RESUMO
This chapter summarizes the epidemiological study design of natural immune epidemiology studies based on recent COVID-19-related research. The epidemiological studies on antiviral innate immunity have mainly included randomized controlled trials (RCTs) and observational studies. Importantly, this chapter will discuss how to use these methodologies to answer an epidemiological question of natural immunity in the viral infection process based on previous studies. An observational case- or cohort-based study of antiviral innate immunity may support this theoretical hypothesis but is not appropriate for clinical practice or treatment. RCTs are the gold standard for epidemiological studies and occupy a greater role in the hierarchy of evidence.
Assuntos
COVID-19 , Imunidade Inata , SARS-CoV-2 , Humanos , COVID-19/imunologia , COVID-19/epidemiologia , COVID-19/virologia , SARS-CoV-2/imunologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Epidemiológicos , Antivirais/uso terapêutico , Estudos Observacionais como AssuntoRESUMO
Silver nanoparticles (AgNPs) are a potential antiviral agent due to their ability to disrupt the viral particle or alter the virus metabolism inside the host cell. In vitro, AgNPs exhibit antiviral activity against the most common human respiratory viruses. However, their capacity to modulate immune responses during respiratory viral infections has yet to be explored. This study demonstrates that administering AgNPs directly into the lungs prior to infection can reduce viral loads and therefore virus-induced cytokines in mice infected with influenza virus or murine pneumonia virus. The prophylactic effect was diminished in mice with depleted lymphoid cells. We showed that AgNPs-treatment resulted in the recruitment and activation of lymphocytes in the lungs, particularly natural killer (NK) cells. Mechanistically, AgNPs enhanced the ability of alveolar macrophages to promote both NK cell migration and IFN-γ production. By contrast, following infection, in mice treated with AgNPs, NK cells exhibited decreased activation, indicating that these nanoparticles can regulate the potentially deleterious activation of these cells. Overall, the data suggest that AgNPs may possess prophylactic antiviral properties by recruiting and controlling the activation of lymphoid cells through interaction with alveolar macrophages.
Assuntos
Células Matadoras Naturais , Pulmão , Nanopartículas Metálicas , Infecções por Orthomyxoviridae , Prata , Animais , Prata/química , Prata/farmacologia , Nanopartículas Metálicas/química , Pulmão/virologia , Pulmão/patologia , Pulmão/efeitos dos fármacos , Infecções por Orthomyxoviridae/prevenção & controle , Infecções por Orthomyxoviridae/tratamento farmacológico , Infecções por Orthomyxoviridae/virologia , Camundongos , Células Matadoras Naturais/efeitos dos fármacos , Macrófagos Alveolares/efeitos dos fármacos , Macrófagos Alveolares/metabolismo , Macrófagos Alveolares/virologia , Camundongos Endogâmicos C57BL , Linfócitos/efeitos dos fármacos , Linfócitos/metabolismo , Antivirais/farmacologia , Antivirais/uso terapêutico , Feminino , Ativação Linfocitária/efeitos dos fármacosRESUMO
Cytomegalovirus is the most common cause of congenital infection worldwide. 90 % of children infected in utero are born without symptoms, but 15 % of them will develop disorders within the first five years of life. The most common disorders affect the inner ear, resulting in sensorineural hearing loss and/or vestibular dysfunction (VD). VD is often unrecognized and confused with conditions -affecting the central nervous system. It can cause delays in psychomotor development and predispose to overall developmental delay. Early diagnosis and treatment are essential to prevent or limit these sequelae. Antiviral treatment during the pre- and neonatal periods should be considered.
Le cytomégalovirus est la cause la plus fréquente d'infection congénitale dans le monde. 90 % des enfants infectés in utero naissent sans symptôme, mais 15 % d'entre eux vont développer des atteintes au cours des cinq premières années de vie. Les plus fréquentes touchent l'oreille interne, engendrant unesurdité neurosensorielle et/ou une dysfonction vestibulaire (DV). La DV est souvent méconnue et confondue avec des atteintes du système nerveux central. Elle peut provoquer des retards du développement psychomoteur et prédisposer à un retard global du développement. Un diagnostic et une prise en charge précoces sont essentiels pour prévenir ou limiter ces séquelles. Un traitement antiviral en période pré et néonatale doit être considéré.
