoV-2 local infection that may impair hormonal function and fertility in men.
Asunto(s)
COVID-19/complicaciones , Orquitis/patología , Orquitis/virología , Testículo/patología , Adulto , Anciano , Anciano de 80 o más Años , Autopsia , Humanos , Masculino , Persona de Mediana Edad , SARS-CoV-2RESUMEN
Human respiratory syncytial virus (HRSV) is the major cause of lower respiratory tract infections in children under 5 years of age and the elderly, causing annual disease outbreaks during the fall and winter. Multiple lineages of the HRSVA and HRSVB serotypes co-circulate within a single outbreak and display a strongly temporal pattern of genetic variation, with a replacement of dominant genotypes occurring during consecutive years. In the present study we utilized phylogenetic methods to detect and map sites subject to adaptive evolution in the G protein of HRSVA and HRSVB. A total of 29 and 23 amino acid sites were found to be putatively positively selected in HRSVA and HRSVB, respectively. Several of these sites defined genotypes and lineages within genotypes in both groups, and correlated well with epitopes previously described in group A. Remarkably, 18 of these positively selected tended to revert in time to a previous codon state, producing a "flip-flop" phylogenetic pattern. Such frequent evolutionary reversals in HRSV are indicative of a combination of frequent positive selection, reflecting the changing immune status of the human population, and a limited repertoire of functionally viable amino acids at specific amino acid sites.
Asunto(s)
Sustitución de Aminoácidos , Evolución Molecular , Proteínas de Unión al GTP/genética , Virus Sincitiales Respiratorios/genética , Proteínas Virales/genética , Epítopos , Variación Genética , Genotipo , Humanos , Filogenia , Infecciones del Sistema RespiratorioRESUMEN
BACKGROUND: HBV-HIV co-infection is associated with an increased liver-related morbidity and mortality. However, little is known about the natural history of chronic hepatitis B in HIV-infected individuals under highly active antiretroviral therapy (HAART) receiving at least one of the two drugs that also affect HBV (TDF and LAM). Information about HBeAg status and HBV viremia in HIV/HBV co-infected patients is scarce. The objective of this study was to search for clinical and virological variables associated with HBeAg status and HBV viremia in patients of an HIV/HBV co-infected cohort. METHODS: A retrospective cross-sectional study was performed, of HBsAg-positive HIV-infected patients in treatment between 1994 and 2007 in two AIDS outpatient clinics located in the São Paulo metropolitan area, Brazil. The baseline data were age, sex, CD4 T+ cell count, ALT level, HIV and HBV viral load, HBV genotype, and duration of antiretroviral use. The variables associated to HBeAg status and HBV viremia were assessed using logistic regression. RESULTS: A total of 86 HBsAg patients were included in the study. Of these, 48 (56%) were using combination therapy that included lamivudine (LAM) and tenofovir (TDF), 31 (36%) were using LAM monotherapy, and 7 patients had no previous use of either one. Duration of use of TDF and LAM varied from 4 to 21 and 7 to 144 months, respectively. A total of 42 (48.9%) patients were HBeAg positive and 44 (51.1%) were HBeAg negative. The multivariate analysis revealed that the use of TDF for longer than 12 months was associated with undetectable HBV DNA viral load (serum HBV DNA level < 60 UI/ml) (p = 0.047). HBeAg positivity was associated with HBV DNA > 60 UI/ml (p = 0.001) and ALT levels above normality (p = 0.038). CONCLUSION: Prolonged use of TDF containing HAART is associated with undetectable HBV DNA viral load. HBeAg positivity is associated with HBV viremia and increased ALT levels.