Assuntos
Infecções por Citomegalovirus , Humanos , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/congênito , Infecções por Citomegalovirus/complicações , Recém-Nascido , Gravidez , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Neurossensorial/etiologia , Perda Auditiva Neurossensorial/virologia , Perda Auditiva Neurossensorial/epidemiologia , Feminino , Complicações Infecciosas na Gravidez/diagnóstico , Doenças Vestibulares/diagnóstico , Doenças Vestibulares/epidemiologia , Doenças Vestibulares/etiologia , Antivirais/uso terapêuticoAssuntos
Herpes Zoster , Inibidores de Janus Quinases , Humanos , Herpes Zoster/tratamento farmacológico , Herpes Zoster/diagnóstico , Inibidores de Janus Quinases/uso terapêutico , Inibidores de Janus Quinases/efeitos adversos , Inibidores de Janus Quinases/administração & dosagem , Masculino , Feminino , Pessoa de Meia-Idade , Pirimidinas/efeitos adversos , Pirimidinas/administração & dosagem , Idoso , Antivirais/administração & dosagem , Antivirais/uso terapêutico , Antivirais/efeitos adversos , Pirazóis/efeitos adversos , Pirazóis/administração & dosagem , Administração Oral , PiperidinasAssuntos
Anticorpos Monoclonais Humanizados , Antivirais , Infecções por Vírus Respiratório Sincicial , Humanos , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Lactente , Antivirais/uso terapêutico , Palivizumab/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Recém-NascidoRESUMO
OBJECTIVES: Influenza A and B viruses cause epidemics every year, with approximately 3-5 million serious cases and about 290,000 to 650,000 deaths worldwide. Most patients die from bacterial complications of influenza. The aim of our study was to describe the clinical pictures of influenza and the development of the complications in seniors over 65 years of age, who were treated in University Hospital Pilsen. The course of the disease and changes in laboratory parameters were evaluated with regard to the method of treatment performed. METHODS: A descriptive retrospective study was performed. Clinical and laboratory data of seniors with the diagnosis of influenza were extracted from electronic medical records and later analysed. The data were processed with Excel 2016 and Statistica. RESULTS: A collection of 261 seniors, of whom 218 were hospitalized and 43 treated in an outpatient setting, has been studied. Patients who later developed complications had elevated values of CRP, procalcitonin, urea, and creatinine. The antiviral drug oseltamivir was administered to 226 of 261 seniors. Forty-seven seniors (18.0%) died from influenza and its complications (severe pneumonia with acute respiratory insufficiency or heart failure). CONCLUSIONS: The course of influenza in seniors was usually more severe and required hospitalization along with antiviral treatment. The mortality rate in the monitored group exceeded 18%. Annual timely vaccination, but also other preventive measures, and maybe considering other risk groups are methods to prevent severe or even fatal cases of influenza.
Assuntos
Antivirais , Influenza Humana , Humanos , Idoso , Influenza Humana/epidemiologia , Influenza Humana/complicações , Masculino , Feminino , Estudos Retrospectivos , Idoso de 80 Anos ou mais , Antivirais/uso terapêutico , Vírus da Influenza A/isolamento & purificação , Oseltamivir/uso terapêutico , Hospitalização/estatística & dados numéricosRESUMO
PURPOSE: Evaluate cytomegalovirus (CMV) post-prophylaxis surveillance in high-risk (D+/R-) kidney and liver transplant recipients. METHODS: Adult D+/R- patients were included if transplanted between 6/1/15 and 11/30/22 and divided into a pre-CMV-stewardship-era (6/1/15-5/31/18), CMV-stewardship-era (6/1/18-6/30/20), and a surveillance-era (7/1/2020-11/30/2022) then followed through 12 months. The primary objective was to evaluate CMV-related outcomes. The secondary objective was to assess graft and patient survival by era. RESULTS: There were 328 patients in the study period; 133 in the pre-stewardship-era, 103 in the stewardship-era, and 92 in the surveillance-era. Replication rates in the surveillance-era were significantly higher, as anticipated due to increased sampling (pre 38.4%, stewardship 33.0%, surveillance 52.2%, p = 0.02). Time from transplant to first replication was similar (pre 214.0 ± 79.0 days, stewardship 231.1 ± 65.5, surveillance 234.9 ± 61.4, p = 0.29). CMV viral load (VL) at first detection, maximum-VL, and incidence of VL > 100 000 IU/mL were numerically lower in the surveillance era, although not statistically significant. CMV end-organ disease (p < 0.0001) and ganciclovir-resistance (p = 0.002) were significantly lower in the surveillance era than in both previous eras. Rejection was not different between eras (p = 0.4). Graft (p = 0.0007) and patient survival (p = 0.008) were significantly improved in the surveillance era. CONCLUSIONS: Post-prophylaxis surveillance significantly reduced CMV end-organ disease and resistance. Despite observing increased replication rates in the surveillance era, rejection was not significantly different and there was no graft loss or patient mortality at 12 months.
Assuntos
Antivirais , Infecções por Citomegalovirus , Citomegalovirus , Farmacorresistência Viral , Ganciclovir , Rejeição de Enxerto , Sobrevivência de Enxerto , Transplante de Rim , Transplante de Fígado , Humanos , Infecções por Citomegalovirus/prevenção & controle , Infecções por Citomegalovirus/virologia , Infecções por Citomegalovirus/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Citomegalovirus/isolamento & purificação , Citomegalovirus/efeitos dos fármacos , Antivirais/uso terapêutico , Ganciclovir/uso terapêutico , Seguimentos , Transplante de Fígado/efeitos adversos , Fatores de Risco , Transplante de Rim/efeitos adversos , Prognóstico , Rejeição de Enxerto/prevenção & controle , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/virologia , Complicações Pós-Operatórias/prevenção & controle , Adulto , Taxa de Sobrevida , Estudos Retrospectivos , Transplantados/estatística & dados numéricosAssuntos
Antivirais , Tratamento Farmacológico da COVID-19 , Combinação de Medicamentos , Hospitalização , Hospedeiro Imunocomprometido , Ritonavir , Humanos , Ritonavir/uso terapêutico , Ritonavir/administração & dosagem , Hospitalização/estatística & dados numéricos , Antivirais/uso terapêutico , Antivirais/administração & dosagem , Citidina/análogos & derivados , Citidina/uso terapêutico , Hidroxilaminas/uso terapêutico , Leucina/análogos & derivados , Leucina/uso terapêutico , Prolina/análogos & derivados , Prolina/uso terapêutico , Sulfonamidas/administração & dosagem , Sulfonamidas/uso terapêutico , COVID-19/prevenção & controle , Lactamas , NitrilasAssuntos
Antivirais , Tratamento Farmacológico da COVID-19 , COVID-19 , Citidina , Hospitalização , Hidroxilaminas , Humanos , Hospitalização/estatística & dados numéricos , COVID-19/prevenção & controle , COVID-19/mortalidade , Antivirais/uso terapêutico , Antivirais/administração & dosagem , Citidina/análogos & derivados , Citidina/uso terapêutico , Hidroxilaminas/uso terapêutico , Hidroxilaminas/administração & dosagem , Vacinas contra COVID-19/administração & dosagem , Adulto , Masculino , Pessoa de Meia-Idade , Feminino , Fatores de Tempo , IdosoRESUMO
Cytomegalovirus (CMV) infection is arguably the most important infectious complication that negatively affects the outcome of solid organ transplantation. For decades, CMV management after transplantation has relied on antiviral drugs that inhibit viral DNA polymerase (ganciclovir, foscarnet, and cidofovir). However, their use has been complicated by myelosuppression, nephrotoxicity, and selection of drug-resistant viruses. During the past few years, the therapeutic armamentarium for the management of CMV in solid organ transplant recipients has expanded with the approval of letermovir for CMV prophylaxis in high-risk CMV D+/R- kidney recipients, and maribavir for the treatment of refractory and resistant CMV infection. Both drugs offer significant improvement when compared to standard anti-CMV therapies; letermovir was as efficacious for CMV prevention, whereas maribavir was more effective in treating refractory and resistant CMV infections. Both letermovir and maribavir have favorable safety profiles compared to CMV DNA polymerase inhibitors, without the risk of neutropenia and leukopenia associated with ganciclovir and renal toxicities associated with foscarnet and cidofovir. Moreover, letermovir and maribavir are orally bioavailable, which allows convenient outpatient treatment. However, letermovir and maribavir have a significant drug interaction potential in solid organ transplant recipients, resulting in higher levels of calcineurin inhibitors (cyclosporine and tacrolimus) and mTOR inhibitors (sirolimus and everolimus). Both letermovir and maribavir are CMV-specific and do not have clinical efficacy against other herpes viruses. Thus, there is a need for additional antiviral drugs to prevent herpes simplex and other herpes viruses when clinically indicated. This article provides a comprehensive review of the clinical data supporting the use of letermovir and maribavir in clinical practice. The author provides perspectives on the role of these newly approved drugs in the current management landscape of CMV infection in solid organ transplantation.
Assuntos
Acetatos , Antivirais , Infecções por Citomegalovirus , Transplante de Órgãos , Quinazolinas , Ribonucleosídeos , Humanos , Infecções por Citomegalovirus/tratamento farmacológico , Antivirais/uso terapêutico , Antivirais/efeitos adversos , Antivirais/farmacologia , Ribonucleosídeos/uso terapêutico , Ribonucleosídeos/efeitos adversos , Ribonucleosídeos/farmacologia , Transplante de Órgãos/efeitos adversos , Acetatos/uso terapêutico , Acetatos/efeitos adversos , Acetatos/farmacologia , Quinazolinas/uso terapêutico , Quinazolinas/farmacologia , Benzimidazóis/uso terapêutico , Benzimidazóis/efeitos adversos , Benzimidazóis/farmacologia , Citomegalovirus/efeitos dos fármacos , Diclororribofuranosilbenzimidazol/análogos & derivadosRESUMO
BACKGROUND: Influenza A (H1N1) is a contagious respiratory infection caused by the influenza A virus. In the majority of cases, H1N1 influenza is benign. However, it can be dangerous for infants and children with underlying chronic diseases. The severity of influenza depends on various factors, including the virulence of the virus strain, preexisting immunity level, and individual health conditions. The aim of this study is to describe the clinical profile of H1N1 influenza in hospitalized infants and children. METHODS: This is a prospective and descriptive study conducted from November 1, 2018, to January 31, 2024. In this study, we included all children under 14 years old hospitalized for suspected severe lower respiratory infection who had gone through virological testing. We used a multiplex polymerase chain reaction (PCR) kit: the Film Array-Respiratory Panel. Due to the depletion of multiplex PCR kits, this study continued using rapid influenza diagnostic tests based on immunochromatographic technique. RESULTS: We report 45 confirmed cases of H1N1 influenza, collected during the period from November 1, 2018, to January 31, 2024. The average age was 2 years and 4 months. The main reason for admission was respiratory distress found in all patients. In 53% of the cases, there was an associated comorbidity, including asthma (17 cases), prematurity (2 cases), congenital adrenal hyperplasia (2 cases), cystic fibrosis (1 case), undetermined etiology bronchial dilation (1 case), and Basedow's disease (1 case). The clinical presentation included viral bronchiolitis (17 cases), moderate asthma exacerbation (10 cases), severe asthma exacerbation (7 cases), pneumonia (9 cases), bronchial dilation exacerbation (1 case), and flu-like syndrome with adrenal insufficiency (1 case). Fever was present in 31 patients. Gastrointestinal symptoms such as diarrhea and vomiting were present in 20 cases. Three patients required intensive care, with 2 children being intubated and ventilated (one severe acute asthma and one severe viral bronchiolitis). Two cases were treated with oseltamivir. The average length of hospital stay was 7.5 days, ranging from 3 to 20 days. All cases showed favorable evolution. CONCLUSIONS: We conclude that preventive measures remain crucial, and influenza vaccination is highly recommended in cases of underlying morbidity.
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Vírus da Influenza A Subtipo H1N1 , Influenza Humana , Humanos , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Influenza Humana/diagnóstico , Influenza Humana/virologia , Influenza Humana/epidemiologia , Influenza Humana/complicações , Pré-Escolar , Feminino , Masculino , Lactente , Estudos Prospectivos , Criança , Hospitalização , Adolescente , Criança Hospitalizada , Antivirais/uso terapêuticoRESUMO
BACKGROUND/AIM: Tenofovir amibufenamide (TMF) employs innovative ProTide technology and a methylation strategy to enhance the lipid solubility and plasma stability of the amide bond, providing advantages over tenofovir alafenamide (TAF). Despite promising Phase III clinical trial results demonstrating its antiviral efficacy, real-world data on TMF remains scarce. This study evaluates the antiviral efficacy and safety of TMF compared to TAF as the initial treatment in patients with high viral loads of chronic hepatitis B (CHB). METHODS: We retrospectively collected clinical data from March 1 2022 to June 30 2022 for highly viremic CHB patients who received either TMF (n = 58) or TAF (n = 32) as their initial monotherapy at Beijing YouAn Hospital. To understand the efficacy and safety of TMF over 48 weeks, we compared the virological response rates and HBeAg/HBsAg serological clearance rates between TMF and TAF groups. Also, the changes in serum creatinine, eGFR and serum lipid levels were assessed. RESULTS: Baseline median HBV DNA levels were 7.85 (6.89, 8.36) IgIU/ml for TMF and 7.44 (6.89, 8.03) IgIU/ml for TAF. Median ALT levels were 102.0 (56.0, 210.0) U/L for TMF and 195.0 (73.5, 371.0) U/L for TAF, with HBeAg positivity rates of 70.7% and 75.0%, respectively. At 48 weeks, virological response rates (HBV DNA <10 IU/ml) were 43.5% (20/46) for TMF and 42.9% (12/28) for TAF (p = 1.000). ALT normalization rates were 87.9% for TMF and 90.6% for TAF (p = .969), and HBeAg serological clearance rates were 21.1% and 18.2%, respectively (p = 1.000). No patients achieved HBsAg clearance. Compared with the baseline, LDL-C levels increased, while eGFR decreased, with no significant differences in serum creatinine, triglycerides and total cholesterol levels noted at week 48 for both TMF and TAF groups. CONCLUSION: TMF demonstrates comparable antiviral efficacy to TAF when used as initial therapy in highly viremic CHB patients, with similar impacts on renal function and lipid profiles.
Assuntos
Antivirais , Hepatite B Crônica , Tenofovir , Carga Viral , Humanos , Tenofovir/uso terapêutico , Tenofovir/análogos & derivados , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/virologia , Hepatite B Crônica/sangue , Masculino , Feminino , Carga Viral/efeitos dos fármacos , Estudos Retrospectivos , Antivirais/uso terapêutico , Antivirais/efeitos adversos , Antivirais/farmacologia , Adulto , Pessoa de Meia-Idade , Resultado do Tratamento , Vírus da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/genética , Alanina/análogos & derivados , Alanina/uso terapêutico , Adenina/análogos & derivados , Adenina/uso terapêutico , Adenina/efeitos adversos , DNA Viral/sangueRESUMO
BACKGROUND: Respiratory syncytial virus (RSV) is associated with substantial morbidity among infants. This study modelled the potential public health and economic impact of nirsevimab, a long-acting monoclonal antibody, as an immunoprophylactic strategy for all infants in Spain in their first RSV season. METHODS: A static decision-analytic model of the Spanish birth cohort during its first RSV season was developed to estimate the impact of nirsevimab on RSV-related health events and costs versus the standard of practice (SoP). Spain-specific costs and epidemiological data were used as model inputs. Modelled outcomes included RSV-related outpatient visits, emerging room (ER) visits, hospitalisations - including pediatric intensive care unit (PICU) admission, mechanical ventilation, and inpatient mortality. RESULTS: Under the current SoP, RSV caused 151,741 primary care visits, 38,798 ER visits, 12,889 hospitalisations, 1,412 PICU admissions, and 16 deaths over a single season, representing a cost of 71.8 million from a healthcare payer perspective. Universal immunisation of all infants with nirsevimab was expected to prevent 97,157 primary care visits (64.0% reduction), 24,789 ER visits (63.9%), 8,185 hospitalisations (63.5%), 869 PICU admissions (61.5%), and 9 inpatient deaths (52.6%), saving 47.8 million (62.4%) in healthcare costs. CONCLUSIONS: These results suggest that immunisation with nirsevimab of all infants experiencing their first RSV season in Spain is likely to prevent thousands of RSV-related health events and save considerable costs versus the current SoP.
Assuntos
Anticorpos Monoclonais Humanizados , Infecções por Vírus Respiratório Sincicial , Humanos , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Infecções por Vírus Respiratório Sincicial/economia , Espanha/epidemiologia , Lactente , Recém-Nascido , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/economia , Hospitalização/estatística & dados numéricos , Hospitalização/economia , Feminino , Masculino , Antivirais/uso terapêutico , Antivirais/economia , Custos de Cuidados de Saúde/estatística & dados numéricosRESUMO
Remdesivir therapy has been declared as efficient in the early stages of Covid-19. Of the 339 patients (males 55.8%, age 71(59;77) years) with a detectable viral load, 140 were treated with remdesivir (of those 103 in the ICU and 57 immunosuppressed) and retrospectively compared with 199 patients (of those 82 in the ICU and 28 immunosuppressed) who were denied therapy due to advanced Covid-19. The viral load was estimated by detecting nucleocapsid antigen in serum (n = 155, median 217(28;1524)pg/ml), antigen in sputum (n = 18, COI 18(4.6;32)), nasopharyngeal antigen (n = 44, COI 17(8;35)) and the real-time PCR (n = 122, Ct 21(18;27)). After adjustment for confounders, patients on remdesivir had better 12-month survival (HR 0.66 (0.44;0.98), p = 0.039), particularly when admitted to the ICU (HR 0.49 (0.29;0.81), p = 0.006). For the immunocompromised patients, the difference did not reach statistical significance (HR 0.55 (0.18;1.69), p = 0.3). The other most significant confounders were age, ICU admission, mechanical ventilation, leukocyte/lymphocyte ratio, admission creatinine and immunosuppression. The impact of monoclonal antibodies or previous vaccinations was not significant. Despite frequent immune suppression including haemato-oncology diseases, lymphopenia, and higher inflammatory markers in the remdesivir group, the results support remdesivir administration with respect to widely available estimates of viral load in patients with high illness severity.
Assuntos
Monofosfato de Adenosina , Alanina , Antivirais , Tratamento Farmacológico da COVID-19 , COVID-19 , SARS-CoV-2 , Carga Viral , Humanos , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Alanina/análogos & derivados , Alanina/uso terapêutico , Masculino , Feminino , Carga Viral/efeitos dos fármacos , Idoso , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/fisiologia , Pessoa de Meia-Idade , COVID-19/virologia , COVID-19/mortalidade , Antivirais/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento , Cuidados Críticos , Unidades de Terapia Intensiva , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Direct acting antivirals (DAAs) for the Hepatitis C virus (HCV) have shifted the World Health Organisation global strategic focus to the elimination of HCV by 2030. In England, the UK Health Security Agency (UKHSA) led a national 'patient re-engagement exercise', using routine surveillance data, which was delivered through the HCV Operational Delivery Networks (ODNs) with support from National Health Service England (NHSE), to help find and support people with a positive HCV PCR test result to access treatment. We report a quantitative evaluation of outcomes of this exercise. METHODS: Individuals with a recorded positive HCV antibody or PCR result between 1996 and 2017 were identified using UKHSA's records of HCV laboratory diagnosis. Linkage with established health-care datasets helped to enhance patient identification and minimise attempts to contact deceased or previously treated individuals. From September to November 2018 each ODN was provided with a local list of diagnosed individuals. ODNs were asked to perform further data quality checks through local systems and then write to each individual's GP to inform them that the individual would be contacted by the ODN to offer confirmatory HCV PCR testing, assessment and treatment unless the GP advised otherwise. Outcomes of interest were receipt of treatment, a negative PCR result, and death. Data were collected in 2022. RESULTS: Of 176,555 individuals with a positive HCV laboratory report, 55,329 individuals were included in the exercise following linkage to healthcare datasets and data reconciliation. Participants in the study had a median age of 51 years (IQR: 43, 59), 36,779 (66.5%) were males, 47,668 (86.2%) were diagnosed before 2016 and 11,148 (20.2%) lived in London. Of the study population, 7,442 (13.4%) had evidence of treatment after the re-engagement exercise commenced, 6,435 (11.6%) were reported as PCR negative (96% had no previous treatment records), 4,195 (7.6%) had prescription data indicating treatment before the exercise commenced or were reported to have been treated previously by their ODN, and 2,990 (5.4%) had died. The status of 32,802 (59.3%) people remains unknown. CONCLUSIONS: A substantial number of those included had treatment recorded after the exercise commenced, however, many more remain unengaged. Evaluation of the exercise highlighted areas that could be streamlined to improve future exercises.
Assuntos
Antivirais , Humanos , Masculino , Antivirais/uso terapêutico , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto , Inglaterra/epidemiologia , Hepatite C/tratamento farmacológico , Hepatite C/diagnóstico , Idoso , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Hepacivirus/isolamento & purificaçãoRESUMO
BACKGROUND: Hydroxychloroquine (HCQ) has proved ineffective in treating patients hospitalised with Coronavirus Disease 2019 (COVID-19), but uncertainty remains over its safety and efficacy in chemoprevention. Previous chemoprevention randomised controlled trials (RCTs) did not individually show benefit of HCQ against COVID-19 and, although meta-analysis did suggest clinical benefit, guidelines recommend against its use. METHODS AND FINDINGS: Healthy adult participants from the healthcare setting, and later from the community, were enrolled in 26 centres in 11 countries to a double-blind, placebo-controlled, randomised trial of COVID-19 chemoprevention. HCQ was evaluated in Europe and Africa, and chloroquine (CQ) was evaluated in Asia, (both base equivalent of 155 mg once daily). The primary endpoint was symptomatic COVID-19, confirmed by PCR or seroconversion during the 3-month follow-up period. The secondary and tertiary endpoints were: asymptomatic laboratory-confirmed Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection; severity of COVID-19 symptoms; all-cause PCR-confirmed symptomatic acute respiratory illness (including SARS-CoV-2 infection); participant reported number of workdays lost; genetic and baseline biochemical markers associated with symptomatic COVID-19, respiratory illness and disease severity (not reported here); and health economic analyses of HCQ and CQ prophylaxis on costs and quality of life measures (not reported here). The primary and safety analyses were conducted in the intention-to-treat (ITT) population. Recruitment of 40,000 (20,000 HCQ arm, 20,000 CQ arm) participants was planned but was not possible because of protracted delays resulting from controversies over efficacy and adverse events with HCQ use, vaccine rollout in some countries, and other factors. Between 29 April 2020 and 10 March 2022, 4,652 participants (46% females) were enrolled (HCQ/CQ n = 2,320; placebo n = 2,332). The median (IQR) age was 29 (23 to 39) years. SARS-CoV-2 infections (symptomatic and asymptomatic) occurred in 1,071 (23%) participants. For the primary endpoint the incidence of symptomatic COVID-19 was 240/2,320 in the HCQ/CQ versus 284/2,332 in the placebo arms (risk ratio (RR) 0.85 [95% confidence interval, 0.72 to 1.00; p = 0.05]). For the secondary and tertiary outcomes asymptomatic SARS-CoV-2 infections occurred in 11.5% of HCQ/CQ recipients and 12.0% of placebo recipients: RR: 0.96 (95% CI, 0.82 to 1.12; p = 0.6). There were no differences in the severity of symptoms between the groups and no severe illnesses. HCQ/CQ chemoprevention was associated with fewer PCR-confirmed all-cause respiratory infections (predominantly SARS-CoV-2): RR 0.61 (95% CI, 0.42 to 0.88; p = 0.009) and fewer days lost to work because of illness: 104 days per 1,000 participants over 90 days (95% CI, 12 to 199 days; p < 0.001). The prespecified meta-analysis of all published pre-exposure RCTs indicates that HCQ/CQ prophylaxis provided a moderate protective benefit against symptomatic COVID-19: RR 0.80 (95% CI, 0.71 to 0.91). Both drugs were well tolerated with no drug-related serious adverse events (SAEs). Study limitations include the smaller than planned study size, the relatively low number of PCR-confirmed infections, and the lower comparative accuracy of serology endpoints (in particular, the adapted dried blood spot method) compared to the PCR endpoint. The COPCOV trial was registered with ClinicalTrials.gov; number NCT04303507. INTERPRETATION: In this large placebo-controlled, double-blind randomised trial, HCQ and CQ were safe and well tolerated in COVID-19 chemoprevention, and there was evidence of moderate protective benefit in a meta-analysis including this trial and similar RCTs. TRIAL REGISTRATION: ClinicalTrials.gov NCT04303507; ISRCTN Registry ISRCTN10207947.
Assuntos
Tratamento Farmacológico da COVID-19 , COVID-19 , Cloroquina , Hidroxicloroquina , SARS-CoV-2 , Humanos , Hidroxicloroquina/uso terapêutico , Hidroxicloroquina/efeitos adversos , Cloroquina/uso terapêutico , Cloroquina/efeitos adversos , Método Duplo-Cego , Feminino , Adulto , Masculino , COVID-19/prevenção & controle , COVID-19/epidemiologia , Pessoa de Meia-Idade , Antivirais/uso terapêutico , Antivirais/efeitos adversos , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Antiviral drugs show significant efficacy in non-severe COVID-19 cases, yet there remains a subset of moderate COVID-19 patients whose pneumonia continues to progress post a complete course of treatment. Plasma-activated water (PAW) possesses anti-SARS-CoV-2 properties. To explore the potential of PAW in improving pneumonia in COVID-19 patients following antiviral treatment failure, we conducted this study. METHODS: This was a randomized, controlled trial. Moderate COVID-19 patients with antiviral treatment failure were randomly assigned to the experimental group or the control group. They inhaled nebulized PAW or saline respectively. This was done twice daily for four consecutive days. We assessed improvement in chest CT on day 5, the rate of symptom resolution within 10 days, and safety. RESULTS: A total of 23 participants were included, with 11 receiving PAW and 12 receiving saline. The baseline characteristics of both groups were comparable. The experimental group showed a higher improvement rate in chest CT on day 5 (81.8% vs. 33.3%, p = 0.036). The cumulative disappearance rate of cough within 10 days was higher in the experimental group. Within 28 days, 4 patients in each group progressed to severe illness, and no patients died. No adverse reactions were reported from inhaling nebulized PAW. CONCLUSION: This pilot trial preliminarily confirmed that nebulized inhalation of PAW can alleviate pneumonia in moderate COVID-19 patients with antiviral treatment failure, with no adverse reactions observed. This still needs to be verified by large-scale studies. TRIAL REGISTRATION: Chinese Clinical Trial Registry; No.: ChiCTR2300078706 (retrospectively registered, 12/15/2023); URL: www.chictr.org.cn .
Assuntos
Antivirais , Tratamento Farmacológico da COVID-19 , COVID-19 , Nebulizadores e Vaporizadores , SARS-CoV-2 , Falha de Tratamento , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Projetos Piloto , Administração por Inalação , Antivirais/uso terapêutico , Antivirais/administração & dosagem , Idoso , Água , Adulto , Resultado do TratamentoRESUMO
A large scale of pandemic coronavirus disease (COVID-19) in the past five years motivates a great deal of endeavors donating to the exploration on therapeutic drugs against COVID-19 as well as other diseases caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Herein is an overview on the organic small molecules that are potentially employed to treat COVID-19 and other SARS-CoV-2-related diseases. These organic small molecules are accessed from both natural resources and synthetic strategies. Notably, typical natural products presented herein consist of polyphenols, lignans, alkaloids, terpenoids, and peptides, which exert an advantage for the further discovery of novel anti-COVID-19 drugs from plant herbs. On the other hand, synthetic prodrugs are composed of a series of inhibitors towards RNA-dependent RNA polymerase (RdRp), main protease (Mpro), 3-chymotrypsin-like cysteine protease (3CLpro), spike protein, papain-like protease (PLpro) of the SARS-CoV-2 as well as the angiotensin-converting enzyme 2 (ACE2) in the host cells. Synthetic strategies are worth taken into consideration because they are beneficial for designing novel anti-COVID-19 drugs in the coming investigations. Although examples collected herein are just a drop in the bucket, developments of organic small molecules against coronavirus infections are believed to pave a promising way for the discovery of multi-targeted therapeutic drugs against not only COVID-19 but also other virus-mediated diseases.
Assuntos
Antivirais , Produtos Biológicos , Tratamento Farmacológico da COVID-19 , SARS-CoV-2 , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Produtos Biológicos/síntese química , Humanos , Antivirais/farmacologia , Antivirais/química , Antivirais/síntese química , Antivirais/uso terapêutico , SARS-CoV-2/efeitos dos fármacos , COVID-19/virologia , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/farmacologia , Bibliotecas de Moléculas Pequenas/síntese química , Pró-Fármacos/farmacologia , Pró-Fármacos/química , Pró-Fármacos/síntese química , Pró-Fármacos/uso terapêuticoRESUMO
BACKGROUND: Nirsevimab is an extended half-life monoclonal antibody (mAb) licensed for the prevention of respiratory syncytial virus (RSV)-associated lower respiratory tract disease in neonates, infants and medically vulnerable children. We characterized RSV isolates recovered from participants enrolled in MEDLEY: a randomized, palivizumab-controlled phase 2/3 trial of nirsevimab in infants born preterm and/or with congenital heart disease or chronic lung disease of prematurity. METHODS: Participants were assessed in two RSV seasons (Season 1 and 2). Season 1 participants were randomized (2:1) to receive a single dose of nirsevimab (50 mg if weight <5 kg or 100 mg if weight ≥5 kg in Season 1; 200 mg in Season 2) followed by four monthly doses of placebo, or five once-monthly doses of palivizumab (15 mg/kg weight per dose). Season 2 participants continued nirsevimab and placebo (nirsevimab/nirsevimab) or were re-randomized (1:1) to switch to nirsevimab (palivizumab/nirsevimab) or continue palivizumab (palivizumab/palivizumab). Cases of RSV infection were identified by central testing of nasal swabs from participants seeking medical attention for respiratory illnesses. Nirsevimab and palivizumab binding site substitutions were assessed via microneutralization assay. RESULTS: Twenty-five cases of confirmed RSV infection were observed during the trial and sequenced: 12 in nirsevimab recipients and 10 in palivizumab recipients during Season 1, and 1 case in each Season 2 group. Molecular sequencing of RSV A (n = 14) isolates detected no nirsevimab binding site substitutions, and 3 palivizumab neutralization-resistant substitutions (Lys272Met, Lys272Thr, Ser275Leu). The nirsevimab binding site Ile206Met:Gln209Arg and Ile206Met:Gln209Arg:Ser211Asn substitutions were the only anti-RSV mAb binding site substitutions detected among RSV B isolates (n = 11). Nirsevimab neutralized all nirsevimab and palivizumab binding site substitutions in RSV A and B isolates recovered from MEDLEY participants. CONCLUSION: No binding site substitution detected during MEDLEY affected RSV susceptibility to nirsevimab neutralization.
Assuntos
Anticorpos Monoclonais Humanizados , Antivirais , Palivizumab , Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Humanos , Palivizumab/uso terapêutico , Palivizumab/administração & dosagem , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Lactente , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Antivirais/uso terapêutico , Antivirais/administração & dosagem , Método Duplo-Cego , Masculino , Vírus Sincicial Respiratório Humano/imunologia , Vírus Sincicial Respiratório Humano/efeitos dos fármacos , Vírus Sincicial Respiratório Humano/genética , Feminino , Recém-Nascido , Anticorpos Antivirais/imunologia , Pré-Escolar , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/sangueRESUMO
BACKGROUND: Studies have found dysbiosis of the gut microbiota in individuals infected with the hepatitis B virus (HBV). Tenofovir dipivoxil (TDF) is one of the preferred oral antiviral drugs used for the treatment of chronic hepatitis B (CHB), but the extent to which TDF is able to affect the gut microbiota and inflammatory factors of a patient remains largely unexplored. In this study, we collected stool samples from HBV patients prior to medication and from CHB patients treated with TDF. RESULTS: The gut microbiota and inflammatory factors were assessed in 42 healthy subjects (HC group), 109 HBV-infected subjects, including 48 CHB patients who were not medicated with nucleoside analogue drugs (No-NAs group), and 61 CHB patients who were medicated with TDF (TDF group). 16 S rRNA sequencing revealed that TDF treatment caused significant changes in the gut microbiota of HBV-infected individuals; however, the gut microbiota of HBV-infected individuals did not fully recover to a pre-dysbiosis state. The relative abundance of Bacteroidota gradually decreased from the HC group to the No-NAs and TDF groups. The relative abundance of Fusobacteriota was significantly higher in the No-NAs group than in the HC group. At the genus level, Dialister, Eubacterium_hallii_group, Halomonas, Collinsella, Sphingomonas, Xanthomonadaceae_unclassified, and Rhizobiaceae_unclassified were overrepresented; while the abundance of Bacteroides and Fusobacterium decreased significantly in the No-NAs and TDF groups. CONCLUSIONS: This study showed that TDF treatment significantly improved the regulation of the gut microbiota and aided in dysbiosis recovery. We did not observe significant improvement in serum inflammatory factor concentrations, which may be related to the relatively short duration of TDF administration in this study.